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Review ArticleSignificance and Biological Importance of Pyrimidine inthe Microbial World

Vinita Sharma1 Nitin Chitranshi23 and Ajay Kumar Agarwal4

1 School of Pharmacy Lloyd Institute of Management amp Technology Plot No 11 Knowledge Park II Greater NoidaUttar Pradesh 201306 India

2 Bioinformatics Centre Biotech Park Sector G Jankipuram Lucknow Uttar Pradesh 226021 India3 Gautam Buddh Technical University IET Campus Sitapur Road Lucknow Uttar Pradesh 226021 India4Department of Pharmaceutical Sciences University Institute of Pharmaceutical Sciences Kurukshetra UniversityKurukshetra Haryana 136119 India

Correspondence should be addressed to Nitin Chitranshi nitinbiotechparkgmailcom

Received 1 September 2013 Revised 13 January 2014 Accepted 14 January 2014 Published 23 March 2014

Academic Editor Armando Rossello

Copyright copy 2014 Vinita Sharma et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Microbes are unique creatures that adapt to varying lifestyles and environment resistance in extreme or adverse conditions Thegenetic architecture of microbe may bear a significant signature not only in the sequences position but also in the lifestyle to whichit is adapted It becomes a challenge for the society to find new chemical entities which can treat microbial infections The presentreview aims to focus on account of important chemical moiety that is pyrimidine and its various derivatives as antimicrobialagents In the current studies we represent more than 200 pyrimidines as antimicrobial agents with different mono- di- tri- andtetrasubstituted classes along with in vitro antimicrobial activities of pyrimidines derivatives which can facilitate the developmentof more potent and effective antimicrobial agents

1 Introduction

Resistance to antimicrobial agents has become an increas-ingly important and pressing global problemOf the 2millionpeople who acquire bacterial infection in US hospitals eachyear 70 of cases now involve strains that are resistantto at least one drug [1] In communities and hospitalsaround the world the number of patients with antibiotic-resistant infections continues to climb [2] A major causefor concern in the UK is methicillin-resistant Staphylococcusaureus (MRSA) which was at low levels a decade ago but nowaccounts for ca 50 of all S aureus isolates [3] Substantialinvestment and research in the field of anti-infectives are nowdesperately needed if a public health crisis is to be avertedThe causes of antimicrobial resistance are multifactorial Incase of an antibiotic it has been well documented thatresistance is mainly caused by continued overreliance onand imprudent use of these antibacterial agents [4] andincreasing evidence is being obtained suggesting that thesame may be true for the emergence of biocide resistance

[5 6] Of particular concern is the possible cross-resistance ofantibiotics and biocide due to common resistancemechanism[7 8] Metal resistance is being observed as the result ofpolluted environments [9 10]The consequence of continuedexposure to antibacterial environment is an enrichment ofbacteria that are intrinsically resistant to antimicrobials orhave acquired resistance mechanism to these substances [1112]

Structural modification of antimicrobial drugs to whichresistance has developed has been proven to be an effectivemeans of extending the lifespan of antifungal agents such asthe azoles [13] antiviral agents such as the nonnucleosidereverse transcriptase inhibitors [14] and various antibacterialagents including 120573-lactams and quinolones [15] It is notsurprising then that in response to antimicrobial resistancemajor pharmaceutical companies have tended to concentratetheir efforts on improving antimicrobial agents in establishedclasses [16] However with the portfolio of chemothera-peutics currently available it has been acknowledged thatresearchers are getting close to the end game in terms of

Hindawi Publishing CorporationInternational Journal of Medicinal ChemistryVolume 2014 Article ID 202784 31 pageshttpdxdoiorg1011552014202784

2 International Journal of Medicinal Chemistry

N1

NN2

N

N

3

N

N4

Figure 1 Pyridine and different isomeric forms of diazine family

parent structure alterations A call has therefore been madefor the development of new classes of drugs that work ondifferent target sites to those in current use [17 18]

Heterocyclic compounds are abundant in nature and areof great significance to life because their structural subunitsexist in many natural products such as vitamins hormonesand antibiotics [19 20] hence they have attracted consider-able attention in the design of biologically active molecules[21 22] and advanced organic chemistry [23 24] Also inthe family of heterocyclic compounds nitrogen containingheterocycles are an important class of compounds in themedicinal chemistry and also contributed to the society frombiological and industrial point which helps to understandlife processes [25] A totally unsaturated membered six-ringcontaining nitrogen is known as azine [26] or pyridine (1)with two nitrogen atoms it is known as diazine [27] and witha nitrogen at 12-position it is known as pyridine (2) at 13-position as pyrimidine (3) and at 14-position as pyrazine (4)(Figure 1) However the current review intends to focus onthe significance of pyrimidine class of antimicrobial agentsalong with clinical and in vitro applications of pyrimidinederivatives to facilitate the development of more potent aswell as effective antimicrobial agents

2 Pyrimidine General Introduction

Pyrimidines (5) are the heterocyclic aromatic compoundssimilar to benzene and pyridine containing two nitrogenatoms at positions 1 and 3 of the six membered ringsHeterocycles containing pyrimidine moiety are of greatinterest because they constitute an important class of naturaland nonnatural products many of which exhibit usefulbiological activities and clinical applications [28 29] Sub-stituted purines and pyrimidines occur very widely in livingorganisms and were some of the first compounds studied bythe organic chemists [30] (Figure 2(a))

Pyrimidines are biologically very important heterocyclesand represent by far the most ubiquitous members of thediazine family with uracil (6) and thymine (7) being con-stituents of ribonucleic acid (RNA) and deoxyribonucleicacid (DNA) and with cytosine (8) both being present inFigure 2(b)

In addition to this pyrimidines skeleton is also presentin many natural products such as vitamin B

1(thiamine) and

many synthetic compounds such as barbituric acid (9) andVeranal (10) which are used as hypnotics [31] (Figure 2(b))

3 Medicinal Properties of Pyrimidines

The presence of pyrimidine base in thymine cytosine anduracil which are the essential building blocks of nucleic

acids DNA and RNA is one possible reason for theirwidespread therapeutic applications The pyrimidines rep-resent one of the most active classes of compounds pos-sessing wide spectrum of biological activities like significantin vitro activity against unrelated DNA and RNA virusesincluding polioherpes viruses diuretic antitumour anti-HIV and cardiovascular [32] The literature survey indicatedthat a wide range of pharmacological activities are exhibitedby the compounds encompassing pyrimidines nucleus Inaddition to this various analogs of pyrimidines have beenfound to posses antibacterial [33ndash39] antifungal [40ndash43]antileishmanial [44] anti-inflammatory [45 46] analgesic[47] antihypertensive [48 49] antipyretic [50] antiviral [51ndash53] antidiabetic [54] antiallerggic [55] anticonvulsant [56]antioxidant [57 58] antihistaminic [59] herbicidal [60]and anticancer activities [61ndash64] and many of pyrimidinesderivatives are reported to possess potential central nervoussystem (CNS) depressant properties [65 66] and also act ascalcium channel blockers [67]

4 Clinical and PharmacologicalApplications of Pyrimidine inthe Microbial World Marketed Drugs

During the last two decades several pyrimidine derivativeshave been developed which are found to have wideclinicaland pharmacological applications [68]

41 Antibacterial Agents Drugs which are included inthis category are antifolates possessing antagonistic activityagainst folic acid and sulfa drugs which are sulphur contain-ing pyrimidine derivative drugs

411 Antifolates 2-Amino-4-hydroxypyrimidines are foundto be antagonists of folic acid [69] hence a large number of24-diaminopyrimidines have been synthesized as antifolatesand it was eventually proved that these pyrimidines areinhibitors dihydrofolate reductase (DHFR) [70 71] Notableamongst the 24-diaminopyrimidine drugs are the following

Trisubstituted Pyrimidine Containing Drugs Brodiprim (11)is found to be an effective antibacterial compound [72]Iclaprim (12) which is a new selective dihydrofolate inhibitorwas synthesized based on rational drug design and thisdrug is found to be active against methicillin- TMP- andvancomycin-resistant strains [73 74] Trimethoprim (13)is an antibacterial drug which selectively inhibits bacterialDHFR [75] (Figure 3)

Tetrasubstituted Pyrimidine Containing Drug Pyrime-thamine (14) is a selective inhibitor of the DHFR of malarialplasmodia [75] (Figure 3)

412 Sulfa Drugs Pyrimidine containing sulfa drugs areclassified on the basis of substitution and the classificationwith the respective example of drug is as follows

International Journal of Medicinal Chemistry 3

2

N3

N1

4

6

5

5

(a)

N

NH

O NH

O

O

NH NHNHNH

NH

O

O

Me

NH

O

OONH

O

OO

6 7 8 9 10

NH2

H3CH3C

(b)

Figure 2 (a) Pyrimidine (b) Pyrimidine containing natural and synthetic products

N

N

Cl

N

N

ON

N

OBr

ON

NO

OO

11 12 13 14

NH2

NH2

NH2

NH2

NH2NH2

NH2

H3CH3C

CH3

CH3

CH3

H2N

H3CO

H3CO

H5C2

Figure 3 Antibacterial drugs (antifolates) containing trisubstituted and tetrasubstituted pyrimidines

Monosubstituted and disubstituted sulfa drugs include sul-fadiazine (15) sulfamerazine (16) sulfadimidine (sulfamet-hazine) (17) sulfameythoxydiazine (18) and methyldiazine(19) (Figure 4) Sulfadiazine sulfamerazine and sulfadimi-dine are superior to other sulfonamides and are used insome acute bacterial infections cerebrospinal meningitisand patients allergic to penicillins [68] Sulfameythoxydi-azine (18) possesses a good half life and methyldiazine (19)possesses a longest half life of about 65 h [76]

Trisubstituted sulfa drugs include sulfadoxine (20) sulfi-somidine (21) sulfadimethoxine (22) sulfamethoxine (23)sulfamethomidine (24) and sulfacytine (25) (Figure 4)

Sulfadoxine which has a half life of 7ndash9 days is used formalarial prophylaxis [77] whereas sulfisomidine with a halflife of 7 hr is used as a combination sulfa therapy in humanserum hemolytic complement system [78] Sulfadimethoxinewas introduced in 1959 with a half life of approximately 40 hrand the related 4-sulfamidopyrimidine and sulfamethoxinehaving two methoxy groups in 5 and 6 positions have byfar the longest half life of about of 65 hr Further a newbroad-spectrum sulfonamide sulfamethomidine is relativelynontoxic and patients do need extra fluid to intake andsulfacytinehas been reported to be 3ndash10 times more potentthan sulfaisoxazole and sulfisomidine [76]

Sulfa drugs are known to possess good antibacterialactivity in combination with trimethoprim [24-diamino-5-(345-trimethoxy benzyl pyrimidine)] resulting in synergis-tic effect [79] Sulfonamide-trimethoprim combinations areused extensively for opportunistic infections in patients withAcquired Immunodeficiency Syndrome (AIDS) [80]

42 Antibiotics Antibiotics containing pyrimidines moietyare further classified on the basis of substitution on the ring

Disubstituted Pyrimidine Containing Antibiotic DrugAmicetin (26) is cytosine derivative which exhibits activityagainst acid fast and Gram-positive bacteria as well as someother organisms [81] (Figure 5)

Trisubstituted Pyrimidine Containing Antibiotic Drug Pli-cacetin (26) is another cytosine derivative which exhibitsactivity against bacteria [81] The simplest pyrimidine antibi-otic of all is bacimethrin (28) (5-hydroxy-2-methoxy-pyrimidin-4-amine) which is active against several staphylo-coccal infections [81] Gourgetin (29) is a cytosine derivativewhich is active against mycobacteria as well as several Gram-positive andGram-negative bacteria (Figure 5) Aminoglyco-side antibiotics phleomycin bleomycin and related familiesare wide-spectrum antibiotics containing the ring pyrimidinering [82] Bleomycin (see Figure S1 in Supplementary Mate-rial available online at httpdxdoiorg1011552014202784)is already in clinical use against certain tumours likeHodgkinrsquos lymphoma and disseminated testicular cancer[83]

43 Antivirals and Anti-HIV (AIDS) Agents Pyrimidinesderivatives also possess good antiviral properties forexample 5-iododeoxyuridine (30) and IDU (5-iodo-21015840-deoxyuridine) (31) have been extensively utilized for viralinfections 5-Trifluoromethyl-21015840-deoxyuridine (32) has beenfound useful against infections resistant to IDU therapy [84]1-(3-Azido-23-dideoxypentofuranosyl)-5-methyl-24(1H3H)-pyrimidinedione (33) is a potent inhibitor of the in vivoreplication and cytopathic effects of HIV and has beenapproved for use against AIDS and severe AIDS-RelatedComplex (ARC) [85] (Figure 6)

Lamivudine (34) is an effective anti-AIDS when usedin combination with zidovudine cidofovir (35) is used for


SO

ON

NN

HSO

ON

NN

H

SO

ON

NN

HSO

ON

NN

H

15 16 17 18

SO

ON

NN

H

SO

ON

NN

HSO

ON

NN

HSO

ON

NN

H

19 20 21 22

NN

SO

OHN

N

NHN

N

NH

HN O

23 24 25

NH2NH2NH2

NH2NH2

NH2

H3C

H3C

H3C

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3CH3

H3CO

H3CO

H3CO

H3CO

OCH3

OCH3

OCH3

OCH3 SO2 SO2

C2H5

Figure 4 Sulfa drugs having monosubstituted (15) disubstituted (16ndash19) and trisubstituted (20ndash25) pyrimidine

26 27

O

NN

HO

HO

OH

NH

ON

NNH

OOO

HO

N

OH O

28 29

N

NH

O

ONH

N NON

N

NH2

NH2

NH2

NH2

H3C

H3C

H3C H3C

CH3

CH3

CH3

H2NCH2OH

Figure 5 Antibiotics representing disubstituted (26) pyrimidine moiety and trisubstituted (27ndash29) pyrimidine moiety

the treatment of cytomegalovirus (CMV) [86] Zidovudine(36) which is an analogue of thymidine in which the azidogroup is substituted at the 3-position of the dideoxyribosemoiety is active against RNA tumour viruses (retroviruses)that are the causative agents of AIDS and T-cell leukaemiaZalcitabine (37) is another useful drug and is given incombination with Zidovudine [87] Stavudine (38) a pyrim-idine nucleoside is found to show significant activity againstHIV virus when given in combination with zidovudine[88]

44 Antifungal Drugs Pyrimidines also exhibit antifungalproperties (see Figure 7) Flucytosine (39) is a fluorinatedpyrimidine and is an orally active antifungal agent which isused for the treatment of serious systemic infections causedby susceptible strains of Candida and Cryptococcus [89 90]and hexetidine (40) is mainly used for the treatment ofaphthous ulceration [91] Recently voriconazole (41) is adisubstituted drug undergoing phase ΙΙΙ comparative clinicaltrials to establish its full potential as a broad-spectrumantifungal agent [92 93]


NH

N O

OI

O

H

HO

OH

NH

N O

O

O

HOH

INH

N O

O

O

HOH

30 31 32 33

NH

N O

O

OHO

N

HN

O

O

O N

HN

O

OO

N

N

OO

N

N O

OS

OH

N

N O

OH

P OHO

OH

34 35 36 37 38

NH2 NH2 NH2

H3C

CH3CH3 CH3

CH2OH CH2OH

F3C

N3

N3

HOH2CHOH2C HOH2C

Figure 6 Antiviral drugs having pyrimidine moiety

N

NH

O

FN

N NN

NN

N

HO

F

F

F

39 40 41NH2

CH3

CH3

CH3

CH3

CH3 CH3

H2N

Figure 7 Pyrimidine containing antifungal drugs

5 In Vitro Antimicrobial Activity Profile ofPyrimidines Literature Review

In the past few years great advances have been made inthe synthesis of novel pyrimidines derivatives with a potentantimicrobial activity The following review will examinethe in vitro antimicrobial activity of pyrimidines a classof heterocyclic compounds possessing a diverse range ofpharmacological properties The in vitro antimicrobial activ-ity is further divided into antibacterial antifungal antimy-cobacterial antituberculosis antileishmanial antiamoebicantiparasitic and antiviral activities on the basis of its activityagainst the particular microorganisms and these activitiesare briefly discussed in turn with particular emphasis onpyrimidine moiety along with their SAR studies (structureactivity relationships)

51 Antibacterial Activity and Antifungal Activity This isthe first category to be described here which consists ofpyrimidine derivatives possessing activity against the variousstrains of bacteria and fungi These various pyrimidinederivatives were further divided on the basis of substitutionon the pyrimidine ring and this classification is as follows

511 Monosubstituted and Disubstituted PyrimidineDerivatives Kolotova et al synthesized dicarboxylicacid 2-pyrimidylamides derivatives and evaluated the invitro antibacterial activity of the synthesized compoundswith respect to the standard strains of E coli and S aureusThe compounds (42ndash45) exhibited an in vitro antibacterialactivity against all the tested strains with MIC valueequal to 500ndash1000120583gmL [94] Hydrazone derivatives ofvanillin are found to possess potent antibacterial activityBased on higher bioactivity of hydrazones new hydrazonederivatives (46) were synthesized from piperidine-4-carboxylic acid methyl ester and checked for antibacterialactivities by paper diffusion method by measuring the zoneof inhibition in millimeters against Pseudomonas aeruginosaand Staphylococcus aureus bacterial strains and comparedwith standard drugs ciprofloxacin and cefaclor The zone ofinhibition of tested compounds shows the vanillin coupledhydrazone derivatives encompass potent bioactivities againstbacterial strains [95] (Figure 8)

Pyrimidine salt such as 4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl ammonium-25-dichloro-4-hydroxy-36-dioxo-cyclohexa-14-dienolate (47) chloranilicacid was synthesized and screened for in vitro antibacterialactivity Results revealed that the above compound exhibited


OON

N NH

OON

N NH

ON

N N OHOHOH

OH

44

OON

N N

OH

H

4542 43

N

N

NHN

47

N N

HN N O

OR

N

N NHN

Cl

N

N

R

O

OHOH

48

H3C

CH3

CH3

CH3

CH3

+H3N

CF3

NO2

O2N

O2N

Osim

49R = H CH3 4-Br-C6H4 4-OCH3-C6H4

46 R = H CH3 C4H9 CH2CH2OCH3

NO2

Figure 8 Monosubstituted pyrimidine derivatives with antibacterial and antifungal activity

good activity with the zone of inhibition in the rangeof 16mm against pathogenic bacterial strains and goodantifungal activity with the 564 inhibition against Foxysporum when compared with the standard drug [96](Figure 8)

In search of new T cruzi inhibitor Zanatta et al in 2008synthesized a series of novel 2-(N1015840-benzylidinehydrazino)-4-trifluoromethyl pyrimidines derivatives and evaluated themto inhibit the growth of T cruzi The compound (48) wasfound to be the most active compound and was able to pro-duce most significant inhibitory effect (80) and presentedan IC50value of 85120583M[97] Balan et al synthesized somenew

diazinium salts with dihydroxyacetophenone and screenedthem for their antibacterial activity against S aureus Ssaprophyticus Sarcina lutea B subtilis B cereus E coli andP aeruginosa and antifungal activity against C albicans andfound that the compound (49) showed excellent antibacterialand antifungal activity which is much more than that ofchloramphenicol and almost similar to that of nystatin [98](Figure 8)

512 Trisubstituted Pyrimidine Derivatives A novel seriesof mercaptopyrimidine and aminopyrimidine derivativesof indoline-2-one were synthesized by Mondal et al and

screened for their in vitro antibacterial activity against Gram-positive bacteria Staphylococcus aureus Bacillus subtilis andGram-negative bacteria Salmonella typhi Shigella dysente-riaePseudomonasmirabilis andEscherichia coli It was foundthat compounds (50) and (51) with a methoxy (OCH

3) sub-

stitution on phenyl ring at para position and hydroxyl (ndashOH)group at ortho position were found potent and (ndashCl) substi-tution showed a very good zone of inhibition at concentrationof 100 120583gmL against both Gram-positive and Gram-negativebacteria comparable to standard drug Ampicillin [99] Fur-ther derivatives of aminopyrimidines were synthesized bySolankee et al and evaluated for their in vitro antibacterialactivity against various bacterial strains Compound (50) wasfound to show small amount of activity against S aureus[100] Sukhwal and Verma synthesized the novel series of 2-piperidin-46-diaryl substituted pyrimidines by carrying outthe reaction between the S-benzylisothiouronium chloride(SBT) with variously substituted chalcones and evaluatedthe synthesized compounds for their in vitro antibacterialactivity Results revealed that the compounds (53) and (54)showed the maximum to moderate activity against Kleb-siella pneumonia Pseudomonas vulgaris E coli and Pseu-domonas aeruginosa [101] A novel series of 2-amino-4-(41015840-chlorophenyl)-6-(substituted)-pyrimidines were synthesizedby Desai et al and they evaluated the compounds for in vitro


N

NN

N

HS

O

Cl

Cl

Cl

Cl

N

NN

N

O NN

R

NH

N

NN

NHNH

50 51 52

N

N N

N

N N NN

S

53 54 55

NN

HNSO

O

NH

O

5657

NN

FCl

F

Cl

56abcdef

ClNH2

NH2

NH2

H3C

CH3

CH3

CH3

NO2

NO2 NO2

NO2

H2N

H3C

OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

R1

R1R2

R2

Figure 9 Trisubstituted pyrimidine derivatives of antibacterial and antifungal activity

antibacterial activity Results revealed that the compound(55) showed the highest antibacterial activity against E coliSalmonella (Gram minusve) and Bacillus pumilus micrococcus(Gram +ve) [102] (Figure 9)

Wasfy and Aly reported some new derivatives ofdiphenylysulfapyrimidine acetates synthesized by the con-densation of sulfaguanidine acetate with chalcones bear-ing an electron withdrawing group Results revealed thatall the compounds were weakly or moderately active andthe compound (56) having combination of substituentslike Cl OCH

3 and NO

2possessed fairly marked activity

whereas compound (56f) bearing 2-nitro group (electronwithdrawing group) had activity comparable to commercialantibacterial agent sulfadiazine [103] With the view of phys-iological importance and pharmaceutical properties of 2-amino pyrimidines Devi et al synthesized some derivatives2-amino-4-(2101584041015840-dichloro51015840 fluro)-6-phenyl pyrimidine andevaluated them for in vitro antibacterial activity Resultsshowed that the compound (55) having chloro group showedmoderate activity on all strains of bacteria [104] (Figure 9)

Some more derivatives of pyrimidines having benzofurylring were reported by Yadav et al who evaluated the invitro antimicrobial activity of the compounds It was foundthat the compounds (58ndash62) showed good activity against

B subtilis E coli A niger and Calbicans [105] Kothariet al synthesized some new 2-(1-piperidinyl1-pyrrolidinyl)-4-substituted phenyl-6 (3101584051015840-dibromo-41015840-hydroxy phenyl)-pyrimidine derivatives and evaluated the synthesized com-pounds against Gram-positive organisms Streptococcus virid-ians and S aureus and Gram-negative organisms E coli andK pneumonia The compound (63) was found to displaymoderate activity [106] (Figure 10)

Some substituted pyrimidines derivatives containingbenzofuran have been synthesized by Babu et al and screenedfor the in vitro antimicrobial activity Results revealed thatthe compounds (64ndash66) if suitably substituted were foundto show antibacterial and antifungal activity that is againstP aeruginosa S aureus and C albicans [107] Pasha et alprepared 46-disubstituted pyrimidine-thiones and 2-amino-46-disubstituted pyrimidines by interaction of various chal-cones and evaluated them for in vitro antibacterial andantitubercular activities and it was found that compounds(67) and (68) showed moderate activity against B subtilis Saureus E coliand Pseudomonas aeruginosa [108] (Figure 10)

Chandrasekharan and Nagarajan synthesized some novel2-amino-6-aryl-4-(2-thienyl) pyrimidines and evaluated thecompounds for in vitro antibacterial activity Results revealedthat the halogen substituted 4-fluoro that is compound (69)


O NN

O NN

O

N

N N

Cl58 59

60

O NN

O NN

Ar

N

N

Br

HO

Br

61 6263

NN

O R

64

NN

O

SH

R

65

NNO

OH

R

66

NH NHN

S

N

67 68

a H fb H gc H hd H ie H

NH2

NH2

NH2

OCH3

OCH3R1

R1

R2

R2 R1

R1

R2

R2R1 R2

R3

C6H5C6H5

NHCOCH3

NHCOCH2Cl NHCOCH2R2

2-Cl2-NO2

3-NO2

4-NO2

345-OCH3

345-OCH3

4-NH2

4-NH2

4-NH2

24-Cl

4-CH3

2-NO2

2-NO2

67-6867-68


was found to be more active than 4-chloro 4-bromo and therest of other compounds [109] Novel pyrimidines quinolineclubbed molecules were synthesized by Patel and Mehtawho studied their in vitro antibacterial activity of all thesynthesized compounds against the S aureus Streptococcuspyogenes E coli and P aeruginosa and antifungal activityagainst C albicansA niger Results showed that the presenceof methoxy and halogen groups (Cl Br and F) in the phenylring of the compound (70) increases the antimicrobial activ-ity [110] In 2006 Kumar et al synthesized aminopyrimidinesbearing benzofuran ring and evaluated them for their invitro antibacterial activity against P aeruginosa and S aureusand antifungal activity against A niger and Curvularia Allcompounds (71) showed comparable antimicrobial activitieswith chloramphenicol and fluconazole which were used asstandards for comparison of antimicrobial and antifungal

activity respectively [111] Recently reported morphilinopyrimidines were synthesized by Kanagarajan et al undermicrowave irradiation and screened for their in vitro antibac-terial activity against B subtilis Bacillus cereus Micrococcusluteusand Salmonella typhi and antifungal activity againstA niger Candida 6 and Candida 51 Structure activityrelationship results for the synthesized compounds showedthat compound (72) which has electron withdrawing chlorofluoro bromo and nitro functional groups at the parametaposition of phenyl rings attached to C-4 and C-6 carbonsof pyrimidine moiety delivered excellent antibacterial andantifungal activities [112] (Figure 11)

In 2007 Naik and Chikhalia synthesized a series of 2-[2-(Morpholino)-3-pyridinyl-5-thio-2-oxoethyl oxadiazolyl]-amino-4-(24-dichloro-5-fluoro phenyl)-6-(aryl)-pyrimidinesand screened them for their antibacterial activity against


NN

S

Br

69

NN

NH

N

X

NN

O

Cl71

NN

NO

NN

Cl

F

Cl R

HNS

O

O

NN

NN

O

N N

R

ONN

Br R

OH

OHOH

ONN

Br R

SH

SH

NN

S R

75 76 77

NNNN

N

N78 79

abcdefghi

R1

R1

R1

R1

R2

R2

R2

NH2

NH2

NH2

NH2

NH2

NH2

CH3

CH3

H3CO

H3C

NHCOCH3

NHCOCH3

4-CH3-C6H4

4-NO2-C6H4

2-Thienyl

2-Thienyl

C6H5C6H5C6H5C6H5C6H5

C6H54-Cl-C6H4

4-NO2-C6H4

4-Br-C6H4

2-Furyl

mdashmdashmdash

70 X = F Br

72 R1= H CH3 Cl F Br OCH3

R2= H Cl F NO2

73 R = 4-CH3-C6H4 345-(OCH3)3-C6H2 74 R = F Cl

78-79


S aureus E coli S typhi and B subtilis It was found thatin comparison to standard drug compound (73) showedmaximum zone of inhibition against Ecoli S aureus S typhiand B subtilis [113] A series of novel 2-amino-4-(1-napthyl)-6-aryl pyrimidines has been synthesized by Ingarsal et al andevaluated for in vitro antibacterial and antifungal activitiesagainst representative bacteriamdashS aureus E coli K pneu-monia and P aeruginosa and fungimdashTrichophyton tonsuransandMicrosporum gypseum It was found that compound (74)having 4-fluoro and 4-chloro groups had the best overallantibacterial and antifungal activities [114] 4-(5-Bromo-1-benzofuran-2-yl)-6-(substituted phenyl)-pyrimidine-2-ol(75) and 4-(5-bromo-1-benzofuran-2-yl)-6-(substitutedphenyl)-pyrimidine-2-thiol (76) were synthesized by Kumaret al and subjected to in vitro antibacterial and antifungalactivity The compound possessed significant antibacterialactivity againstB subtilisP aeruginosa and antifungal againstA niger and C albican [115] Recently Ramesh and Sumana

synthesized novel pyrimidines derivatives by combiningchalcones of 2-acetyl thiophene with guanidine hydrochlo-ride in the presence of alcohol and subjected the synthesisedcompounds to in vitro antibacterial and antifungal activity Itwas found that among the synthesized compounds the com-pound (77) showed maximum antibacterial and antifungalactivity at both 005mL and 01mL of concentration due tothe presence of chloro and nitro groups as pharmacophores[116] Patil et al reported the synthesis of some newpyrimidines derivatives bearing paracetamol and imidazolylmoieties The synthesized compounds (78) and (79) havebeen found to be active against Rhizobium species E coliFusarium oxysporum andCurvularia lunata [117] (Figure 11)

More recently a novel series of 4-[4-(24-dichloro-5-fluo-rophenyl)-6-(4-methoxyphenyl)pyrimidine-2-yl]-1-(arylam-inocarbnylthiocarbonyl)semicarbazides (80) weresynthesized by Patel et al and evaluated for their invitro antibacterial activity against Gram-positive bacteria


(S aureus and B subtilis) and Gram-negative bacteria(E coli and P aeruginosa) Results revealed that all thesynthesized compounds exhibited excellent or moderateactivity also the substitution of electron withdrawing groupon aromatic ring always optimizez the lead compound[118] Data of antimicrobial activity of compound (81)synthesized by Forsch et al revealed that the compoundshowed potent in vitro antibacterial activity in comparison totrimethoprim and was found to be 12000 times more potentthan trimethoprim and its potency actually exceeded that oftrimethoprim by a factor of at least 10 [119] A subsequentpaper has checked out the in vitro antibacterial activity of4-substituted 2-amino-6-(aniline) pyrimidines and screenedthem as selective inhibitors of DNA polymerase ΙΙΙ in Saureus The compound (82) was found to be 5-fold moreactive than the prototype of 4-chloro compound having97 inhibition because the presence of small hydrophobicsubstituents on the 3 and 4 positions of the aniline groupcombined with 4-halosubstituted phenoxy substituentswas always found to increase the anti-Pol ΙΙΙ activitiesof these Gram-positive selective inhibitors [120] NN-Dimethyl-4-phenyl-5-[phenyl (1H-124-triazol-1-yl) methyl]pyrimidine-2-amine was synthesized by Menozzi et aland screened for antibacterial activity The compound(83) showed activity against S aureus with MIC value 66120583M and this was the only compound showing antifungalactivity against C albicans and C neoformans due to thepresence of pyrimidine nucleus bearing a double aromaticsubstitution at positions 2 and 4 [121] Nassar synthesizedthe oxo- and thioxopyrimidines derivatives and screenedthem for their in vitro bactericidal activity against S aureusE coli and P aeruginosa The screened compound (84)showed high or moderate bactericidal activity compared tothat of ciprofloxacin [122] Novel 4-[3-(2-Amino-4-(4-chlo-rophenyl)pyrimidine-6-yl)-4-hydroxybenzyl]-2-(amino-4-(4-methoxyphenyl)pyrimidine-6-yl) phenol derivativeshave been reported by Nagaraj and Reddy in 2008 andthe compound (85) was found to be highly active againstpathogenic bacteria E coli S aureus and B subtilis and fungiC albicans due to the presence of methoxy group at position4 [123] (Figure 12)

A novel series of 2-thiouracil-5-sulfonamide derivativeswere synthesized and investigated for in vitro antibacterialantifungal antiviral and antitumour activities Outcome ofStructure Activity Relationship (SAR) study depicted thethiouracil nucleus as essential for the antimicrobial activityand substitution at position 5 of 2-thiouracil gave activecompounds as antibacterial antiviral and antineoplastichence the substituents group like thiourea in compound(86) pyridine moiety in compound (87) benzene nucleuswith NO

2group in compound (88) and thiazole ring in

compound (89) were found to show potent in vitro antimi-crobial activity [124] Chikhalia et al in 2008 synthesizedsome newly substituted quinolinyl chalcones containingpyrimidines moiety and evaluated the in vitro antibacterialactivity The compound (90) and its various derivativeswith an electron withdrawing group on the aromatic ringlike 4-chloro or 2-methoxy and presence of more than oneelectron withdrawing group like 345-methoxy were found

to show excellent activity against S aureus and B subtilliswhen compared with standard Ampicillin trihydrate [125](Figure 12)

In another study novel 24-diaminopyrimidines bearingNN-disubstituted aminomethyl residues at the position 5were designed as dihydrofolate reductase (DHFR) inhibitorsResults revealed that a number of compounds belongingmostly to the bi-(91) tri-(92) and tetra-(93) cyclic amineseries showed a potent inhibitory activity mainly againstTMP-sensitive andTMP-resistantDHFR from S pneumoniae[126] Some new derivatives of natural dipeptide antibioticsTAN 1057 A B containing heterocyclic ring and 120573-aminoacid as a side chain were synthesized and screened for the invitro antimicrobial activity by Brands et al Results revealedthat the amino pyridyl derivative that is compound (94) andamino quinolyl derivative that is (95) showed considerableantistreptococcal activity [127] (Figure 13)

With the view of potent antibacterial activity a newseries of 4-(1-napthyl)-6-arylpyrimidine-2-(1H)-ones (96)was synthesized by Vijayaramalingam et al and evalu-ated for in vitro antibacterial activity It was demonstratedfrom the data of in vitro antibacterial activity that thereis an increase in activity profile when groups such aschloro nitro and fluoro are present in the phenyl ring[128] Novel adamantylated pyrimidines were synthesized byOrzeszko et al and compound (97) was found to possesssignificant in vitro antibacterial and antifungal activitiesagainst all the selected strains [129] (Figure 13)

In the year of 2008 Moustafa et al synthesized somenew derivatives pyrimidines and selected members of thesynthesized compounds were screened for in vitro antimicro-bial activityThe compound (98) showed higher antibacterialactivity than the standard drug (penicillin) while compound(99) showed higher activity against C albicans than thestandard drug (Nystatin) [130] In another paper Ramiz etal reported the synthesis of 2 6 disubstituted pyrimidinederivatives and evaluated their in vitro antibacterial activityIt was demonstrated from the SAR studies that the oxoanalogue of pyrimidine that is compound (100) showed lessactivity than the corresponding substituted thiopyrimidinederivatives that is compound (101) and 2-hydrazinyl dihy-dropyrimidine derivative (102) exhibited the highest activityagainst B subtilis P aeruginosa and Streptomyces specieswith MIC values of 75120583gmL [131] (Figure 14)

Utilising 2-ethoxymethylene-3-oxobutanenitrile Cern-uchova et al synthesized the pyrimidines derivatives All thesynthesized compounds displayed biological activity againstbacteria filamentous fungi and tumour HeLa cells and thewidest antimicrobial activity has been manifested by thecompound (103) containing biologically active subunit anitro group in position 3 on the phenyl ring against Bsubtilis S aureus and A niger [132] Further a series oftruncated carbocyclic pyrimidine nucleosides were synthe-sized and evaluated for the in vitro antibacterial activityThe compound (104) (11015840S 21015840R 31015840S)-1-[(2101584031015840-dihydroxy)-41015840-cyclopenten-11015840-yl] cytosine was found to be the mostactive against the selected bacterial strains by inhibitingthe S-adenosyl-homocysteine (SAH) hydrolase enzyme [133]


NN

Cl Cl

F

NH

NHHN

O

X NH Ar

N

N

COOH

81

N

N

NH

O

Br

82

N

N N N

NH

HNN

X

NN

NN

HO

OH

83

84 85

NH

HN

O

O

SO

O

NHN

N NHS

H

86

NH

HN

O

O

SO

O

NN O

CNH

87

NH

HN

O

O

SO

O

N

H

88

NH

HN

O

O

SO

O

NHN

S

NH N

89

N

N

Cl

Cl

F

R

NH

NHOO

N

N

O

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

H3C

CH3

CH3

CH3 NO2

NH2

NH2

NH2

H3CO

H2N

H2N

C2H5

C6H5

C6H5H5C6

90 R = 345-(OCH3)3 4-Cl 2-OCH3

80 X = O S


Another prominent work was reported by Micky et alwho synthesized the 1-arylethylene benzofuranyl ketonederivatives having pyrimidine moiety and tested their invitro antibacterial activity The compounds (105) and (106)due to the presence of pyrimidine-2-thione moiety werefound to show moderate activity against two strains ofbacteria B cerens (Gram positive) and E coli (Gram negative)by agar diffusion technique [134] Patel and Gorgamwala

reported the synthesis of 2-(pyrazine-2-carboxamido)-4-(2ndasho-aminobenzene sulfonamide-46ndashdimehylpyrimidine)-6-arylthiouredio)-s-triazine derivatives and screened themfor in vitro antibacterial activity against S aureus and E coliAmongst the synthesized derivatives compound (107) withthe presence of phenyl ring and ndashCH

3at positions 3 and 4

on the phenyl ring respectively showed good activity andthe presence of ndashOCH

3at position 2 displayed good activity


N

N NO

O

91

N

N N NH

92

N

N N

N

93

NH

N NH

N

OO NH

N NH

N

OO

94 95

N N

R

S

97

NH2

NH2

NH2

NH2

NH2

CH3

CH3

CH3

CH3

CH3CH3

H3C

H3C

H2NH2N

H2N

H2N

H2N

OCH3

CH2CH2N(CH3)2

96 R =C6H5 4-NO2-C6H4 3-NO2-C6H4 4-Cl-C6H4 3-Cl-C6H4


HN

NHN

S

S

Cl

NN

S

Cl

N

NCN

NO

HO OH101 102 103 104

O

N NO

O

N NO

SHSH

NN

NHSO

ONH

NN

NNH

S

NHRNH

N N

O

105 106

CH3

CH3

CH3

NH2

NO2

H3C

H3CH3C

NHNH2

OCOCH3OCOCH3

107 R =C6H5 3-OCH3-C6H4 2-OCH3-C6H4 2-NO2-C6H4

N

N

SH

CH3

O

SN

N

S

O

S

O

N N

SHNHN

S

O

Cl

98 99 100



NN

NNH

HNHN Ar

ArAr

N

NN

R

NN

O

OH

O

S

CH3

NH2

SCH2Ph

3-NO2-C6H4 4-F-C6H4 2-thienyl

H3C

108 Ar = 2-F-C6H4 2-Cl-C6H4 3Cl-C6H4 4-Br-C6H4 109 Ar = 2-Cl-C6H4 3-NO2-C6H4 4-OCH3-C6H4 4-OH-C6H4

= 4-F-C6H4 2-thienyl 4-pyridyl110 Ar = 4-NO2-C6H4 4-Cl-C6H4 4-OC3-C6H4111 Ar


while its presence at the fourth position and NO2group

on the second position of phenyl ring displayed slight tomoderate activity [135] (Figure 14)

For the treatment of commonly occurring microbialdisease Rahman et al synthesized some new 2-amino-46-diarylpyrimidine derivatives (108) by the condensationof chalcone derivatives with guanidine hydrochloride andscreened them for in vitro antimicrobial activity againstBacillus subtilis Bacillus pumilus Proteus vulgaris and EcoliAmong the synthesized pyrimidine derivatives particularlyhalogen substituted derivatives showed more activity whencompared with the standard drug ciprofloxacin [136] LaterKhanage et al described an efficient method for the syn-thesis 6-(substituted aryl)-4-(35-diphenyl)-1H-124-triazol-1-yl)-16-dihydropyrimidine-2-thiol (109) and screened thesynthesized compounds for their in vitro antimicrobial activ-ity by agar well method at 50120583gmL and 100 120583gmL concen-trations Exclusively studied SARs revealed that the presenceof methoxy chloro nitro and hydroxyl substitution onphenyl ring of the pyrimidine nucleus produced remarkablein vitro antimicrobial activity against S aureus E coli Calbicans and A niger [137] (Figure 15)

Pyrimidine derivatives bearing a pyronyl side in theposition 4 have been synthesized by using commerciallyavailable dehydroacetic acid (DHA) aromatic aldehydes andS-benzylthiouronium chloride (SBT) and tested for in vitroantimicrobial activity Among the synthesized derivativescompound (110) showed mild activity against Gram +veBacillus subtilis bacteria andminor activity against Gram minusveP aeruginosa [138] A novel series of 2-mercaptopyrimidines(111) were synthesized by combining (E)-thienyl chalconeswith thiourea in alcohol medium and evaluated for theirin vitro antibacterial and antifungal activities against Gram-positive organisms (E faecalis and S aureus)Gram-negativeorganisms (K Pneumoniae and E coli) and fungi (C albicansand A niger) also compared with that of the standard drugsciprofloxacin and fluconazole The antitubercular activity

was carried out by using Middle brook 7H9 agar BlueAssay (MABA) method The antibacterial results revealedthat compounds showed significant activity against Gram-positive organisms and moderate activity against the Gram-negativeorganisms when compared with the standard drugand showed significant antitubercular activity with MICranging from 08 to 625 120583g [139] (Figure 15)

513 Tetrasubstituted Pyrimidine Derivatives of Antibacterialand Antifungal Activities A variety of pyrimidines deriva-tives were synthesized by Aly and Nassar by utilizing N-(dicyclomethylazo) phenyl]-2-saccharin-2-ylacetamide andevaluated the derivatives for in vitro antibacterial activity andresults revealed that compounds (112ndash117) showed promisingactivity towards bacteria [140] Some novel series of pyrim-idines derivatives were also reported by Waheed et al andscreened for their in vitro antibacterial activity It is foundthat all the compounds were effective against Gram-negativetest and compound (118) having bromo substituent onthe meta position of aminopyrimidines showed appreciableactivity against E coli [141] Parmar and Parikh reported thesynthesis of some novel derivatives of pyrimidinethiones andthe products have been screened for their in vitro growthinhibitory activities against several microbes like Bacillusmegaterium B subtilis E coli Pseudomonas Fluorescensand Aspergillus awamori It was found that the compounds(119) and (120) exhibited the significant activity [142] KhirEldin et al utilized the 6-amino-2 thiouracil for the syn-thesis of several heterocyclic derivatives and examined thein vitro antibacterial activity of some products It is foundthat the phosphorous containing derivative (121) showedthe highest activity and the compounds (122) and (123)showed the moderate activity [143] Purohi et al reportedthe synthesis of the 5-[51015840(mercapto)]-134-oxadiazol-21015840-yl6-methyl-4-aryl-34-dihydro pyrimidine2(1H) ones and 5-[51015840-(aryl)]-134-oxadiazol-21015840-yl6-methyl-4-aryl-34 dihydro


pyrimidine 2(1H)-ones and evaluated them for the the in vitroantimicrobial activities of the compounds It was found thatin comparison to the standard drug the compounds (124)and (125) exhibited the highest activity against S aureus andEcoli and moderate activity against fungal organisms [144](Figure 16)

Some new derivatives of S-120573-D-glucosides 4-mercaptopyrimidine were synthesized by Moustafa et al andevaluated for in vitro antimicrobial activity Results revealedthat the compound (126) showed the higher activity againstB subtilis (Gram-positive) and E coli (Gram-negative) whilethe compound (127) showed good activity towards fungiwhereas compound (128) showed moderate activity [145](Figure 16)

Upadhyay and Ram synthesized some pyrimidines andazolopyrimidines and evaluated the biodynamic properties ofthe synthesized compounds and found that the compound(129) was the most potent amongst all and inhibited thein vitro growth of the microbes up to 88 [146] Newderivatives containing 5-acetyl-4(34-dimethoxyphenyl)-6-methyl 2-oxo- 1234-tetrahydropyrimidine moiety incorpo-rated with different biologically active heterocycles such aspyridon iminopyridines thiazolidinones and chalcones and2-alkoxypyridines derivatives were synthesized and screenedfor their in vitro antibacterial and antifungal activity by El-Fattah et al The compound (130) in 100 120583gmL gave thehighest antibacterial activity against all the tested strains witha mean zone of inhibition equal to 85mm [147] Moustafaet al synthesized and evaluated the 2-amino-5-cyano-6-hydroxy-4-phenyl pyrimidines against Gram-positive andGram-negative bacteria The synthesized compound (131)was found to be selectively active against Gram-positive Saureus bacteria also substitution on the aromatic aldehy-des reduces the activity [148] Tomasic et al synthesized5-(345-trifluorobenzylidene) pyrimidine-246 (1H3H5H)-trione and tested it for in vitro antibacterial activity Thecompound (132) had a great influence on antibacterialactivity since 234-trifluorobenzylidenebarbituric acid pos-sessed activity against S aureus and mehticillin-resistantS aureus with minimum inhibitory concentration (MIC)values of 32 120583gmL and 128120583gmL respectively [149]The significant antimicrobial activity was found in 4-[(acetylphenyl) amino]-6-(2-methoxyphenyl)]-2-thioxo-12-dihydropyrimidine-5-carbonitrile derivatives when tested fortheir in vitro antimicrobial activity by Fathalla et al Resultsrevealed that the compound (133) possessed the highestantibacterial activity against E coli Salmonella typhimuriumListeria monoctyogenes S aureus P aeruginosus and Bacilluscereus [150] (Figure 17)

The novel series of indole dihydropyrimidine derivatives(134) were synthesized by Heda et al and screened for theirin vitro antibacterial activity against E coli and P aeruginosaand in vitro antifungal activity against A niger and Fusiformoxyporum The MIC was determined which showed promis-ing results when compared with the standard drug [151]The novel series of substituted 6-n-propyl thiouracils wassynthesized by Prachayasittikul et al and screened for in vitroantibacterial antimalarial activities and as cytotoxic agentsThe results showed that the compounds (135) and (136)

exhibited complete growth inhibition against S pyogenesB catarrhalis and M lutens with a minimum inhibitoryconcentration ranges of 32ndash128120583gmL [152] Akbari et al syn-thesized newN-(4-chlorophenyl)-6-methyl-4-aryl-2-thioxo-1234-tetrahydropyrimidine-5-carboxamide (137) and eval-uated its in vitro antibacterial and antifungal activitiesagainst S aureus S epidermidis E coli P aeruginosa andC albicans respectively All the synthesized compoundsexhibited moderate activity as compared to the standard[153] In another work Moustafa et al synthesized some S-and N-120573-D-glucosides derivatives of pyrimidine-4-thiol andevaluated the in vitro antibacterial activity The compound(138) showed higher activity against B subtilis as Gram +veand E coli as Gram minusve bacteria [154] (Figure 17)

Three novel series of tetrazolo [15-a] quinoline deriva-tives containing pyrimidine moiety were synthesized byBekhit et al and screened for their in vitro antibacterial activ-ityThe activity of compounds (139) was 50 of that of ampi-cillin against E coli and the compound (140) showed activityagainst S aureus comparable or half-fold of that of ampicillin[155] As a result of pioneering work of Qin Yan a novelseries of 5-benzylidene thiobarbiturates (141) derivatives havebeen synthesized and screened for their antibacterial activityThese compounds exhibited selectively antibacterial activityagainst S aureus with the MIC value of 31 120583gm [156] Anew class of 13-thiazolidine pyrimidine nucleoside analogueswere synthesized and evaluated by Sriharsha et al for the invitro antibacterial activity The compound (142) due to thepresence of free NH group in the pyrimidine moiety alongwith chloro or bromo substitution was always found to showincreased and significant activity when compared with baci-tracin and ciprofloxacin [157] A new class of thiopyrimidinederivatives was synthesized by Padmaja et al and evaluatedfor its in vitro antibacterial activity against Gram +ve andGramminusve bacteriaThe compounds (143) and (144) exhibitedmoderate to high activity towards Gram +ve bacteria with aninhibitory zone of 17ndash22mm and moderate activity towardsGramminusve bacteriawith an inhibitory zone of 18ndash25mm[158]Ethyl 2-(4-(dimethylamino)-4-methyl-6-phenylpyrimidine-5-carboxylate was synthesized regioselectively and evaluatedfor its in vitro antibacterial activity by Gholap et al Thecompound (145) with no substituents on the phenyl ringshowed more potent activities having MIC 16 120583gmL whichis comparable to that of the standard erythromycin [159](Figure 18)

A series of dihydropyrimidines (DHPM) derivativeswere synthesized and screened for the in vitro antibacterialactivity The compounds (146-147) were found to havesignificant zone of inhibition against Ecoli E aerogenesBacillus spizizenii P aeruginosa E coli and some otherstrains [160] A new series of 5-[2-(2-methylpropyl-enyl)-1Hbenzimidazolyl-46-diphenyl-pyrimidin-2-(5H)-thione (148)derivatives have been synthesized and subjected to evaluationof their in vitro antibacterial activity against B subtilis Saureus E coli and Pseudomonas diminuta by Sharma et al Itwas deduced from the data that the compounds containingelectron withdrawing groups that is nitro chloro andmethoxy substitution were found to show enhanced andremarkable antibacterial activity [161] Septioglu et al


NHN

S

NN

Ar

N

NH

ON

N

NH

OHN

O

NH

N

S

N

112 113 114 115

NH

NH

SN

O

NH

NH

S

SN

O

116 117

NN

ONN

O O

NH

O

118

NH

NH

SH

O

NH NH

NH

O

NH

NH

HN

NS Ar NH

HN

O

NH

S

CN

S

119 120 121 122

NH

NH

O

N

OHN

S

R

NH

HN

O

NHS

CN

S

123

NH

NH

O

N

OHN

Ar

R

N

N

Cl

S

O

N

N

S

OO

N

N

S

HO OH

HO126 127128

NH2

NH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

P+

= 3-Cl-C6H4 34-(OCH3)2-C6H3

= C6H5 4-Cl 2NO2 345-C6H234-(OCH3)2-C6H3

125R = H 4-(OCH3) Ar = 34-(NO2)2-C6H3

H2N

ArN2 ArN2

ArN2ArN2

ArN2

NHC6H5

C6H5

H3C

H3CH3C

H3CH3C

SCH3

SCH2CN

SCH2CN

COCH3

COCH3

COCH3

CH3COO

CH3COO

CH3COO

CH3COO

OCOCH3OCOCH3

OCOCH3

OCOCH3

OH3C

= H 4-(OCH3) 4-NO2124 R

Ominus

R1

R2 R2

R1

R1

R2

Figure 16 Tetrasubstituted pyrimidine derivatives of antibacterial and antifungal activity


CH3

CH3

CH3

CH3

CH3

CH3

CH3

C6H5

OCOCH3

OCOCH3

OH3C

OH3C

SH3C

H2N

137 R = 34-(OCH3) 24-OCH32-OCH3 3-NO2 3-OH 2-Cl

H3COCO

H3COCO

H3COCH3

H3CH2CO

131 R = Cl OCH3 OH

134 R = H Br Cl I and X = O S

135 R = CH3C6H11

N

N

N

ClCN NHHN

OO

OH

N

NCN

OH

R

129 130

FF

F

NH

NH

O

O O NH

N

HN

S

CNO

NH

NH

NH

X

RO

132 133

NH

HN

SR

O

NH

S

O

NH

NH

S

OCl

N

N

S

Cl O

136

138


synthesized some new NN-disubstituted dithiocarbamicacid 2-(6-arylhexahydropyrimidine-24-dione-3-yl) ethylesters derivatives and evaluated their in vitro antibacterialactivity against S aureus E faecalis Ecoli and P aeruginosaand antifungal activity against C albicans Candida kruseiand Candida parapsilosis and found that the compound(149) having MIC value 16 120583g showed the most favourableantibacterial activity [162] A few years later in 1997 Robsonet al synthesized novel 24-diamino-5-(41015840-benzylamino) and24-diamino-5-[41015840-N-methylbenzylamino)-31015840-nitrophenyl]-6-ethylpyrimidines bearing 4-substituents on thebenzylamino or N-methyl-benzylamino aryl ring andevaluated them for their antibacterial activity Structureactivity relationship study from the given data revealedthat the compound (150) with the introduction of parasubstituent like COOH CONH

2 CONHMe and SO

2NH2

exhibited potent inhibitory activity against Toxoplasmagondii as compared to benzoprim or methylbenzoprim [163](Figure 18)

Although chloropyrimidines appeared to haveeffective antimicrobial activity Agrawal et al synthesizedsome new derivatives containing aryl heteroaryl andalkylthio substituents at position 6 and also alkylthiosubstituents at position 2 because structure activity dataof chloropyrimidine revealed that substitution at positions2 and 6 has great influence on antitubercular activityhence synthesized derivatives were screened for in vitroantibacterial antitubercular and antifungal activitiesThe compound (151) with its various derivatives wasfound to display good antibacterial and antitubercularactivity with MIC value 078120583gmL and compound(152) demonstrated a good antifungal activity when


NHN

N

S

NNN

NHN

N

S

NNN

Br NH

NH

O S

OR O

139 140

N

HN

O

O

R

NH

SOH

NN

S

O

Ar Ar

O

NN

S

SO

ArS Ar

OO

O

N

N

O

N143 144 145

NH

NH

S

NH

O

Cl

146 147

R

NH

NH

S

NH

O

ClR

N N

N

N

S

R

NN

O

O

Cl

SS

N O149

N

N

O

Et

CH3

CH3

CH3

CH3

H2N

H2NH2N

NH2

NH2NH2

C6H5

NO2

H5C2O

H3C

H3CH3CH3C

Ar = C6H5 4-Cl-C6H4 4-CH3-C6H4

H5C6

= H CH2CH2OC4H9141 R

= Br Cl142 R

= 5-OCH3 5NO2 5-Cl148 R

150 R1= H CH3 and R2

= COOH CONHCH3 SO2NH2

R1 R2


compared with the standard drug clotrimoxazole [36](Figure 19)

In the hope of potent antifungal activity some pyrimidi-none derivatives were synthesized and screened for in vitroantifungal activity and compound (153) demonstrated thesignificant activity against Phytophthora infestans and Col-letotrichum falcatum with the introduction of chloro group[164] A new series of 4(41015840-bromophenyl)-6-substituted aryl-1-acetylpyrimidine-2-thiol derivatives were synthesized andscreened for the in vitro antimicrobial activity The resultsshowed that all the synthesized compounds (154) haveshown significant good to moderate antimicrobial activitydue to the presence of thio group which enhanced therespective activities with varied substituent groups againstselected pathogens [165] Trantolo et al synthesized a seriesof N6-substituted 6-aminopyrimidines and examined theeffects of substituents governing the inhibition of DNApolymerase ΙΙΙ from B subtilis The compounds (155) and

(156) having bromo and iodo substituents on position 5of 6-(benzylamino) uracils and 6-p-toluidinouracils wereequipotent with the parent compound [166] However Shiv-kumar et al also reported some pyrimidinone derivatives andevaluated their in vitro antifungal activity Results indicatedthat the compound (157) showed significant activity againstC albicans [167] (Figure 19)

A series of eleven 5-((E)-3-phenylacryloyl) pyrimidine-246-(1H3H5H)-triones (5-acetyl pyrimidine 246-(1H3H5H) trione based chalcones) were synthesizedand screened for antibacterial and antifungal activitiesby Dhorajiya et al Results revealed that compound (158)was comparable with the standard drug ciprofloxacinin case of P aeruginosa [168] For developing some newantimicrobial drugs Elumalai et al in the year of 2013developed some new isoniazid cyclocondensed 1234-tetrahydropyrimidine derivatives and evaluated them for invitro antimicrobial and antimycobacterial activities against


N

N

ClCN

SR

N

N

ClCN

ArSR

151

151 Ar Rabc

NH

HN

N

S

N

Cl

SH

O

153

N

N SH

Br

R

154

NH

HN

O

XO

NHNH

HN

O

O

X

NHNH

N

Ar

O

NHO

NNN

SH

O

R

154 Rabcdefghijk H

NH

HN

O

O

O

O

RNH

NH

R

X

O

NHNH

O

N

NH

NH

O

O

NN

160

CH3

CH3

CH3

CH3

H3C

H3C

2-Thienyl3-F-C6H42-Furyl

C2H5C3H7

COCH3

4-OCH3

3-OCH3

4-Cl2-Cl4-OH3-OH4-NO2

2-NO2

4-N(CH3)26-furyl

=CH3 C2H5 CH3152 R

= 2-Cl 4-Cl 4-CH3 4-NO2 4-OH and 157 R Ar = C6H5 C6H4-NO2= Br I NO2156 X= Br I NO2155 X

= OCH3 NO2 CH3158 R = chloro fluoro X = O S159 R


Bacillus subtilis E coli Mycobacterium tuberculosis CIPand H37Rv strain Exclusively studied SARs revealed that1234-tetrahydropyrimidines contain substituted phenyland hetero aromatic rings responsible for antimicrobial andantimycobacterial activities Substituted atom or group ofatoms must be of strong electron withdrawing nature forpotent activity because it decreases electron density in thering due to inductive effect Substitution of fluoride andchloride substitution at fourth and third positions of phenylring showed potent activity also introduction of heterocyclicring at fourth position showed moderate activity Henceit was concluded that compound (159) was arguably themost potent when compared with current therapeuticagents norfloxacin and rifampicin because fluoride andchloride substituted phenyl ring present at 4th position of1234-tetrahydropyrimidines enhancing the antimicrobialand antimycobacterial activities [169] In the recent 2013a series of pyrimidine bearing 134-oxadiazole derivativeshave been synthesized and evaluated for antifungal activityagainst Candida albicans Penicillium spp and Aspergillus

niger It was found that compound (160) has shownpromising antifungal activity at 10 120583gmL concentrationwhen compared with the standard drug amphotericin-B[170] (Figure 19)

52 Antimycobacterial Activity of Pyrimidines From thestudy of vast literature it was found that pyrimidine deriva-tives possessing antimycobacterial activity consist of onlytrisubstituted and tetrasubstituted pyrimidines derivatives

521 Trisubstituted PyrimidineDerivatives withAntimycobac-terial Activity Sohn et al reported a paper in which around100 anologues of sulfonylureas were screened for antimy-cobacterial activity against M tuberculosis The compound(161) was found to show comparable antimycobacterial activ-ity with that of sulfometuron methyl inhibitor of acetohy-droxyacid synthase (AHAS) and after demonstrated SARinformation it was concluded that both 2-alkylcarbonyl and2-hydroxyalkyl with 6-ethythio substituents at the aromatic


OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

CH3

CH3CH3

NH2

NH2NH2NH2

NH2NH2

H2N

O2N O2N O2N

H3CO

H3CO H3CO

H3CO

H3CO

O(CH2)4COOH B10H10NN

NHNH

SO

ONN

O

O

N

N NN

161

162 163

OHO

NN

NN

OH

R

N

N

O

N N

N

O

NCl

165 166

167 168 169

NN

N

Cl

ClCl

Cl

NN

N

Cl

NN

N

Cl

Cl

170 171 172

= 2-NO2-C6H4 3-NO2-C6H4 4-OCH3-C6H4164 R

Figure 20 Trisubstituted pyrimidine derivatives of antimycobacterial activity

backbone might be a good scaffold in the sulfonylureaspossessing potent activity [171] 24-Diamino-5-[2-methoxy-5-(120596-carboxyalkoxy) benzyl] pyrimidines derivatives weresynthesized by Rosowsky et al and tested for their abilityto inhibit partially purified foam P carinii T gondii andM avium 51015840-O-(120596-Carboxyalkyl) analogs were found to bethe most potent and the compound (162) was found to be245 times more potent than trimethoprim against Pc and 33-fold higher than that of trimethoprim againstMycobacteriumavium [172] Also 24-diamino-6-methylpyrimidine contain-ing 5-(78-nido-dicarbaundecarboran-7-yl) methyl or 5-(12-closo-dicabadodecarboran-1-yl) methyl substituents weresynthesized and screened for their activity against P carnii

T gondii M avium M tuberculosis and Lactobacillus caseiThe compound (163) was found to show 10 times greateractivity [173] Trivedi et al carried out the synthesis of somenew pyrimidines derivatives via a novel chalcone series andevaluated them for their antimycobacterial activities againstM tuberculosis H

37Rv The compound (164) produced the

highest efficacy and exhibited gt90 inhibition at 625120583gmLdue to the presence of 2-nitro 3-nitro and 4-methoxysubstitution at phenyl ring added remarkable improvementsin anti-tubercular activity [174] (Figure 20)

Pyrimidine analogs of antimycobacterial 6-aryl-9-benzylpurines were synthesized by Read et aland screened for their in vitro antibacterial activity


againstM tuberculosisH37Rv Among the screened

furylpyrimidines the compounds having N-methylbenzylamino group showed better activitiesand the compounds (165-166) were identified as themost active compounds having minimum inhibitoryconcentration of 30120583gmL [175] In another workagain some substituted pyrimidines were synthesizedfrom chalcones by Umaa et al and evaluated for theirantitubercular potential and we found that three compounds(167ndash169) exhibited significant activity being equipotentwith the standard drug [176] A variety of novel 4-(4-substituted phenyl)-6-(4-nitrophenyl)-2-substituted imino)pyrimidines were reported by Siddiqui et al and weinvestigated their antiviral antitubercular and antibacterialactivities Results indicated that the pyrimidines withchloro and p-methoxyphenyl (170) trimethoxy (171)showed more potent activity than the reference drug andpyrimidines with chloro and chlorophenyl (172) and p-N-dimethylaminophenyl substitutions showed equipotentactivity in comparison with that of reference drugs [177](Figure 20)

522 Tetrasubstituted Pyrimidine Derivatives Having Antimy-cobacterial Activity N-Phenyl-6-methyl-2-oxo-4-phenyl-1234-tetrahydropyrimidines-5-carboxamides derivativeswere synthesized by Virsodia et al and evaluated for theirantitubercular activity against Mycobacterium tuberculosisand we found that compounds (173) and (174) with23-dimethylphenyl and 34-dimethyl carbomyl side chainsrespectively showed 65and63 inhibition hence presenceof methyl groups on phenyl ring of C5 side chain withmeta-substituted 4-phenyl was found to show good activity [178]Srivastav et al evaluated the antimycobacterial activities of 1-(2-hydroxyethoxy)methyl-5-(1-azido-2-haloethyl or 1-azido-vinyl) analogs and 1-[(2-hydroxy-1-(hydroxymethyl) ethox-y)methyl-5-decynyluracil and 1-[(2-hydroxy-1-(hydrox-ymethyl) ethoxy)methyl]-5-dodecynluracil against Mtuberculosis Mycobacterium bovis and Mycobacteriumavium It was found that 5-substituted acyclic pyrimidinecompounds that is (175ndash177) were found to exhibitsignificant in vitro antimycobacterial activity [179](Figure 21)

Srivastav et al investigated the in vitro antimycobacterialactivities of 5-alkyl 5-alkynyl furanopyrimidines and 21015840-deoxynucleosides derivatives It was found that compoundswith 5-arylalkynyl substituents that is (178ndash180) displayedpotent in vitro antitubercular activity against M bovis andM tuberculosis [180] Johar et al synthesized a series of1-120573-D-21015840-arabinofuranosyl and 1-(21015840-dedoxy-21015840-fluoro-120573-D-ribofuransoyl) pyrimidine nucleosides possessing a diversesets of alkenyl alkyl and halo substituents at the C-5 positionof the uracil and investigated their effect on activity againstMtuberculosisM bovis and M avium From a comprehensiveoverview and thorough study of SAR it is suggested that thecompounds of 5-alkynyl series that is (181ndash183) showed thehighest antimycobacterial potency which was similar or closeto that of the rifampicin [181] (Figure 21)

53 Antimalarial Activity of Pyrimidines Pyrimidine deriva-tives which were known to have antimalarial activity mainlyconsist of trisubstituted derivatives

531 Trisubstituted Pyrimidine Derivatives of AntimalarialActivity A series of 246 trisubstituted-pyrimidines (184)were synthesized and evaluated for their in vitro antimalarialactivity Out of total screened compounds 14 compoundshave shown in vitro antimalarial activity against Plasmodiumfalciparum with MIC in the range of 025ndash2 120583gmL and SARstudy revealed that the substitution on phenyl ring showsan increased activity as substitution of methyl group at thepara position of the compound represents a remarkableincrease in activity [182] The novel pyrimethamine andtrimethoprim analogs were developed and tested for the invitro antimalarial activities of synthesized compounds againstP falciparum Pyrimethamine analogues (185) bearing m-Cl and unsubstituted 5-phenyl group together with long 6-alkyl substituents and trimethoprimanalogues (186)were 10ndash25 times more effective than their parent compounds [183](Figure 22)

Recently the optimization studies of the 2-pyrimidinecarbonitrile as lead series were done by Coteron et al whostudied the different heteroarylnitrile derivatives as poten-tial falcipain inhibitors and therefore potential antiparasiticlead compounds with the 5-substituted-2-cyanopyrimidinechemical class emerging as the most potent and promisinglead series Results revealed that the introduction of a proton-able amine in the structure of compoundmarkedly improvedthe antiparasitic activity The compounds (187ndash190) andderivatives of (191) presented excellent in vitro enzymaticactivity and antiparasitic activity against P falciparum [184](Figure 22)

54 Antileishmanial Activity of Pyrimidines

541 Monosubstituted Pyrimidine Derivatives of Antileish-manial Activity A series of compounds containing thenitrobenzene and sulfonamido moieties monosubstitutedpyrimidine derivatives were synthesized and their leish-manicidal effect was assessed in vitro against L infantumpromastigotes Among the evaluated compounds the p-nitrobenzenesulfonamides (192) showed significant activitydue to the presence of electron withdrawing nitro group [185](Figure 23)

542 Trisubstituted Pyrimidine Derivatives PossessingAntileishmanial Activity Some novel N- and O-substitutedterpenyl trisubstituted pyrimidines derivatives weredeveloped and screened for their in vitro antileishmanialactivity profile in promastigote model by Chandra et alThe compound (193) with p-anisidino substitution showed988 inhibition at a 1 120583gmL concentration whereaswith OEt and OBu substitution the same compoundshowed 99 inhibition at 5120583gmL concentration [186]A series of [1 2 4] triazino[56-b]indol-3-ylthio-135-triazines and pyrimidines derivatives were synthesizedand screened for their in vitro antileishmanial activity


O

N

N OH

O

N

N OH

HN

N

O

OHOO

173 174

HO

HN

N

O

O

HO

HN

N

O

O

HO

HN

N

O

OO

HO

HO

N

176177 178

179

HN

NOO

HO

HO

N

180

HN

NH

O

O R

180 Rabcd

N

HN

HO

O

O

HO

HO

181

N

HN

HO

O

O

HO F

HO

182

N

HN

HO

O

O

HO F

HO

183

CH3

NH2

NO2

CH(N3)CH2XOC6H5

C(CH2)7CH3C(CH2)9CH3

C6H5

C6H4-n-propylC6H4-n-pentyl

2-Pyridyl

C10H21 C10H21 C11H23

= Br I Cl175 X

H3C

H3C

H3C

H3C

H3C

H3CH3C

H3C

H3C

Figure 21 Tetrasubstituted pyrimidine derivatives of antimycobacterial activity

against Leishmania donovani The pyrimidine derivatives(194) having piperidine at position 2 were found to showcomparable activity against leishmaniasis with an IC

50of 401

and MIC of 2054 120583M and to be the least toxic compoundswhich made them 20- and 10-fold more selective than thatof the standard drugs pentamidine and stibogluconate [187]A few years later in 1999 Chawdhury et al synthesizedcompounds based on 5-benzyl-24-diaminopyrimidinesand evaluated the compounds as inhibitors of leishmanialand trypanosomal dihydrofolate reductase Results revealedthat the compounds (195ndash197) were found to show goodactivity against Trypanosoma brucei Trypanosoma cruziand marginal activity against Leishmania infantum [188](Figure 23)

55 In Vitro Antiamoebic Activity and Antiparsitic Activityof Pyrimidine Praveen et al synthesized a new series of 6-ferrocenyl aryl 2-substituted pyrimidines and evaluated them

for their in vitro antiamoebic activity against HMI1MSSstrain of Entamoeba histolytica Out of 16 compounds 10compounds have methoxy substitution thio group andchloro group exhibited higher antiamoebic activity thanthe reference drug metronidazole and compound (198) wasfound to be most active and least toxic [189] (Figure 24)

Some new tetrasubstituted pyrimidine derivatives weredeveloped as a new class of antifilarial agents as a seriesof 2-sulfonyl-6methyl-14-dihydropyrimidines were synthe-sized by Singh et al and evaluated for their antifilarialactivity against adult parasites of human lymphatic filarialparasitesBrugiamalayi in vitro at various concentrationsThecompound (199) showed promising antifilarial activity [190](Figure 24)

56 In Vitro Antiviral Activity of Pyrimidines To study invitro antiviral activity of various pyrimidine derivatives we


NNN

N

( )n

N

N

Cl

RN

N

186

N

N

O

HN

N

N

NN

N

N

O

HN N

N

N

BrBr

N

N

N

O

HN

N

N

N

Br

N

187 188 189

N

NNN

O

N

N

Br

N

H

N

NNN

O

Br

N

R

H

190

191

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2NH2

H3CO OCH3

OCH3

OCH2CH3

OCH2sim[345(OCH3)3]-C6H5H2NH2N

184 n = 01

= CH2CH2C6H5(OCH3)-p185 R

Figure 22 Trisubstituted pyrimidine derivatives possessing antimalarial activity

N

N NH

SO

ON N

R

NN

N

SN

NN

N

192 194

N

NOR

N

NOR

N

NOR

CH3CH3

CH3

CH3

NH2 NH2 NH2

H2N H2N H2N

NO2

195 R = hexyl heptyl

193 R =OC2H5 OBu

196 R = C2H5 C3H7 197 R = CH3 C2H5

H3C

H3C

Figure 23 Monosubstituted (192) and trisubstituted (193ndash197) pyrimidine derivatives having antileishmanial activity

have classified the pyrimidine containing derivatives on thebasis of substitution and this substitution is as follows

561 Trisubstituted Pyrimidine Derivatives With the viewof potency of sulfonamides Selvam et al synthesized

the 4-[(12-dihydro-2-oxo-3H-indole-3-ylidene)amino]-N-(46- dimethyl-2-pyrimidinyl)-benzene sulfonamide deriv-atives and carried out anti-HIV assay on them and foundthat the compound (200) was more active against thereplication of HIV-1 and HIV-2 in membrane type 4[MT-4] [191] The discovery in 2002 by Holy et al showed


NH

NH

O

O

SR

NN

N

ClFe

198 199

H3C

H3C

CH3

Figure 24 Trisubstituted pyrimidine derivatives with antiamoebic(198) and antiparasitic activity (199)

the antiviral activity of 6-[2-(Phosphonomethoxy) alkoxy]pyrimidines derivatives Several analogues among the 6-[2-(phosphonomethoxy)ethoxy] (PMEO] pyrimidinesderivatives showed pronounced antiviral activity incell culture and the derivatives that carry an aminogroup at C-2 of the pyrimidine ring that is (201) and(202) emerged as the most potent compounds [192](Figure 25)

562 Tetrasubstituted Pyrimidines Derivatives Sriram et aldesigned the aminopyrimidinimino istain derivatives as anovel nonnucleosidase reverse transcriptase inhibitor withbroad-spectrum chemotherapeutic properties for the effec-tive treatment of AIDS (Figure S2) The compounds (203)and (204) with their different derivatives like ciprofloxacinmoiety and lomefloxacin moiety at N-1 position emergedas the most potent broad-spectrum chemotherapeutic agentactive against HIV HCV M tuberculosis and variouspathogenic bacteria [193] In the early 1999 the novelpotent and selective dihydro-alkoxy-benzyl-oxypyrimidinederivatives namely 5-alkyl-2-(thio)-26-(-diphenylmethyl)-34-dihydropyrimidine-4(3H)-ones derivatives were synthe-sized and tested as anti-HIV agent in both cell based andenzyme based assays Result revealed that the compoundshaving 6-(26-difluorophenylmethyl) substituents (205) werefound to bemost potent significantly higher than that of nevi-rapine with EC

50rsquos ranging between 40 and 90 120583M [194] 24-

Diamino-5-cyano-6-[(diisopropoxyphosphoryl) methoxy]ethoxy pyrimidines derivatives (206) were synthesized byHockova et al and evaluated for their in vitro antiviral activityand they found that 5-cyano and 5-formyl derivatives showedremarkable activity against herpes simplex virus type 1 ortype 2 cytomegalovirus and vaccinia virus with inhibitoryconcentration of 00027ndash0011120583molmL [195] (Figure 26)

A subsequent paper has been reviewed on antiviralactivity in which Mohamed et al prepared the 2-(24-dioxopentan-3-ylthio)-16-dihydro-4-(1234-tetrahydronap-thalen-6-yl)-6-(34-dimethoxyphenyl)pyrimidin-5(4H)-onederivatives and screened them for their in vitro antiviralactivity and compound (207) was found to have goodantiviral activity with 90 inhibition hence it wasconsidered to be highly promising compound by confirmingand comparing its activity with the antiviral activity of

acyclovir [196] A series of dihydro-alkylthio-benzyl-oxopyrimidines were synthesized by Nawrozkij et alwho evaluated the compounds for their in vitro antiviralactivity The compound (208) with 26-dichloro- 2-chloro-6-fluoro- and 26-difluoro-benzyl substitutionat C-6 and ethyl iso-propyl at C-5 was found to be themost potent derivatives due to its capability to inhibitthe HIV-1 strain by 50 [197] A novel and new class ofthe dihydroxypyrimidinecarboxylic acid derivatives andcorresponding N-methylpyrimidinone were prepared bySumma et al and tested in the HCV replicon assay Thecompound (209) having the desired phenolic function inthe meta position was found to be the most active havingIC50

of 58 120583M [198] Another paper reported the 2-(2-thienyl)-56-dihydroxy-4-carboxypyrimidines derivativeswhich were screened as inhibitors of the hepatitis C virusNS5B and the compound (210) showed the best cell basedactivity which was 60-fold much better than enzymebased assay and showed no cytotoxicity up to 100 120583M[199] Manetti et al carried out the parallel solution phaseand microwave-assisted synthesis of dihydroxy-alkoxy-benzyl-oxypyrimidines (DABOs) and screened them fortheir antiviral activity toward both the highly purifiedrecombinant human immunodeficiency virus type 1 (HIV-1)reverse transcriptase (RT) enzyme (wild-type and mutants)and wild-type (wt) and mutant HIV-1 strains Results fromanti-HIV reverse transcriptase assay and anti-HIV activityin lymphoid cells revealed that compound (211) had an anti-HIV profile comparable to that of nevirapine and efavirenz[200] Novel C-6 fluorinated acyclic side chain pyrimidinederivatives were synthesized by Prekupec et al and evaluatedfor their in vitro antiviral activity against cytomegalovirus(CMVa AD-169 and Davis strain) in human embryonic lung(HEL) cells Varicella-zoster virus parainfluenza virus-3retrovirus-1 Sindbis and Punta Toro virus in vero cell The5-bromopyrimidine derivatives (212) and (213) showed thehighest activity [201] (Figure 26)

6 Conclusion

As a result of vigorous research and vast literature surveythe dogma laid down by chemistry of pyrimidines hasengendered long considerable interest which makes themoccupy a very distinct and unique place in our lives Fromthe above review it was concluded that the trisubstituted andtetrasubstituted pyrimidines containing electron withdraw-ing group like nitro on the phenyl ring were found to showmore potent in vitro antimicrobial activity as compared to thechloro or methoxy group This offers the medicinal chemistcontinued interest in pyrimidinemoiety in drug developmentagainst microbes It will also ensure the development ofreliable methods for the construction of important area ofresearch in heterocyclic chemistry

Abbreviations

MRSA Methicillin-resistant Staphylococcus aureusDHFR Dihydrofolate reductaseAIDS Acquired Immune Deficiency Syndrome


CH3

CH3

NH2

H2N

200 R = H COCH3

P(O)(OH)2 P(O)(OH)2

N

N

O

SO

ONH

NN

R

H

N

N

O

O

N

N

OH

O

O

201 202

H3C

Figure 25 Trisubstituted pyrimidine derivatives of antiviral activity

N

N

O

N

NBr

N

O

N

N

O

N

N

Br

NNN

F

F

OHOOC

203 204

N

N

OR

F FS

N

N R

O O

P OHOOH

NH

N

O

S

207

N

HN

S

O

O

ClCl

208

N

NHO

OHOH

O

OH

209

N

NS

OHOH

O

OH

NH

NHOCl

210

N

HN

O

SClCl

211

N

NBr

212

N

NBr

Br

Br

213

CH3

CH3

CH3

NH2NH2

NH2

H3COH3CO

H3COH3CO

H3CO

H2N

H3C

H3C

OCH3

OCH3

OCH3OCH3

OCH3

OCH3

OCH3

OCH3

C2H5

205 R = H Me 206 R = H Me

COCH3

COCH3

CH2CH3

CH2Br


IDU 5-Iodo-21015840-deoxyuridineCMV CytomegalovirusSBT S-Benzyl isothiouronium chlorideMIC Minimum inhibitory concentrationDABOs Dihydroxy alkoxy-benzyloxy pyrimidinesHIV-1 Human deficiency virus type 1HEL Human embryonic lung cellsRT Reverse transcriptase

Conflict of Interests

The authors have no relevant affiliations or financial involve-ment with any organization or entity with a financial interestin or financial conflict with the subject matter or materialsdiscussed in the paperThis includes employment consultan-cies honoraria stock ownership or options expert testimonygrants or patents received or pending or royalties Nowritingassistance was utilized for writing this paper


Acknowledgments

The authors are thankful to the Department of Pharma-ceutical Sciences Kurukshetra University Haryana Indiaand Bioinformatics Centre Biotech Park Lucknow UttarPradesh India for providing the necessary help to completethe paper

References

[1] Infectious Society of America Statement of the IDSA Con-cerning ldquoBioshield II Responding to an Diseases Ever-ChangingThreatrdquo IDSA Alexandria Va USA 2004

[2] J S Bradley R Guidos S Baragona et al ldquoAnti-infectiveresearch and development-problems challenges and solu-tionsrdquo The Lancet Infectious Diseases vol 7 no 1 pp 68ndash782007

[3] A L Panlilio D H Culver R P Gaynes et al ldquoMethicillin-resistant Staphylococcus aureus in US hospitals 1975ndash1991rdquoInfection Control and Hospital Epidemiology vol 13 no 10 pp582ndash586 1992

[4] J Davies ldquoOrigins and evolution of antibiotic resistancerdquoMicrobiologia vol 12 no 1 pp 9ndash16 1996

[5] A D Russell ldquoMechanisms of bacterial insusceptibility tobiocidesrdquoThe American Journal of Infection Control vol 29 no4 pp 259ndash261 2001

[6] H P Schweizer ldquoTriclosan a widely used biocide and its link toantibioticsrdquo FEMS Microbiology Letters vol 202 no 1 pp 1ndash72001

[7] S B Levy ldquoAntibiotic and antiseptic resistance impact onpublic healthrdquo Pediatric Infectious Disease Journal vol 19 no10 pp S120ndashS122 2000

[8] S B Levy ldquoActive efflux a commonmechanism for biocide andantibiotic resistancerdquo Journal of Applied Microbiology vol 92no 1 pp 65Sndash71S 2002

[9] K Poole ldquoMechanisms of bacterial biocide and antibioticresistancerdquo Journal of Applied Microbiology vol 92 no 1 pp55Sndash64S 2002

[10] M Hassan D van der Lelie D Springael U Romling NAhmed and M Mergeay ldquoIdentification of a gene clusterCZR involved in cadmium and zinc resistance in Pseudomonasaeruginosardquo Gene vol 238 no 2 pp 417ndash425 1999

[11] S A Lerner ldquoClinical impact of antibiotic resistancerdquo Advancesin Experimental Medicine and Biology vol 456 pp 7ndash15 1998

[12] DM Livermore ldquoEpidemiology of antibiotic resistancerdquo Inten-sive Care Medicine vol 26 Supplement 1 pp S14ndashS21 2000

[13] L Jeu F J Piacenti A G Lyakhovetskiy and H B FungldquoVoriconazolerdquo Clinical Therapeutics vol 25 no 5 pp 1321ndash1381 2003

[14] E de Clercq ldquoNew developments in anti-HIV chemotherapyrdquoIl Farmaco vol 56 no 1-2 pp 3ndash12 2001

[15] K Poole ldquoOvercoming antimicrobial resistance by targetingresistance mechanismsrdquo Journal of Pharmacy and Pharmacol-ogy vol 53 no 3 pp 283ndash294 2001

[16] P W Taylor P D Stapleton and J P Luzio ldquoNew ways to treatbacterial infectionsrdquo Drug Discovery Today vol 7 no 21 pp1086ndash1091 2002

[17] A R M Coates and Y Hu ldquoNovel approaches to developingnew antibiotics for bacterial infectionsrdquo The British Journal ofPharmacology vol 152 no 8 pp 1147ndash1154 2007

[18] DW Kimberlin and R JWhitley ldquoAntiviral resistance mecha-nisms clinical significance and future implicationsrdquo Journal ofAntimicrobial Chemotherapy vol 37 no 3 pp 403ndash421 1996

[19] Y Ju and R S Varma ldquoAqueous N-heterocyclization of primaryamines and hydrazines with dihalides microwave-assisted syn-theses of N-azacycloalkanes isoindole pyrazole pyrazolidineand phthalazine derivativesrdquo Journal of Organic Chemistry vol71 no 1 pp 135ndash141 2006

[20] Y Ju D Kumar and R S Varma ldquoRevisiting nucleophilicsubstitution reactions microwave-assisted synthesis of azidesthiocyanates and sulfones in an aqueous mediumrdquo Journal ofOrganic Chemistry vol 71 no 17 pp 6697ndash6700 2006

[21] P D Lokhande B Y Waghamare and S S Sakate ldquoRegioselec-tive one-pot synthesis of 35-diarylpyrazolesrdquo Indian Journal ofChemistry B vol 44 no 11 pp 2338ndash2342 2005

[22] G J Reddy DManjula K S Rao M Khalilullah and D LathaldquoA Direct single step synthesis of 13-diaryl-4-cyanopyrazolesand their conversion to 13-diaryl-4-(46-diamino 135-triazin-2-yl)pyrazolesrdquo Indian Journal of Chemistry B vol 44 pp 2412ndash2415 2005

[23] C A Zificsak and D J Hlasta ldquoCurrent methods for thesynthesis of 2-substituted azolesrdquo Tetrahedron vol 60 no 41pp 8991ndash9016 2004

[24] T Haino M Tanaka K Ideta K Kubo A Mori and YFukazawa ldquoSolid-phase synthesis of liquid crystalline isoxazolelibraryrdquo Tetrahedron Letters vol 45 no 11 pp 2277ndash2279 2004

[25] M Garcıa-Valverde and T Torroba ldquoSpecial issue sulfur-nitrogen heterocyclesrdquo Molecules vol 10 no 2 pp 318ndash3202005

[26] D W Hopper A L Crombie J J Clemens and S KwonldquoSix-membered ring systems pyridine and benzo derivativesrdquoProgress in Heterocyclic Chemistry vol 21 pp 330ndash374 2009

[27] A Manlove and M P Groziak ldquoSix-membered ring systemsdiazines and benzo derivativesrdquo Progress in Heterocyclic Chem-istry vol 21 pp 375ndash414 2009

[28] D J Brown Comprehensive Heterocyclic Chemistry vol 14Pergamon Press Oxford UK 1984 edited by A R Katritzkyand C W Rees

[29] R C Elderfield Heterocyclic Compounds vol 6 John Wiley ampSons New York NY USA 1957

[30] P Y Bruice Organic Chemistry Pearson Education Singapore3rd edition 2007

[31] A E A Porter Diazines and Benzodiazines vol 14 PregamonPress Elsevier Science BV Amsterdam The Netherlands 1979

[32] C O Kappe ldquo100 years of the biginelli dihydropyrimidinesynthesisrdquo Tetrahedron vol 49 no 32 pp 6937ndash6963 1993

[33] P Sharma N Rane and V K Gurram ldquoSynthesis andQSAR studies of pyrimido[45-d]pyrimidine-25-dione deriva-tives as potential antimicrobial agentsrdquo Bioorganic and Medici-nal Chemistry Letters vol 14 no 16 pp 4185ndash4190 2004

[34] O Prakash V Bhardwaj R Kumar P Tyagi and K RAneja ldquoOrganoiodine (III) mediated synthesis of 3-arylhetryl-57-dimethyl-124-triazolo[43-a]pyrimidines as antibacterialagentsrdquo European Journal of Medicinal Chemistry vol 39 no12 pp 1073ndash1077 2004

[35] M Botta M Artico S Massa et al ldquoSynthesis antimicrobialand antiviral activities of isotrimethoprim and some relatedderivativesrdquo European Journal of Medicinal Chemistry vol 27no 3 pp 251ndash257 1992

[36] N Agarwal P Srivastava S K Raghuwanshi et al ldquoChloropy-rimidines as a new class of antimicrobial agentsrdquoBioorganic andMedicinal Chemistry vol 10 no 4 pp 869ndash874 2002


[37] B Roth and B S Rauckman ldquo24-Diamino-5-(1234-tetrahydro-(substituted or unsubstituted)-6-quinolylmethyl)-pyrimidines useful as antimicrobialsrdquo US Patent 4 587 3411986

[38] S Marquais-Bienewald W Holzol A Preuss and A MehlinldquoUse of substituted 24-bis (alkylamino) pyrimidinesrdquo USPatent 0188453 A1 2006

[39] S M Daluge P Skonezny B Roth and B S Raukman ldquo24-Diamino-5-(substituted) pyrimidine useful as antimicrobialsrdquoUS Patent 4 590 271 1986

[40] S Ito K Masuda S Kusano et al ldquoPyrimidine derivativeprocess for preparing same and agricultural or horticulturalfungicidal composition containing samerdquo US Patent 4 988704 1991

[41] Y Nakagawa S Bobrov C R Semer T A Kucharek and MHarmoto ldquoFungicidal pyrimidine derivativesrdquo US Patent 6818 631 B1 2004

[42] N Agarwal S K Raghuwanshi D N Upadhyay P K Shuklaand V J Ram ldquoSuitably functionalised pyrimidines as potentialantimycotic agentsrdquo Bioorganic and Medicinal Chemistry Let-ters vol 10 no 8 pp 703ndash706 2000

[43] H S Basavaraja G M Sreenivasa and E Jayachandran ldquoSyn-thesis and biological activity of novel pyrimidino imidazolinesrdquoIndian Journal of Heterocyclic Chemistry vol 15 p 69 2005

[44] V J Ram N Haque and P Y Guru ldquoChemotherapeutic agentsXXV synthesis and leishmanicidal activity of carbazolylpyrim-idinesrdquo European Journal of Medicinal Chemistry vol 27 no 8pp 851ndash855 1992

[45] M Amir S A Javed and H Kumar ldquoPyrimidine as anti-inflammatory agent a reviewrdquo Indian Journal of PharmaceuticalSciences vol 68 p 337 2007

[46] SM Sondhi S Jain A D Dwivedi R Shukla and R RaghubirldquoSynthesis of condensed pyrimidines and their evaluation foranti-inflammatory and analgesic activitiesrdquo Indian Journal ofChemistry B vol 47 no 1 pp 136ndash143 2008

[47] S Vega J Alonso J A Diaz and F Junquera ldquoSynthesis of 3-substituted-4-phenyl-2-thioxo-12345678-octahydrobenzo[45]thieno[23-d]pyrimidinesrdquo Journal of HeterocyclicChemistry vol 27 no 2 pp 269ndash273 1990

[48] D R Hannah and M F G Stevens ldquoStructural studieson bioactive compoundsmdashpart 381 reactions of 5-aminoimidazole-4-carboxamide synthesis of imidazo[15-a]quinazoline-3-carboxamidesrdquo Journal of Chemical ResearchS no 7 pp 398ndash401 2003

[49] K Rana B Kaur and B Kumar ldquoSynthesis and anti-hypertensive activity of some dihydropyrimidinesrdquo Indian Jour-nal of Chemistry B vol 43 no 7 pp 1553ndash1557 2004

[50] P A S Smith and R O Kan ldquoCyclization of isothiocyanates asa route to phthalic and homophthalic acid derivativesrdquo Journalof Organic Chemistry vol 29 no 8 pp 2261ndash2265 1964

[51] J Balzarini and C McGuigan ldquoBicyclic pyrimidine nucleosideanalogues (BCNAs) as highly selective and potent inhibitorsof varicella-zoster virus replicationrdquo Journal of AntimicrobialChemotherapy vol 50 no 1 pp 5ndash9 2002

[52] R W von Borstel ldquoTreatment of chemotherapeutic agent andantiviral agent toxicity with acylated pyrimidine nucleosidesrdquoUS Patent 6 344 447 B2 2002

[53] R Storer A Moussa P La Colla and M Artico ldquoOxo-pyrimidine compoundsrdquo US Patent 0014774 A1 2005

[54] H W Lee Y K Bok B A Joong et al ldquoMolecular designsynthesis and hypoglycemic and hypolipidemic activities of

novel pyrimidine derivatives having thiazolidinedionerdquo Euro-pean Journal of Medicinal Chemistry vol 40 no 9 pp 862ndash8742005

[55] P F Juby T W Hudyma M Brown J M Essery andR A Partyka ldquoAntiallergy agents 1 16-dihydro-6-oxo-2-phenylpyrimidine-5-carboxylic acids and estersrdquo Journal ofMedicinal Chemistry vol 22 no 3 pp 263ndash269 1979

[56] A K Gupta Sanjay H P Kayath A Singh G Sharma and KCMishra ldquoAnticonvulsant activity of pyrimidine thiolsrdquo IndianJournal of Pharmacology vol 26 no 3 pp 227ndash228 1994

[57] A A Abu-Hashem M M Youssef and H A R HusseinldquoSynthesis antioxidant antituomer activities of some new thi-azolopyrimidines pyrrolothiazolopyrimidines and triazolopy-rrolothiazolopyrimidines derivativesrdquo Journal of the ChineseChemical Society vol 58 no 1 pp 41ndash48 2011

[58] A A Abu-Hashem M F El-Shehry and F A Badria ldquoDesignand synthesis of novel thiophenecarbohydrazide thienopy-razole and thienopyrimidine derivatives as antioxidant andantitumor agentsrdquo Acta Pharmaceutica vol 60 no 3 pp 311ndash323 2010

[59] S A Rahaman Y R Pasad P Kumar and B Kumar ldquoSynthesisand anti-histaminic activity of some novel pyrimidinesrdquo SaudiPharmaceutical Journal vol 17 no 3 pp 255ndash258 2009

[60] Y Nezu M Miyazaki K Sugiyama and I KajiwaraldquoDimethoxypyrimidine as novel herbicidesmdashpart 1synthesis and herbicidal activity of dimethoxyphenox-yphenoxypyrimidines and analoguesrdquo Pesticide Science vol 47pp 103ndash113 1996

[61] J W Coe A F J Fliri T Kaneko and E R Larson ldquoPyrimidinederivatives enhancing antitumour activityrdquo US Patent 5 491234 1996

[62] G A Breault N J Newcombe and A P Thomas ldquoImidazolo-5-YL-2-anilino-pyrimidines as agents for the inhibition of thecell proliferationrdquo US Patent 6 969 714 B2 2005

[63] F Xie H Zhao L Zhao L Lou and Y Hu ldquoSynthesisand biological evaluation of novel 245-substituted pyrimidinederivatives for anticancer activityrdquo Bioorganic and MedicinalChemistry Letters vol 19 no 1 pp 275ndash278 2009

[64] M A Kaldrikyan L A Grigoryan V A Geboyan F GArsenyan G M Stepanyan and B T Garibdzhanyan ldquoSynthe-sis and antitumor activity of some disubstituted 5-(3-methyl-4-alkoxybenzyl)pyrimidinesrdquo Pharmaceutical Chemistry Journalvol 34 no 10 pp 521ndash524 2000

[65] A L S Rodrigues J M Rosa V M Gadotti et alldquoAntidepressant-like and antinociceptive-like actions of 4-(41015840-chlorophenyl)-6-(4

10158401015840

-methylphenyl)-2-hydrazinepyrimidineMannich base in micerdquo Pharmacology Biochemistry andBehavior vol 82 no 1 pp 156ndash162 2005

[66] J Tani Y Yamada T Oine T Ochiai R Ishida and IInoue ldquoStudies on biologically active halogenated compounds1 Synthesis and central nervous system depressant activityof 2-(fluoromethyl)-3-aryl-4(3H)-quinazolinone derivativesrdquoJournal of Medicinal Chemistry vol 22 no 1 pp 95ndash99 1979

[67] B Kumar B Kaur J Kaur A Parmar R D Anand and HKumar ldquoThermalmicrowave assisted synthesis of substitutedtetrahydropyrimidines as potent calcium channel blockersrdquoIndian Journal of Chemistry B vol 41 no 7 pp 1526ndash1530 2002

[68] K S Jain T S Chitre P B Miniyar et al ldquoBiological andmedicinal significance of pyrimidinesrdquo Current Science vol 90no 6 pp 793ndash803 2006


[69] G H Hitchings G B Elion H Vanderwerff and E A FalcoldquoPyrimidine derivatives as antagonists of pteroylglutamic acidrdquoThe Journal of Biological Chemistry vol 174 no 2 pp 765ndash7661948

[70] S Futterman ldquoEnzymatic reduction of folic acid and dihy-drofolic acid to tetrahydrofolic acidrdquo The Journal of BiologicalChemistry vol 228 no 2 pp 1031ndash1038 1957

[71] W C Werkheiser ldquoSpecific binding of 4-amino folic acidanalogues by folic acid reductaserdquo The Journal of BiologicalChemistry vol 236 no 3 pp 888ndash893 1961

[72] I Kompis and A Wick ldquoSynthese von 4-halogensubstituiertenanalogen von trimethoprimrdquo Helvetica Chimica Acta vol 60no 8 pp 3025ndash3034 1977

[73] S Hawser S Lociuro and K Islam ldquoDihydrofolate reductaseinhibitors as antibacterial agentsrdquo Biochemical Pharmacologyvol 71 no 7 pp 941ndash948 2006

[74] P Schneider S Hawser and K Islam ldquoIclaprim a noveldiaminopyrimidinewith potent activity on trimethoprim sensi-tive and resistant bacteriardquo Bioorganic andMedicinal ChemistryLetters vol 13 no 23 pp 4217ndash4221 2003

[75] C C Cheng and B Roth ldquo6 recent progress in the medicinalchemistry of 24-diaminopyrimidinesrdquo Progress in MedicinalChemistry vol 19 pp 269ndash331 1982

[76] J Hughes L C Roberts and A J Coppridge ldquoSulfacytine anew sulfonamide double blind comparison with sulfisoxazolein acute uncomplicated urinary tract infectionsrdquo Journal ofUrology vol 114 no 6 pp 912ndash914 1975

[77] N J White ldquoThe treatment of malariardquo The New EnglandJournal of Medicine vol 335 no 11 pp 800ndash806 1996

[78] I Von Zabern R Nolte H Przyklenk and W Vogt ldquoEffect ofdifferent sulfonamides on the human serum complement sys-temrdquo International Archives of Allergy and Applied Immunologyvol 76 no 3 pp 205ndash213 1985

[79] M E Stolar ldquoSynergistic antibacterial compositionrdquo US Patent4 470 978 1984

[80] A Carr R Penny and D A Cooper ldquoEfficacy and safety ofrechallengewith low-dose trimethoprim-sulphamethoxazole inpreviously hypersensitive HIV-infected patientsrdquo AIDS vol 7no 1 pp 65ndash71 1993

[81] J J Reddick S Saha J Lee J S Melnick J Perkins and T PBegley ldquoThe mechanism of action of bacimethrin a naturallyoccurring thiamin antimetaboliterdquo Bioorganic and MedicinalChemistry Letters vol 11 no 17 pp 2245ndash2248 2001

[82] P Singh R Kumar and B K Sharma ldquoQuantitative structure-activity relationship study of 5-iodo- and diaryl-analogues oftubercidin inhibitors of adenosine kinaserdquo Journal of EnzymeInhibition and Medicinal Chemistry vol 18 no 5 pp 395ndash4022003

[83] L P G Wakelin and M J Waring Comprehensive MedicinalChemistry Drug Compendium vol 2 Pergamon Press OxfordUK 1990 edited by P G Sammers

[84] E de Clercq ldquoAntiviral drugs in current clinical userdquo Journal ofClinical Virology vol 30 no 2 pp 115ndash133 2004

[85] H Mitsuya K J Weinhold and P A Furman ldquo31015840-Azido-31015840-deoxythymidine (BW A509U) an antiviral agent that inhibitsthe infectivity and cytopathic effect of human T-lymphotropicvirus type IIIlymphadenopathy-associated virus in vitrordquo Pro-ceedings of the National Academy of Sciences of the United Statesof America vol 82 no 20 pp 7096ndash7100 1985

[86] R van Leeuwen C Katlama V Kitchen et al ldquoEvaluation ofsafety and efficacy of 3TC (lamivudine) in patients with asymp-tomatic ormildly symptomatic human immunodeficiency virus

infection a phase III studyrdquo Journal of Infectious Diseases vol171 no 5 pp 1166ndash1171 1995

[87] H Mitsuya ldquoAnti-HIV nucleosides past present and futurerdquoJournal of Immunoassay vol 18 no 3 pp 285ndash287 1997

[88] P M Woster Foyersquos Principles of Medicinal Chemistry Lippin-cott Williams amp Wilkins Wolters Kluwar Business Philadel-phia Pa USA 6th edition 2008

[89] J Smith and D Andes ldquoTherapeutic drug monitoring ofantifungals pharmacokinetic and pharmacodynamic consider-ationsrdquoTherapeutic Drug Monitoring vol 30 no 2 pp 167ndash1722008

[90] B Chadwick M Addy and D M Walker ldquoHexetidinemouthrinse in the management of minor aphthous ulcerationand as an adjunct to oral hygienerdquo The British Dental Journalvol 171 no 3-4 pp 83ndash87 1991

[91] M Butters J Ebbs S P Green et al ldquoProcess developmentof voriconazole a novel broad-spectrum triazole antifungalagentrdquo Organic Process Research and Development vol 5 no 1pp 28ndash36 2001

[92] R Gage and D A Stopher ldquoA rapid HPLC assay for voricona-zole in human plasmardquo Journal of Pharmaceutical and Biomed-ical Analysis vol 17 no 8 pp 1449ndash1453 1998

[93] V K Kapoor and H Singh Medicinal and PharmaceuticalChemistry edited by M K Jain Vallabh Prakashan DelhiIndia 2nd edition 2005

[94] N V Kolotova V O Kozrsquominykh A V Dolzhenko et alldquoSubstituted amides and hydrazides of dicarboxylic acids Part9 Pharmacological activity of the products of interaction of 2-aminopyridines and 2-aminopyrimidine with dicarboxylic acidanhydridesrdquo Pharmaceutical Chemistry Journal vol 35 no 3pp 146ndash150 2001

[95] T Govindasami A Pandey N Palanivelu and A Pandey ldquoSyn-thesis characterization and antibacterial activity of biologicallyimportant vanillin related hydrazone derivativesrdquo InternationalJournal of Organic Chemistry vol 1 pp 71ndash77 2011

[96] C Mallikarjunaswamy D G Bhadregowda and L MalleshaldquoSynthesis and antimicrobial activity of pyrimidine salts withchloranilic and picric acidsrdquo Journal of Chemistry vol 2013Article ID 727182 5 pages 2013

[97] N Zanatta S S Amaral J M dos Santos et al ldquoConver-gent synthesis and cruzain inhibitory activity of novel 2-(N1015840-benzylidenehydrazino)-4-trifluoromethyl-pyrimidinesrdquo Bioor-ganic and Medicinal Chemistry vol 16 no 24 pp 10236ndash102432008

[98] A M Balan O Florea C Moldoveanu G Zbancioc D Iureaand I I Mangalagiu ldquoDiazinium salts with dihydroxyacetophe-none skeleton syntheses and antimicrobial activityrdquo EuropeanJournal of Medicinal Chemistry vol 44 no 5 pp 2275ndash22792009

[99] P Mondal S Jana and L K Kanthal ldquoSynthesis of novelmercapto-pyrimidine and amino-pyrimidine derivatives ofindoline-2-one as potential antioxidant amp antibacterial agentsrdquoThe Pharma Research vol 3 pp 17ndash26 2010

[100] A Solankee S Lad S Solankee and G Patel ldquoChalconespyrazolines and aminopyrimidines as antibacterial agentsrdquoIndian Journal of Chemistry B vol 48 no 10 pp 1442ndash14462009

[101] S Sukhwal and B L Verma ldquoA new route to 2-piperidino-46-diarylpyrimidinesrdquo Indian Journal of Heterocyclic Chemistryvol 4 no 1 pp 67ndash68 1994


[102] V Desai C M Desai and D Patel ldquo2-Amino-4-(41015840-chlorophenyl)-6-substituted)-pyrimidinesrdquo Journal of theInstitution of Chemists vol 11 pp 104ndash105 2005

[103] A A F Wasfy and A A Aly ldquoSimple synthesis of somediphenylsulfapyrimidine acetates from chalcones and theirantimicrobial activityrdquo Chemical Papers vol 57 no 5 pp 364ndash368 2003

[104] E S Devi E O Prakash and J T Rao ldquoPyrimidine derivativespart-1rdquo Journal of the Institution of Chemists vol 74 no 5 pp167ndash168 2002

[105] D B Yadav K B Venkatesh and S S Sangapure ldquoSynthesisand biological evaluation of 3-aryl-1-(2-benzofuryl)-2-propen-1-one analoguesrdquo Indian Journal of Heterocyclic Chemistry vol19 no 2 pp 117ndash120 2009

[106] S Kothari R Vyas and B L Verma ldquoA facile one potconversion of 3101584051015840-dibromo-41015840-hydroxy substituted chalconesto pyrimidine derivatives and their antibacterial and herbicidalactivityrdquo Indian Journal of Heterocyclic Chemistry vol 8 no 4pp 285ndash288 1999

[107] V H Babu P S Kumar K K Srinivasan and G V BhatldquoSynthesis antitumor and antibacterial activities of certainsubstituted pyrimidines bearing benzofuranrdquo Indian Journal ofPharmaceutical Sciences vol 66 no 5 pp 647ndash652 2004

[108] T Y Pasha R H Udupi and A R Bhat ldquoSynthesis andantimicrobial screening of some pyrimidine derivativesrdquo IndianJournal of Heterocyclic Chemistry vol 15 no 2 pp 149ndash1522005

[109] S Chandrasekaran and S Nagarajan ldquoMicrowave-assisted syn-thesis and anti-bacterial activity of some 2-amino-6-aryl-4-(2-thienyl)pyrimidinesrdquo Il Farmaco vol 60 no 4 pp 279ndash2822005

[110] A A Patel and A G Mehta ldquoSynthesis and characterizationof some pyrimidine-quinoline clubbed molecules and theirmicrobicidal efficacyrdquo Journal of Saudi Chemical Society vol 14no 2 pp 203ndash208 2010

[111] D B A Kumar G K Prakash M N Kumaraswamy BP Nandeshwarappa B S Sherigara and K M MahadevanldquoMicrowave assisted facile synthesis of amino pyrimidinesbearing benzofuran and investigation of their antimicrobialactivityrdquo Indian Journal of Chemistry B vol 45 no 7 pp 1699ndash1703 2006

[112] V Kanagarajan J Thanusu and M Gopalakrishnan ldquoA greenchemical approach towards the ldquoone-potrdquo synthesis spectralcharacterization and in vitro antibacterial and antifungal activi-ties ofmorpholino pyrimidinesrdquo Journal of the KoreanChemicalSociety vol 53 no 6 pp 731ndash741 2009

[113] T A Naik and K H Chikhalia ldquoStudies on synthesis ofpyrimidine derivatives and their pharmacological evaluationrdquoE-Journal of Chemistry vol 4 no 1 pp 60ndash66 2007

[114] V K Tirlapur N Gandhi R Basawaraj and P Y RajendraldquoSynthesis characterization and biological activities of somenew pyrimidines and isoxazoles bearing benzofuran moietyrdquoInternational Journal of ChemTech Research vol 2 no 3 pp1434ndash1440 2010

[115] N Ingarsal G Saravanan P Amutha and S Nagarajan ldquoSyn-thesis in vitro antibacterial and antifungal evaluations of 2-amino-4-(1-naphthyl)-6-arylpyrimidinesrdquo European Journal ofMedicinal Chemistry vol 42 no 4 pp 517ndash520 2007

[116] B Ramesh and T Sumana ldquoSynthesis and anti-microbialscreening of some new pyrimidine derivativesrdquo InternationalJournal of Pharmaceutical Sciences vol 1 no 2 pp 320ndash3222009

[117] L R Patil V S Ingle S P Bondge V E Bhingolikar and R AMane ldquoSynthesis of new pyrimidines bearing paracetamol andimidazolyl moietiesrdquo Indian Journal of Heterocyclic Chemistryvol 11 no 2 pp 131ndash134 2001

[118] DH Patel KHChikhaliaNK ShahD P Patel P BKaswalaand V M Buha ldquoDesign synthesis and antimicrobial studyof some pyrimidine derivativesrdquo Pharmaceutical ChemistryJournal vol 44 no 2 pp 94ndash98 2010

[119] R A Forsch S F Queener and A Rosowsky ldquoPreliminaryin vitro studies on two potent water-soluble trimethoprimanalogues with exceptional species selectivity against dihydro-folate reductase from Pneumocystis carinii and Mycobacteriumaviumrdquo Bioorganic and Medicinal Chemistry Letters vol 14 no7 pp 1811ndash1815 2004

[120] A Ali S D Aster DW Graham et al ldquoDesign and synthesis ofnovel antibacterial agents with inhibitory activity against DNApolymerase IIIrdquo Bioorganic and Medicinal Chemistry Lettersvol 11 no 16 pp 2185ndash2188 2001

[121] G Menozzi L Mosti P Fossa C Musiu C Murgioni andP La Colla ldquoSynthesis and biological evaluation of azolederivatives analogues of bifonazole with a phenylisoxazolyl orphenylpyrimidinyl moietyrdquo Il Farmaco vol 56 no 9 pp 633ndash640 2001

[122] E Nassar ldquoSynthesis (in vitro) antitumour and antimicrobialactivity of some pyrazoline pyridine and pyrimidine derivativeslinked to indole moietyrdquo Journal of American Science vol 6 no8 pp 338ndash347 2010

[123] A Nagaraj and C S Reddy ldquoSynthesis and biological study ofnovel bis-chalcones bis-thiazines and bis-pyrimidinesrdquo Journalof the Iranian Chemical Society vol 5 no 2 pp 262ndash267 2008

[124] O A Fathalla W A Zaghary H H Radwan S M Awad andM S Mohamed ldquoSynthesis of new 2-thiouracil-5-sulfonamidederivatives with biological activityrdquo Archives of PharmacalResearch vol 25 no 3 pp 258ndash269 2002

[125] K H Chikhalia M J Patel and D B Vashi ldquoDesign synthesisand evaluation of novel quinolyl chalcones as antibacterialagentsrdquo Arkivoc vol 2008 no 13 pp 189ndash197 2008

[126] P C Wyss P Gerber P G Hartman et al ldquoNovel dihydrofolatereductase inhibitors Structure-based versus diversity-basedlibrary design and high-throughput synthesis and screeningrdquoJournal of Medicinal Chemistry vol 46 no 12 pp 2304ndash23122003

[127] M Brands Y C Grande R Endermann R GahlmannJ Kruger and S Raddatz ldquoPyrimidinone antibioticsmdashheterocyclic analogues with improved antibacterial spectrumrdquoBioorganic and Medicinal Chemistry Letters vol 13 no 16 pp2641ndash2645 2003

[128] K Vijayaramalingam S Chandrasekaran and S Nagara-jan ldquoSynthesis and antibacterial activity of 4-(1-naphthyl)-6-arylpyrimidin-2-(1H)-onesrdquoPharmaceutical Chemistry Journalvol 41 no 5 pp 253ndash255 2007

[129] B Orzeszko Z Kazimierczuk J K Maurin et al ldquoNoveladamantylated pyrimidines and their preliminary biologicalevaluationsrdquo Il Farmaco vol 59 no 12 pp 929ndash937 2004

[130] A H Moustafa H A Saad W S Shehab and M M El-Mobayed ldquoSynthesis of some new pyrimidine derivatives ofexpected antimicrobial activityrdquo Phosphorus Sulfur and Siliconand the Related Elements vol 183 no 1 pp 115ndash135 2008

[131] M M M Ramiz W A El-Sayed A I El-Tantawy andA A H Abdel-Rahman ldquoAntimicrobial activity of new 46-disubstituted pyrimidine pyrazoline and pyran derivativesrdquoArchives of Pharmacal Research vol 33 no 5 pp 647ndash654 2010


[132] P Cernuchova G Vo-Thanh V Milata A Loupy S Jan-tova and M Theiszova ldquoUtilization of 2-ethoxymethylene-3-oxobutanenitrile in the synthesis of heterocycles possessingbiological activityrdquo Tetrahedron vol 61 no 22 pp 5379ndash53872005

[133] S LMosley B A Bakke J M Sadler et al ldquoCarbocyclic pyrim-idine nucleosides as inhibitors of S-adenosylhomocysteinehydrolaserdquo Bioorganic and Medicinal Chemistry vol 14 no 23pp 7967ndash7971 2006

[134] J A A Micky N M Saleh S M Mohamed S A Mohamedand M M Salem ldquoReaction and antimicrobial activity of 1-arylethylene benzofuranyl ketone derivativesrdquo Indian Journal ofChemistry B vol 45 no 6 pp 1579ndash1583 2006

[135] N B Patel and Y S Gorgamwala ldquoAntibacterial study of2-(Pyrazine-21015840-carboxamido)-4-(21015840-p-aminobenzene-sulfon-amido-4101584061015840-dimethyl pyrimidine)-6-(arylthiouriedo)-s-triazine derivativesrdquo Journal of Indian Council of Chemists vol19 no 2 pp 17ndash20 2002

[136] S A Rahaman Y R Prasad K P Kumar D Hareesh and A PRani ldquoSynthesis and in vitro antibacterial activity of some novel2-amino-46-D derivativesrdquo Journal of Sciences Islamic Republicof Iran vol 22 no 1 pp 27ndash31 2011

[137] SGKhanage S A Raju P BMohite andR B Pandhare ldquoSyn-thesis and pharmacological evaluation of some new pyrimidinederivatives containing 124-triazolerdquo Advanced PharmaceuticalBulletin vol 2 no 2 pp 213ndash222 2012

[138] N Kaur A K Aggarwal N Sharma and B ChoudharyldquoSynthesis and in-vitro antimicrobial activity of pyrimidinederivativesrdquo International Journal of Pharmaceutical Sciencesand Drug Research vol 4 no 3 pp 199ndash204 2012

[139] M M M Hussain K I Bhat B C Revanasiddappa and D RBharthi ldquoSynthesis and biological evaluation of some novel 2-mercapto pyrimidinesrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 5 no 2 pp 471ndash473 2013

[140] A A Aly and S A Nassar ldquoN-[4-(dicyanomethylazo)phenyl]-2-saccharin-2-ylacetamide in the synthesis of pyridazine andpyrimidine derivativesrdquoHeteroatomChemistry vol 15 no 1 pp2ndash8 2004

[141] A Waheed M S Alorainy A A Alghasham S A Khan andM Raza ldquoSynthesis of a new series of substituted pyrimidinesand its evaluation for antibacterial and antinociceptive effectsrdquoInternational Journal of Health Sciences vol 2 no 1 pp 39ndash482008

[142] J M Parmar and A R Parikh ldquoSynthesis and biologicalevaluation of somepyrimidinethiones and related heterocyclesrdquoIndian Journal of Heterocyclic Chemistry vol 10 no 3 pp 205ndash208 2001

[143] N Y Khir EldinWAGad YMAli andN RMohamed ldquoTheutility of 6-amino-2-thiouracil for synthesis of bioactive sulfurand phosphorus heterocyclic derivativesrdquo Egyptian Journal ofChemistry vol 50 no 4 pp 531ndash540 2007

[144] M N Purohi C Kunal G V Pujar Y C Mayur andS M Shantakumar ldquoSynthesis and antibacterial activity of5-(51015840-substituted 134-oxadiazol-21015840-YL) dihydropyrimidinonederivativesrdquo Indian Journal ofHeterocyclic Chemistry vol 16 no4 pp 349ndash352 2007

[145] A H Moustafa H A Morsy M G Assy and A Z HaikalldquoSynthesis and antimicrobial activity of some S-120573-D-glucosidesof 4-mercaptopyrimidinerdquo Nucleosides Nucleotides and NucleicAcids vol 28 no 9 pp 835ndash845 2009

[146] D N Upadhyay and V J Ram ldquoSynthesis of pyrimidineand azolopyrimidines as biodynamic agentsrdquo Indian Journal ofChemistry B vol 38 no 2 pp 173ndash177 1999

[147] O A El-Fattah E M H Abbas N A Mohamed and S I Abd-Elmoez ldquoSynthesis and evaluation of some tetrahydropyrimi-dine derivatives as antimicrobialrdquo Australian Journal of Basicand Applied Sciences vol 4 no 1 pp 27ndash36 2010

[148] A H Moustafa H A Morsy and A Z Haikal ldquoSynthesisand antimicrobial activity of some S-and-N-120573-D-glucosidesof pyrimidin-4-thiolrdquo in Proceedings of the 4th EnvironmentalConference pp 47ndash63 Faculty of Science Zigzag University2009

[149] T Tomasic N Zidar M Mueller-Premru D Kikeljand L P Masic ldquoSynthesis and antibacterial activityof 5-ylidenethiazolidin-4-ones and 5-benzylidene-46-pyrimidinedionesrdquo European Journal of Medicinal Chemistryvol 45 no 4 pp 1667ndash1672 2010

[150] O A Fathalla I F Zied M E Haiba et al ldquoSynthesisantibacterial and anticancer evaluation of some pyrimidinederivativesrdquo World Journal of Chemistry vol 4 pp 127ndash1322009

[151] L C Heda R Sharma C Pareek and P B ChaudharildquoSynthesis and antimicrobial activity of some derivatives of 5-substituted indole dihydropyrimidinesrdquoE-Journal of Chemistryvol 6 no 3 pp 770ndash774 2009

[152] S Prachayasittikul N Sornsongkhram R Pingaew STechatanachai S Ruchirawat and V PrachayasittikulldquoSynthesis and novel bioactivities of substituted 6-propylthiouracilsrdquo European Journal of Scientific Researchvol 36 no 2 pp 236ndash245 2009

[153] H S Basavaraja K V Jayadevaiah M M Hussain V Kumarand B Padmashali ldquoSynthesis of novel piperazine andmorpho-line linked substituted pyrimidine derivatives as antimicrobialagentsrdquo Journal of Pharmaceutical Sciences and Research vol 2no 1 pp 5ndash12 2010

[154] J D Akbari P K Kachhadia S D Tala et al ldquoSynthesisof some new 1234-tetrahydropyrimidine-2-thiones and theirthiazolo[32-120572]pyrimidine derivatives as potential biologicalagentsrdquo Phosphorus Sulfur and Silicon and the Related Elementsvol 183 no 8 pp 1911ndash1922 2008

[155] A A Bekhit O A El-Sayed E Aboulmagd and J Y ParkldquoTetrazolo[15-a]quinoline as a potential promising new scaf-fold for the synthesis of novel anti-inflammatory and antibac-terial agentsrdquo European Journal of Medicinal Chemistry vol 39no 3 pp 249ndash255 2004

[156] Q Yan R Cao W Yi et al ldquoInhibitory effects of 5-benzylidenebarbiturate derivatives on mushroom tyrosinase and theirantibacterial activitiesrdquo European Journal of Medicinal Chem-istry vol 44 no 10 pp 4235ndash4243 2009

[157] S N Sriharsha S Satish S Shashikanth and K A Ravee-sha ldquoDesign synthesis and antibacterial activity of novel 13-thiazolidine pyrimidine nucleoside analoguesrdquo Bioorganic andMedicinal Chemistry vol 14 no 22 pp 7476ndash7481 2006

[158] A Padmaja T Payani G D Reddy and V PadmavathildquoSynthesis antimicrobial and antioxidant activities of substi-tuted pyrazoles isoxazoles pyrimidine and thioxopyrimidinederivativesrdquo European Journal of Medicinal Chemistry vol 44no 11 pp 4557ndash4566 2009

[159] A R Gholap K S Toti F Shirazi M V Deshpande and KV Srinivasan ldquoEfficient synthesis of antifungal pyrimidines via


palladium catalyzed SuzukiSonogashira cross-coupling reac-tion from Biginelli 34-dihydropyrimidin-2(1H)-onesrdquo Tetrahe-dron vol 64 no 44 pp 10214ndash10223 2008

[160] K K Joshi J Akbari and H S Joshi ldquoEvaluations of antimi-crobial activity of some pharmacological important dihydropy-rimidines compoundsrdquo Journal of Cell and Tissue Research vol10 no 2 pp 2243ndash2250 2010

[161] P Sharma A Kumar and M Sharma ldquoSynthesis and QSARstudies on 5-[2-(2-methylprop1-enyl)-1H benzimidazol-1yl]-46-diphenyl-pyrimidin-2-(5H)-thione derivatives as antibac-terial agentsrdquo European Journal of Medicinal Chemistry vol 41no 7 pp 833ndash840 2006

[162] E Septioglu M D Aytemir E Kilic M Ozalp and U CalisldquoSynthesis of some new NN-disubstituted dithiocarbamic acid2-(6-arylhexahydropyrimidine-24-dion-3-yl)ethyl esters andin vitro evaluation of antimicrobial activitiesrdquo FABAD Journalof Pharmaceutical Sciences vol 29 no 1 pp 1ndash6 2004

[163] C Robson M A Meek J-D Grunwaldt et al ldquoNonclassical24-diamino-5-aryl-6-ethylpyrimidine antifolates activity asinhibitors of dihydrofolate reductase from Pneumocystis cariniiand Toxoplasma gondii and as antitumor agentsrdquo Journal ofMedicinal Chemistry vol 40 no 19 pp 3040ndash3048 1997

[164] D V Singh A R Mishra and R M Mishra ldquoSynthesis andcharacterization of some antifungal pyrimidinone derivativesrdquoIndian Journal of Heterocyclic Chemistry vol 14 no 1 pp 43ndash46 2004

[165] R Bamnela and S P Shrivastava ldquoSynthesis and in vitroantimicrobial anthelmintic and insecticidal activities studyof 4(41015840-bromophenyl)-6-substituted-aryl-1-acetyl pyrimidine-2-thiolsrdquo E-Journal of Chemistry vol 7 no 3 pp 935ndash941 2010

[166] D J Trantolo G E Wright and N C Brown ldquoInhibitorsof Bacillus subtilis DNA polymerase III Influence of mod-ifications in the pyrimidine ring of anilino- and (benzy-lamino)pyrimidinesrdquo Journal of Medicinal Chemistry vol 29no 5 pp 676ndash681 1986

[167] B Shivkumar S Singh T Y Pasha et al ldquoSynthesis of certainpyrimidines as antimicrobial agentsrdquo Indian Journal of Hetero-cyclic Chemistry vol 17 no 2 pp 197ndash198 2007

[168] B D Dhorajiya M H Malani J R Patel and B Z DholakiyaldquoAntimicrobial activities of synthesized and characterized 5-acetyl pyrimidine-246-(1H3H5H)-trione based chalconesrdquoDer Pharma Chemica vol 4 no 1 pp 141ndash146 2012

[169] K Elumalai M A Ali M Elumalai K Eluri and S SrinivasanldquoNovel isoniazid cyclocondensed 1234-tetrahydropyrimidinederivatives for treating infectious disease a synthesis and invitro biological evaluationrdquo Journal of Acute Disease vol 2 no4 pp 316ndash321 2013

[170] B Andrews and M Ahmed ldquoSynthesis and characterizationof pyrimidine bearing 134-oxadiazole derivatives and theirpotential antifungal actionrdquo International Journal of ChemicalStudies vol 1 no 4 pp 32ndash39 2013

[171] H Sohn K-S Lee Y-K Ko et al ldquoIn vitro and ex vivo activity ofnew derivatives of acetohydroxyacid synthase inhibitors againstMycobacterium tuberculosis and non-tuberculous mycobacte-riardquo International Journal of Antimicrobial Agents vol 31 no 6pp 567ndash571 2008

[172] A Rosowsky R A Forsch and S F Queener ldquoInhibition ofPneumocystis carinii Toxoplasma gondii and Mycobacteriumavium dihydrofolate reductases by 24-diamino-5-[2-methoxy-5-(120596-carboxyalkyloxy)benzyl]pyrimidines marked improve-ment in potency relative to trimethoprim and species selectivity

relative to piritreximrdquo Journal of Medicinal Chemistry vol 45no 1 pp 233ndash241 2002

[173] R C Reynolds S R Campbell R G Fairchild et al ldquoNovelboron-containing nonclassical antifolates synthesis and pre-liminary biological and structural evaluationrdquo Journal ofMedic-inal Chemistry vol 50 no 14 pp 3283ndash3289 2007

[174] A R Trivedi D K Dodiya N R Ravat and V H ShahldquoSynthesis and biological evaluation of some new pyrimidinesvia a novel chalcone seriesrdquoArkivoc vol 2008 no 11 pp 131ndash1412008

[175] M L Read M Braeligndvang P O Miranda and L GundersenldquoSynthesis and biological evaluation of pyrimidine analogs ofantimycobacterial purinesrdquo Bioorganic and Medicinal Chem-istry vol 18 no 11 pp 3885ndash3897 2010

[176] K Umaa M Ramanathan K Krishnakumar and K KannanldquoElucidation and evaluation of substituted pyrimidinesrdquo AsianJournal of Chemistry vol 21 no 9 pp 6674ndash6678 2009

[177] A A Siddiqui R Rajesh M Islam V Alagarsamy and Ede Clercq ldquoSynthesis antiviral antituberculostic and antibac-terial activities of some novel 4-(4-substituted phenyl)-6-(4-nitrophenyl)-2-(substituted imino)pyrimidinesrdquo Archiv derPharmazie vol 340 no 2 pp 95ndash102 2007

[178] V Virsodia R R S Pissurlenkar D Manvar et al ldquoSynthe-sis screening for antitubercular activity and 3D-QSAR stud-ies of substituted N-phenyl-6-methyl-2-oxo-4-phenyl-1234-tetrahydro-pyrimidine-5-carboxamidesrdquo European Journal ofMedicinal Chemistry vol 43 no 10 pp 2103ndash2115 2008

[179] N C Srivastav T Manning D Y Kunimoto and R KumarldquoStudies on acyclic pyrimidines as inhibitors of mycobacteriardquoBioorganic and Medicinal Chemistry vol 15 no 5 pp 2045ndash2053 2007

[180] N C Srivastav D Rai C Tse B Agrawal D Y Kunimoto andR Kumar ldquoInhibition of mycobacterial replication by pyrim-idines possessing various C-5 functionalities and related 21015840-deoxynucleoside analogues using in vitro and in vivo modelsrdquoJournal of Medicinal Chemistry vol 53 no 16 pp 6180ndash61872010

[181] M Johar T Manning C Tse et al ldquoGrowth inhibitionof Mycobacterium bovis Mycobacterium tuberculosisand Mycobacterium avium in vitro effect of 1-120573-D-21015840-arabinofuranosyl and 1-(21015840-deoxy-21015840-fluoro-120573-D-21015840-ribofur-anosyl) pyrimidine nucleoside analogsrdquo Journal of MedicinalChemistry vol 50 no 15 pp 3696ndash3705 2007

[182] A Agarwal K Srivastava S K Puri and P M S ChauhanldquoSynthesis of 246-trisubstituted pyrimidines as antimalarialagentsrdquo Bioorganic and Medicinal Chemistry vol 13 no 15 pp4645ndash4650 2005

[183] B Tarnchompoo C Sirichaiwat W Phupong et al ldquoDevel-opment of 24-diaminopyrimidines as antimalarials based oninhibition of the S108N and C59R+S108N mutants of dihy-drofolate reductase from pyrimethamine resistant Plasmodiumfalciparumrdquo Journal of Medicinal Chemistry vol 45 no 6 pp1244ndash1252 2002

[184] J M Coteron D Catterick J Castro et al ldquoFalcipaininhibitors optimization studies of the 2-pyrimidinecarbonitrilelead seriesrdquo Journal of Medicinal Chemistry vol 53 no 16 pp6129ndash6152 2010

[185] M A Dea-Ayuela E Castillo M Gonzalez-Alvarez et alldquoIn vivo and in vitro anti-leishmanial activities of 4-nitro-N-pyrimidinandN-pyrazin-2-ylbenzenesulfonamides andN2-(4-nitrophenyl)-N1propylglycinamiderdquo Bioorganic and Medici-nal Chemistry vol 17 no 21 pp 7449ndash7456 2009


[186] L Gupta N Sunduru A Verma et al ldquoSynthesis and biologi-cal evaluation of new [124]triazino[56-b]indol-3-ylthio-135-triazines and [124]triazino[56-b]indol-3-ylthio-pyrimidinesagainst Leishmania donovanirdquo European Journal of MedicinalChemistry vol 45 no 6 pp 2359ndash2365 2010

[187] S F Chowdhury V B Villamor R H Guerrero et al ldquoDesignsynthesis and evaluation of inhibitors of trypanosomal andleishmanial dihydrofolate reductaserdquo Journal of MedicinalChemistry vol 42 no 21 pp 4300ndash4312 1999

[188] NChandra R RameshAAshutoshNGoyal S N Suryawan-shi and S Gupta ldquoAntileishmanial agents part-IV synthesisand antileishmanial activity of novel terpenyl pyrimidinesrdquoEuropean Journal ofMedicinal Chemistry vol 40 no 6 pp 552ndash556 2005

[189] H Parveen F Hayat A Salahuddin and A Azam ldquoSyn-thesis characterization and biological evaluation of novel 6-ferrocenyl-4-aryl-2-substituted pyrimidine derivativesrdquo Euro-pean Journal of Medicinal Chemistry vol 45 no 8 pp 3497ndash3503 2010

[190] B K SinghMMishra N Saxena et al ldquoSynthesis of 2-sulfanyl-6-methyl-14-dihydropyrimidines as a new class of antifilarialagentsrdquo European Journal of Medicinal Chemistry vol 43 no12 pp 2717ndash2723 2008

[191] P Selvam M Chandramohan E de Clercq M Witvrouw andC Pannecouque ldquoSynthesis and anti-HIV activity of 4-[(12-dihydro-2-oxo-3H-indol-3-ylidene) amino]-N(46-dimethyl-2-pyrimidinyl)-benzene sulfonamide and its derivativesrdquoEuropean Journal of Pharmaceutical Sciences vol 14 no 4 pp313ndash316 2001

[192] A Holy I Votruba M Masojıdkova et al ldquo6-[2-(Phosphonomethoxy)alkoxy]pyrimidines with antiviralactivityrdquo Journal of Medicinal Chemistry vol 45 no 9 pp1918ndash1929 2002

[193] D Sriram T R Bal and P Yogeeswari ldquoAminopyimidinimoisatin analogues design of novel non-nucleoside HIV-1 reversetranscriptase inhibitors with broadspectrum chemotherapeuticpropertiesrdquo Journal of Pharmacy and Pharmaceutical Sciencesvol 8 no 3 pp 565ndash577 2005

[194] A Mai M Artico G Sbardella et al ldquo5-alkyl-2-(alkylthio)-6-(26-dihalophenylmethyl)-34-dihydropyrimidin-4(3H)-ones novel potent and selective dihydro-alkoxy-benzyl-oxopyrimidine derivativesrdquo Journal of Medicinal Chemistryvol 42 no 4 pp 619ndash627 1999

[195] D Hockova A Holy M Masojıdkova et al ldquoSynthe-sis and antiviral activity of 24-diamino-5-cyano-6-[2-(phos-phonomethoxy)ethoxy]pyrimidine and related compoundsrdquoBioorganic and Medicinal Chemistry vol 12 no 12 pp 3197ndash3202 2004

[196] S F Mohamed E M Flefel A E E Amr and D N Abd El-Shafy ldquoAnti-HSV-1 activity and mechanism of action of somenew synthesized substituted pyrimidine thiopyrimidine andthiazolopyrimidine derivativesrdquo European Journal of MedicinalChemistry vol 45 no 4 pp 1494ndash1501 2010

[197] M B Nawrozkij D Rotili D Tarantino et al ldquo5-alkyl-6-benzyl-2-(2-oxo-2-phenylethylsulfanyl)pyrimidin-4(3H)-ones a series of anti-HIV-1 agents of the dihydro-alkoxy-benzyl-oxopyrimidine family with peculiar structure-activityrelationship profilerdquo Journal of Medicinal Chemistry vol 51 no15 pp 4641ndash4652 2008

[198] V Summa A Petrocchi V G Matassa et al ldquoHCV NS5bRNA-dependent RNA polymerase inhibitors from 120572120574-diketoacids to 45-dihydroxypyrimidine- or 3-methyl-5-hydroxypyrimidinonecarboxylic acids Design and synthesisrdquoJournal of Medicinal Chemistry vol 47 no 22 pp 5336ndash53392004

[199] U Koch B Attenni S Malancona et al ldquo2-(2-Thienyl)-56-dihydroxy-4-carboxypyrimidines as inhibitors of the hepatitisC virus NS5B polymerase discovery SAR modeling andmutagenesisrdquo Journal of Medicinal Chemistry vol 49 no 5 pp1693ndash1705 2006

[200] F Manetti J A Este I Clotet-Codina et al ldquoParallel solution-phase and microwave-assisted synthesis of new S-DABOderivatives endowed with subnanomolar anti-HIV-1 activityrdquoJournal of Medicinal Chemistry vol 48 no 25 pp 8000ndash80082005

[201] S Prekupec D Makuc J Plavec et al ldquoNovel C-6 fluorinatedacyclic side chain pyrimidine derivatives synthesis 1H and13C NMR conformational studies and antiviral and cytostaticevaluationsrdquo Journal of Medicinal Chemistry vol 50 no 13 pp3037ndash3045 2007

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy


Carbohydrate Chemistry

International Journal of


Journal of

Chemistry


Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of


The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of


Chromatography Research International


Applied ChemistryJournal of



Theoretical ChemistryJournal of


Journal of

Spectroscopy

Analytical ChemistryInternational Journal of


Journal of


Quantum Chemistry


Organic Chemistry International

ElectrochemistryInternational Journal of



CatalystsJournal of


N1

NN2

N

N

3

N

N4

Figure 1 Pyridine and different isomeric forms of diazine family

parent structure alterations A call has therefore been madefor the development of new classes of drugs that work ondifferent target sites to those in current use [17 18]

Heterocyclic compounds are abundant in nature and areof great significance to life because their structural subunitsexist in many natural products such as vitamins hormonesand antibiotics [19 20] hence they have attracted consider-able attention in the design of biologically active molecules[21 22] and advanced organic chemistry [23 24] Also inthe family of heterocyclic compounds nitrogen containingheterocycles are an important class of compounds in themedicinal chemistry and also contributed to the society frombiological and industrial point which helps to understandlife processes [25] A totally unsaturated membered six-ringcontaining nitrogen is known as azine [26] or pyridine (1)with two nitrogen atoms it is known as diazine [27] and witha nitrogen at 12-position it is known as pyridine (2) at 13-position as pyrimidine (3) and at 14-position as pyrazine (4)(Figure 1) However the current review intends to focus onthe significance of pyrimidine class of antimicrobial agentsalong with clinical and in vitro applications of pyrimidinederivatives to facilitate the development of more potent aswell as effective antimicrobial agents

2 Pyrimidine General Introduction

Pyrimidines (5) are the heterocyclic aromatic compoundssimilar to benzene and pyridine containing two nitrogenatoms at positions 1 and 3 of the six membered ringsHeterocycles containing pyrimidine moiety are of greatinterest because they constitute an important class of naturaland nonnatural products many of which exhibit usefulbiological activities and clinical applications [28 29] Sub-stituted purines and pyrimidines occur very widely in livingorganisms and were some of the first compounds studied bythe organic chemists [30] (Figure 2(a))

Pyrimidines are biologically very important heterocyclesand represent by far the most ubiquitous members of thediazine family with uracil (6) and thymine (7) being con-stituents of ribonucleic acid (RNA) and deoxyribonucleicacid (DNA) and with cytosine (8) both being present inFigure 2(b)

In addition to this pyrimidines skeleton is also presentin many natural products such as vitamin B

1(thiamine) and

many synthetic compounds such as barbituric acid (9) andVeranal (10) which are used as hypnotics [31] (Figure 2(b))

3 Medicinal Properties of Pyrimidines

The presence of pyrimidine base in thymine cytosine anduracil which are the essential building blocks of nucleic

acids DNA and RNA is one possible reason for theirwidespread therapeutic applications The pyrimidines rep-resent one of the most active classes of compounds pos-sessing wide spectrum of biological activities like significantin vitro activity against unrelated DNA and RNA virusesincluding polioherpes viruses diuretic antitumour anti-HIV and cardiovascular [32] The literature survey indicatedthat a wide range of pharmacological activities are exhibitedby the compounds encompassing pyrimidines nucleus Inaddition to this various analogs of pyrimidines have beenfound to posses antibacterial [33ndash39] antifungal [40ndash43]antileishmanial [44] anti-inflammatory [45 46] analgesic[47] antihypertensive [48 49] antipyretic [50] antiviral [51ndash53] antidiabetic [54] antiallerggic [55] anticonvulsant [56]antioxidant [57 58] antihistaminic [59] herbicidal [60]and anticancer activities [61ndash64] and many of pyrimidinesderivatives are reported to possess potential central nervoussystem (CNS) depressant properties [65 66] and also act ascalcium channel blockers [67]

4 Clinical and PharmacologicalApplications of Pyrimidine inthe Microbial World Marketed Drugs

During the last two decades several pyrimidine derivativeshave been developed which are found to have wideclinicaland pharmacological applications [68]

41 Antibacterial Agents Drugs which are included inthis category are antifolates possessing antagonistic activityagainst folic acid and sulfa drugs which are sulphur contain-ing pyrimidine derivative drugs

411 Antifolates 2-Amino-4-hydroxypyrimidines are foundto be antagonists of folic acid [69] hence a large number of24-diaminopyrimidines have been synthesized as antifolatesand it was eventually proved that these pyrimidines areinhibitors dihydrofolate reductase (DHFR) [70 71] Notableamongst the 24-diaminopyrimidine drugs are the following

Trisubstituted Pyrimidine Containing Drugs Brodiprim (11)is found to be an effective antibacterial compound [72]Iclaprim (12) which is a new selective dihydrofolate inhibitorwas synthesized based on rational drug design and thisdrug is found to be active against methicillin- TMP- andvancomycin-resistant strains [73 74] Trimethoprim (13)is an antibacterial drug which selectively inhibits bacterialDHFR [75] (Figure 3)

Tetrasubstituted Pyrimidine Containing Drug Pyrime-thamine (14) is a selective inhibitor of the DHFR of malarialplasmodia [75] (Figure 3)

412 Sulfa Drugs Pyrimidine containing sulfa drugs areclassified on the basis of substitution and the classificationwith the respective example of drug is as follows


2

N3

N1

4

6

5

5

(a)

N

NH

O NH

O

O

NH NHNHNH

NH

O

O

Me

NH

O

OONH

O

OO

6 7 8 9 10

NH2

H3CH3C

(b)


N

N

Cl

N

N

ON

N

OBr

ON

NO

OO

11 12 13 14

NH2

NH2

NH2

NH2

NH2NH2

NH2

H3CH3C

CH3

CH3

CH3

H2N

H3CO

H3CO

H5C2












SO

ON

NN

HSO

ON

NN

H

SO

ON

NN

HSO

ON

NN

H

15 16 17 18

SO

ON

NN

H

SO

ON

NN

HSO

ON

NN

HSO

ON

NN

H

19 20 21 22

NN

SO

OHN

N

NHN

N

NH

HN O

23 24 25

NH2NH2NH2

NH2NH2

NH2

H3C

H3C

H3C

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3CH3

H3CO

H3CO

H3CO

H3CO

OCH3

OCH3

OCH3

OCH3 SO2 SO2

C2H5


26 27

O

NN

HO

HO

OH

NH

ON

NNH

OOO

HO

N

OH O

28 29

N

NH

O

ONH

N NON

N

NH2

NH2

NH2

NH2

H3C

H3C

H3C H3C

CH3

CH3

CH3

H2NCH2OH





NH

N O

OI

O

H

HO

OH

NH

N O

O

O

HOH

INH

N O

O

O

HOH

30 31 32 33

NH

N O

O

OHO

N

HN

O

O

O N

HN

O

OO

N

N

OO

N

N O

OS

OH

N

N O

OH

P OHO

OH

34 35 36 37 38

NH2 NH2 NH2

H3C

CH3CH3 CH3

CH2OH CH2OH

F3C

N3

N3

HOH2CHOH2C HOH2C


N

NH

O

FN

N NN

NN

N

HO

F

F

F

39 40 41NH2

CH3

CH3

CH3

CH3

CH3 CH3

H2N








OON

N NH

OON

N NH

ON

N N OHOHOH

OH

44

OON

N N

OH

H

4542 43

N

N

NHN

47

N N

HN N O

OR

N

N NHN

Cl

N

N

R

O

OHOH

48

H3C

CH3

CH3

CH3

CH3

+H3N

CF3

NO2

O2N

O2N

Osim

49R = H CH3 4-Br-C6H4 4-OCH3-C6H4


NO2







3) sub-



N

NN

N

HS

O

Cl

Cl

Cl

Cl

N

NN

N

O NN

R

NH

N

NN

NHNH

50 51 52

N

N N

N

N N NN

S

53 54 55

NN

HNSO

O

NH

O

5657

NN

FCl

F

Cl

56abcdef

ClNH2

NH2

NH2

H3C

CH3

CH3

CH3

NO2

NO2 NO2

NO2

H2N

H3C

OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

R1

R1R2

R2




3 and NO








O NN

O NN

O

N

N N

Cl58 59

60

O NN

O NN

Ar

N

N

Br

HO

Br

61 6263

NN

O R

64

NN

O

SH

R

65

NNO

OH

R

66

NH NHN

S

N

67 68


NH2

NH2

NH2

OCH3

OCH3R1

R1

R2

R2 R1

R1

R2

R2R1 R2

R3

C6H5C6H5

NHCOCH3

NHCOCH2Cl NHCOCH2R2

2-Cl2-NO2

3-NO2

4-NO2

345-OCH3

345-OCH3

4-NH2

4-NH2

4-NH2

24-Cl

4-CH3

2-NO2

2-NO2

67-6867-68






NN

S

Br

69

NN

NH

N

X

NN

O

Cl71

NN

NO

NN

Cl

F

Cl R

HNS

O

O

NN

NN

O

N N

R

ONN

Br R

OH

OHOH

ONN

Br R

SH

SH

NN

S R

75 76 77

NNNN

N

N78 79

abcdefghi

R1

R1

R1

R1

R2

R2

R2

NH2

NH2

NH2

NH2

NH2

NH2

CH3

CH3

H3CO

H3C

NHCOCH3

NHCOCH3

4-CH3-C6H4

4-NO2-C6H4

2-Thienyl

2-Thienyl


C6H54-Cl-C6H4

4-NO2-C6H4

4-Br-C6H4

2-Furyl

mdashmdashmdash

70 X = F Br


R2= H Cl F NO2

73 R = 4-CH3-C6H4 345-(OCH3)3-C6H2 74 R = F Cl

78-79
















NN

Cl Cl

F

NH

NHHN

O

X NH Ar

N

N

COOH

81

N

N

NH

O

Br

82

N

N N N

NH

HNN

X

NN

NN

HO

OH

83

84 85

NH

HN

O

O

SO

O

NHN

N NHS

H

86

NH

HN

O

O

SO

O

NN O

CNH

87

NH

HN

O

O

SO

O

N

H

88

NH

HN

O

O

SO

O

NHN

S

NH N

89

N

N

Cl

Cl

F

R

NH

NHOO

N

N

O

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

H3C

CH3

CH3

CH3 NO2

NH2

NH2

NH2

H3CO

H2N

H2N

C2H5

C6H5

C6H5H5C6

90 R = 345-(OCH3)3 4-Cl 2-OCH3

80 X = O S








N

N NO

O

91

N

N N NH

92

N

N N

N

93

NH

N NH

N

OO NH

N NH

N

OO

94 95

N N

R

S

97

NH2

NH2

NH2

NH2

NH2

CH3

CH3

CH3

CH3

CH3CH3

H3C

H3C

H2NH2N

H2N

H2N

H2N

OCH3

CH2CH2N(CH3)2



HN

NHN

S

S

Cl

NN

S

Cl

N

NCN

NO

HO OH101 102 103 104

O

N NO

O

N NO

SHSH

NN

NHSO

ONH

NN

NNH

S

NHRNH

N N

O

105 106

CH3

CH3

CH3

NH2

NO2

H3C

H3CH3C

NHNH2

OCOCH3OCOCH3


N

N

SH

CH3

O

SN

N

S

O

S

O

N N

SHNHN

S

O

Cl

98 99 100



NN

NNH

HNHN Ar

ArAr

N

NN

R

NN

O

OH

O

S

CH3

NH2

SCH2Ph


H3C



















NHN

S

NN

Ar

N

NH

ON

N

NH

OHN

O

NH

N

S

N

112 113 114 115

NH

NH

SN

O

NH

NH

S

SN

O

116 117

NN

ONN

O O

NH

O

118

NH

NH

SH

O

NH NH

NH

O

NH

NH

HN

NS Ar NH

HN

O

NH

S

CN

S

119 120 121 122

NH

NH

O

N

OHN

S

R

NH

HN

O

NHS

CN

S

123

NH

NH

O

N

OHN

Ar

R

N

N

Cl

S

O

N

N

S

OO

N

N

S

HO OH

HO126 127128

NH2

NH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

P+

= 3-Cl-C6H4 34-(OCH3)2-C6H3

= C6H5 4-Cl 2NO2 345-C6H234-(OCH3)2-C6H3

125R = H 4-(OCH3) Ar = 34-(NO2)2-C6H3

H2N

ArN2 ArN2

ArN2ArN2

ArN2

NHC6H5

C6H5

H3C

H3CH3C

H3CH3C

SCH3

SCH2CN

SCH2CN

COCH3

COCH3

COCH3

CH3COO

CH3COO

CH3COO

CH3COO

OCOCH3OCOCH3

OCOCH3

OCOCH3

OH3C

= H 4-(OCH3) 4-NO2124 R

Ominus

R1

R2 R2

R1

R1

R2



CH3

CH3

CH3

CH3

CH3

CH3

CH3

C6H5

OCOCH3

OCOCH3

OH3C

OH3C

SH3C

H2N


H3COCO

H3COCO

H3COCH3

H3CH2CO

131 R = Cl OCH3 OH


135 R = CH3C6H11

N

N

N

ClCN NHHN

OO

OH

N

NCN

OH

R

129 130

FF

F

NH

NH

O

O O NH

N

HN

S

CNO

NH

NH

NH

X

RO

132 133

NH

HN

SR

O

NH

S

O

NH

NH

S

OCl

N

N

S

Cl O

136

138



2 CONHMe and SO

2NH2




NHN

N

S

NNN

NHN

N

S

NNN

Br NH

NH

O S

OR O

139 140

N

HN

O

O

R

NH

SOH

NN

S

O

Ar Ar

O

NN

S

SO

ArS Ar

OO

O

N

N

O

N143 144 145

NH

NH

S

NH

O

Cl

146 147

R

NH

NH

S

NH

O

ClR

N N

N

N

S

R

NN

O

O

Cl

SS

N O149

N

N

O

Et

CH3

CH3

CH3

CH3

H2N

H2NH2N

NH2

NH2NH2

C6H5

NO2

H5C2O

H3C

H3CH3CH3C


H5C6


= Br Cl142 R

= 5-OCH3 5NO2 5-Cl148 R



R1 R2







N

N

ClCN

SR

N

N

ClCN

ArSR

151

151 Ar Rabc

NH

HN

N

S

N

Cl

SH

O

153

N

N SH

Br

R

154

NH

HN

O

XO

NHNH

HN

O

O

X

NHNH

N

Ar

O

NHO

NNN

SH

O

R

154 Rabcdefghijk H

NH

HN

O

O

O

O

RNH

NH

R

X

O

NHNH

O

N

NH

NH

O

O

NN

160

CH3

CH3

CH3

CH3

H3C

H3C


C2H5C3H7

COCH3

4-OCH3

3-OCH3


2-NO2

4-N(CH3)26-furyl

=CH3 C2H5 CH3152 R









OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

CH3

CH3CH3

NH2

NH2NH2NH2

NH2NH2

H2N

O2N O2N O2N

H3CO

H3CO H3CO

H3CO

H3CO


NHNH

SO

ONN

O

O

N

N NN

161

162 163

OHO

NN

NN

OH

R

N

N

O

N N

N

O

NCl

165 166

167 168 169

NN

N

Cl

ClCl

Cl

NN

N

Cl

NN

N

Cl

Cl

170 171 172

= 2-NO2-C6H4 3-NO2-C6H4 4-OCH3-C6H4164 R



















O

N

N OH

O

N

N OH

HN

N

O

OHOO

173 174

HO

HN

N

O

O

HO

HN

N

O

O

HO

HN

N

O

OO

HO

HO

N

176177 178

179

HN

NOO

HO

HO

N

180

HN

NH

O

O R

180 Rabcd

N

HN

HO

O

O

HO

HO

181

N

HN

HO

O

O

HO F

HO

182

N

HN

HO

O

O

HO F

HO

183

CH3

NH2

NO2

CH(N3)CH2XOC6H5


C6H5


2-Pyridyl

C10H21 C10H21 C11H23

= Br I Cl175 X

H3C

H3C

H3C

H3C

H3C

H3CH3C

H3C

H3C



50of 401







NNN

N

( )n

N

N

Cl

RN

N

186

N

N

O

HN

N

N

NN

N

N

O

HN N

N

N

BrBr

N

N

N

O

HN

N

N

N

Br

N

187 188 189

N

NNN

O

N

N

Br

N

H

N

NNN

O

Br

N

R

H

190

191

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2NH2

H3CO OCH3

OCH3

OCH2CH3


184 n = 01



N

N NH

SO

ON N

R

NN

N

SN

NN

N

192 194

N

NOR

N

NOR

N

NOR

CH3CH3

CH3

CH3

NH2 NH2 NH2

H2N H2N H2N

NO2


193 R =OC2H5 OBu

196 R = C2H5 C3H7 197 R = CH3 C2H5

H3C

H3C






NH

NH

O

O

SR

NN

N

ClFe

198 199

H3C

H3C

CH3









6 Conclusion


Abbreviations



CH3

CH3

NH2

H2N

200 R = H COCH3

P(O)(OH)2 P(O)(OH)2

N

N

O

SO

ONH

NN

R

H

N

N

O

O

N

N

OH

O

O

201 202

H3C


N

N

O

N

NBr

N

O

N

N

O

N

N

Br

NNN

F

F

OHOOC

203 204

N

N

OR

F FS

N

N R

O O

P OHOOH

NH

N

O

S

207

N

HN

S

O

O

ClCl

208

N

NHO

OHOH

O

OH

209

N

NS

OHOH

O

OH

NH

NHOCl

210

N

HN

O

SClCl

211

N

NBr

212

N

NBr

Br

Br

213

CH3

CH3

CH3

NH2NH2

NH2

H3COH3CO

H3COH3CO

H3CO

H2N

H3C

H3C

OCH3

OCH3

OCH3OCH3

OCH3

OCH3

OCH3

OCH3

C2H5

205 R = H Me 206 R = H Me

COCH3

COCH3

CH2CH3

CH2Br






Acknowledgments


References




































































10158401015840



























































































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


2

N3

N1

4

6

5

5

(a)

N

NH

O NH

O

O

NH NHNHNH

NH

O

O

Me

NH

O

OONH

O

OO

6 7 8 9 10

NH2

H3CH3C

(b)


N

N

Cl

N

N

ON

N

OBr

ON

NO

OO

11 12 13 14

NH2

NH2

NH2

NH2

NH2NH2

NH2

H3CH3C

CH3

CH3

CH3

H2N

H3CO

H3CO

H5C2












SO

ON

NN

HSO

ON

NN

H

SO

ON

NN

HSO

ON

NN

H

15 16 17 18

SO

ON

NN

H

SO

ON

NN

HSO

ON

NN

HSO

ON

NN

H

19 20 21 22

NN

SO

OHN

N

NHN

N

NH

HN O

23 24 25

NH2NH2NH2

NH2NH2

NH2

H3C

H3C

H3C

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3CH3

H3CO

H3CO

H3CO

H3CO

OCH3

OCH3

OCH3

OCH3 SO2 SO2

C2H5


26 27

O

NN

HO

HO

OH

NH

ON

NNH

OOO

HO

N

OH O

28 29

N

NH

O

ONH

N NON

N

NH2

NH2

NH2

NH2

H3C

H3C

H3C H3C

CH3

CH3

CH3

H2NCH2OH





NH

N O

OI

O

H

HO

OH

NH

N O

O

O

HOH

INH

N O

O

O

HOH

30 31 32 33

NH

N O

O

OHO

N

HN

O

O

O N

HN

O

OO

N

N

OO

N

N O

OS

OH

N

N O

OH

P OHO

OH

34 35 36 37 38

NH2 NH2 NH2

H3C

CH3CH3 CH3

CH2OH CH2OH

F3C

N3

N3

HOH2CHOH2C HOH2C


N

NH

O

FN

N NN

NN

N

HO

F

F

F

39 40 41NH2

CH3

CH3

CH3

CH3

CH3 CH3

H2N








OON

N NH

OON

N NH

ON

N N OHOHOH

OH

44

OON

N N

OH

H

4542 43

N

N

NHN

47

N N

HN N O

OR

N

N NHN

Cl

N

N

R

O

OHOH

48

H3C

CH3

CH3

CH3

CH3

+H3N

CF3

NO2

O2N

O2N

Osim

49R = H CH3 4-Br-C6H4 4-OCH3-C6H4


NO2







3) sub-



N

NN

N

HS

O

Cl

Cl

Cl

Cl

N

NN

N

O NN

R

NH

N

NN

NHNH

50 51 52

N

N N

N

N N NN

S

53 54 55

NN

HNSO

O

NH

O

5657

NN

FCl

F

Cl

56abcdef

ClNH2

NH2

NH2

H3C

CH3

CH3

CH3

NO2

NO2 NO2

NO2

H2N

H3C

OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

R1

R1R2

R2




3 and NO








O NN

O NN

O

N

N N

Cl58 59

60

O NN

O NN

Ar

N

N

Br

HO

Br

61 6263

NN

O R

64

NN

O

SH

R

65

NNO

OH

R

66

NH NHN

S

N

67 68


NH2

NH2

NH2

OCH3

OCH3R1

R1

R2

R2 R1

R1

R2

R2R1 R2

R3

C6H5C6H5

NHCOCH3

NHCOCH2Cl NHCOCH2R2

2-Cl2-NO2

3-NO2

4-NO2

345-OCH3

345-OCH3

4-NH2

4-NH2

4-NH2

24-Cl

4-CH3

2-NO2

2-NO2

67-6867-68






NN

S

Br

69

NN

NH

N

X

NN

O

Cl71

NN

NO

NN

Cl

F

Cl R

HNS

O

O

NN

NN

O

N N

R

ONN

Br R

OH

OHOH

ONN

Br R

SH

SH

NN

S R

75 76 77

NNNN

N

N78 79

abcdefghi

R1

R1

R1

R1

R2

R2

R2

NH2

NH2

NH2

NH2

NH2

NH2

CH3

CH3

H3CO

H3C

NHCOCH3

NHCOCH3

4-CH3-C6H4

4-NO2-C6H4

2-Thienyl

2-Thienyl


C6H54-Cl-C6H4

4-NO2-C6H4

4-Br-C6H4

2-Furyl

mdashmdashmdash

70 X = F Br


R2= H Cl F NO2

73 R = 4-CH3-C6H4 345-(OCH3)3-C6H2 74 R = F Cl

78-79
















NN

Cl Cl

F

NH

NHHN

O

X NH Ar

N

N

COOH

81

N

N

NH

O

Br

82

N

N N N

NH

HNN

X

NN

NN

HO

OH

83

84 85

NH

HN

O

O

SO

O

NHN

N NHS

H

86

NH

HN

O

O

SO

O

NN O

CNH

87

NH

HN

O

O

SO

O

N

H

88

NH

HN

O

O

SO

O

NHN

S

NH N

89

N

N

Cl

Cl

F

R

NH

NHOO

N

N

O

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

H3C

CH3

CH3

CH3 NO2

NH2

NH2

NH2

H3CO

H2N

H2N

C2H5

C6H5

C6H5H5C6

90 R = 345-(OCH3)3 4-Cl 2-OCH3

80 X = O S








N

N NO

O

91

N

N N NH

92

N

N N

N

93

NH

N NH

N

OO NH

N NH

N

OO

94 95

N N

R

S

97

NH2

NH2

NH2

NH2

NH2

CH3

CH3

CH3

CH3

CH3CH3

H3C

H3C

H2NH2N

H2N

H2N

H2N

OCH3

CH2CH2N(CH3)2



HN

NHN

S

S

Cl

NN

S

Cl

N

NCN

NO

HO OH101 102 103 104

O

N NO

O

N NO

SHSH

NN

NHSO

ONH

NN

NNH

S

NHRNH

N N

O

105 106

CH3

CH3

CH3

NH2

NO2

H3C

H3CH3C

NHNH2

OCOCH3OCOCH3


N

N

SH

CH3

O

SN

N

S

O

S

O

N N

SHNHN

S

O

Cl

98 99 100



NN

NNH

HNHN Ar

ArAr

N

NN

R

NN

O

OH

O

S

CH3

NH2

SCH2Ph


H3C



















NHN

S

NN

Ar

N

NH

ON

N

NH

OHN

O

NH

N

S

N

112 113 114 115

NH

NH

SN

O

NH

NH

S

SN

O

116 117

NN

ONN

O O

NH

O

118

NH

NH

SH

O

NH NH

NH

O

NH

NH

HN

NS Ar NH

HN

O

NH

S

CN

S

119 120 121 122

NH

NH

O

N

OHN

S

R

NH

HN

O

NHS

CN

S

123

NH

NH

O

N

OHN

Ar

R

N

N

Cl

S

O

N

N

S

OO

N

N

S

HO OH

HO126 127128

NH2

NH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

P+

= 3-Cl-C6H4 34-(OCH3)2-C6H3

= C6H5 4-Cl 2NO2 345-C6H234-(OCH3)2-C6H3

125R = H 4-(OCH3) Ar = 34-(NO2)2-C6H3

H2N

ArN2 ArN2

ArN2ArN2

ArN2

NHC6H5

C6H5

H3C

H3CH3C

H3CH3C

SCH3

SCH2CN

SCH2CN

COCH3

COCH3

COCH3

CH3COO

CH3COO

CH3COO

CH3COO

OCOCH3OCOCH3

OCOCH3

OCOCH3

OH3C

= H 4-(OCH3) 4-NO2124 R

Ominus

R1

R2 R2

R1

R1

R2



CH3

CH3

CH3

CH3

CH3

CH3

CH3

C6H5

OCOCH3

OCOCH3

OH3C

OH3C

SH3C

H2N


H3COCO

H3COCO

H3COCH3

H3CH2CO

131 R = Cl OCH3 OH


135 R = CH3C6H11

N

N

N

ClCN NHHN

OO

OH

N

NCN

OH

R

129 130

FF

F

NH

NH

O

O O NH

N

HN

S

CNO

NH

NH

NH

X

RO

132 133

NH

HN

SR

O

NH

S

O

NH

NH

S

OCl

N

N

S

Cl O

136

138



2 CONHMe and SO

2NH2




NHN

N

S

NNN

NHN

N

S

NNN

Br NH

NH

O S

OR O

139 140

N

HN

O

O

R

NH

SOH

NN

S

O

Ar Ar

O

NN

S

SO

ArS Ar

OO

O

N

N

O

N143 144 145

NH

NH

S

NH

O

Cl

146 147

R

NH

NH

S

NH

O

ClR

N N

N

N

S

R

NN

O

O

Cl

SS

N O149

N

N

O

Et

CH3

CH3

CH3

CH3

H2N

H2NH2N

NH2

NH2NH2

C6H5

NO2

H5C2O

H3C

H3CH3CH3C


H5C6


= Br Cl142 R

= 5-OCH3 5NO2 5-Cl148 R



R1 R2







N

N

ClCN

SR

N

N

ClCN

ArSR

151

151 Ar Rabc

NH

HN

N

S

N

Cl

SH

O

153

N

N SH

Br

R

154

NH

HN

O

XO

NHNH

HN

O

O

X

NHNH

N

Ar

O

NHO

NNN

SH

O

R

154 Rabcdefghijk H

NH

HN

O

O

O

O

RNH

NH

R

X

O

NHNH

O

N

NH

NH

O

O

NN

160

CH3

CH3

CH3

CH3

H3C

H3C


C2H5C3H7

COCH3

4-OCH3

3-OCH3


2-NO2

4-N(CH3)26-furyl

=CH3 C2H5 CH3152 R









OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

CH3

CH3CH3

NH2

NH2NH2NH2

NH2NH2

H2N

O2N O2N O2N

H3CO

H3CO H3CO

H3CO

H3CO


NHNH

SO

ONN

O

O

N

N NN

161

162 163

OHO

NN

NN

OH

R

N

N

O

N N

N

O

NCl

165 166

167 168 169

NN

N

Cl

ClCl

Cl

NN

N

Cl

NN

N

Cl

Cl

170 171 172

= 2-NO2-C6H4 3-NO2-C6H4 4-OCH3-C6H4164 R



















O

N

N OH

O

N

N OH

HN

N

O

OHOO

173 174

HO

HN

N

O

O

HO

HN

N

O

O

HO

HN

N

O

OO

HO

HO

N

176177 178

179

HN

NOO

HO

HO

N

180

HN

NH

O

O R

180 Rabcd

N

HN

HO

O

O

HO

HO

181

N

HN

HO

O

O

HO F

HO

182

N

HN

HO

O

O

HO F

HO

183

CH3

NH2

NO2

CH(N3)CH2XOC6H5


C6H5


2-Pyridyl

C10H21 C10H21 C11H23

= Br I Cl175 X

H3C

H3C

H3C

H3C

H3C

H3CH3C

H3C

H3C



50of 401







NNN

N

( )n

N

N

Cl

RN

N

186

N

N

O

HN

N

N

NN

N

N

O

HN N

N

N

BrBr

N

N

N

O

HN

N

N

N

Br

N

187 188 189

N

NNN

O

N

N

Br

N

H

N

NNN

O

Br

N

R

H

190

191

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2NH2

H3CO OCH3

OCH3

OCH2CH3


184 n = 01



N

N NH

SO

ON N

R

NN

N

SN

NN

N

192 194

N

NOR

N

NOR

N

NOR

CH3CH3

CH3

CH3

NH2 NH2 NH2

H2N H2N H2N

NO2


193 R =OC2H5 OBu

196 R = C2H5 C3H7 197 R = CH3 C2H5

H3C

H3C






NH

NH

O

O

SR

NN

N

ClFe

198 199

H3C

H3C

CH3









6 Conclusion


Abbreviations



CH3

CH3

NH2

H2N

200 R = H COCH3

P(O)(OH)2 P(O)(OH)2

N

N

O

SO

ONH

NN

R

H

N

N

O

O

N

N

OH

O

O

201 202

H3C


N

N

O

N

NBr

N

O

N

N

O

N

N

Br

NNN

F

F

OHOOC

203 204

N

N

OR

F FS

N

N R

O O

P OHOOH

NH

N

O

S

207

N

HN

S

O

O

ClCl

208

N

NHO

OHOH

O

OH

209

N

NS

OHOH

O

OH

NH

NHOCl

210

N

HN

O

SClCl

211

N

NBr

212

N

NBr

Br

Br

213

CH3

CH3

CH3

NH2NH2

NH2

H3COH3CO

H3COH3CO

H3CO

H2N

H3C

H3C

OCH3

OCH3

OCH3OCH3

OCH3

OCH3

OCH3

OCH3

C2H5

205 R = H Me 206 R = H Me

COCH3

COCH3

CH2CH3

CH2Br






Acknowledgments


References




































































10158401015840



























































































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


SO

ON

NN

HSO

ON

NN

H

SO

ON

NN

HSO

ON

NN

H

15 16 17 18

SO

ON

NN

H

SO

ON

NN

HSO

ON

NN

HSO

ON

NN

H

19 20 21 22

NN

SO

OHN

N

NHN

N

NH

HN O

23 24 25

NH2NH2NH2

NH2NH2

NH2

H3C

H3C

H3C

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3CH3

H3CO

H3CO

H3CO

H3CO

OCH3

OCH3

OCH3

OCH3 SO2 SO2

C2H5


26 27

O

NN

HO

HO

OH

NH

ON

NNH

OOO

HO

N

OH O

28 29

N

NH

O

ONH

N NON

N

NH2

NH2

NH2

NH2

H3C

H3C

H3C H3C

CH3

CH3

CH3

H2NCH2OH





NH

N O

OI

O

H

HO

OH

NH

N O

O

O

HOH

INH

N O

O

O

HOH

30 31 32 33

NH

N O

O

OHO

N

HN

O

O

O N

HN

O

OO

N

N

OO

N

N O

OS

OH

N

N O

OH

P OHO

OH

34 35 36 37 38

NH2 NH2 NH2

H3C

CH3CH3 CH3

CH2OH CH2OH

F3C

N3

N3

HOH2CHOH2C HOH2C


N

NH

O

FN

N NN

NN

N

HO

F

F

F

39 40 41NH2

CH3

CH3

CH3

CH3

CH3 CH3

H2N








OON

N NH

OON

N NH

ON

N N OHOHOH

OH

44

OON

N N

OH

H

4542 43

N

N

NHN

47

N N

HN N O

OR

N

N NHN

Cl

N

N

R

O

OHOH

48

H3C

CH3

CH3

CH3

CH3

+H3N

CF3

NO2

O2N

O2N

Osim

49R = H CH3 4-Br-C6H4 4-OCH3-C6H4


NO2







3) sub-



N

NN

N

HS

O

Cl

Cl

Cl

Cl

N

NN

N

O NN

R

NH

N

NN

NHNH

50 51 52

N

N N

N

N N NN

S

53 54 55

NN

HNSO

O

NH

O

5657

NN

FCl

F

Cl

56abcdef

ClNH2

NH2

NH2

H3C

CH3

CH3

CH3

NO2

NO2 NO2

NO2

H2N

H3C

OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

R1

R1R2

R2




3 and NO








O NN

O NN

O

N

N N

Cl58 59

60

O NN

O NN

Ar

N

N

Br

HO

Br

61 6263

NN

O R

64

NN

O

SH

R

65

NNO

OH

R

66

NH NHN

S

N

67 68


NH2

NH2

NH2

OCH3

OCH3R1

R1

R2

R2 R1

R1

R2

R2R1 R2

R3

C6H5C6H5

NHCOCH3

NHCOCH2Cl NHCOCH2R2

2-Cl2-NO2

3-NO2

4-NO2

345-OCH3

345-OCH3

4-NH2

4-NH2

4-NH2

24-Cl

4-CH3

2-NO2

2-NO2

67-6867-68






NN

S

Br

69

NN

NH

N

X

NN

O

Cl71

NN

NO

NN

Cl

F

Cl R

HNS

O

O

NN

NN

O

N N

R

ONN

Br R

OH

OHOH

ONN

Br R

SH

SH

NN

S R

75 76 77

NNNN

N

N78 79

abcdefghi

R1

R1

R1

R1

R2

R2

R2

NH2

NH2

NH2

NH2

NH2

NH2

CH3

CH3

H3CO

H3C

NHCOCH3

NHCOCH3

4-CH3-C6H4

4-NO2-C6H4

2-Thienyl

2-Thienyl


C6H54-Cl-C6H4

4-NO2-C6H4

4-Br-C6H4

2-Furyl

mdashmdashmdash

70 X = F Br


R2= H Cl F NO2

73 R = 4-CH3-C6H4 345-(OCH3)3-C6H2 74 R = F Cl

78-79
















NN

Cl Cl

F

NH

NHHN

O

X NH Ar

N

N

COOH

81

N

N

NH

O

Br

82

N

N N N

NH

HNN

X

NN

NN

HO

OH

83

84 85

NH

HN

O

O

SO

O

NHN

N NHS

H

86

NH

HN

O

O

SO

O

NN O

CNH

87

NH

HN

O

O

SO

O

N

H

88

NH

HN

O

O

SO

O

NHN

S

NH N

89

N

N

Cl

Cl

F

R

NH

NHOO

N

N

O

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

H3C

CH3

CH3

CH3 NO2

NH2

NH2

NH2

H3CO

H2N

H2N

C2H5

C6H5

C6H5H5C6

90 R = 345-(OCH3)3 4-Cl 2-OCH3

80 X = O S








N

N NO

O

91

N

N N NH

92

N

N N

N

93

NH

N NH

N

OO NH

N NH

N

OO

94 95

N N

R

S

97

NH2

NH2

NH2

NH2

NH2

CH3

CH3

CH3

CH3

CH3CH3

H3C

H3C

H2NH2N

H2N

H2N

H2N

OCH3

CH2CH2N(CH3)2



HN

NHN

S

S

Cl

NN

S

Cl

N

NCN

NO

HO OH101 102 103 104

O

N NO

O

N NO

SHSH

NN

NHSO

ONH

NN

NNH

S

NHRNH

N N

O

105 106

CH3

CH3

CH3

NH2

NO2

H3C

H3CH3C

NHNH2

OCOCH3OCOCH3


N

N

SH

CH3

O

SN

N

S

O

S

O

N N

SHNHN

S

O

Cl

98 99 100



NN

NNH

HNHN Ar

ArAr

N

NN

R

NN

O

OH

O

S

CH3

NH2

SCH2Ph


H3C



















NHN

S

NN

Ar

N

NH

ON

N

NH

OHN

O

NH

N

S

N

112 113 114 115

NH

NH

SN

O

NH

NH

S

SN

O

116 117

NN

ONN

O O

NH

O

118

NH

NH

SH

O

NH NH

NH

O

NH

NH

HN

NS Ar NH

HN

O

NH

S

CN

S

119 120 121 122

NH

NH

O

N

OHN

S

R

NH

HN

O

NHS

CN

S

123

NH

NH

O

N

OHN

Ar

R

N

N

Cl

S

O

N

N

S

OO

N

N

S

HO OH

HO126 127128

NH2

NH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

P+

= 3-Cl-C6H4 34-(OCH3)2-C6H3

= C6H5 4-Cl 2NO2 345-C6H234-(OCH3)2-C6H3

125R = H 4-(OCH3) Ar = 34-(NO2)2-C6H3

H2N

ArN2 ArN2

ArN2ArN2

ArN2

NHC6H5

C6H5

H3C

H3CH3C

H3CH3C

SCH3

SCH2CN

SCH2CN

COCH3

COCH3

COCH3

CH3COO

CH3COO

CH3COO

CH3COO

OCOCH3OCOCH3

OCOCH3

OCOCH3

OH3C

= H 4-(OCH3) 4-NO2124 R

Ominus

R1

R2 R2

R1

R1

R2



CH3

CH3

CH3

CH3

CH3

CH3

CH3

C6H5

OCOCH3

OCOCH3

OH3C

OH3C

SH3C

H2N


H3COCO

H3COCO

H3COCH3

H3CH2CO

131 R = Cl OCH3 OH


135 R = CH3C6H11

N

N

N

ClCN NHHN

OO

OH

N

NCN

OH

R

129 130

FF

F

NH

NH

O

O O NH

N

HN

S

CNO

NH

NH

NH

X

RO

132 133

NH

HN

SR

O

NH

S

O

NH

NH

S

OCl

N

N

S

Cl O

136

138



2 CONHMe and SO

2NH2




NHN

N

S

NNN

NHN

N

S

NNN

Br NH

NH

O S

OR O

139 140

N

HN

O

O

R

NH

SOH

NN

S

O

Ar Ar

O

NN

S

SO

ArS Ar

OO

O

N

N

O

N143 144 145

NH

NH

S

NH

O

Cl

146 147

R

NH

NH

S

NH

O

ClR

N N

N

N

S

R

NN

O

O

Cl

SS

N O149

N

N

O

Et

CH3

CH3

CH3

CH3

H2N

H2NH2N

NH2

NH2NH2

C6H5

NO2

H5C2O

H3C

H3CH3CH3C


H5C6


= Br Cl142 R

= 5-OCH3 5NO2 5-Cl148 R



R1 R2







N

N

ClCN

SR

N

N

ClCN

ArSR

151

151 Ar Rabc

NH

HN

N

S

N

Cl

SH

O

153

N

N SH

Br

R

154

NH

HN

O

XO

NHNH

HN

O

O

X

NHNH

N

Ar

O

NHO

NNN

SH

O

R

154 Rabcdefghijk H

NH

HN

O

O

O

O

RNH

NH

R

X

O

NHNH

O

N

NH

NH

O

O

NN

160

CH3

CH3

CH3

CH3

H3C

H3C


C2H5C3H7

COCH3

4-OCH3

3-OCH3


2-NO2

4-N(CH3)26-furyl

=CH3 C2H5 CH3152 R









OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

CH3

CH3CH3

NH2

NH2NH2NH2

NH2NH2

H2N

O2N O2N O2N

H3CO

H3CO H3CO

H3CO

H3CO


NHNH

SO

ONN

O

O

N

N NN

161

162 163

OHO

NN

NN

OH

R

N

N

O

N N

N

O

NCl

165 166

167 168 169

NN

N

Cl

ClCl

Cl

NN

N

Cl

NN

N

Cl

Cl

170 171 172

= 2-NO2-C6H4 3-NO2-C6H4 4-OCH3-C6H4164 R



















O

N

N OH

O

N

N OH

HN

N

O

OHOO

173 174

HO

HN

N

O

O

HO

HN

N

O

O

HO

HN

N

O

OO

HO

HO

N

176177 178

179

HN

NOO

HO

HO

N

180

HN

NH

O

O R

180 Rabcd

N

HN

HO

O

O

HO

HO

181

N

HN

HO

O

O

HO F

HO

182

N

HN

HO

O

O

HO F

HO

183

CH3

NH2

NO2

CH(N3)CH2XOC6H5


C6H5


2-Pyridyl

C10H21 C10H21 C11H23

= Br I Cl175 X

H3C

H3C

H3C

H3C

H3C

H3CH3C

H3C

H3C



50of 401







NNN

N

( )n

N

N

Cl

RN

N

186

N

N

O

HN

N

N

NN

N

N

O

HN N

N

N

BrBr

N

N

N

O

HN

N

N

N

Br

N

187 188 189

N

NNN

O

N

N

Br

N

H

N

NNN

O

Br

N

R

H

190

191

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2NH2

H3CO OCH3

OCH3

OCH2CH3


184 n = 01



N

N NH

SO

ON N

R

NN

N

SN

NN

N

192 194

N

NOR

N

NOR

N

NOR

CH3CH3

CH3

CH3

NH2 NH2 NH2

H2N H2N H2N

NO2


193 R =OC2H5 OBu

196 R = C2H5 C3H7 197 R = CH3 C2H5

H3C

H3C






NH

NH

O

O

SR

NN

N

ClFe

198 199

H3C

H3C

CH3









6 Conclusion


Abbreviations



CH3

CH3

NH2

H2N

200 R = H COCH3

P(O)(OH)2 P(O)(OH)2

N

N

O

SO

ONH

NN

R

H

N

N

O

O

N

N

OH

O

O

201 202

H3C


N

N

O

N

NBr

N

O

N

N

O

N

N

Br

NNN

F

F

OHOOC

203 204

N

N

OR

F FS

N

N R

O O

P OHOOH

NH

N

O

S

207

N

HN

S

O

O

ClCl

208

N

NHO

OHOH

O

OH

209

N

NS

OHOH

O

OH

NH

NHOCl

210

N

HN

O

SClCl

211

N

NBr

212

N

NBr

Br

Br

213

CH3

CH3

CH3

NH2NH2

NH2

H3COH3CO

H3COH3CO

H3CO

H2N

H3C

H3C

OCH3

OCH3

OCH3OCH3

OCH3

OCH3

OCH3

OCH3

C2H5

205 R = H Me 206 R = H Me

COCH3

COCH3

CH2CH3

CH2Br






Acknowledgments


References




































































10158401015840



























































































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


NH

N O

OI

O

H

HO

OH

NH

N O

O

O

HOH

INH

N O

O

O

HOH

30 31 32 33

NH

N O

O

OHO

N

HN

O

O

O N

HN

O

OO

N

N

OO

N

N O

OS

OH

N

N O

OH

P OHO

OH

34 35 36 37 38

NH2 NH2 NH2

H3C

CH3CH3 CH3

CH2OH CH2OH

F3C

N3

N3

HOH2CHOH2C HOH2C


N

NH

O

FN

N NN

NN

N

HO

F

F

F

39 40 41NH2

CH3

CH3

CH3

CH3

CH3 CH3

H2N








OON

N NH

OON

N NH

ON

N N OHOHOH

OH

44

OON

N N

OH

H

4542 43

N

N

NHN

47

N N

HN N O

OR

N

N NHN

Cl

N

N

R

O

OHOH

48

H3C

CH3

CH3

CH3

CH3

+H3N

CF3

NO2

O2N

O2N

Osim

49R = H CH3 4-Br-C6H4 4-OCH3-C6H4


NO2







3) sub-



N

NN

N

HS

O

Cl

Cl

Cl

Cl

N

NN

N

O NN

R

NH

N

NN

NHNH

50 51 52

N

N N

N

N N NN

S

53 54 55

NN

HNSO

O

NH

O

5657

NN

FCl

F

Cl

56abcdef

ClNH2

NH2

NH2

H3C

CH3

CH3

CH3

NO2

NO2 NO2

NO2

H2N

H3C

OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

R1

R1R2

R2




3 and NO








O NN

O NN

O

N

N N

Cl58 59

60

O NN

O NN

Ar

N

N

Br

HO

Br

61 6263

NN

O R

64

NN

O

SH

R

65

NNO

OH

R

66

NH NHN

S

N

67 68


NH2

NH2

NH2

OCH3

OCH3R1

R1

R2

R2 R1

R1

R2

R2R1 R2

R3

C6H5C6H5

NHCOCH3

NHCOCH2Cl NHCOCH2R2

2-Cl2-NO2

3-NO2

4-NO2

345-OCH3

345-OCH3

4-NH2

4-NH2

4-NH2

24-Cl

4-CH3

2-NO2

2-NO2

67-6867-68






NN

S

Br

69

NN

NH

N

X

NN

O

Cl71

NN

NO

NN

Cl

F

Cl R

HNS

O

O

NN

NN

O

N N

R

ONN

Br R

OH

OHOH

ONN

Br R

SH

SH

NN

S R

75 76 77

NNNN

N

N78 79

abcdefghi

R1

R1

R1

R1

R2

R2

R2

NH2

NH2

NH2

NH2

NH2

NH2

CH3

CH3

H3CO

H3C

NHCOCH3

NHCOCH3

4-CH3-C6H4

4-NO2-C6H4

2-Thienyl

2-Thienyl


C6H54-Cl-C6H4

4-NO2-C6H4

4-Br-C6H4

2-Furyl

mdashmdashmdash

70 X = F Br


R2= H Cl F NO2

73 R = 4-CH3-C6H4 345-(OCH3)3-C6H2 74 R = F Cl

78-79
















NN

Cl Cl

F

NH

NHHN

O

X NH Ar

N

N

COOH

81

N

N

NH

O

Br

82

N

N N N

NH

HNN

X

NN

NN

HO

OH

83

84 85

NH

HN

O

O

SO

O

NHN

N NHS

H

86

NH

HN

O

O

SO

O

NN O

CNH

87

NH

HN

O

O

SO

O

N

H

88

NH

HN

O

O

SO

O

NHN

S

NH N

89

N

N

Cl

Cl

F

R

NH

NHOO

N

N

O

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

H3C

CH3

CH3

CH3 NO2

NH2

NH2

NH2

H3CO

H2N

H2N

C2H5

C6H5

C6H5H5C6

90 R = 345-(OCH3)3 4-Cl 2-OCH3

80 X = O S








N

N NO

O

91

N

N N NH

92

N

N N

N

93

NH

N NH

N

OO NH

N NH

N

OO

94 95

N N

R

S

97

NH2

NH2

NH2

NH2

NH2

CH3

CH3

CH3

CH3

CH3CH3

H3C

H3C

H2NH2N

H2N

H2N

H2N

OCH3

CH2CH2N(CH3)2



HN

NHN

S

S

Cl

NN

S

Cl

N

NCN

NO

HO OH101 102 103 104

O

N NO

O

N NO

SHSH

NN

NHSO

ONH

NN

NNH

S

NHRNH

N N

O

105 106

CH3

CH3

CH3

NH2

NO2

H3C

H3CH3C

NHNH2

OCOCH3OCOCH3


N

N

SH

CH3

O

SN

N

S

O

S

O

N N

SHNHN

S

O

Cl

98 99 100



NN

NNH

HNHN Ar

ArAr

N

NN

R

NN

O

OH

O

S

CH3

NH2

SCH2Ph


H3C



















NHN

S

NN

Ar

N

NH

ON

N

NH

OHN

O

NH

N

S

N

112 113 114 115

NH

NH

SN

O

NH

NH

S

SN

O

116 117

NN

ONN

O O

NH

O

118

NH

NH

SH

O

NH NH

NH

O

NH

NH

HN

NS Ar NH

HN

O

NH

S

CN

S

119 120 121 122

NH

NH

O

N

OHN

S

R

NH

HN

O

NHS

CN

S

123

NH

NH

O

N

OHN

Ar

R

N

N

Cl

S

O

N

N

S

OO

N

N

S

HO OH

HO126 127128

NH2

NH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

P+

= 3-Cl-C6H4 34-(OCH3)2-C6H3

= C6H5 4-Cl 2NO2 345-C6H234-(OCH3)2-C6H3

125R = H 4-(OCH3) Ar = 34-(NO2)2-C6H3

H2N

ArN2 ArN2

ArN2ArN2

ArN2

NHC6H5

C6H5

H3C

H3CH3C

H3CH3C

SCH3

SCH2CN

SCH2CN

COCH3

COCH3

COCH3

CH3COO

CH3COO

CH3COO

CH3COO

OCOCH3OCOCH3

OCOCH3

OCOCH3

OH3C

= H 4-(OCH3) 4-NO2124 R

Ominus

R1

R2 R2

R1

R1

R2



CH3

CH3

CH3

CH3

CH3

CH3

CH3

C6H5

OCOCH3

OCOCH3

OH3C

OH3C

SH3C

H2N


H3COCO

H3COCO

H3COCH3

H3CH2CO

131 R = Cl OCH3 OH


135 R = CH3C6H11

N

N

N

ClCN NHHN

OO

OH

N

NCN

OH

R

129 130

FF

F

NH

NH

O

O O NH

N

HN

S

CNO

NH

NH

NH

X

RO

132 133

NH

HN

SR

O

NH

S

O

NH

NH

S

OCl

N

N

S

Cl O

136

138



2 CONHMe and SO

2NH2




NHN

N

S

NNN

NHN

N

S

NNN

Br NH

NH

O S

OR O

139 140

N

HN

O

O

R

NH

SOH

NN

S

O

Ar Ar

O

NN

S

SO

ArS Ar

OO

O

N

N

O

N143 144 145

NH

NH

S

NH

O

Cl

146 147

R

NH

NH

S

NH

O

ClR

N N

N

N

S

R

NN

O

O

Cl

SS

N O149

N

N

O

Et

CH3

CH3

CH3

CH3

H2N

H2NH2N

NH2

NH2NH2

C6H5

NO2

H5C2O

H3C

H3CH3CH3C


H5C6


= Br Cl142 R

= 5-OCH3 5NO2 5-Cl148 R



R1 R2







N

N

ClCN

SR

N

N

ClCN

ArSR

151

151 Ar Rabc

NH

HN

N

S

N

Cl

SH

O

153

N

N SH

Br

R

154

NH

HN

O

XO

NHNH

HN

O

O

X

NHNH

N

Ar

O

NHO

NNN

SH

O

R

154 Rabcdefghijk H

NH

HN

O

O

O

O

RNH

NH

R

X

O

NHNH

O

N

NH

NH

O

O

NN

160

CH3

CH3

CH3

CH3

H3C

H3C


C2H5C3H7

COCH3

4-OCH3

3-OCH3


2-NO2

4-N(CH3)26-furyl

=CH3 C2H5 CH3152 R









OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

CH3

CH3CH3

NH2

NH2NH2NH2

NH2NH2

H2N

O2N O2N O2N

H3CO

H3CO H3CO

H3CO

H3CO


NHNH

SO

ONN

O

O

N

N NN

161

162 163

OHO

NN

NN

OH

R

N

N

O

N N

N

O

NCl

165 166

167 168 169

NN

N

Cl

ClCl

Cl

NN

N

Cl

NN

N

Cl

Cl

170 171 172

= 2-NO2-C6H4 3-NO2-C6H4 4-OCH3-C6H4164 R



















O

N

N OH

O

N

N OH

HN

N

O

OHOO

173 174

HO

HN

N

O

O

HO

HN

N

O

O

HO

HN

N

O

OO

HO

HO

N

176177 178

179

HN

NOO

HO

HO

N

180

HN

NH

O

O R

180 Rabcd

N

HN

HO

O

O

HO

HO

181

N

HN

HO

O

O

HO F

HO

182

N

HN

HO

O

O

HO F

HO

183

CH3

NH2

NO2

CH(N3)CH2XOC6H5


C6H5


2-Pyridyl

C10H21 C10H21 C11H23

= Br I Cl175 X

H3C

H3C

H3C

H3C

H3C

H3CH3C

H3C

H3C



50of 401







NNN

N

( )n

N

N

Cl

RN

N

186

N

N

O

HN

N

N

NN

N

N

O

HN N

N

N

BrBr

N

N

N

O

HN

N

N

N

Br

N

187 188 189

N

NNN

O

N

N

Br

N

H

N

NNN

O

Br

N

R

H

190

191

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2NH2

H3CO OCH3

OCH3

OCH2CH3


184 n = 01



N

N NH

SO

ON N

R

NN

N

SN

NN

N

192 194

N

NOR

N

NOR

N

NOR

CH3CH3

CH3

CH3

NH2 NH2 NH2

H2N H2N H2N

NO2


193 R =OC2H5 OBu

196 R = C2H5 C3H7 197 R = CH3 C2H5

H3C

H3C






NH

NH

O

O

SR

NN

N

ClFe

198 199

H3C

H3C

CH3









6 Conclusion


Abbreviations



CH3

CH3

NH2

H2N

200 R = H COCH3

P(O)(OH)2 P(O)(OH)2

N

N

O

SO

ONH

NN

R

H

N

N

O

O

N

N

OH

O

O

201 202

H3C


N

N

O

N

NBr

N

O

N

N

O

N

N

Br

NNN

F

F

OHOOC

203 204

N

N

OR

F FS

N

N R

O O

P OHOOH

NH

N

O

S

207

N

HN

S

O

O

ClCl

208

N

NHO

OHOH

O

OH

209

N

NS

OHOH

O

OH

NH

NHOCl

210

N

HN

O

SClCl

211

N

NBr

212

N

NBr

Br

Br

213

CH3

CH3

CH3

NH2NH2

NH2

H3COH3CO

H3COH3CO

H3CO

H2N

H3C

H3C

OCH3

OCH3

OCH3OCH3

OCH3

OCH3

OCH3

OCH3

C2H5

205 R = H Me 206 R = H Me

COCH3

COCH3

CH2CH3

CH2Br






Acknowledgments


References




































































10158401015840



























































































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


OON

N NH

OON

N NH

ON

N N OHOHOH

OH

44

OON

N N

OH

H

4542 43

N

N

NHN

47

N N

HN N O

OR

N

N NHN

Cl

N

N

R

O

OHOH

48

H3C

CH3

CH3

CH3

CH3

+H3N

CF3

NO2

O2N

O2N

Osim

49R = H CH3 4-Br-C6H4 4-OCH3-C6H4


NO2







3) sub-



N

NN

N

HS

O

Cl

Cl

Cl

Cl

N

NN

N

O NN

R

NH

N

NN

NHNH

50 51 52

N

N N

N

N N NN

S

53 54 55

NN

HNSO

O

NH

O

5657

NN

FCl

F

Cl

56abcdef

ClNH2

NH2

NH2

H3C

CH3

CH3

CH3

NO2

NO2 NO2

NO2

H2N

H3C

OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

R1

R1R2

R2




3 and NO








O NN

O NN

O

N

N N

Cl58 59

60

O NN

O NN

Ar

N

N

Br

HO

Br

61 6263

NN

O R

64

NN

O

SH

R

65

NNO

OH

R

66

NH NHN

S

N

67 68


NH2

NH2

NH2

OCH3

OCH3R1

R1

R2

R2 R1

R1

R2

R2R1 R2

R3

C6H5C6H5

NHCOCH3

NHCOCH2Cl NHCOCH2R2

2-Cl2-NO2

3-NO2

4-NO2

345-OCH3

345-OCH3

4-NH2

4-NH2

4-NH2

24-Cl

4-CH3

2-NO2

2-NO2

67-6867-68






NN

S

Br

69

NN

NH

N

X

NN

O

Cl71

NN

NO

NN

Cl

F

Cl R

HNS

O

O

NN

NN

O

N N

R

ONN

Br R

OH

OHOH

ONN

Br R

SH

SH

NN

S R

75 76 77

NNNN

N

N78 79

abcdefghi

R1

R1

R1

R1

R2

R2

R2

NH2

NH2

NH2

NH2

NH2

NH2

CH3

CH3

H3CO

H3C

NHCOCH3

NHCOCH3

4-CH3-C6H4

4-NO2-C6H4

2-Thienyl

2-Thienyl


C6H54-Cl-C6H4

4-NO2-C6H4

4-Br-C6H4

2-Furyl

mdashmdashmdash

70 X = F Br


R2= H Cl F NO2

73 R = 4-CH3-C6H4 345-(OCH3)3-C6H2 74 R = F Cl

78-79
















NN

Cl Cl

F

NH

NHHN

O

X NH Ar

N

N

COOH

81

N

N

NH

O

Br

82

N

N N N

NH

HNN

X

NN

NN

HO

OH

83

84 85

NH

HN

O

O

SO

O

NHN

N NHS

H

86

NH

HN

O

O

SO

O

NN O

CNH

87

NH

HN

O

O

SO

O

N

H

88

NH

HN

O

O

SO

O

NHN

S

NH N

89

N

N

Cl

Cl

F

R

NH

NHOO

N

N

O

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

H3C

CH3

CH3

CH3 NO2

NH2

NH2

NH2

H3CO

H2N

H2N

C2H5

C6H5

C6H5H5C6

90 R = 345-(OCH3)3 4-Cl 2-OCH3

80 X = O S








N

N NO

O

91

N

N N NH

92

N

N N

N

93

NH

N NH

N

OO NH

N NH

N

OO

94 95

N N

R

S

97

NH2

NH2

NH2

NH2

NH2

CH3

CH3

CH3

CH3

CH3CH3

H3C

H3C

H2NH2N

H2N

H2N

H2N

OCH3

CH2CH2N(CH3)2



HN

NHN

S

S

Cl

NN

S

Cl

N

NCN

NO

HO OH101 102 103 104

O

N NO

O

N NO

SHSH

NN

NHSO

ONH

NN

NNH

S

NHRNH

N N

O

105 106

CH3

CH3

CH3

NH2

NO2

H3C

H3CH3C

NHNH2

OCOCH3OCOCH3


N

N

SH

CH3

O

SN

N

S

O

S

O

N N

SHNHN

S

O

Cl

98 99 100



NN

NNH

HNHN Ar

ArAr

N

NN

R

NN

O

OH

O

S

CH3

NH2

SCH2Ph


H3C



















NHN

S

NN

Ar

N

NH

ON

N

NH

OHN

O

NH

N

S

N

112 113 114 115

NH

NH

SN

O

NH

NH

S

SN

O

116 117

NN

ONN

O O

NH

O

118

NH

NH

SH

O

NH NH

NH

O

NH

NH

HN

NS Ar NH

HN

O

NH

S

CN

S

119 120 121 122

NH

NH

O

N

OHN

S

R

NH

HN

O

NHS

CN

S

123

NH

NH

O

N

OHN

Ar

R

N

N

Cl

S

O

N

N

S

OO

N

N

S

HO OH

HO126 127128

NH2

NH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

P+

= 3-Cl-C6H4 34-(OCH3)2-C6H3

= C6H5 4-Cl 2NO2 345-C6H234-(OCH3)2-C6H3

125R = H 4-(OCH3) Ar = 34-(NO2)2-C6H3

H2N

ArN2 ArN2

ArN2ArN2

ArN2

NHC6H5

C6H5

H3C

H3CH3C

H3CH3C

SCH3

SCH2CN

SCH2CN

COCH3

COCH3

COCH3

CH3COO

CH3COO

CH3COO

CH3COO

OCOCH3OCOCH3

OCOCH3

OCOCH3

OH3C

= H 4-(OCH3) 4-NO2124 R

Ominus

R1

R2 R2

R1

R1

R2



CH3

CH3

CH3

CH3

CH3

CH3

CH3

C6H5

OCOCH3

OCOCH3

OH3C

OH3C

SH3C

H2N


H3COCO

H3COCO

H3COCH3

H3CH2CO

131 R = Cl OCH3 OH


135 R = CH3C6H11

N

N

N

ClCN NHHN

OO

OH

N

NCN

OH

R

129 130

FF

F

NH

NH

O

O O NH

N

HN

S

CNO

NH

NH

NH

X

RO

132 133

NH

HN

SR

O

NH

S

O

NH

NH

S

OCl

N

N

S

Cl O

136

138



2 CONHMe and SO

2NH2




NHN

N

S

NNN

NHN

N

S

NNN

Br NH

NH

O S

OR O

139 140

N

HN

O

O

R

NH

SOH

NN

S

O

Ar Ar

O

NN

S

SO

ArS Ar

OO

O

N

N

O

N143 144 145

NH

NH

S

NH

O

Cl

146 147

R

NH

NH

S

NH

O

ClR

N N

N

N

S

R

NN

O

O

Cl

SS

N O149

N

N

O

Et

CH3

CH3

CH3

CH3

H2N

H2NH2N

NH2

NH2NH2

C6H5

NO2

H5C2O

H3C

H3CH3CH3C


H5C6


= Br Cl142 R

= 5-OCH3 5NO2 5-Cl148 R



R1 R2







N

N

ClCN

SR

N

N

ClCN

ArSR

151

151 Ar Rabc

NH

HN

N

S

N

Cl

SH

O

153

N

N SH

Br

R

154

NH

HN

O

XO

NHNH

HN

O

O

X

NHNH

N

Ar

O

NHO

NNN

SH

O

R

154 Rabcdefghijk H

NH

HN

O

O

O

O

RNH

NH

R

X

O

NHNH

O

N

NH

NH

O

O

NN

160

CH3

CH3

CH3

CH3

H3C

H3C


C2H5C3H7

COCH3

4-OCH3

3-OCH3


2-NO2

4-N(CH3)26-furyl

=CH3 C2H5 CH3152 R









OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

CH3

CH3CH3

NH2

NH2NH2NH2

NH2NH2

H2N

O2N O2N O2N

H3CO

H3CO H3CO

H3CO

H3CO


NHNH

SO

ONN

O

O

N

N NN

161

162 163

OHO

NN

NN

OH

R

N

N

O

N N

N

O

NCl

165 166

167 168 169

NN

N

Cl

ClCl

Cl

NN

N

Cl

NN

N

Cl

Cl

170 171 172

= 2-NO2-C6H4 3-NO2-C6H4 4-OCH3-C6H4164 R



















O

N

N OH

O

N

N OH

HN

N

O

OHOO

173 174

HO

HN

N

O

O

HO

HN

N

O

O

HO

HN

N

O

OO

HO

HO

N

176177 178

179

HN

NOO

HO

HO

N

180

HN

NH

O

O R

180 Rabcd

N

HN

HO

O

O

HO

HO

181

N

HN

HO

O

O

HO F

HO

182

N

HN

HO

O

O

HO F

HO

183

CH3

NH2

NO2

CH(N3)CH2XOC6H5


C6H5


2-Pyridyl

C10H21 C10H21 C11H23

= Br I Cl175 X

H3C

H3C

H3C

H3C

H3C

H3CH3C

H3C

H3C



50of 401







NNN

N

( )n

N

N

Cl

RN

N

186

N

N

O

HN

N

N

NN

N

N

O

HN N

N

N

BrBr

N

N

N

O

HN

N

N

N

Br

N

187 188 189

N

NNN

O

N

N

Br

N

H

N

NNN

O

Br

N

R

H

190

191

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2NH2

H3CO OCH3

OCH3

OCH2CH3


184 n = 01



N

N NH

SO

ON N

R

NN

N

SN

NN

N

192 194

N

NOR

N

NOR

N

NOR

CH3CH3

CH3

CH3

NH2 NH2 NH2

H2N H2N H2N

NO2


193 R =OC2H5 OBu

196 R = C2H5 C3H7 197 R = CH3 C2H5

H3C

H3C






NH

NH

O

O

SR

NN

N

ClFe

198 199

H3C

H3C

CH3









6 Conclusion


Abbreviations



CH3

CH3

NH2

H2N

200 R = H COCH3

P(O)(OH)2 P(O)(OH)2

N

N

O

SO

ONH

NN

R

H

N

N

O

O

N

N

OH

O

O

201 202

H3C


N

N

O

N

NBr

N

O

N

N

O

N

N

Br

NNN

F

F

OHOOC

203 204

N

N

OR

F FS

N

N R

O O

P OHOOH

NH

N

O

S

207

N

HN

S

O

O

ClCl

208

N

NHO

OHOH

O

OH

209

N

NS

OHOH

O

OH

NH

NHOCl

210

N

HN

O

SClCl

211

N

NBr

212

N

NBr

Br

Br

213

CH3

CH3

CH3

NH2NH2

NH2

H3COH3CO

H3COH3CO

H3CO

H2N

H3C

H3C

OCH3

OCH3

OCH3OCH3

OCH3

OCH3

OCH3

OCH3

C2H5

205 R = H Me 206 R = H Me

COCH3

COCH3

CH2CH3

CH2Br






Acknowledgments


References




































































10158401015840



























































































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


N

NN

N

HS

O

Cl

Cl

Cl

Cl

N

NN

N

O NN

R

NH

N

NN

NHNH

50 51 52

N

N N

N

N N NN

S

53 54 55

NN

HNSO

O

NH

O

5657

NN

FCl

F

Cl

56abcdef

ClNH2

NH2

NH2

H3C

CH3

CH3

CH3

NO2

NO2 NO2

NO2

H2N

H3C

OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

R1

R1R2

R2




3 and NO








O NN

O NN

O

N

N N

Cl58 59

60

O NN

O NN

Ar

N

N

Br

HO

Br

61 6263

NN

O R

64

NN

O

SH

R

65

NNO

OH

R

66

NH NHN

S

N

67 68


NH2

NH2

NH2

OCH3

OCH3R1

R1

R2

R2 R1

R1

R2

R2R1 R2

R3

C6H5C6H5

NHCOCH3

NHCOCH2Cl NHCOCH2R2

2-Cl2-NO2

3-NO2

4-NO2

345-OCH3

345-OCH3

4-NH2

4-NH2

4-NH2

24-Cl

4-CH3

2-NO2

2-NO2

67-6867-68






NN

S

Br

69

NN

NH

N

X

NN

O

Cl71

NN

NO

NN

Cl

F

Cl R

HNS

O

O

NN

NN

O

N N

R

ONN

Br R

OH

OHOH

ONN

Br R

SH

SH

NN

S R

75 76 77

NNNN

N

N78 79

abcdefghi

R1

R1

R1

R1

R2

R2

R2

NH2

NH2

NH2

NH2

NH2

NH2

CH3

CH3

H3CO

H3C

NHCOCH3

NHCOCH3

4-CH3-C6H4

4-NO2-C6H4

2-Thienyl

2-Thienyl


C6H54-Cl-C6H4

4-NO2-C6H4

4-Br-C6H4

2-Furyl

mdashmdashmdash

70 X = F Br


R2= H Cl F NO2

73 R = 4-CH3-C6H4 345-(OCH3)3-C6H2 74 R = F Cl

78-79
















NN

Cl Cl

F

NH

NHHN

O

X NH Ar

N

N

COOH

81

N

N

NH

O

Br

82

N

N N N

NH

HNN

X

NN

NN

HO

OH

83

84 85

NH

HN

O

O

SO

O

NHN

N NHS

H

86

NH

HN

O

O

SO

O

NN O

CNH

87

NH

HN

O

O

SO

O

N

H

88

NH

HN

O

O

SO

O

NHN

S

NH N

89

N

N

Cl

Cl

F

R

NH

NHOO

N

N

O

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

H3C

CH3

CH3

CH3 NO2

NH2

NH2

NH2

H3CO

H2N

H2N

C2H5

C6H5

C6H5H5C6

90 R = 345-(OCH3)3 4-Cl 2-OCH3

80 X = O S








N

N NO

O

91

N

N N NH

92

N

N N

N

93

NH

N NH

N

OO NH

N NH

N

OO

94 95

N N

R

S

97

NH2

NH2

NH2

NH2

NH2

CH3

CH3

CH3

CH3

CH3CH3

H3C

H3C

H2NH2N

H2N

H2N

H2N

OCH3

CH2CH2N(CH3)2



HN

NHN

S

S

Cl

NN

S

Cl

N

NCN

NO

HO OH101 102 103 104

O

N NO

O

N NO

SHSH

NN

NHSO

ONH

NN

NNH

S

NHRNH

N N

O

105 106

CH3

CH3

CH3

NH2

NO2

H3C

H3CH3C

NHNH2

OCOCH3OCOCH3


N

N

SH

CH3

O

SN

N

S

O

S

O

N N

SHNHN

S

O

Cl

98 99 100



NN

NNH

HNHN Ar

ArAr

N

NN

R

NN

O

OH

O

S

CH3

NH2

SCH2Ph


H3C



















NHN

S

NN

Ar

N

NH

ON

N

NH

OHN

O

NH

N

S

N

112 113 114 115

NH

NH

SN

O

NH

NH

S

SN

O

116 117

NN

ONN

O O

NH

O

118

NH

NH

SH

O

NH NH

NH

O

NH

NH

HN

NS Ar NH

HN

O

NH

S

CN

S

119 120 121 122

NH

NH

O

N

OHN

S

R

NH

HN

O

NHS

CN

S

123

NH

NH

O

N

OHN

Ar

R

N

N

Cl

S

O

N

N

S

OO

N

N

S

HO OH

HO126 127128

NH2

NH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

P+

= 3-Cl-C6H4 34-(OCH3)2-C6H3

= C6H5 4-Cl 2NO2 345-C6H234-(OCH3)2-C6H3

125R = H 4-(OCH3) Ar = 34-(NO2)2-C6H3

H2N

ArN2 ArN2

ArN2ArN2

ArN2

NHC6H5

C6H5

H3C

H3CH3C

H3CH3C

SCH3

SCH2CN

SCH2CN

COCH3

COCH3

COCH3

CH3COO

CH3COO

CH3COO

CH3COO

OCOCH3OCOCH3

OCOCH3

OCOCH3

OH3C

= H 4-(OCH3) 4-NO2124 R

Ominus

R1

R2 R2

R1

R1

R2



CH3

CH3

CH3

CH3

CH3

CH3

CH3

C6H5

OCOCH3

OCOCH3

OH3C

OH3C

SH3C

H2N


H3COCO

H3COCO

H3COCH3

H3CH2CO

131 R = Cl OCH3 OH


135 R = CH3C6H11

N

N

N

ClCN NHHN

OO

OH

N

NCN

OH

R

129 130

FF

F

NH

NH

O

O O NH

N

HN

S

CNO

NH

NH

NH

X

RO

132 133

NH

HN

SR

O

NH

S

O

NH

NH

S

OCl

N

N

S

Cl O

136

138



2 CONHMe and SO

2NH2




NHN

N

S

NNN

NHN

N

S

NNN

Br NH

NH

O S

OR O

139 140

N

HN

O

O

R

NH

SOH

NN

S

O

Ar Ar

O

NN

S

SO

ArS Ar

OO

O

N

N

O

N143 144 145

NH

NH

S

NH

O

Cl

146 147

R

NH

NH

S

NH

O

ClR

N N

N

N

S

R

NN

O

O

Cl

SS

N O149

N

N

O

Et

CH3

CH3

CH3

CH3

H2N

H2NH2N

NH2

NH2NH2

C6H5

NO2

H5C2O

H3C

H3CH3CH3C


H5C6


= Br Cl142 R

= 5-OCH3 5NO2 5-Cl148 R



R1 R2







N

N

ClCN

SR

N

N

ClCN

ArSR

151

151 Ar Rabc

NH

HN

N

S

N

Cl

SH

O

153

N

N SH

Br

R

154

NH

HN

O

XO

NHNH

HN

O

O

X

NHNH

N

Ar

O

NHO

NNN

SH

O

R

154 Rabcdefghijk H

NH

HN

O

O

O

O

RNH

NH

R

X

O

NHNH

O

N

NH

NH

O

O

NN

160

CH3

CH3

CH3

CH3

H3C

H3C


C2H5C3H7

COCH3

4-OCH3

3-OCH3


2-NO2

4-N(CH3)26-furyl

=CH3 C2H5 CH3152 R









OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

CH3

CH3CH3

NH2

NH2NH2NH2

NH2NH2

H2N

O2N O2N O2N

H3CO

H3CO H3CO

H3CO

H3CO


NHNH

SO

ONN

O

O

N

N NN

161

162 163

OHO

NN

NN

OH

R

N

N

O

N N

N

O

NCl

165 166

167 168 169

NN

N

Cl

ClCl

Cl

NN

N

Cl

NN

N

Cl

Cl

170 171 172

= 2-NO2-C6H4 3-NO2-C6H4 4-OCH3-C6H4164 R



















O

N

N OH

O

N

N OH

HN

N

O

OHOO

173 174

HO

HN

N

O

O

HO

HN

N

O

O

HO

HN

N

O

OO

HO

HO

N

176177 178

179

HN

NOO

HO

HO

N

180

HN

NH

O

O R

180 Rabcd

N

HN

HO

O

O

HO

HO

181

N

HN

HO

O

O

HO F

HO

182

N

HN

HO

O

O

HO F

HO

183

CH3

NH2

NO2

CH(N3)CH2XOC6H5


C6H5


2-Pyridyl

C10H21 C10H21 C11H23

= Br I Cl175 X

H3C

H3C

H3C

H3C

H3C

H3CH3C

H3C

H3C



50of 401







NNN

N

( )n

N

N

Cl

RN

N

186

N

N

O

HN

N

N

NN

N

N

O

HN N

N

N

BrBr

N

N

N

O

HN

N

N

N

Br

N

187 188 189

N

NNN

O

N

N

Br

N

H

N

NNN

O

Br

N

R

H

190

191

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2NH2

H3CO OCH3

OCH3

OCH2CH3


184 n = 01



N

N NH

SO

ON N

R

NN

N

SN

NN

N

192 194

N

NOR

N

NOR

N

NOR

CH3CH3

CH3

CH3

NH2 NH2 NH2

H2N H2N H2N

NO2


193 R =OC2H5 OBu

196 R = C2H5 C3H7 197 R = CH3 C2H5

H3C

H3C






NH

NH

O

O

SR

NN

N

ClFe

198 199

H3C

H3C

CH3









6 Conclusion


Abbreviations



CH3

CH3

NH2

H2N

200 R = H COCH3

P(O)(OH)2 P(O)(OH)2

N

N

O

SO

ONH

NN

R

H

N

N

O

O

N

N

OH

O

O

201 202

H3C


N

N

O

N

NBr

N

O

N

N

O

N

N

Br

NNN

F

F

OHOOC

203 204

N

N

OR

F FS

N

N R

O O

P OHOOH

NH

N

O

S

207

N

HN

S

O

O

ClCl

208

N

NHO

OHOH

O

OH

209

N

NS

OHOH

O

OH

NH

NHOCl

210

N

HN

O

SClCl

211

N

NBr

212

N

NBr

Br

Br

213

CH3

CH3

CH3

NH2NH2

NH2

H3COH3CO

H3COH3CO

H3CO

H2N

H3C

H3C

OCH3

OCH3

OCH3OCH3

OCH3

OCH3

OCH3

OCH3

C2H5

205 R = H Me 206 R = H Me

COCH3

COCH3

CH2CH3

CH2Br






Acknowledgments


References




































































10158401015840



























































































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


O NN

O NN

O

N

N N

Cl58 59

60

O NN

O NN

Ar

N

N

Br

HO

Br

61 6263

NN

O R

64

NN

O

SH

R

65

NNO

OH

R

66

NH NHN

S

N

67 68


NH2

NH2

NH2

OCH3

OCH3R1

R1

R2

R2 R1

R1

R2

R2R1 R2

R3

C6H5C6H5

NHCOCH3

NHCOCH2Cl NHCOCH2R2

2-Cl2-NO2

3-NO2

4-NO2

345-OCH3

345-OCH3

4-NH2

4-NH2

4-NH2

24-Cl

4-CH3

2-NO2

2-NO2

67-6867-68






NN

S

Br

69

NN

NH

N

X

NN

O

Cl71

NN

NO

NN

Cl

F

Cl R

HNS

O

O

NN

NN

O

N N

R

ONN

Br R

OH

OHOH

ONN

Br R

SH

SH

NN

S R

75 76 77

NNNN

N

N78 79

abcdefghi

R1

R1

R1

R1

R2

R2

R2

NH2

NH2

NH2

NH2

NH2

NH2

CH3

CH3

H3CO

H3C

NHCOCH3

NHCOCH3

4-CH3-C6H4

4-NO2-C6H4

2-Thienyl

2-Thienyl


C6H54-Cl-C6H4

4-NO2-C6H4

4-Br-C6H4

2-Furyl

mdashmdashmdash

70 X = F Br


R2= H Cl F NO2

73 R = 4-CH3-C6H4 345-(OCH3)3-C6H2 74 R = F Cl

78-79
















NN

Cl Cl

F

NH

NHHN

O

X NH Ar

N

N

COOH

81

N

N

NH

O

Br

82

N

N N N

NH

HNN

X

NN

NN

HO

OH

83

84 85

NH

HN

O

O

SO

O

NHN

N NHS

H

86

NH

HN

O

O

SO

O

NN O

CNH

87

NH

HN

O

O

SO

O

N

H

88

NH

HN

O

O

SO

O

NHN

S

NH N

89

N

N

Cl

Cl

F

R

NH

NHOO

N

N

O

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

H3C

CH3

CH3

CH3 NO2

NH2

NH2

NH2

H3CO

H2N

H2N

C2H5

C6H5

C6H5H5C6

90 R = 345-(OCH3)3 4-Cl 2-OCH3

80 X = O S








N

N NO

O

91

N

N N NH

92

N

N N

N

93

NH

N NH

N

OO NH

N NH

N

OO

94 95

N N

R

S

97

NH2

NH2

NH2

NH2

NH2

CH3

CH3

CH3

CH3

CH3CH3

H3C

H3C

H2NH2N

H2N

H2N

H2N

OCH3

CH2CH2N(CH3)2



HN

NHN

S

S

Cl

NN

S

Cl

N

NCN

NO

HO OH101 102 103 104

O

N NO

O

N NO

SHSH

NN

NHSO

ONH

NN

NNH

S

NHRNH

N N

O

105 106

CH3

CH3

CH3

NH2

NO2

H3C

H3CH3C

NHNH2

OCOCH3OCOCH3


N

N

SH

CH3

O

SN

N

S

O

S

O

N N

SHNHN

S

O

Cl

98 99 100



NN

NNH

HNHN Ar

ArAr

N

NN

R

NN

O

OH

O

S

CH3

NH2

SCH2Ph


H3C



















NHN

S

NN

Ar

N

NH

ON

N

NH

OHN

O

NH

N

S

N

112 113 114 115

NH

NH

SN

O

NH

NH

S

SN

O

116 117

NN

ONN

O O

NH

O

118

NH

NH

SH

O

NH NH

NH

O

NH

NH

HN

NS Ar NH

HN

O

NH

S

CN

S

119 120 121 122

NH

NH

O

N

OHN

S

R

NH

HN

O

NHS

CN

S

123

NH

NH

O

N

OHN

Ar

R

N

N

Cl

S

O

N

N

S

OO

N

N

S

HO OH

HO126 127128

NH2

NH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

P+

= 3-Cl-C6H4 34-(OCH3)2-C6H3

= C6H5 4-Cl 2NO2 345-C6H234-(OCH3)2-C6H3

125R = H 4-(OCH3) Ar = 34-(NO2)2-C6H3

H2N

ArN2 ArN2

ArN2ArN2

ArN2

NHC6H5

C6H5

H3C

H3CH3C

H3CH3C

SCH3

SCH2CN

SCH2CN

COCH3

COCH3

COCH3

CH3COO

CH3COO

CH3COO

CH3COO

OCOCH3OCOCH3

OCOCH3

OCOCH3

OH3C

= H 4-(OCH3) 4-NO2124 R

Ominus

R1

R2 R2

R1

R1

R2



CH3

CH3

CH3

CH3

CH3

CH3

CH3

C6H5

OCOCH3

OCOCH3

OH3C

OH3C

SH3C

H2N


H3COCO

H3COCO

H3COCH3

H3CH2CO

131 R = Cl OCH3 OH


135 R = CH3C6H11

N

N

N

ClCN NHHN

OO

OH

N

NCN

OH

R

129 130

FF

F

NH

NH

O

O O NH

N

HN

S

CNO

NH

NH

NH

X

RO

132 133

NH

HN

SR

O

NH

S

O

NH

NH

S

OCl

N

N

S

Cl O

136

138



2 CONHMe and SO

2NH2




NHN

N

S

NNN

NHN

N

S

NNN

Br NH

NH

O S

OR O

139 140

N

HN

O

O

R

NH

SOH

NN

S

O

Ar Ar

O

NN

S

SO

ArS Ar

OO

O

N

N

O

N143 144 145

NH

NH

S

NH

O

Cl

146 147

R

NH

NH

S

NH

O

ClR

N N

N

N

S

R

NN

O

O

Cl

SS

N O149

N

N

O

Et

CH3

CH3

CH3

CH3

H2N

H2NH2N

NH2

NH2NH2

C6H5

NO2

H5C2O

H3C

H3CH3CH3C


H5C6


= Br Cl142 R

= 5-OCH3 5NO2 5-Cl148 R



R1 R2







N

N

ClCN

SR

N

N

ClCN

ArSR

151

151 Ar Rabc

NH

HN

N

S

N

Cl

SH

O

153

N

N SH

Br

R

154

NH

HN

O

XO

NHNH

HN

O

O

X

NHNH

N

Ar

O

NHO

NNN

SH

O

R

154 Rabcdefghijk H

NH

HN

O

O

O

O

RNH

NH

R

X

O

NHNH

O

N

NH

NH

O

O

NN

160

CH3

CH3

CH3

CH3

H3C

H3C


C2H5C3H7

COCH3

4-OCH3

3-OCH3


2-NO2

4-N(CH3)26-furyl

=CH3 C2H5 CH3152 R









OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

CH3

CH3CH3

NH2

NH2NH2NH2

NH2NH2

H2N

O2N O2N O2N

H3CO

H3CO H3CO

H3CO

H3CO


NHNH

SO

ONN

O

O

N

N NN

161

162 163

OHO

NN

NN

OH

R

N

N

O

N N

N

O

NCl

165 166

167 168 169

NN

N

Cl

ClCl

Cl

NN

N

Cl

NN

N

Cl

Cl

170 171 172

= 2-NO2-C6H4 3-NO2-C6H4 4-OCH3-C6H4164 R



















O

N

N OH

O

N

N OH

HN

N

O

OHOO

173 174

HO

HN

N

O

O

HO

HN

N

O

O

HO

HN

N

O

OO

HO

HO

N

176177 178

179

HN

NOO

HO

HO

N

180

HN

NH

O

O R

180 Rabcd

N

HN

HO

O

O

HO

HO

181

N

HN

HO

O

O

HO F

HO

182

N

HN

HO

O

O

HO F

HO

183

CH3

NH2

NO2

CH(N3)CH2XOC6H5


C6H5


2-Pyridyl

C10H21 C10H21 C11H23

= Br I Cl175 X

H3C

H3C

H3C

H3C

H3C

H3CH3C

H3C

H3C



50of 401







NNN

N

( )n

N

N

Cl

RN

N

186

N

N

O

HN

N

N

NN

N

N

O

HN N

N

N

BrBr

N

N

N

O

HN

N

N

N

Br

N

187 188 189

N

NNN

O

N

N

Br

N

H

N

NNN

O

Br

N

R

H

190

191

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2NH2

H3CO OCH3

OCH3

OCH2CH3


184 n = 01



N

N NH

SO

ON N

R

NN

N

SN

NN

N

192 194

N

NOR

N

NOR

N

NOR

CH3CH3

CH3

CH3

NH2 NH2 NH2

H2N H2N H2N

NO2


193 R =OC2H5 OBu

196 R = C2H5 C3H7 197 R = CH3 C2H5

H3C

H3C






NH

NH

O

O

SR

NN

N

ClFe

198 199

H3C

H3C

CH3









6 Conclusion


Abbreviations



CH3

CH3

NH2

H2N

200 R = H COCH3

P(O)(OH)2 P(O)(OH)2

N

N

O

SO

ONH

NN

R

H

N

N

O

O

N

N

OH

O

O

201 202

H3C


N

N

O

N

NBr

N

O

N

N

O

N

N

Br

NNN

F

F

OHOOC

203 204

N

N

OR

F FS

N

N R

O O

P OHOOH

NH

N

O

S

207

N

HN

S

O

O

ClCl

208

N

NHO

OHOH

O

OH

209

N

NS

OHOH

O

OH

NH

NHOCl

210

N

HN

O

SClCl

211

N

NBr

212

N

NBr

Br

Br

213

CH3

CH3

CH3

NH2NH2

NH2

H3COH3CO

H3COH3CO

H3CO

H2N

H3C

H3C

OCH3

OCH3

OCH3OCH3

OCH3

OCH3

OCH3

OCH3

C2H5

205 R = H Me 206 R = H Me

COCH3

COCH3

CH2CH3

CH2Br






Acknowledgments


References




































































10158401015840



























































































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


NN

S

Br

69

NN

NH

N

X

NN

O

Cl71

NN

NO

NN

Cl

F

Cl R

HNS

O

O

NN

NN

O

N N

R

ONN

Br R

OH

OHOH

ONN

Br R

SH

SH

NN

S R

75 76 77

NNNN

N

N78 79

abcdefghi

R1

R1

R1

R1

R2

R2

R2

NH2

NH2

NH2

NH2

NH2

NH2

CH3

CH3

H3CO

H3C

NHCOCH3

NHCOCH3

4-CH3-C6H4

4-NO2-C6H4

2-Thienyl

2-Thienyl


C6H54-Cl-C6H4

4-NO2-C6H4

4-Br-C6H4

2-Furyl

mdashmdashmdash

70 X = F Br


R2= H Cl F NO2

73 R = 4-CH3-C6H4 345-(OCH3)3-C6H2 74 R = F Cl

78-79
















NN

Cl Cl

F

NH

NHHN

O

X NH Ar

N

N

COOH

81

N

N

NH

O

Br

82

N

N N N

NH

HNN

X

NN

NN

HO

OH

83

84 85

NH

HN

O

O

SO

O

NHN

N NHS

H

86

NH

HN

O

O

SO

O

NN O

CNH

87

NH

HN

O

O

SO

O

N

H

88

NH

HN

O

O

SO

O

NHN

S

NH N

89

N

N

Cl

Cl

F

R

NH

NHOO

N

N

O

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

H3C

CH3

CH3

CH3 NO2

NH2

NH2

NH2

H3CO

H2N

H2N

C2H5

C6H5

C6H5H5C6

90 R = 345-(OCH3)3 4-Cl 2-OCH3

80 X = O S








N

N NO

O

91

N

N N NH

92

N

N N

N

93

NH

N NH

N

OO NH

N NH

N

OO

94 95

N N

R

S

97

NH2

NH2

NH2

NH2

NH2

CH3

CH3

CH3

CH3

CH3CH3

H3C

H3C

H2NH2N

H2N

H2N

H2N

OCH3

CH2CH2N(CH3)2



HN

NHN

S

S

Cl

NN

S

Cl

N

NCN

NO

HO OH101 102 103 104

O

N NO

O

N NO

SHSH

NN

NHSO

ONH

NN

NNH

S

NHRNH

N N

O

105 106

CH3

CH3

CH3

NH2

NO2

H3C

H3CH3C

NHNH2

OCOCH3OCOCH3


N

N

SH

CH3

O

SN

N

S

O

S

O

N N

SHNHN

S

O

Cl

98 99 100



NN

NNH

HNHN Ar

ArAr

N

NN

R

NN

O

OH

O

S

CH3

NH2

SCH2Ph


H3C



















NHN

S

NN

Ar

N

NH

ON

N

NH

OHN

O

NH

N

S

N

112 113 114 115

NH

NH

SN

O

NH

NH

S

SN

O

116 117

NN

ONN

O O

NH

O

118

NH

NH

SH

O

NH NH

NH

O

NH

NH

HN

NS Ar NH

HN

O

NH

S

CN

S

119 120 121 122

NH

NH

O

N

OHN

S

R

NH

HN

O

NHS

CN

S

123

NH

NH

O

N

OHN

Ar

R

N

N

Cl

S

O

N

N

S

OO

N

N

S

HO OH

HO126 127128

NH2

NH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

P+

= 3-Cl-C6H4 34-(OCH3)2-C6H3

= C6H5 4-Cl 2NO2 345-C6H234-(OCH3)2-C6H3

125R = H 4-(OCH3) Ar = 34-(NO2)2-C6H3

H2N

ArN2 ArN2

ArN2ArN2

ArN2

NHC6H5

C6H5

H3C

H3CH3C

H3CH3C

SCH3

SCH2CN

SCH2CN

COCH3

COCH3

COCH3

CH3COO

CH3COO

CH3COO

CH3COO

OCOCH3OCOCH3

OCOCH3

OCOCH3

OH3C

= H 4-(OCH3) 4-NO2124 R

Ominus

R1

R2 R2

R1

R1

R2



CH3

CH3

CH3

CH3

CH3

CH3

CH3

C6H5

OCOCH3

OCOCH3

OH3C

OH3C

SH3C

H2N


H3COCO

H3COCO

H3COCH3

H3CH2CO

131 R = Cl OCH3 OH


135 R = CH3C6H11

N

N

N

ClCN NHHN

OO

OH

N

NCN

OH

R

129 130

FF

F

NH

NH

O

O O NH

N

HN

S

CNO

NH

NH

NH

X

RO

132 133

NH

HN

SR

O

NH

S

O

NH

NH

S

OCl

N

N

S

Cl O

136

138



2 CONHMe and SO

2NH2




NHN

N

S

NNN

NHN

N

S

NNN

Br NH

NH

O S

OR O

139 140

N

HN

O

O

R

NH

SOH

NN

S

O

Ar Ar

O

NN

S

SO

ArS Ar

OO

O

N

N

O

N143 144 145

NH

NH

S

NH

O

Cl

146 147

R

NH

NH

S

NH

O

ClR

N N

N

N

S

R

NN

O

O

Cl

SS

N O149

N

N

O

Et

CH3

CH3

CH3

CH3

H2N

H2NH2N

NH2

NH2NH2

C6H5

NO2

H5C2O

H3C

H3CH3CH3C


H5C6


= Br Cl142 R

= 5-OCH3 5NO2 5-Cl148 R



R1 R2







N

N

ClCN

SR

N

N

ClCN

ArSR

151

151 Ar Rabc

NH

HN

N

S

N

Cl

SH

O

153

N

N SH

Br

R

154

NH

HN

O

XO

NHNH

HN

O

O

X

NHNH

N

Ar

O

NHO

NNN

SH

O

R

154 Rabcdefghijk H

NH

HN

O

O

O

O

RNH

NH

R

X

O

NHNH

O

N

NH

NH

O

O

NN

160

CH3

CH3

CH3

CH3

H3C

H3C


C2H5C3H7

COCH3

4-OCH3

3-OCH3


2-NO2

4-N(CH3)26-furyl

=CH3 C2H5 CH3152 R









OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

CH3

CH3CH3

NH2

NH2NH2NH2

NH2NH2

H2N

O2N O2N O2N

H3CO

H3CO H3CO

H3CO

H3CO


NHNH

SO

ONN

O

O

N

N NN

161

162 163

OHO

NN

NN

OH

R

N

N

O

N N

N

O

NCl

165 166

167 168 169

NN

N

Cl

ClCl

Cl

NN

N

Cl

NN

N

Cl

Cl

170 171 172

= 2-NO2-C6H4 3-NO2-C6H4 4-OCH3-C6H4164 R



















O

N

N OH

O

N

N OH

HN

N

O

OHOO

173 174

HO

HN

N

O

O

HO

HN

N

O

O

HO

HN

N

O

OO

HO

HO

N

176177 178

179

HN

NOO

HO

HO

N

180

HN

NH

O

O R

180 Rabcd

N

HN

HO

O

O

HO

HO

181

N

HN

HO

O

O

HO F

HO

182

N

HN

HO

O

O

HO F

HO

183

CH3

NH2

NO2

CH(N3)CH2XOC6H5


C6H5


2-Pyridyl

C10H21 C10H21 C11H23

= Br I Cl175 X

H3C

H3C

H3C

H3C

H3C

H3CH3C

H3C

H3C



50of 401







NNN

N

( )n

N

N

Cl

RN

N

186

N

N

O

HN

N

N

NN

N

N

O

HN N

N

N

BrBr

N

N

N

O

HN

N

N

N

Br

N

187 188 189

N

NNN

O

N

N

Br

N

H

N

NNN

O

Br

N

R

H

190

191

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2NH2

H3CO OCH3

OCH3

OCH2CH3


184 n = 01



N

N NH

SO

ON N

R

NN

N

SN

NN

N

192 194

N

NOR

N

NOR

N

NOR

CH3CH3

CH3

CH3

NH2 NH2 NH2

H2N H2N H2N

NO2


193 R =OC2H5 OBu

196 R = C2H5 C3H7 197 R = CH3 C2H5

H3C

H3C






NH

NH

O

O

SR

NN

N

ClFe

198 199

H3C

H3C

CH3









6 Conclusion


Abbreviations



CH3

CH3

NH2

H2N

200 R = H COCH3

P(O)(OH)2 P(O)(OH)2

N

N

O

SO

ONH

NN

R

H

N

N

O

O

N

N

OH

O

O

201 202

H3C


N

N

O

N

NBr

N

O

N

N

O

N

N

Br

NNN

F

F

OHOOC

203 204

N

N

OR

F FS

N

N R

O O

P OHOOH

NH

N

O

S

207

N

HN

S

O

O

ClCl

208

N

NHO

OHOH

O

OH

209

N

NS

OHOH

O

OH

NH

NHOCl

210

N

HN

O

SClCl

211

N

NBr

212

N

NBr

Br

Br

213

CH3

CH3

CH3

NH2NH2

NH2

H3COH3CO

H3COH3CO

H3CO

H2N

H3C

H3C

OCH3

OCH3

OCH3OCH3

OCH3

OCH3

OCH3

OCH3

C2H5

205 R = H Me 206 R = H Me

COCH3

COCH3

CH2CH3

CH2Br






Acknowledgments


References




































































10158401015840



























































































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of












NN

Cl Cl

F

NH

NHHN

O

X NH Ar

N

N

COOH

81

N

N

NH

O

Br

82

N

N N N

NH

HNN

X

NN

NN

HO

OH

83

84 85

NH

HN

O

O

SO

O

NHN

N NHS

H

86

NH

HN

O

O

SO

O

NN O

CNH

87

NH

HN

O

O

SO

O

N

H

88

NH

HN

O

O

SO

O

NHN

S

NH N

89

N

N

Cl

Cl

F

R

NH

NHOO

N

N

O

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

H3C

CH3

CH3

CH3 NO2

NH2

NH2

NH2

H3CO

H2N

H2N

C2H5

C6H5

C6H5H5C6

90 R = 345-(OCH3)3 4-Cl 2-OCH3

80 X = O S








N

N NO

O

91

N

N N NH

92

N

N N

N

93

NH

N NH

N

OO NH

N NH

N

OO

94 95

N N

R

S

97

NH2

NH2

NH2

NH2

NH2

CH3

CH3

CH3

CH3

CH3CH3

H3C

H3C

H2NH2N

H2N

H2N

H2N

OCH3

CH2CH2N(CH3)2



HN

NHN

S

S

Cl

NN

S

Cl

N

NCN

NO

HO OH101 102 103 104

O

N NO

O

N NO

SHSH

NN

NHSO

ONH

NN

NNH

S

NHRNH

N N

O

105 106

CH3

CH3

CH3

NH2

NO2

H3C

H3CH3C

NHNH2

OCOCH3OCOCH3


N

N

SH

CH3

O

SN

N

S

O

S

O

N N

SHNHN

S

O

Cl

98 99 100



NN

NNH

HNHN Ar

ArAr

N

NN

R

NN

O

OH

O

S

CH3

NH2

SCH2Ph


H3C



















NHN

S

NN

Ar

N

NH

ON

N

NH

OHN

O

NH

N

S

N

112 113 114 115

NH

NH

SN

O

NH

NH

S

SN

O

116 117

NN

ONN

O O

NH

O

118

NH

NH

SH

O

NH NH

NH

O

NH

NH

HN

NS Ar NH

HN

O

NH

S

CN

S

119 120 121 122

NH

NH

O

N

OHN

S

R

NH

HN

O

NHS

CN

S

123

NH

NH

O

N

OHN

Ar

R

N

N

Cl

S

O

N

N

S

OO

N

N

S

HO OH

HO126 127128

NH2

NH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

P+

= 3-Cl-C6H4 34-(OCH3)2-C6H3

= C6H5 4-Cl 2NO2 345-C6H234-(OCH3)2-C6H3

125R = H 4-(OCH3) Ar = 34-(NO2)2-C6H3

H2N

ArN2 ArN2

ArN2ArN2

ArN2

NHC6H5

C6H5

H3C

H3CH3C

H3CH3C

SCH3

SCH2CN

SCH2CN

COCH3

COCH3

COCH3

CH3COO

CH3COO

CH3COO

CH3COO

OCOCH3OCOCH3

OCOCH3

OCOCH3

OH3C

= H 4-(OCH3) 4-NO2124 R

Ominus

R1

R2 R2

R1

R1

R2



CH3

CH3

CH3

CH3

CH3

CH3

CH3

C6H5

OCOCH3

OCOCH3

OH3C

OH3C

SH3C

H2N


H3COCO

H3COCO

H3COCH3

H3CH2CO

131 R = Cl OCH3 OH


135 R = CH3C6H11

N

N

N

ClCN NHHN

OO

OH

N

NCN

OH

R

129 130

FF

F

NH

NH

O

O O NH

N

HN

S

CNO

NH

NH

NH

X

RO

132 133

NH

HN

SR

O

NH

S

O

NH

NH

S

OCl

N

N

S

Cl O

136

138



2 CONHMe and SO

2NH2




NHN

N

S

NNN

NHN

N

S

NNN

Br NH

NH

O S

OR O

139 140

N

HN

O

O

R

NH

SOH

NN

S

O

Ar Ar

O

NN

S

SO

ArS Ar

OO

O

N

N

O

N143 144 145

NH

NH

S

NH

O

Cl

146 147

R

NH

NH

S

NH

O

ClR

N N

N

N

S

R

NN

O

O

Cl

SS

N O149

N

N

O

Et

CH3

CH3

CH3

CH3

H2N

H2NH2N

NH2

NH2NH2

C6H5

NO2

H5C2O

H3C

H3CH3CH3C


H5C6


= Br Cl142 R

= 5-OCH3 5NO2 5-Cl148 R



R1 R2







N

N

ClCN

SR

N

N

ClCN

ArSR

151

151 Ar Rabc

NH

HN

N

S

N

Cl

SH

O

153

N

N SH

Br

R

154

NH

HN

O

XO

NHNH

HN

O

O

X

NHNH

N

Ar

O

NHO

NNN

SH

O

R

154 Rabcdefghijk H

NH

HN

O

O

O

O

RNH

NH

R

X

O

NHNH

O

N

NH

NH

O

O

NN

160

CH3

CH3

CH3

CH3

H3C

H3C


C2H5C3H7

COCH3

4-OCH3

3-OCH3


2-NO2

4-N(CH3)26-furyl

=CH3 C2H5 CH3152 R









OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

CH3

CH3CH3

NH2

NH2NH2NH2

NH2NH2

H2N

O2N O2N O2N

H3CO

H3CO H3CO

H3CO

H3CO


NHNH

SO

ONN

O

O

N

N NN

161

162 163

OHO

NN

NN

OH

R

N

N

O

N N

N

O

NCl

165 166

167 168 169

NN

N

Cl

ClCl

Cl

NN

N

Cl

NN

N

Cl

Cl

170 171 172

= 2-NO2-C6H4 3-NO2-C6H4 4-OCH3-C6H4164 R



















O

N

N OH

O

N

N OH

HN

N

O

OHOO

173 174

HO

HN

N

O

O

HO

HN

N

O

O

HO

HN

N

O

OO

HO

HO

N

176177 178

179

HN

NOO

HO

HO

N

180

HN

NH

O

O R

180 Rabcd

N

HN

HO

O

O

HO

HO

181

N

HN

HO

O

O

HO F

HO

182

N

HN

HO

O

O

HO F

HO

183

CH3

NH2

NO2

CH(N3)CH2XOC6H5


C6H5


2-Pyridyl

C10H21 C10H21 C11H23

= Br I Cl175 X

H3C

H3C

H3C

H3C

H3C

H3CH3C

H3C

H3C



50of 401







NNN

N

( )n

N

N

Cl

RN

N

186

N

N

O

HN

N

N

NN

N

N

O

HN N

N

N

BrBr

N

N

N

O

HN

N

N

N

Br

N

187 188 189

N

NNN

O

N

N

Br

N

H

N

NNN

O

Br

N

R

H

190

191

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2NH2

H3CO OCH3

OCH3

OCH2CH3


184 n = 01



N

N NH

SO

ON N

R

NN

N

SN

NN

N

192 194

N

NOR

N

NOR

N

NOR

CH3CH3

CH3

CH3

NH2 NH2 NH2

H2N H2N H2N

NO2


193 R =OC2H5 OBu

196 R = C2H5 C3H7 197 R = CH3 C2H5

H3C

H3C






NH

NH

O

O

SR

NN

N

ClFe

198 199

H3C

H3C

CH3









6 Conclusion


Abbreviations



CH3

CH3

NH2

H2N

200 R = H COCH3

P(O)(OH)2 P(O)(OH)2

N

N

O

SO

ONH

NN

R

H

N

N

O

O

N

N

OH

O

O

201 202

H3C


N

N

O

N

NBr

N

O

N

N

O

N

N

Br

NNN

F

F

OHOOC

203 204

N

N

OR

F FS

N

N R

O O

P OHOOH

NH

N

O

S

207

N

HN

S

O

O

ClCl

208

N

NHO

OHOH

O

OH

209

N

NS

OHOH

O

OH

NH

NHOCl

210

N

HN

O

SClCl

211

N

NBr

212

N

NBr

Br

Br

213

CH3

CH3

CH3

NH2NH2

NH2

H3COH3CO

H3COH3CO

H3CO

H2N

H3C

H3C

OCH3

OCH3

OCH3OCH3

OCH3

OCH3

OCH3

OCH3

C2H5

205 R = H Me 206 R = H Me

COCH3

COCH3

CH2CH3

CH2Br






Acknowledgments


References




































































10158401015840



























































































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


N

N NO

O

91

N

N N NH

92

N

N N

N

93

NH

N NH

N

OO NH

N NH

N

OO

94 95

N N

R

S

97

NH2

NH2

NH2

NH2

NH2

CH3

CH3

CH3

CH3

CH3CH3

H3C

H3C

H2NH2N

H2N

H2N

H2N

OCH3

CH2CH2N(CH3)2



HN

NHN

S

S

Cl

NN

S

Cl

N

NCN

NO

HO OH101 102 103 104

O

N NO

O

N NO

SHSH

NN

NHSO

ONH

NN

NNH

S

NHRNH

N N

O

105 106

CH3

CH3

CH3

NH2

NO2

H3C

H3CH3C

NHNH2

OCOCH3OCOCH3


N

N

SH

CH3

O

SN

N

S

O

S

O

N N

SHNHN

S

O

Cl

98 99 100



NN

NNH

HNHN Ar

ArAr

N

NN

R

NN

O

OH

O

S

CH3

NH2

SCH2Ph


H3C



















NHN

S

NN

Ar

N

NH

ON

N

NH

OHN

O

NH

N

S

N

112 113 114 115

NH

NH

SN

O

NH

NH

S

SN

O

116 117

NN

ONN

O O

NH

O

118

NH

NH

SH

O

NH NH

NH

O

NH

NH

HN

NS Ar NH

HN

O

NH

S

CN

S

119 120 121 122

NH

NH

O

N

OHN

S

R

NH

HN

O

NHS

CN

S

123

NH

NH

O

N

OHN

Ar

R

N

N

Cl

S

O

N

N

S

OO

N

N

S

HO OH

HO126 127128

NH2

NH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

P+

= 3-Cl-C6H4 34-(OCH3)2-C6H3

= C6H5 4-Cl 2NO2 345-C6H234-(OCH3)2-C6H3

125R = H 4-(OCH3) Ar = 34-(NO2)2-C6H3

H2N

ArN2 ArN2

ArN2ArN2

ArN2

NHC6H5

C6H5

H3C

H3CH3C

H3CH3C

SCH3

SCH2CN

SCH2CN

COCH3

COCH3

COCH3

CH3COO

CH3COO

CH3COO

CH3COO

OCOCH3OCOCH3

OCOCH3

OCOCH3

OH3C

= H 4-(OCH3) 4-NO2124 R

Ominus

R1

R2 R2

R1

R1

R2



CH3

CH3

CH3

CH3

CH3

CH3

CH3

C6H5

OCOCH3

OCOCH3

OH3C

OH3C

SH3C

H2N


H3COCO

H3COCO

H3COCH3

H3CH2CO

131 R = Cl OCH3 OH


135 R = CH3C6H11

N

N

N

ClCN NHHN

OO

OH

N

NCN

OH

R

129 130

FF

F

NH

NH

O

O O NH

N

HN

S

CNO

NH

NH

NH

X

RO

132 133

NH

HN

SR

O

NH

S

O

NH

NH

S

OCl

N

N

S

Cl O

136

138



2 CONHMe and SO

2NH2




NHN

N

S

NNN

NHN

N

S

NNN

Br NH

NH

O S

OR O

139 140

N

HN

O

O

R

NH

SOH

NN

S

O

Ar Ar

O

NN

S

SO

ArS Ar

OO

O

N

N

O

N143 144 145

NH

NH

S

NH

O

Cl

146 147

R

NH

NH

S

NH

O

ClR

N N

N

N

S

R

NN

O

O

Cl

SS

N O149

N

N

O

Et

CH3

CH3

CH3

CH3

H2N

H2NH2N

NH2

NH2NH2

C6H5

NO2

H5C2O

H3C

H3CH3CH3C


H5C6


= Br Cl142 R

= 5-OCH3 5NO2 5-Cl148 R



R1 R2







N

N

ClCN

SR

N

N

ClCN

ArSR

151

151 Ar Rabc

NH

HN

N

S

N

Cl

SH

O

153

N

N SH

Br

R

154

NH

HN

O

XO

NHNH

HN

O

O

X

NHNH

N

Ar

O

NHO

NNN

SH

O

R

154 Rabcdefghijk H

NH

HN

O

O

O

O

RNH

NH

R

X

O

NHNH

O

N

NH

NH

O

O

NN

160

CH3

CH3

CH3

CH3

H3C

H3C


C2H5C3H7

COCH3

4-OCH3

3-OCH3


2-NO2

4-N(CH3)26-furyl

=CH3 C2H5 CH3152 R









OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

CH3

CH3CH3

NH2

NH2NH2NH2

NH2NH2

H2N

O2N O2N O2N

H3CO

H3CO H3CO

H3CO

H3CO


NHNH

SO

ONN

O

O

N

N NN

161

162 163

OHO

NN

NN

OH

R

N

N

O

N N

N

O

NCl

165 166

167 168 169

NN

N

Cl

ClCl

Cl

NN

N

Cl

NN

N

Cl

Cl

170 171 172

= 2-NO2-C6H4 3-NO2-C6H4 4-OCH3-C6H4164 R



















O

N

N OH

O

N

N OH

HN

N

O

OHOO

173 174

HO

HN

N

O

O

HO

HN

N

O

O

HO

HN

N

O

OO

HO

HO

N

176177 178

179

HN

NOO

HO

HO

N

180

HN

NH

O

O R

180 Rabcd

N

HN

HO

O

O

HO

HO

181

N

HN

HO

O

O

HO F

HO

182

N

HN

HO

O

O

HO F

HO

183

CH3

NH2

NO2

CH(N3)CH2XOC6H5


C6H5


2-Pyridyl

C10H21 C10H21 C11H23

= Br I Cl175 X

H3C

H3C

H3C

H3C

H3C

H3CH3C

H3C

H3C



50of 401







NNN

N

( )n

N

N

Cl

RN

N

186

N

N

O

HN

N

N

NN

N

N

O

HN N

N

N

BrBr

N

N

N

O

HN

N

N

N

Br

N

187 188 189

N

NNN

O

N

N

Br

N

H

N

NNN

O

Br

N

R

H

190

191

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2NH2

H3CO OCH3

OCH3

OCH2CH3


184 n = 01



N

N NH

SO

ON N

R

NN

N

SN

NN

N

192 194

N

NOR

N

NOR

N

NOR

CH3CH3

CH3

CH3

NH2 NH2 NH2

H2N H2N H2N

NO2


193 R =OC2H5 OBu

196 R = C2H5 C3H7 197 R = CH3 C2H5

H3C

H3C






NH

NH

O

O

SR

NN

N

ClFe

198 199

H3C

H3C

CH3









6 Conclusion


Abbreviations



CH3

CH3

NH2

H2N

200 R = H COCH3

P(O)(OH)2 P(O)(OH)2

N

N

O

SO

ONH

NN

R

H

N

N

O

O

N

N

OH

O

O

201 202

H3C


N

N

O

N

NBr

N

O

N

N

O

N

N

Br

NNN

F

F

OHOOC

203 204

N

N

OR

F FS

N

N R

O O

P OHOOH

NH

N

O

S

207

N

HN

S

O

O

ClCl

208

N

NHO

OHOH

O

OH

209

N

NS

OHOH

O

OH

NH

NHOCl

210

N

HN

O

SClCl

211

N

NBr

212

N

NBr

Br

Br

213

CH3

CH3

CH3

NH2NH2

NH2

H3COH3CO

H3COH3CO

H3CO

H2N

H3C

H3C

OCH3

OCH3

OCH3OCH3

OCH3

OCH3

OCH3

OCH3

C2H5

205 R = H Me 206 R = H Me

COCH3

COCH3

CH2CH3

CH2Br






Acknowledgments


References




































































10158401015840



























































































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


NN

NNH

HNHN Ar

ArAr

N

NN

R

NN

O

OH

O

S

CH3

NH2

SCH2Ph


H3C



















NHN

S

NN

Ar

N

NH

ON

N

NH

OHN

O

NH

N

S

N

112 113 114 115

NH

NH

SN

O

NH

NH

S

SN

O

116 117

NN

ONN

O O

NH

O

118

NH

NH

SH

O

NH NH

NH

O

NH

NH

HN

NS Ar NH

HN

O

NH

S

CN

S

119 120 121 122

NH

NH

O

N

OHN

S

R

NH

HN

O

NHS

CN

S

123

NH

NH

O

N

OHN

Ar

R

N

N

Cl

S

O

N

N

S

OO

N

N

S

HO OH

HO126 127128

NH2

NH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

P+

= 3-Cl-C6H4 34-(OCH3)2-C6H3

= C6H5 4-Cl 2NO2 345-C6H234-(OCH3)2-C6H3

125R = H 4-(OCH3) Ar = 34-(NO2)2-C6H3

H2N

ArN2 ArN2

ArN2ArN2

ArN2

NHC6H5

C6H5

H3C

H3CH3C

H3CH3C

SCH3

SCH2CN

SCH2CN

COCH3

COCH3

COCH3

CH3COO

CH3COO

CH3COO

CH3COO

OCOCH3OCOCH3

OCOCH3

OCOCH3

OH3C

= H 4-(OCH3) 4-NO2124 R

Ominus

R1

R2 R2

R1

R1

R2



CH3

CH3

CH3

CH3

CH3

CH3

CH3

C6H5

OCOCH3

OCOCH3

OH3C

OH3C

SH3C

H2N


H3COCO

H3COCO

H3COCH3

H3CH2CO

131 R = Cl OCH3 OH


135 R = CH3C6H11

N

N

N

ClCN NHHN

OO

OH

N

NCN

OH

R

129 130

FF

F

NH

NH

O

O O NH

N

HN

S

CNO

NH

NH

NH

X

RO

132 133

NH

HN

SR

O

NH

S

O

NH

NH

S

OCl

N

N

S

Cl O

136

138



2 CONHMe and SO

2NH2




NHN

N

S

NNN

NHN

N

S

NNN

Br NH

NH

O S

OR O

139 140

N

HN

O

O

R

NH

SOH

NN

S

O

Ar Ar

O

NN

S

SO

ArS Ar

OO

O

N

N

O

N143 144 145

NH

NH

S

NH

O

Cl

146 147

R

NH

NH

S

NH

O

ClR

N N

N

N

S

R

NN

O

O

Cl

SS

N O149

N

N

O

Et

CH3

CH3

CH3

CH3

H2N

H2NH2N

NH2

NH2NH2

C6H5

NO2

H5C2O

H3C

H3CH3CH3C


H5C6


= Br Cl142 R

= 5-OCH3 5NO2 5-Cl148 R



R1 R2







N

N

ClCN

SR

N

N

ClCN

ArSR

151

151 Ar Rabc

NH

HN

N

S

N

Cl

SH

O

153

N

N SH

Br

R

154

NH

HN

O

XO

NHNH

HN

O

O

X

NHNH

N

Ar

O

NHO

NNN

SH

O

R

154 Rabcdefghijk H

NH

HN

O

O

O

O

RNH

NH

R

X

O

NHNH

O

N

NH

NH

O

O

NN

160

CH3

CH3

CH3

CH3

H3C

H3C


C2H5C3H7

COCH3

4-OCH3

3-OCH3


2-NO2

4-N(CH3)26-furyl

=CH3 C2H5 CH3152 R









OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

CH3

CH3CH3

NH2

NH2NH2NH2

NH2NH2

H2N

O2N O2N O2N

H3CO

H3CO H3CO

H3CO

H3CO


NHNH

SO

ONN

O

O

N

N NN

161

162 163

OHO

NN

NN

OH

R

N

N

O

N N

N

O

NCl

165 166

167 168 169

NN

N

Cl

ClCl

Cl

NN

N

Cl

NN

N

Cl

Cl

170 171 172

= 2-NO2-C6H4 3-NO2-C6H4 4-OCH3-C6H4164 R



















O

N

N OH

O

N

N OH

HN

N

O

OHOO

173 174

HO

HN

N

O

O

HO

HN

N

O

O

HO

HN

N

O

OO

HO

HO

N

176177 178

179

HN

NOO

HO

HO

N

180

HN

NH

O

O R

180 Rabcd

N

HN

HO

O

O

HO

HO

181

N

HN

HO

O

O

HO F

HO

182

N

HN

HO

O

O

HO F

HO

183

CH3

NH2

NO2

CH(N3)CH2XOC6H5


C6H5


2-Pyridyl

C10H21 C10H21 C11H23

= Br I Cl175 X

H3C

H3C

H3C

H3C

H3C

H3CH3C

H3C

H3C



50of 401







NNN

N

( )n

N

N

Cl

RN

N

186

N

N

O

HN

N

N

NN

N

N

O

HN N

N

N

BrBr

N

N

N

O

HN

N

N

N

Br

N

187 188 189

N

NNN

O

N

N

Br

N

H

N

NNN

O

Br

N

R

H

190

191

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2NH2

H3CO OCH3

OCH3

OCH2CH3


184 n = 01



N

N NH

SO

ON N

R

NN

N

SN

NN

N

192 194

N

NOR

N

NOR

N

NOR

CH3CH3

CH3

CH3

NH2 NH2 NH2

H2N H2N H2N

NO2


193 R =OC2H5 OBu

196 R = C2H5 C3H7 197 R = CH3 C2H5

H3C

H3C






NH

NH

O

O

SR

NN

N

ClFe

198 199

H3C

H3C

CH3









6 Conclusion


Abbreviations



CH3

CH3

NH2

H2N

200 R = H COCH3

P(O)(OH)2 P(O)(OH)2

N

N

O

SO

ONH

NN

R

H

N

N

O

O

N

N

OH

O

O

201 202

H3C


N

N

O

N

NBr

N

O

N

N

O

N

N

Br

NNN

F

F

OHOOC

203 204

N

N

OR

F FS

N

N R

O O

P OHOOH

NH

N

O

S

207

N

HN

S

O

O

ClCl

208

N

NHO

OHOH

O

OH

209

N

NS

OHOH

O

OH

NH

NHOCl

210

N

HN

O

SClCl

211

N

NBr

212

N

NBr

Br

Br

213

CH3

CH3

CH3

NH2NH2

NH2

H3COH3CO

H3COH3CO

H3CO

H2N

H3C

H3C

OCH3

OCH3

OCH3OCH3

OCH3

OCH3

OCH3

OCH3

C2H5

205 R = H Me 206 R = H Me

COCH3

COCH3

CH2CH3

CH2Br






Acknowledgments


References




































































10158401015840



























































































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of










NHN

S

NN

Ar

N

NH

ON

N

NH

OHN

O

NH

N

S

N

112 113 114 115

NH

NH

SN

O

NH

NH

S

SN

O

116 117

NN

ONN

O O

NH

O

118

NH

NH

SH

O

NH NH

NH

O

NH

NH

HN

NS Ar NH

HN

O

NH

S

CN

S

119 120 121 122

NH

NH

O

N

OHN

S

R

NH

HN

O

NHS

CN

S

123

NH

NH

O

N

OHN

Ar

R

N

N

Cl

S

O

N

N

S

OO

N

N

S

HO OH

HO126 127128

NH2

NH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

P+

= 3-Cl-C6H4 34-(OCH3)2-C6H3

= C6H5 4-Cl 2NO2 345-C6H234-(OCH3)2-C6H3

125R = H 4-(OCH3) Ar = 34-(NO2)2-C6H3

H2N

ArN2 ArN2

ArN2ArN2

ArN2

NHC6H5

C6H5

H3C

H3CH3C

H3CH3C

SCH3

SCH2CN

SCH2CN

COCH3

COCH3

COCH3

CH3COO

CH3COO

CH3COO

CH3COO

OCOCH3OCOCH3

OCOCH3

OCOCH3

OH3C

= H 4-(OCH3) 4-NO2124 R

Ominus

R1

R2 R2

R1

R1

R2



CH3

CH3

CH3

CH3

CH3

CH3

CH3

C6H5

OCOCH3

OCOCH3

OH3C

OH3C

SH3C

H2N


H3COCO

H3COCO

H3COCH3

H3CH2CO

131 R = Cl OCH3 OH


135 R = CH3C6H11

N

N

N

ClCN NHHN

OO

OH

N

NCN

OH

R

129 130

FF

F

NH

NH

O

O O NH

N

HN

S

CNO

NH

NH

NH

X

RO

132 133

NH

HN

SR

O

NH

S

O

NH

NH

S

OCl

N

N

S

Cl O

136

138



2 CONHMe and SO

2NH2




NHN

N

S

NNN

NHN

N

S

NNN

Br NH

NH

O S

OR O

139 140

N

HN

O

O

R

NH

SOH

NN

S

O

Ar Ar

O

NN

S

SO

ArS Ar

OO

O

N

N

O

N143 144 145

NH

NH

S

NH

O

Cl

146 147

R

NH

NH

S

NH

O

ClR

N N

N

N

S

R

NN

O

O

Cl

SS

N O149

N

N

O

Et

CH3

CH3

CH3

CH3

H2N

H2NH2N

NH2

NH2NH2

C6H5

NO2

H5C2O

H3C

H3CH3CH3C


H5C6


= Br Cl142 R

= 5-OCH3 5NO2 5-Cl148 R



R1 R2







N

N

ClCN

SR

N

N

ClCN

ArSR

151

151 Ar Rabc

NH

HN

N

S

N

Cl

SH

O

153

N

N SH

Br

R

154

NH

HN

O

XO

NHNH

HN

O

O

X

NHNH

N

Ar

O

NHO

NNN

SH

O

R

154 Rabcdefghijk H

NH

HN

O

O

O

O

RNH

NH

R

X

O

NHNH

O

N

NH

NH

O

O

NN

160

CH3

CH3

CH3

CH3

H3C

H3C


C2H5C3H7

COCH3

4-OCH3

3-OCH3


2-NO2

4-N(CH3)26-furyl

=CH3 C2H5 CH3152 R









OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

CH3

CH3CH3

NH2

NH2NH2NH2

NH2NH2

H2N

O2N O2N O2N

H3CO

H3CO H3CO

H3CO

H3CO


NHNH

SO

ONN

O

O

N

N NN

161

162 163

OHO

NN

NN

OH

R

N

N

O

N N

N

O

NCl

165 166

167 168 169

NN

N

Cl

ClCl

Cl

NN

N

Cl

NN

N

Cl

Cl

170 171 172

= 2-NO2-C6H4 3-NO2-C6H4 4-OCH3-C6H4164 R



















O

N

N OH

O

N

N OH

HN

N

O

OHOO

173 174

HO

HN

N

O

O

HO

HN

N

O

O

HO

HN

N

O

OO

HO

HO

N

176177 178

179

HN

NOO

HO

HO

N

180

HN

NH

O

O R

180 Rabcd

N

HN

HO

O

O

HO

HO

181

N

HN

HO

O

O

HO F

HO

182

N

HN

HO

O

O

HO F

HO

183

CH3

NH2

NO2

CH(N3)CH2XOC6H5


C6H5


2-Pyridyl

C10H21 C10H21 C11H23

= Br I Cl175 X

H3C

H3C

H3C

H3C

H3C

H3CH3C

H3C

H3C



50of 401







NNN

N

( )n

N

N

Cl

RN

N

186

N

N

O

HN

N

N

NN

N

N

O

HN N

N

N

BrBr

N

N

N

O

HN

N

N

N

Br

N

187 188 189

N

NNN

O

N

N

Br

N

H

N

NNN

O

Br

N

R

H

190

191

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2NH2

H3CO OCH3

OCH3

OCH2CH3


184 n = 01



N

N NH

SO

ON N

R

NN

N

SN

NN

N

192 194

N

NOR

N

NOR

N

NOR

CH3CH3

CH3

CH3

NH2 NH2 NH2

H2N H2N H2N

NO2


193 R =OC2H5 OBu

196 R = C2H5 C3H7 197 R = CH3 C2H5

H3C

H3C






NH

NH

O

O

SR

NN

N

ClFe

198 199

H3C

H3C

CH3









6 Conclusion


Abbreviations



CH3

CH3

NH2

H2N

200 R = H COCH3

P(O)(OH)2 P(O)(OH)2

N

N

O

SO

ONH

NN

R

H

N

N

O

O

N

N

OH

O

O

201 202

H3C


N

N

O

N

NBr

N

O

N

N

O

N

N

Br

NNN

F

F

OHOOC

203 204

N

N

OR

F FS

N

N R

O O

P OHOOH

NH

N

O

S

207

N

HN

S

O

O

ClCl

208

N

NHO

OHOH

O

OH

209

N

NS

OHOH

O

OH

NH

NHOCl

210

N

HN

O

SClCl

211

N

NBr

212

N

NBr

Br

Br

213

CH3

CH3

CH3

NH2NH2

NH2

H3COH3CO

H3COH3CO

H3CO

H2N

H3C

H3C

OCH3

OCH3

OCH3OCH3

OCH3

OCH3

OCH3

OCH3

C2H5

205 R = H Me 206 R = H Me

COCH3

COCH3

CH2CH3

CH2Br






Acknowledgments


References




































































10158401015840



























































































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


CH3

CH3

CH3

CH3

CH3

CH3

CH3

C6H5

OCOCH3

OCOCH3

OH3C

OH3C

SH3C

H2N


H3COCO

H3COCO

H3COCH3

H3CH2CO

131 R = Cl OCH3 OH


135 R = CH3C6H11

N

N

N

ClCN NHHN

OO

OH

N

NCN

OH

R

129 130

FF

F

NH

NH

O

O O NH

N

HN

S

CNO

NH

NH

NH

X

RO

132 133

NH

HN

SR

O

NH

S

O

NH

NH

S

OCl

N

N

S

Cl O

136

138



2 CONHMe and SO

2NH2




NHN

N

S

NNN

NHN

N

S

NNN

Br NH

NH

O S

OR O

139 140

N

HN

O

O

R

NH

SOH

NN

S

O

Ar Ar

O

NN

S

SO

ArS Ar

OO

O

N

N

O

N143 144 145

NH

NH

S

NH

O

Cl

146 147

R

NH

NH

S

NH

O

ClR

N N

N

N

S

R

NN

O

O

Cl

SS

N O149

N

N

O

Et

CH3

CH3

CH3

CH3

H2N

H2NH2N

NH2

NH2NH2

C6H5

NO2

H5C2O

H3C

H3CH3CH3C


H5C6


= Br Cl142 R

= 5-OCH3 5NO2 5-Cl148 R



R1 R2







N

N

ClCN

SR

N

N

ClCN

ArSR

151

151 Ar Rabc

NH

HN

N

S

N

Cl

SH

O

153

N

N SH

Br

R

154

NH

HN

O

XO

NHNH

HN

O

O

X

NHNH

N

Ar

O

NHO

NNN

SH

O

R

154 Rabcdefghijk H

NH

HN

O

O

O

O

RNH

NH

R

X

O

NHNH

O

N

NH

NH

O

O

NN

160

CH3

CH3

CH3

CH3

H3C

H3C


C2H5C3H7

COCH3

4-OCH3

3-OCH3


2-NO2

4-N(CH3)26-furyl

=CH3 C2H5 CH3152 R









OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

CH3

CH3CH3

NH2

NH2NH2NH2

NH2NH2

H2N

O2N O2N O2N

H3CO

H3CO H3CO

H3CO

H3CO


NHNH

SO

ONN

O

O

N

N NN

161

162 163

OHO

NN

NN

OH

R

N

N

O

N N

N

O

NCl

165 166

167 168 169

NN

N

Cl

ClCl

Cl

NN

N

Cl

NN

N

Cl

Cl

170 171 172

= 2-NO2-C6H4 3-NO2-C6H4 4-OCH3-C6H4164 R



















O

N

N OH

O

N

N OH

HN

N

O

OHOO

173 174

HO

HN

N

O

O

HO

HN

N

O

O

HO

HN

N

O

OO

HO

HO

N

176177 178

179

HN

NOO

HO

HO

N

180

HN

NH

O

O R

180 Rabcd

N

HN

HO

O

O

HO

HO

181

N

HN

HO

O

O

HO F

HO

182

N

HN

HO

O

O

HO F

HO

183

CH3

NH2

NO2

CH(N3)CH2XOC6H5


C6H5


2-Pyridyl

C10H21 C10H21 C11H23

= Br I Cl175 X

H3C

H3C

H3C

H3C

H3C

H3CH3C

H3C

H3C



50of 401







NNN

N

( )n

N

N

Cl

RN

N

186

N

N

O

HN

N

N

NN

N

N

O

HN N

N

N

BrBr

N

N

N

O

HN

N

N

N

Br

N

187 188 189

N

NNN

O

N

N

Br

N

H

N

NNN

O

Br

N

R

H

190

191

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2NH2

H3CO OCH3

OCH3

OCH2CH3


184 n = 01



N

N NH

SO

ON N

R

NN

N

SN

NN

N

192 194

N

NOR

N

NOR

N

NOR

CH3CH3

CH3

CH3

NH2 NH2 NH2

H2N H2N H2N

NO2


193 R =OC2H5 OBu

196 R = C2H5 C3H7 197 R = CH3 C2H5

H3C

H3C






NH

NH

O

O

SR

NN

N

ClFe

198 199

H3C

H3C

CH3









6 Conclusion


Abbreviations



CH3

CH3

NH2

H2N

200 R = H COCH3

P(O)(OH)2 P(O)(OH)2

N

N

O

SO

ONH

NN

R

H

N

N

O

O

N

N

OH

O

O

201 202

H3C


N

N

O

N

NBr

N

O

N

N

O

N

N

Br

NNN

F

F

OHOOC

203 204

N

N

OR

F FS

N

N R

O O

P OHOOH

NH

N

O

S

207

N

HN

S

O

O

ClCl

208

N

NHO

OHOH

O

OH

209

N

NS

OHOH

O

OH

NH

NHOCl

210

N

HN

O

SClCl

211

N

NBr

212

N

NBr

Br

Br

213

CH3

CH3

CH3

NH2NH2

NH2

H3COH3CO

H3COH3CO

H3CO

H2N

H3C

H3C

OCH3

OCH3

OCH3OCH3

OCH3

OCH3

OCH3

OCH3

C2H5

205 R = H Me 206 R = H Me

COCH3

COCH3

CH2CH3

CH2Br






Acknowledgments


References




































































10158401015840



























































































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


NHN

N

S

NNN

NHN

N

S

NNN

Br NH

NH

O S

OR O

139 140

N

HN

O

O

R

NH

SOH

NN

S

O

Ar Ar

O

NN

S

SO

ArS Ar

OO

O

N

N

O

N143 144 145

NH

NH

S

NH

O

Cl

146 147

R

NH

NH

S

NH

O

ClR

N N

N

N

S

R

NN

O

O

Cl

SS

N O149

N

N

O

Et

CH3

CH3

CH3

CH3

H2N

H2NH2N

NH2

NH2NH2

C6H5

NO2

H5C2O

H3C

H3CH3CH3C


H5C6


= Br Cl142 R

= 5-OCH3 5NO2 5-Cl148 R



R1 R2







N

N

ClCN

SR

N

N

ClCN

ArSR

151

151 Ar Rabc

NH

HN

N

S

N

Cl

SH

O

153

N

N SH

Br

R

154

NH

HN

O

XO

NHNH

HN

O

O

X

NHNH

N

Ar

O

NHO

NNN

SH

O

R

154 Rabcdefghijk H

NH

HN

O

O

O

O

RNH

NH

R

X

O

NHNH

O

N

NH

NH

O

O

NN

160

CH3

CH3

CH3

CH3

H3C

H3C


C2H5C3H7

COCH3

4-OCH3

3-OCH3


2-NO2

4-N(CH3)26-furyl

=CH3 C2H5 CH3152 R









OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

CH3

CH3CH3

NH2

NH2NH2NH2

NH2NH2

H2N

O2N O2N O2N

H3CO

H3CO H3CO

H3CO

H3CO


NHNH

SO

ONN

O

O

N

N NN

161

162 163

OHO

NN

NN

OH

R

N

N

O

N N

N

O

NCl

165 166

167 168 169

NN

N

Cl

ClCl

Cl

NN

N

Cl

NN

N

Cl

Cl

170 171 172

= 2-NO2-C6H4 3-NO2-C6H4 4-OCH3-C6H4164 R



















O

N

N OH

O

N

N OH

HN

N

O

OHOO

173 174

HO

HN

N

O

O

HO

HN

N

O

O

HO

HN

N

O

OO

HO

HO

N

176177 178

179

HN

NOO

HO

HO

N

180

HN

NH

O

O R

180 Rabcd

N

HN

HO

O

O

HO

HO

181

N

HN

HO

O

O

HO F

HO

182

N

HN

HO

O

O

HO F

HO

183

CH3

NH2

NO2

CH(N3)CH2XOC6H5


C6H5


2-Pyridyl

C10H21 C10H21 C11H23

= Br I Cl175 X

H3C

H3C

H3C

H3C

H3C

H3CH3C

H3C

H3C



50of 401







NNN

N

( )n

N

N

Cl

RN

N

186

N

N

O

HN

N

N

NN

N

N

O

HN N

N

N

BrBr

N

N

N

O

HN

N

N

N

Br

N

187 188 189

N

NNN

O

N

N

Br

N

H

N

NNN

O

Br

N

R

H

190

191

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2NH2

H3CO OCH3

OCH3

OCH2CH3


184 n = 01



N

N NH

SO

ON N

R

NN

N

SN

NN

N

192 194

N

NOR

N

NOR

N

NOR

CH3CH3

CH3

CH3

NH2 NH2 NH2

H2N H2N H2N

NO2


193 R =OC2H5 OBu

196 R = C2H5 C3H7 197 R = CH3 C2H5

H3C

H3C






NH

NH

O

O

SR

NN

N

ClFe

198 199

H3C

H3C

CH3









6 Conclusion


Abbreviations



CH3

CH3

NH2

H2N

200 R = H COCH3

P(O)(OH)2 P(O)(OH)2

N

N

O

SO

ONH

NN

R

H

N

N

O

O

N

N

OH

O

O

201 202

H3C


N

N

O

N

NBr

N

O

N

N

O

N

N

Br

NNN

F

F

OHOOC

203 204

N

N

OR

F FS

N

N R

O O

P OHOOH

NH

N

O

S

207

N

HN

S

O

O

ClCl

208

N

NHO

OHOH

O

OH

209

N

NS

OHOH

O

OH

NH

NHOCl

210

N

HN

O

SClCl

211

N

NBr

212

N

NBr

Br

Br

213

CH3

CH3

CH3

NH2NH2

NH2

H3COH3CO

H3COH3CO

H3CO

H2N

H3C

H3C

OCH3

OCH3

OCH3OCH3

OCH3

OCH3

OCH3

OCH3

C2H5

205 R = H Me 206 R = H Me

COCH3

COCH3

CH2CH3

CH2Br






Acknowledgments


References




































































10158401015840



























































































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


N

N

ClCN

SR

N

N

ClCN

ArSR

151

151 Ar Rabc

NH

HN

N

S

N

Cl

SH

O

153

N

N SH

Br

R

154

NH

HN

O

XO

NHNH

HN

O

O

X

NHNH

N

Ar

O

NHO

NNN

SH

O

R

154 Rabcdefghijk H

NH

HN

O

O

O

O

RNH

NH

R

X

O

NHNH

O

N

NH

NH

O

O

NN

160

CH3

CH3

CH3

CH3

H3C

H3C


C2H5C3H7

COCH3

4-OCH3

3-OCH3


2-NO2

4-N(CH3)26-furyl

=CH3 C2H5 CH3152 R









OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

CH3

CH3CH3

NH2

NH2NH2NH2

NH2NH2

H2N

O2N O2N O2N

H3CO

H3CO H3CO

H3CO

H3CO


NHNH

SO

ONN

O

O

N

N NN

161

162 163

OHO

NN

NN

OH

R

N

N

O

N N

N

O

NCl

165 166

167 168 169

NN

N

Cl

ClCl

Cl

NN

N

Cl

NN

N

Cl

Cl

170 171 172

= 2-NO2-C6H4 3-NO2-C6H4 4-OCH3-C6H4164 R



















O

N

N OH

O

N

N OH

HN

N

O

OHOO

173 174

HO

HN

N

O

O

HO

HN

N

O

O

HO

HN

N

O

OO

HO

HO

N

176177 178

179

HN

NOO

HO

HO

N

180

HN

NH

O

O R

180 Rabcd

N

HN

HO

O

O

HO

HO

181

N

HN

HO

O

O

HO F

HO

182

N

HN

HO

O

O

HO F

HO

183

CH3

NH2

NO2

CH(N3)CH2XOC6H5


C6H5


2-Pyridyl

C10H21 C10H21 C11H23

= Br I Cl175 X

H3C

H3C

H3C

H3C

H3C

H3CH3C

H3C

H3C



50of 401







NNN

N

( )n

N

N

Cl

RN

N

186

N

N

O

HN

N

N

NN

N

N

O

HN N

N

N

BrBr

N

N

N

O

HN

N

N

N

Br

N

187 188 189

N

NNN

O

N

N

Br

N

H

N

NNN

O

Br

N

R

H

190

191

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2NH2

H3CO OCH3

OCH3

OCH2CH3


184 n = 01



N

N NH

SO

ON N

R

NN

N

SN

NN

N

192 194

N

NOR

N

NOR

N

NOR

CH3CH3

CH3

CH3

NH2 NH2 NH2

H2N H2N H2N

NO2


193 R =OC2H5 OBu

196 R = C2H5 C3H7 197 R = CH3 C2H5

H3C

H3C






NH

NH

O

O

SR

NN

N

ClFe

198 199

H3C

H3C

CH3









6 Conclusion


Abbreviations



CH3

CH3

NH2

H2N

200 R = H COCH3

P(O)(OH)2 P(O)(OH)2

N

N

O

SO

ONH

NN

R

H

N

N

O

O

N

N

OH

O

O

201 202

H3C


N

N

O

N

NBr

N

O

N

N

O

N

N

Br

NNN

F

F

OHOOC

203 204

N

N

OR

F FS

N

N R

O O

P OHOOH

NH

N

O

S

207

N

HN

S

O

O

ClCl

208

N

NHO

OHOH

O

OH

209

N

NS

OHOH

O

OH

NH

NHOCl

210

N

HN

O

SClCl

211

N

NBr

212

N

NBr

Br

Br

213

CH3

CH3

CH3

NH2NH2

NH2

H3COH3CO

H3COH3CO

H3CO

H2N

H3C

H3C

OCH3

OCH3

OCH3OCH3

OCH3

OCH3

OCH3

OCH3

C2H5

205 R = H Me 206 R = H Me

COCH3

COCH3

CH2CH3

CH2Br






Acknowledgments


References




































































10158401015840



























































































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


OCH3

OCH3

OCH3

OCH3

OCH3OCH3

OCH3

CH3

CH3CH3

NH2

NH2NH2NH2

NH2NH2

H2N

O2N O2N O2N

H3CO

H3CO H3CO

H3CO

H3CO


NHNH

SO

ONN

O

O

N

N NN

161

162 163

OHO

NN

NN

OH

R

N

N

O

N N

N

O

NCl

165 166

167 168 169

NN

N

Cl

ClCl

Cl

NN

N

Cl

NN

N

Cl

Cl

170 171 172

= 2-NO2-C6H4 3-NO2-C6H4 4-OCH3-C6H4164 R



















O

N

N OH

O

N

N OH

HN

N

O

OHOO

173 174

HO

HN

N

O

O

HO

HN

N

O

O

HO

HN

N

O

OO

HO

HO

N

176177 178

179

HN

NOO

HO

HO

N

180

HN

NH

O

O R

180 Rabcd

N

HN

HO

O

O

HO

HO

181

N

HN

HO

O

O

HO F

HO

182

N

HN

HO

O

O

HO F

HO

183

CH3

NH2

NO2

CH(N3)CH2XOC6H5


C6H5


2-Pyridyl

C10H21 C10H21 C11H23

= Br I Cl175 X

H3C

H3C

H3C

H3C

H3C

H3CH3C

H3C

H3C



50of 401







NNN

N

( )n

N

N

Cl

RN

N

186

N

N

O

HN

N

N

NN

N

N

O

HN N

N

N

BrBr

N

N

N

O

HN

N

N

N

Br

N

187 188 189

N

NNN

O

N

N

Br

N

H

N

NNN

O

Br

N

R

H

190

191

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2NH2

H3CO OCH3

OCH3

OCH2CH3


184 n = 01



N

N NH

SO

ON N

R

NN

N

SN

NN

N

192 194

N

NOR

N

NOR

N

NOR

CH3CH3

CH3

CH3

NH2 NH2 NH2

H2N H2N H2N

NO2


193 R =OC2H5 OBu

196 R = C2H5 C3H7 197 R = CH3 C2H5

H3C

H3C






NH

NH

O

O

SR

NN

N

ClFe

198 199

H3C

H3C

CH3









6 Conclusion


Abbreviations



CH3

CH3

NH2

H2N

200 R = H COCH3

P(O)(OH)2 P(O)(OH)2

N

N

O

SO

ONH

NN

R

H

N

N

O

O

N

N

OH

O

O

201 202

H3C


N

N

O

N

NBr

N

O

N

N

O

N

N

Br

NNN

F

F

OHOOC

203 204

N

N

OR

F FS

N

N R

O O

P OHOOH

NH

N

O

S

207

N

HN

S

O

O

ClCl

208

N

NHO

OHOH

O

OH

209

N

NS

OHOH

O

OH

NH

NHOCl

210

N

HN

O

SClCl

211

N

NBr

212

N

NBr

Br

Br

213

CH3

CH3

CH3

NH2NH2

NH2

H3COH3CO

H3COH3CO

H3CO

H2N

H3C

H3C

OCH3

OCH3

OCH3OCH3

OCH3

OCH3

OCH3

OCH3

C2H5

205 R = H Me 206 R = H Me

COCH3

COCH3

CH2CH3

CH2Br






Acknowledgments


References




































































10158401015840



























































































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of













O

N

N OH

O

N

N OH

HN

N

O

OHOO

173 174

HO

HN

N

O

O

HO

HN

N

O

O

HO

HN

N

O

OO

HO

HO

N

176177 178

179

HN

NOO

HO

HO

N

180

HN

NH

O

O R

180 Rabcd

N

HN

HO

O

O

HO

HO

181

N

HN

HO

O

O

HO F

HO

182

N

HN

HO

O

O

HO F

HO

183

CH3

NH2

NO2

CH(N3)CH2XOC6H5


C6H5


2-Pyridyl

C10H21 C10H21 C11H23

= Br I Cl175 X

H3C

H3C

H3C

H3C

H3C

H3CH3C

H3C

H3C



50of 401







NNN

N

( )n

N

N

Cl

RN

N

186

N

N

O

HN

N

N

NN

N

N

O

HN N

N

N

BrBr

N

N

N

O

HN

N

N

N

Br

N

187 188 189

N

NNN

O

N

N

Br

N

H

N

NNN

O

Br

N

R

H

190

191

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

NH2NH2

H3CO OCH3

OCH3

OCH2CH3


184 n = 01



N

N NH

SO

ON N

R

NN

N

SN

NN

N

192 194

N

NOR

N

NOR

N

NOR

CH3CH3

CH3

CH3

NH2 NH2 NH2

H2N H2N H2N

NO2


193 R =OC2H5 OBu

196 R = C2H5 C3H7 197 R = CH3 C2H5

H3C

H3C






NH

NH

O

O

SR

NN

N

ClFe

198 199

H3C

H3C

CH3









6 Conclusion


Abbreviations



CH3

CH3

NH2

H2N

200 R = H COCH3

P(O)(OH)2 P(O)(OH)2

N

N

O

SO

ONH

NN

R

H

N

N

O

O

N

N

OH

O

O

201 202

H3C


N

N

O

N

NBr

N

O

N

N

O

N

N

Br

NNN

F

F

OHOOC

203 204

N

N

OR

F FS

N

N R

O O

P OHOOH

NH

N

O

S

207

N

HN

S

O

O

ClCl

208

N

NHO

OHOH

O

OH

209

N

NS

OHOH

O

OH

NH

NHOCl

210

N

HN

O

SClCl

211

N

NBr

212

N

NBr

Br

Br

213

CH3

CH3

CH3

NH2NH2

NH2

H3COH3CO

H3COH3CO

H3CO

H2N

H3C

H3C

OCH3

OCH3

OCH3OCH3

OCH3

OCH3

OCH3

OCH3

C2H5

205 R = H Me 206 R = H Me

COCH3

COCH3

CH2CH3

CH2Br






Acknowledgments


References




































































10158401015840



























































































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of

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