curs 8
DESCRIPTION
ch farmTRANSCRIPT
1
• PF: FANSIDAR – cp. continând 500 mg sulfadoxina si 25 mg pirimetamina.
SULFAMIDE PIRAZINICE
SULFAMETOXIPIRAZINA
SULFAMETOXIPIRAZINUM (DCI)NH2
SO2 NHN
NH3CO
2-sulfanilamido-3-metoxi-pirazina
• Sinonime: SULFALEN, Sulfametopirazina.
• PF: LONGUM –cp.;
KELFIZINA.
2
SULFACLOZINA
SULFACLOZINUM (DCI)NH2
SO2 NHN
N
Cl
2-sulfanilamido-6-cloro-pirazina
• Sinonim: Sulfacloropirazina.
• PF: ESB3 – pulbere de uz vet.
SULFAQUINOXALINA
SULFAQUINOXALINUM (DCI)
NH2
SO2 NH
N
N
2-sulfanilamido-chinoxalina
Sinonim: Sulfabenzpirazina.
3
SULFAMIDE PIRIDAZINICE
SULFAMETOXIPIRIDAZINA
SULFAMETHOXYPYRIDAZINUM (DCI)
NH2
SO2 NHN N
OCH3
3-sulfanilamido-6-metoxi-piridazina
• preparare: prin reactia sulfanilamidei cu 3,6-dicloro-piridazina:
4
NH2
SO2 NHN N
OCH3
NH2
SO2 NH2
+
N NClCl
- HCl
NH2
SO2 NHN N
Cl
NaOCH3
- NaCl
• 3,6-dicloro-piridazina se obtine din anhidrida maleica si hidrazina:
HC
C
C
C
O
O
OH
+NH2
NH2
HC CO
NH
HC CO
NH
3,6-diceto-tetrahidro-piridazina
HC CN
OH
HC CN
OH
3,6-dihidroxi- piridazina
POCl3HC C
N
Cl
HC CN
Cl3,6-dicloro- piridazina
5
SULFACLORPIRIDAZINA
SULFACHLORPYRIDAZINUM (DCI)
NH2
SO2 NH
N N
Cl
3-sulfanilamido-6-cloro-piridazina
SULFAMIDE PIRIDINICE
SULFAPIRIDINA
SULFAPYRIDINUM (DCI)
NH2
SO2 NH
N
2-sulfanilamido-piridina
• PF: DAGENAN – cp.
6
SULFAMIDE N1-SUBSTITUITE, N4-ACILATE
FTALILSULFATIAZOL
PHTALYLSULFATHIAZOLUM (DCI)
NH
SO2 NH
C
O
HOOC
N
S
2-(N4-ftaloil)-sulfanilamido-tiazol
• Sinonim: Ftalazol.
• preparare: pornind de la anilina si anhidrida ftalica:
7
NH2
anilina
HOSO2Cl+
+ HOH
NH
SO2 NH
C
O
HOOC
N
S
C
C
O
O
O
anhidrida ftalica
+- HOH
C
C
O
O
N
N SO2Cl
C
C
O
O
N
SH2N
+
- HCl
C
C
O
O
N SO2NH
N
S
8
• PF: FTALILSULFATIAZOL –cp. 500 mg;
SUCCINILSULFATIAZOL
SUCCYNYLSULFATHIAZOLUM (DCI)
N
S
NH
SO2 NH
C
O
CH2CH2 COOH
2-(N4-succinil)-sulfanilamido-tiazol
9
AZODERIVATI DE TIP ANALOG SULFAMIDELOR N1-SUBSTITUITE, N4-ACILATE
SULFASALAZINA
SULFASALAZINUM (DCI)N
SO2 NHN
N OH
COOH
Acid 4-hidroxi-4’-(2-piridil sulfamoil)-azobenzen-3-carboxilic
• Sinonim: Salazosulfapiridina.
• preparare: tratarea CAS-ului cu 2-amino-piridina:
10
NH
SO2
C
O
CH3
Cl
- HCl
+
NH
SO2
C
O
CH3
NHN
+H2NN
HOH
- CH3COOH
NH2
SO2 NHN
+ NaNO2
+ 2 HCl
- NaCl- 2 HOH
N
SO2 NHN
N]+Cl
- OH
COOH
+ N
SO2 NHN
N OH
COOH
• 2-Amino-piridina se obtine prin reactia Cicibabin, din piridina si amidura de sodiu:
N
+ NaNH2
N NHNa
+ HOH
- NaOHN NH2
• PF: SALAZOPYRIN – cp 500 mg
AZULFIDINE
11
SULFAMIDE CU STRUCTURI DIVERSE
MAFENID
MAFENIDUM (DCI)
CH2
SO2 NH2
NH2
p-aminometil-benzensulfonamida
Sinonim: Homosulfanilamida.
CH2 NHCOCH3
SO2 NH2
CH2 NHCOCH3CH2 ClCH3
CH2
SO2 NH2
NH2
CH3COOH-
HOH
- HOH
HOSO2Cl+
acetilbenzilaminaclorura de benzil
- HCl
acetamida
H2N COCH3+
C150o
luminaCl2+
toluen
NH3+
- HCl
12
• PF: SULFAMYLON – crema.
ANTIMICOBACTERIENE
ANTITUBERCULOASE (TUBERCULOSTATICE)
ACID p-AMINOSALICILIC
ACIDUM AMINOSALICYLICUM (DCI)
COOH
OH
NH2
Acid 4-amino-2-hidroxibenzoic
• Sinonim: PAS
• preparare: prin sulfonarea p-nitrotoluenului:
13
COOH
OH
NH2
CH3
NO2
H2SO4 conc.
CH3
NO2
SO3H
acid 2-metil-5-nitro- benzensulfonic
KMnO4/H2SO4
COOH
NO2
SO3H3H2
(Zn + HCl)
COOH
NH2
SO3HKOH
300 oC
• PF: PASER – pachet cu 4 g granule
IZONIAZIDA
ISONIAZIDUM (DCI, FR X)
N
CO NH NH2
Hidrazida acidului 4-piridincarboxilic
• Sinonim: HIN
14
• preparare: prin oxidarea -picolinei:
N
CO NH NH2
N
CH3
KMnO4/H2SO4
N
COOH
CH3OH+
H2SO4 N
COOCH3
H2N NH2. H2O
- CH3OH
• PF: RIFAMPICINA ŞI IZONIAZIDA – capsule 300 mg rifampicina si 150 mg izoniazida.
PASINIAZIDA
PASINIAZIDUM (DCI)N
CO NH NH3+
COO-
NH2
OH.
p-aminosalicilat de izonicotinoilhidrazida
15
IZONICOTINOILHIDRAZONE
FTIVAZIDA
FTIVAZIDUM (DCI)
N
CO NH N CH OH
OCH3
Vanilidenhidrazida acidului izonicotinic
• preparare: condensarea HIN-ului cu vanilina (4-hidroxi-3-metoxi-benzaldehida):
N
CO NH N CH OH
OCH3
N
CO NH NH2
OHC OH
OCH3
+
16
CROTONIAZIDA
CROTONIAZIDUM (DCI)
N
CO NH N CH CH CH CH3
2-butenilidenhidrazida acidului izonicotinic
• preparare: condensarea HIN-ului cu aldehida crotonica:
N
CO NH NH2
N
CO NH N CH CH CH CH3
OHC CH CH CH3+
17
METAZIDA
METAZIDUM (DCI)
N
CO NH NH CH2 NH NH CO
N
2,2’-metilendihidrazida acidului izonicotinic
• preparare: condensarea a 2 moli de HIN cu formaldehida:
N
CO NH NH2
+
N
CO NH NH CH2 NH NH CO
N
2 CH2O
METANIAZIDA
METHANIAZIDUM (DCI)
N
CO NH NH CH2 SO3H
izoniazid metansulfonat
18
DERIVAŢI TIOAMIDICI AI ACIDULUI IZONICOTINIC
ETIONAMIDA
ETHIONAMIDUM (DCI) (FR X)
N
CS
NH2
C2H5
2-etil-izonicotin-tioamida
Preparare: oxidarea cu perhidrol a 2-etil-piridinei:
N
CS
NH2
C2H5
N C2H5
+ H2O2
CH3COOHN C2H5
O
+HNO3
H2SO4N C2H5
NO2
Fe/H2SO4
N C2H5
NH2
CuBr
N C2H5
Br
CuCN
N C2H5
CN
N(CH2CH2OH)3
H2S
19
• PF: TRECATOR – cp 250 mg.
PROTIONAMIDA
PROTIONAMIDUM (DCI)
N
CS
NH2
CH2 CH2 CH3
2-propil-tio-izonicotinamida
• PF: PROTIONAMIDA –cp. 250 mg
DERIVAŢI AI PIRAZINEI
PIRAZINAMIDA
PYRAZINAMIDUM (DCI) N
NC
O
NH21 2
34
Amida acidului pirazin-2-carboxilic
20
• preparare: condensarea o-fenilen-diaminei cu glioxalul:
N
NC
O
NH2
H2N
H2N
+HC O
C OH -2 HOHN
N
chinoxalina
+ KMnO4
NaOHN
N COOH
COOH
(CH3CO)2O
N
N C
C
O
O
OCH3OH
N
N COOCH3
COOH- CO2
N
N COOCH3
NH3
• PF: RIFATER – cp (120 mg rifampicina, 50 mg izoniazida si 300 mg pirazinamida).
21
MORFAZINAMIDA
MORPHAZINAMIDUM (DCI)N
NC
O
NH CH2 N O
N-(morfolinometil)-pirazincarboxamida
• Sinonim: Morinamida
• preparare: pirazinamida, formaldehida si morfolina:
N
NC
O
NH CH2 N O
N
NC
O
NH2 + CH2O + N OH- HOH
DERIVAŢI DE TIOUREE
TIOCARLID
TIOCARLIDUM (DCI)
NH
OCH2CH2CHCH3
CH3
C
S
NH
OCH2CH2CHCH3
CH3
4,4'-Bis(izopentiloxi)-tiocarbanilida
22
• Sinonim: izoxil.OH
NH2
(CH3CO)2O+
OH
NH CO CH3
p-acetilaminofenol
Br CH2CH2CHCH3
CH3
+
- CH3COOH
+ HOH
CH2CH2CHCH3
CH3
O
NH CO CH3
CH2CH2CHCH3
CH3
O
NH2
p-izoamiloxi- anilina
CH2CH2CHCH3
CH3
O
NH2
2
CS2
H2S-
+
NH
OCH2CH2CHCH3
CH3
C
S
NH
OCH2CH2CHCH3
CH3
p-amino-fenol
bromura de izoamil
23
ETOXID
AETHOXIDUM (DCI) H5C2O NH C NH
S
OC2H5
4,4’-bis-etoxi-tiocarbanilida
• preparare:
H5C2O NH C NH
S
OC2H5H5C2O NH2. HCl2
+ NH4SCN
- NH4Cl
fenetidina
H5C2O NH C NH
S
OC2H5H5C2O NH22+ CS2
- H2S
Sau
fenetidina
BUTOMELID
BUTOMELIDUM (DCI)N NH C NH
S
OC4H9NH3C
4-(n-butoxi)-4'(4''-metilpiperazino-1'')tiocarbanilida
24
TIOSEMICARBAZONELE ALDEHIDELOR AROMATICE
TIOACETAZONA
THIOACETAZONUM (DCI)
CH
NH CO CH3
N NH C
S
NH2
N-4-(carbamo-tioilhidrazin-iliden) metilfenilacetamida
HIDROXIALCHILDIAMINE
ETAMBUTOL
ETAMBUTOLUM (DCI) (FR X)
HO CH2
CH
CH2
CH3
NH CH2CH2 NH
CH2
CH
CH2
CH3
OH
2-2-(1-hidroxibutan-2-ilamino)etilaminobutan-1-ol
25
HO CH2
CH
CH2
CH3
NH CH2CH2 NH
CH2
CH
CH2
CH3
OH
CH2
CH2
Cl
Cl+ 2
CH2
CH
CH2
CH3
OH
NH2
dicloretan 2-amino-1-butanol
CH2
CH2
CH3
NO2
CH2
CH
CH2
CH3
OH
NO2+ CH2O
NaHCO3
CH2
CH
CH2
CH3
OH
NH2H2
1-nitropropan formaldehida
ANTILEPROASE
DIAFENILSULFONA
DIAPHENYLSULFONUM (DCI) SH2N
O
O
NH2
4,4’-diaminodifenil-sulfona
26
• Sinonim: Dapsona• preparare:
SH2N
O
O
NH2
ClO2NNa2S
NO2SO2N
SO2N S NO2
oxidare
SO2N
O
O
NO2
red.
p-clor-nitrobenzen
p,p’-dinitro-difenil-disulfura
p,p’-dinitro-difenil-sulfura
PF: DAPSONE – cp. 25 mg si 100 mg;
DISULONE – cp. 100 mg.
27
CLOFAZIMINA
CLOFAZIMINUM (DCI)
N
N
N
NH Cl
CH(CH3)2
Cl
N-5-bis(4-clorofenil)-3,5-dihidro-3-(1-metiletil)imino-2-fenazinamina
• PF: LAMPRENE – capsule a 50 mg clofazimina.
ALDESULFONA
ALDESULFONUM (DCI)Na2OSH2C NH SO2 NH CH2SO2Na
Sarea de sodiu a acidului sulfonil bis (1,4-fenilenimino) bis-metansulfonic
28
TIAMBUTOSINA
THIAMBUTOSINUM (DCI) O NHH9C4 C
S
NH NCH3
CH3
N-(4-n-butoxifenil)-N’-(4-dimetilaminofenil)tiouree
ANTIMALARICE
se clasifica in:
• antimalarice naturale (alcaloizi cu nucleu
chinolinic –
chinina si chinidina)
• antimalarice de sinteza:
-derivati de 8-aminochinolina;
-derivati de 4-aminochinolina;
-alti derivati de chinolina;
-derivati acridinici;
-derivati biguanidici;
-derivati pirimidinici.
29
ANTIMALARICE NATURALE
ALCALOIZI CU NUCLEU CHINOLINIC
CHININA
QUININUM (DCI)
N
H3CO
CH
OH
N
CH CH2} nucleu chinuclidinic
} nucleu chinolinic
2-etenil-4-azabiciclos2.2.2toct-5-il)- (6-metoxichinolin-4-il)-metanol
ANTIMALARICE DE SINTEZĂ
DERIVAŢI DE 8-AMINOCHINOLINĂ
PAMACHINA
PAMAQUINUM (DCI) N
H3CO
NH CH
CH3
CH2 CH2 CH2 N(C2H5)2
1 2
3
45
6
78
H
+1' 2' 3' 4'
COOH
OH
CH2
OH
COO-
Sarea 6-metoxi-8-(4’-dietilamino-1’-metil-butilamino)-chinolinei cu acidul 1,1’-metilen-bis-(2-hidroxi-3-naftoic)
30
• Sinonim: Plasmochina
N
H3CO
NH CH
CH3
CH2 CH2 CH2 N(C2H5)2H
+
COOH
OH
CH2
OH
COOH
N
H3CO
NH2
6-metoxi-8-amino- chinolina
CH
CH3
CH2 CH2 CH2 N(C2H5)2Cl+
1-dietilamino-4-clor-pentan
- HCl
+
pamachina embonat
31
PRIMACHINA
PRIMAQUINUM (DCI)
N
H3CO
NH CH
CH3
CH2 CH2 CH2 NH3+
H2PO4- sau Cl
-
6-metoxi-8-(4’-amino-1’-metil-butilamino)-chinolina fosfat (sau clorhidrat)
• PF: PRIMACIN –cp. 13,2 mg fosfat echivalent cu 7,5 mg de primachina
PLASMOCID
PLASMOCIDUM (DCI)
N
H3CO
NH CH2 CH2 CH2 NH(C2H5)2+
CH2
COO-
OH
OH
COOH
Sarea 6-metoxi-8-(3’-dietilamino-propilamino)-chinolinei cu acidul metilendisalicilic
32
N
H3CO
NH2
6-metoxi-8-amino- chinolina
+
1-dietilamino-3-clor-propan
- HCl
+
plasmocid
N
H3CO
NH CH2 CH2 CH2 N(C2H5)2
CH2
COOH
OH
OH
COOH
CH2 CH2 CH2 N(C2H5)2Cl
33
• Acidul metilen-disalicilic se obtine prin condensarea acidului salicilic cu formaldehida:
CH2
COOH
OH
OH
COOH
COOH
OH
OH
COOH
+ CH2O- HOH
PENTACHINA
PENTAQUINUM (DCI)N
H3CO
NH (CH2)5 NH2 CH
CH3
CH3
+H2PO4
-
6-metoxi-8-(5’-izopropilamino-pentametilenamino)-chinolina
34
TAFENOCHINA
TAFENOQUINUM (DCI)
CH2 CH2 CH2 NH2
N
H3CO
NH CH
O
OCH3
CH3
CH3
CF3
N-[2,6-dimetoxi-4-metil-5-[3-(trifluorometil)fenoxi]chinolin-8-il]pentan-1,4-diamina
DERIVAŢI DE 4-AMINOCHINOLINĂ
CLOROCHINA DIHIDROGENOFOSFAT
CLOROQUINI
DIHYDROGENOPHOSPHAS (DCI) (FR X)
N
NH2
Cl
CHH3C (CH2)3 NH(C2H5)2
1
2
345
6
7
+
+
2 H2PO4-
Bishidrogenofosfat de 7-cloro-4-4-(dietilamino)-1-metil-butilaminochinolina
35
N
NH
Cl
CHH3C (CH2)3 N(C2H5)2
N
Cl
Cl
+
4,7-diclorochinolina
NH2
CHH3C (CH2)3 N(C2H5)2
2-amino-5-dietilaminopentan
+ 2 H3PO4 clorochina
• PF: NIVAQUINE –cp. a 200 mg sulfat de clorochina; sirop; ARALEN – cp. a 500 mg fosfat de clorochina.
36
HIDROXICLOROCHINA
HIDROXYCHLOROQUINUM (DCI)
N
NH
Cl
CHH3C (CH2)3 NCH2
CH2
CH3
CH2 OH
7-cloro-4-(4-(N-etil-N--hidroxi-etilamino)-1-metil-butilaminochinolina
• PF: PLAQUENIL – comprimate filmate 200 mg sulfat de hidroxiclorochina.
AMODIACHINA
AMODIAQUINUM (DCI)
N
NH
Cl
OH
CH2 NCH2
CH2
CH3
CH3
4-(7’-clor-4’-chinolinamino)-o-dietilamino-o-crezolSinonim: Camochina.
37
HO NHCOCH3 + CH2O + HN(C2H5)2N
CH2
CH2
CH3
CH3
NH OH
CH2
COH3C
3-dietilamino-metil-p-acetilaminofenol
HO-
NCH2
CH2
CH3
CH3
H2N OH
CH2
N
Cl
Cl
4,7-diclorochinolina
+
amodiachina
• PF: FLAVOQUINE – cp a 200 mg clorhidrat de amodiachina.
CICLOCHINA
CICLOQUINUM (DCI)
N
NH
Cl
OH
CH2
CH2
NCH2
CH2
CH3
CH3
NCH2
CH2
CH3
CH3
4-(7’-clor-4’-chinolinamino-, ’-dietil-aminoxilenol)
38
PROPACHINA
PROPAQUINUM (DCI)
N
NH
Cl
OH
CH2 N
4-(7’-clor-4’-chinolinamino)--pirolidin-o-crezol
ALŢI DERIVAŢI DE CHINOLINĂ
MEFLOCHINA
MEFLOQUINUM (DCI)
N
CH
CF3
CF3
OHNH
2,8-bis((trifluorometil)chinolin-4-il)-(2-piperidil)-metanol
• PF: LARIAM –cp. a 250 mg clorhidrat de meflochina