synthesis of some novel thieno[2, 3-d] pyrimidines and...

ISSN: 0973-4945; CODEN ECJHAO

E-Journal of Chemistry

http://www.e-journals.net 2009, 6(3), 801-808

Synthesis of Some Novel Thieno[2, 3-d]

pyrimidines and their Antibacterial Activity

Md SALAHUDDIN*, SUNIL KAKAD and S.M.SHANTAKUMAR

Department of Pharmaceutical Chemistry,

V.L.College of Pharmacy, Raichur-584103,

Karnataka, India.

[email protected]

Received 14 December 2008; Accepted 5 February 2009

Abstract: Bromination of intermediate 1-[4-(6, 7-dihydro-5H-cyclopenta [4, 5]

thieno[2, 3-d]pyrimidin-4-yl amino) phenyl] ethanone (4) yielded (5). Which

upon reaction with different substituted benzothiazoles give a novel series of

pyrimidine [6(a-g)]. However reaction of (5) with 4-chloro-2-triflouro acetyl

aniline provided (6h). Similarly reaction of (5) with 5-amino tetrazole & 2-amino

benzimidazole produced (6i) & (6j) respectively. All the synthesized compounds

were tested against bacteria (Gram positive and Gram negative).

Keywords: Thienopyrimidine, Benzothiazole, Tetrazole, Benzimidazole.

Introduction

Antibiotics have revolutionized the medical care in the 20th

century. With the discovery of

antibiotics people were convinced that infectious diseases might some day be wiped out.

Diseases that were once life threatening, such as pneumonia, had become curable. The

success of antibiotics in therapy related fields has made them one of the most important

products of the drug industry today1. However, the emergence of superbugs i.e. bacteria that

resist the effects of the most powerful antibiotics are posing a great challenge to the field of

medicines. Thus scientists are working to find new ways to defeat bacteria that are

increasingly resistant to the antibiotics already available2. It is well known that pyrimidine

and fused heterocyclic pyrimidine derivatives are of great biological interest, especially as

antiviral, antitumor and antimicrobial agents3–14

. Also, the rapid growth in the literature

dealing with the synthesis and biological activity of the thienopyrimidine derivatives

prompted us to synthesize new derivatives of fused pyrimidine, and thieno[2,3-d]pyrimidine

derivatives. Aromatic and heteroaromatic compounds are useful substrates for the

preparation of various condensed pyrimidine heterocyclic systems15

. In this present work,

interest is expressed in synthesizing (Scheme 1) some new thieno[2, 3-d]pyrimidine

derivatives (6a-g), (6h), (6i) & (6j) and are evaluated for their antimicrobial activity.

802 Md. SALAHUDDIN et al.

S NH2

NH2

O

S N

NH

O

S N

N

ClCOCH

3NH

S N

N

(4)COCH

3NH

2

COCH2BrNH

S N

N

Formamide

Br2 in

glacial acetic acid

(1) (2)

(3)

POCl3

(5)

COCH2BrNH

S N

N

NH2

Cl

F3COC

N

NH

NH2

N

NN

NH

NH2

N

SNH

2

R

Cl

F3COC

NH

S N

N

COCH2NHN

NN

NH

NH

S N

N

COCH2NH

N

SNNH

S N

N

NH

S N

N

COCH2NH

N

NH

R

(5)

6(h)

6(i)

6(j)6(a-g) Where R= H, Cl, OMe, CH3, F, COOC2H5, NO2

Scheme 1.

Synthesis of Some Novel Thieno[2, 3-d]pyrimidines 803

Experimental

Melting points (oC, uncorrected) were recorded on an Electro thermal I A 9100 Digital Melting

Point Apparatus. IR spectra (νmax in cm-1) were recorded on a Shimadzu FT-IR 8300

Spectrophotometer using KBr pellets technique. 1H NMR Spectra were recorded using Bruker

WM-400 spectrophotometer using DMSO-d6 or CDCl3 as the solvent and TMS as the internal reference (Chemical Shifts in ppm). TLC using silica gel G60 (Merck, Germany) routinely checked the purity of the compounds and the spots were exposed in iodine vapour for visualization.

Synthesis of Compounds

2-Amino-5, 6-dihydro-4H-cyclopenta[b]thiophene-3-carboxamide (1)16

Cyclopentanone (0.1 mol, 8.4 g), cyanoacetamide17

(0.01 mol, 0.84 g), sulphur powder (0.01

mol, 0.32 g) and diethyl amine (10 mL) in absolute ethanol (30 mL) was stirred in a round

bottomed flask for 3 h. After the completion of the reaction time the mixture was poured on

crushed ice. The separated solid was filtered, washed with water and recrystallized from

alcohol to furnish compound (1).

Yield: 67%; Melting Point: 175 οC; Anal.: Calculated for C8H10N2OS: C, 52.72; H, 5.53; N,

15.37. Found: C, 52.67; H, 5.95; N, 15.61; IR: ν(cm-1

) IR: ν (cm-1

) 1595 (C=O), 3315 (NH2),

3008 (CH of Aromatic), 777(C-S); 1H NMR: δ (ppm) 6.3-6.5 (s, 2H of CONH2), 5.4-5.6 (s, 2H

of NH2), 2.6-2.8 (m, 4H of Aliphatic), 1.15-1.30 (2H of Aliphatic); LCMS (m/z): 183 [M+].

3, 5, 6, 7-Tetrahydro-4H-cyclopenta[4, 5]thieno[2,3-d]pyrimidin-4-one (2)

The compound (1) was heated with formamide 20 mL in a round bottomed flask in an oil bath at 60

οC. The temperature was then gradually raised. The reaction mixture gets

dissolved completely with the formation of brown solution at 110 οC. The temperature of the

oil bath was raised to 180-200 οC, when the reaction mixture was heated at this temperature

for 3 h. After, the completion of the reaction, reaction mixture was allowed to cool at room temperature. The product separated as yellow needles was collected by filtration and washed with water several times and finally with 25 mL of acetone and then dried. The product was recrystallized from alcohol. Yield: 70%; Melting Point: 235

οC; Anal.: Calculated for

C9H8N2OS: C, 56.23; H, 4.19; N, 14.57. Found: C, 56.57; H, 4.95; N, 15.01; IR: ν (cm-1

) 1595 (C=O), 3420 (NH), 3008 (CH of Aromatic), 1540 (N=CH), 753 (C-S);

1H NMR: δ

(ppm) 7.50- 7.70 (s, 1H of CH of Pyrimidine), 7.20- 7.30 (s, 1H of NH of Pyrimidine), 2.1-2.3 & 3.0- 3.1 (m, 4H of Aliphatic), 0.98-1.10 (d, 2H of Aliphatic); LCMS (m/z): 192 [M

+].

4-Chloro-6, 7-dihydro-5H-cyclopenta[4, 5]thieno[2, 3-d]pyrimidine (3)

A mixture of compound (2) (0.01 mol) and 25 mL of POCl3 was refluxed for 8-10 h in round

bottomed flask. After completion of the reaction (monitored by TLC), the excess of POCl3

was removed by distillation the resulting thick yellow liquid was poured over crushed ice,

filtered washed with water and dried. The product was recrystallized from alcohol.

Yield: 60%; Melting Point: 130 οC. Anal.: Calculated for C9H7ClN2S: C, 51.32; H, 3.35;

N, 13.30. Found: C, 51.55; H, 3.95; N, 13.25; IR: v (cm-1

) 686 (C-Cl), 3078 (CH of

Aromatic), 825 (C-N), 711 (C-S); 1H NMR: δ (ppm) 8.4- 8.6 (s, 1H of CH of Pyrimidine),

2.9-3.3 (m, 4H of Aliphatic), 1.0-1.2 (d, 2H of Aliphatic); LCMS (m/z): 211 [M+].

1-[4-(6, 7-Dihydro-5H-cyclopenta[4, 5]thieno[2, 3-d]pyrimidin-4-yl amino) phenyl]

ethanone (4)

Compound (3) (0.01 mol) and equimolar concentration of p-amino acetophenone and 3-5

drops conc. HCl was refluxed with alcohol in round bottomed flask for about 6 hours. After

completion of the reaction (monitored by TLC), the mixture is poured over crushed ice. The

solid formed was filtered off and residue washed with 10% dilute ammonium hydroxide, the

product is recrystallized from alcohol. Yield: 67%; Melting Point: 215 οC. Anal.: Calculated

for C17H15N3OS: C, 66.00; H, 4.89; N, 13.58. Found: C, 52.95; H, 5.10; N, 13.61;


IR: ν(cm-1

) 3387 (N-H Streching), 2961 and 2941 (Aromatic CH Streching), 2850, 2802

(CH2 Streching), 1673 (C=O Absorption band), 848 (1, 4-di substituted Benzene).; 1H NMR: δ

(ppm) 8.5 (s, 1H of pyrimidine), 7.1(s, 1H, NH), 7.4-8.2 (m, 4H, Ar- H), 3.1-3.3(t, 2H, CH2),

2.9-3.0 (t, 2H of CH2), 2.4-2.8 (m, 5H, 2H of CH2 and 3H of CH3); LCMS (m/z): 310 [M+].

Preparation of 2-bromo-1-[4-(6, 7-dihydro-5H-cyclopenta[4, 5]thieno[2, 3-d]

pyrimidin-4-yl-amino) phenyl] ethanone (5)

The product 1-[4-(3, 5, 6, 7, -tetrahydro-4H-cyclopenta-thieno[2, 3-d]pyrimidine-4-yl-

amino) phenyl] ethanone(4) (0.01 mol) was dissolved in glacial acetic acid and then stirred

with Br2 in acetic acid (0.01 M, 1.60 mL) drop by drop addition with constant stirring for

5-6 h. The precipitate formed was filtered, dried and then recrystallized from alcohol.

Yield 65%; Melting point: 160 oC. Anal.: Calculated for C17H14BrN3OS: C, 52.59; H,

3.63; N, 10.82. Found: C, 52.77; H, 3.18; N, 10.61; IR: ν(cm-1

) 3422 (N-H), 2924 and 2850

(C-H of Ar-H), 1670 (C=O), 844 (1, 4-disubstituted Benzene); 1H NMR: δ (ppm) 8.5-8.6 (s,

1H, Pyrimidine), 7.7-8.2 (m, 4H, Aromatic), 7.1(s, 1H, NH), 4.45 (s, 2H, CH2), 2.9-3.0 (t,

2H, CH2 of Cyclopentanone), 3.1-3.2 (t, 2H, CH2 of Cyclopentanone), 2.4-2.6 (s, 2H, CH2 of

Cyclopentanone); LCMS (m/z): 389 [M+].

N-[4-(7-(Substituted or unsubstituted) imidazo[2, 1-b]-[1, 3]benzothiazol-2-yl)

phenyl]-6, 7-dihydro-5H-cyclopenta [4, 5]thieno[2, 3-d] pyrimidin-4 - amine[6(a-g)]

An equimolar quantity of 2-bromo-1-[4-(6, 7-dihydro-5H-cyclopenta[4,5]thieno[2, 3-d] pyrimidin-

4-ylamino) phenyl] ethanone (5) (0.01 mol) and appropriate 2-amino substituted benzothiazole

(0.01 mol) was refluxed with alcohol (40 mL) for about 10 h. After completion of the reaction

(monitored by TLC), the mixture is poured over crushed ice. The precipitate formed was filtered,

dried and then recrystallized with alcohol. The physical properties of 6 shown in Table 1.

6a: Anal.: Calculated for C24H17N5S2: C, 65.58; H, 3.90; N, 15.93. Found: C, 65.00; H,

3.95; N, 15.68; IR: ν(cm-1

) 3486 (N-H), 2850 (C-H of Ar-H), 2924 (CH2), 844 (1, 4-

disubstituted benzene), 615 (C-S), 1558 (C=N); 1H NMR: δ (ppm) 8.4- 8.5 (s, 1H,

Pyrimidine), 7.2-8.1(m, 8H, Aromatic), 11.2 (s, 1H, NH), 7.8 (s, 1H, CH), 2.9-3.2 (m, 4H,

CH2 of Cyclopentanone), 1.9-2.0 (s, 2H, CH2 of Cyclopentanone); LCMS (m/z): 440 [M+].

6b: Anal.: Calculated for C24H16ClN5S2: C, 60.81; H, 3.40; N, 14.77. Found: C, 60.88; H, 3.55;

N, 14.59; IR: ν(cm-1) 3330 (N-H Stretching), 3080 (C-H of Ar-H), 2912 (CH2 stretching), 890 (1, 4-

disubstituted Benzene), 588 (C-S stretching), 1545 (C=N), 678 (C-Cl); 1H NMR: δ (ppm) 8.6-8.7 (s,

1H, Pyrimidine), 7.2-7.9 (m, 7H, Aromatic), 11.3 (s, 1H, NH), 7.6 (s, 1H, CH) 2.2-3.0 (m, 4H, CH2

of Cyclopentanone), 1.9-2.0 (s, 2H, CH2 of Cyclopentanone).; LCMS (m/z): 475 [M+].

6c: Anal.: Calculated for C25H19N5OS2: C, 63.94; H, 4.08; N, 14.91. Found: C, 63.39; H, 4.61; N, 14.89; IR: ν(cm

-1) 3404 (N-H), 3125 (C-H of Ar-H), 2815 (CH2), 810 (1, 4-disubstituted

Benzene), 664 (C-S), 1550 (C=N), 1117 (OCH3); 1H NMR: δ (ppm) 8.3-8.4 (s, 1H, Pyrimidine),

7.0-7.9(m, 7H, Aromatic), 11.4 (s, 1H, NH), 8.0 (s, 1H, CH), 3.7 (m, 3H of OCH3), 2.6-3.0 (m, 4H, CH2 of Cyclopentanone), 1.7-2.2 (s, 2H, CH2 of Cyclopentanone); LCMS (m/z): 470 [M

+].

6d: Anal.: Calculated for C25H19N5S2: C, 66.20; H, 4.22; N, 15.44. Found: C, 60.02; H, 4.65; N, 15.86; IR: ν(cm


Benzene), 600 (C-S), 1488 (C=N), 1330 (CH3); 1H NMR: δ (ppm) 8.6-8.7 (s, 1H, Pyrimidine),

7.2-8.1(m, 7H, Aromatic), 8.5 (s, 1H, NH), 7.7 (s, 1H, CH), 2.2 (s, 3H of CH3), 2.2-2.8 (m, 4H, CH2 of Cyclopentanone), 1.9-2.0 (s, 2H, CH2 of Cyclopentanone).; LCMS (m/z): 454 [M

+].

6e: Anal.: Calculated for C24H16FN5S2: C, 63.00; H, 3.52; N, 15.31. Found: C, 62.88; H, 3.51; N, 15.41; IR: ν(cm


Benzene), 580 (C-S), 1556 (C=N), 1212 (C-F); 1H NMR: δ (ppm) 8.6-8.8 (s, 1H, Pyrimidine),

7.2-7.8 (m, 7H, Aromatic), 8.4 (s, 1H, NH), 7.9 (s, 1H, CH), 2.1-3.1 (m, 4H, CH2 of Cyclopentanone), 1.5-1.7 (s, 2H, CH2 of Cyclopentanone).; LCMS (m/z): 458 [M

+].


6f: Anal.: Calculated for C27H21N5O2S2: C, 63.38; H, 4.14; N, 13.69. Found: C, 63.67; H, 4.77; N, 13.55; IR: ν(cm

-1) 3290 (N-H), 3000 (C-H of Ar-H), 2844 (CH2), 816 (1, 4-

disubstituted Benzene), 665 (C-S), 1540 (C=N), 1180 (OC2H5); 1H NMR: δ (ppm) 8.6-8.7 (s,

1H, Pyrimidine), 7.2-8.1 (m, 7H, Aromatic), 8.3 (s, 1H, NH), 7.8 (s, 1H, CH) 1.33 (t, 3H of CH3), 4.3 (m, 2H of CH2), 2.9-3.2 (m, 4H, CH2 of Cyclopentanone), 1.5-1.8 (s, 2H, CH2 of Cyclopentanone).; LCMS (m/z): 512 [M

+].

6g: Anal.: Calculated for C24H16N6O2S2: C, 59.49; H, 3.33; N, 17.34. Found: C, 59.98;

H, 3.91; N, 17.01; IR: ν(cm-1

) 3211 (N-H), 3121 (C-H of Ar-H), 816 (1, 4-disubstituted

Benzene), 610 (C-S), 1515 (C=N), 1447 (NO2); 1H NMR: δ (ppm) 8.6-8.7 (s, 1H,

Pyrimidine), 7.2-8.1(m, 7H, Aromatic), 8.5 (s, 1H, NH), 7.8 (s, 1H, CH), 2.9-3.2 (m, 4H,

CH2 of Cyclopentanone), 1.9-2.0 (s, 2H, CH2 of Cyclopentanone).; LCMS (m/z): 485 [M+].

Preparation of 2-[(2- triflouro carbonyl- 4-chlorophenyl) amino]-1-[4-(6, 7-

dihydro-5H-cyclopenta [4, 5] thieno[2, 3-d]pyrimidin-4-ylamino) phenyl]

ethanone[6(h)] A mixture of 2-bromo-1-[4-(6, 7-dihydro- 5H- cyclopenta[4, 5]thieno[2, 3-d]pyrimidin-4-

ylamino) phenyl] ethanone (5) (0.001 mol) and 4-chloro-2 triflouro acetyl aniline (0.001

mol) was refluxed with alcohol for about 10 h. After the completion of the reaction

(monitored by TLC) the mixture is poured over crushed ice. The precipitate formed was

filtered, dried and then recrystallized with alcohol. Yield 64%; Melting point: 138 oC;

Molecular weight: 520; Rf value: 0. 41, soluble in cold: glacial acetic acid, DMF.

6h: Anal.: Calculated for C25H18ClF3N4O2S: C, 56.55; H, 3.42; N, 10.55. Found: C,

56.27; H, 2.95; N, 10.13; IR: ν(cm-1

) 3200 (N-H), 3215 (C-H of Ar-H), 2831 (CH2), 878 (1,

4-disubstituted Benzene), 600 (C-S), 1593 (C=N), 688 (C-Cl); 1H NMR: δ (ppm) 8.4-8.6 (s,

2H, [1H of Pyrimidine and 1H of NH), 7.7-8.2 (m, 7H, Aromatic), 4.6 (s, 2H, CH2), 2.9-3.0

(t, 2H,of CH2 of Cyclopentanone), 3.1-3.2 (t, 2H, CH2 of Cyclopentanone), 2.4-2.6 (s, 2H,

CH2 Cyclopentanone); LCMS (m/z): 531 [M+].

Preparation of 1-[4-(6, 7-dihydro-5H-cyclopenta [4, 5] thieno [2, 3-d] pyrimidin-4-

ylamino) phenyl]-2-(1H-tetrazol-5-ylamino) ethanone [6(i)]

A mixture of 2-bromo-1-[4-(6, 7-dihydro-5H-cyclopenta [4, 5] thieno[2, 3-d]pyrimidin-4-

ylamino) phenyl] ethanone (5) (0.01 mol) and 5 amino tetrazole (0.01 mol) was refluxed

with alcohol for about 10 h. After the completion of the reaction (monitored by TLC) the

mixture was poured over crushed ice. The precipitate formed was filtered, dried and then

recrystallized with alcohol. Yield 55%; Melting point: 110 oC; Molecular weight: 392;

Rf value: 0. 43 soluble in cold: glacial acetic acid, DMF.

6i: Anal.: Calculated for C18H16N8OS: C, 55.09; H, 4.11; N, 28.55. Found: C, 55.55; H,

4.35; N, 28.61; IR: ν(cm-1

) 3319 and 3383 (N-H), 2925 (Aromatic C-H), 2851 (CH2), 1674

(C=O absorption), 839 (1, 4 disubstituted benzene); 1H NMR: δ (ppm) 8.2 (s, 1H,

Pyrimidine), 7.1-6.8-7.5 (m, 4H, Aromatic), 4.3 (s, 2H, CH2), 2.9-3.0 (t, 2H, CH2 of

Cyclopentanone), 3.1-3.2 (t, 2H, CH2 of Cyclopentanone), 2.4-2.6 (s, 2H, CH2

Cyclopentanone), 4.0 (s, 2H, NH); LCMS (m/z): 393 [M+].

Preparation of 1-[4-(6, 7-dihydro-5H-cyclopenta [4, 5] thieno [2, 3-d] pyrimidin-4-

ylamino) phenyl] -2-(1H-benzimidazol-2-ylamino) ethanone [6(j)]

A mixture of 2-bromo-1-[4-(6, 7-dihydro-5H-cyclopenta [4, 5] thieno [2, 3-d] pyrimidin-4-

ylamino) phenyl] ethanone (5) (0.001 mol) and 2- amino benzimidazole (0.001 mol) was refluxed

with alcohol for about 10 h. After Completion the reaction mixture was cooled and the poured on

crushed ice. The solid formed was filtered off, recrystallized from alcohol. Yield 67%; Melting

point: 105 oC; Molecular weight: 439; Rf value: 0. 47 soluble in cold: glacial acetic acid, DMF.


6j: Anal.: Calculated for C24H20N6OS: C, 65.54; H, 4.58; N, 19.08. Found: C, 65.67; H,

4.35; N, 19.91; IR: ν(cm-1

) 3277 and 3383 (N-H), 3000 (C-H of Aromatic), 2831 (CH2),1624

(C=O absorption), 836 (1, 4 disubstituted benzene); 1H NMR: δ (ppm) 8.4 (s, 1H,

Pyrimidine), 6.8-7.7 (m, 8H, Aromatic), 4.4 (s, 2H, CH2), 1.9-2.3 (t, 2H, CH2 of

Cyclopentanone), 2.8-3.0 (d, 2H, CH2 of Cyclopentanone), 2.4-2.6 (s, 2H, CH2 of

Cyclopentanone), 4.2 (s, 2H, NH); LCMS (m/z): 441 [M+].

Antimicrobial Activity18

The antimicrobial activity of representative new compounds (6a-g), (6h), (6i) & (6j) was

investigated against a variety of microorganisms, including the gram positive bacteria

Bacillus subtilis, Bacillus pumilis and Staphylococcus aureus, Escherichia coli the gram-

negative bacteria. Antimicrobial activity was determined by the disc diffusion method

Table 1. The physical properties of synthesized compounds (6a-j).

S.No. Compound Mol. Formula Molecular

Wt.

Rf

Value

Melting

Point, oC

Yield

%

1 6a C18H17N5S2 439 0.41 90 54

2 6b C24H16N5S2Cl 473 0.45 100 54

3 6c C25H19N5OS2 469 0.47 98 65

4 6d C25H19N5S2 453 0.43 105 58

5 6e C24H16N5S2F 553 0.48 136 67

6 6f C27H21N5O2S2 511 0.49 120 76

7 6g C24H16N6O2S2 484 0.45 116 59

8 6h C25H18N4O2S F3 Cl 530 0.41 138 64

9 6i C18H16N8SO 392 0.43 110 55

10 6j C24H20N6SO 439 0.47 105 67

Sample preparation

Sterilized filter paper discs (6 mm in diameter) were wetted with 10 µL each of a solution of

the tested compound (50 µg & 100 µg/mL of the compound in DMF). The discs were then

allowed to dry and placed on the surface of agar plates seeded with the test organism.

Medium inoculation and cultivation condition

Each plate contained 15 mL of the agar medium, previously seeded with 0.2 mL of an 18 h

old broth culture of each organism. The inoculated plates were incubated at 37 oC for 48 h

with the test discs in place and the inhibition zones were measured in mm. Discs

impregnated with DMF were used as controls. The antibacterial reference ampicillin discs

tested as standard.

Results and Discussion

The data in Table 2 indicates that most of the synthesized Compounds are active against the

bacteria like Bacillus subtilis, Bacillus pumilis, Escherichia coli and Staphylococcus aureus.

The compound 6(c), 6(d), 6(f), 6(h) and 6(j) shown significant activity and compound 6(a),

6(b), 6(g) and 6(i) have shown moderate activity.


Table 2. Antibacterial activity of synthesized compounds.

*Inhibition zone diameter in mm

Gram +ve Gram –ve

B.subtilis B.pumilis E.coli S. aureus

Sample

Code

50 µg 100 µg 50 µg 100 µg 50 µg 100 µg 50 µg 100 µg

6a 9 15 10 14 9 12 10 15

6b 8 10 9 11 9 13 9 12

6c 9 14 10 18 8 15 9 14

6d 8 15 9 13 9 16 12 19

6e 9 13 8 11 8 12 7 10

6f 12 18 8 16 9 16 9 12

6g 9 13 9 14 7 13 9 16

6h 8 11 8 12 12 19 10 13

6i 8 16 10 12 9 11 8 12

6j 8 14 10 14 9 15 12 19

Ampicillin 20 29 27 35 21 31 23 36

DMF - - - - - - - -

*Average of triplicate ± Standard deviation

Note: ‘-‘denotes no activity, 7-10 mm poor activity, 11-17 mm moderate activity, 18-20 above

significant.

Acknowledgement

The authors wish to express their thanks & gratitude to the Management of V.L.College of

Pharmacy, Raichur for providing necessary facilities to carry out this work. We gratefully

acknowledge Mr. G.Amarnath, Aurobindo, Hyderabad. Indian Institute of Science, Astra

Zeneca Ltd., & Quest Research Centre, Bangalore for providing IR, 1H NMR and MASS

spectral data. We profusely thank Prof. N.Sreenivasulu, VLCP., Raichur for moral support.

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