International Journal of Pharma and Bio Sciences

Transcription

1 SYTHESIS AD ATIBACTEIAL ACTIVITY F SME EW PYIDIYL/QUIAZLIYL/AZETIDIYL/THIAZLIDIYL IDU SIGH, HEMLATA KAU, SUIL KUMA, AU KUMA** AD ASHK KUMA* * Medicinal Chemistry Division, Department of Pharmacology, L.L..M. Medical College, Meerut , U. P. India ** Department of SPM, L.L..M. Medical College, Meerut , U. P. India. *Corresponding author ashokraj.kumar744@gmail.com ABSTACT A series of -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2-(4-(3-chloro-2-(substitutedphenyl)-4- oxoazetidin-1-yl)-5-(pyridin-4-yl)-5-thio)acetamido-1,2,4-triazoles (5a-5g) have been prepared by the condensation of 6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl-2-(4-(substitutedbenzylideneamino)-5-(pyridin-4- yl)-3-thio)acetamido-1,2,4-triazoles (4a-4g) with chloroacetyl chloride in presence of trimethylamine. -(6- bromo-2-methyl-4-oxoquinazolin-3(4h)-yl)-2-(4-(2-(substitutedphenyl)-4-oxothiazolidin-3-yl)-5-(pyridin-4-yl)- 3-thio)acetamido-1,2,4-triazoles (6a-6g) have been synthesized by the reaction of compounds 4a-4g with thioglycolic acid in presence of anhydrous zinc chloride. All the newly synthesized compounds were screened for their antibacterial activity against S.aureus, E.coli, P.vulgaris, K. pneumoniae. Structures of all the compounds were established by elemental and spectral (I, 1 H M and Mass) analysis. KEYWD Pyridinyltriazoles, Quinazolinyltriazoles, Azetidinonyltriazoles, Thiazolidinonyltriazoles. ITDUCTI It has been reported that triazole is the biodynamic heterocyclic moiety. Several triazole derivatives have also been reported to show significant antibacterial 1, antifungal 2, anticonvulsant 3 and anti-inflammatory 4 activities. Screening the literature reveals that pyridine 5 and quinazolinone 6 1 derivatives also exhibited antibacterial activity. The scientific literature reveals that this activity is due to presence of azetidinones 7 and thiazolidinones 8 moieties in a molecule and change in activity depends on the nature of substituents. In light of above observations it was thought worthwhile to synthesized some new substituted triazole derivatives by

2 SYTHESIS AD ATIBACTEIAL ACTIVITY F SME EW PYIDIYL/QUIAZLIYL/AZETIDIYL/THIAZLIDIYL incorporation of pyridine, quinazolinone, azetidinone compounds were administered by i.p. route in one and thiazolidinone moieties with the hope to get group and the same volume of propylene glycol in better antibacterial agents. MATEIAL AD METHDS All the synthesized compounds were tested for their antibacterial activity. The effect of unknown compounds were compared with the standard drugs ampicillin and gattifloxacin. The propylene glycol treated group served as control. All the newly synthesized compounds were also screened for their approximate lethal dose (ALD 50 ). Cup-Plate Method (CUPS): This activity was performed by following the method of Chuinckshank et. al. 9 in albino rats. utrient agar was poured onto the sterilized petri dishes (20-25 ml each pertri dish). The poured material was allowed to set (1-1.5 h) and thereafter the CUPS (10 mm diameter) were made by punching into the agar surface with a sterile cork borer and scooping out the punched part of the agar. Into these cups the test compound solution was added with the help of sterile syringe. The plates were incubated at 37 0 C for 48 h and the results were noted. A solvent control (10% DMS in methanol) was also run to not the activity of the blank (solvent). The above said standard drugs were also screened under similar conditions for comparison. Approximate lethal dose (ALD 50 ): The LD 50 was determined in albino rats weighing gm of either sex by the method of Smith 10. The test another group of animals consisting six rats in graded doses. The animals were allowed to take food and water adlibidum. After 24 h of drug administration percent mortality in each group was observed. From the data obtained ALD 50 was calculated. EXPEIMETAL 4-amino-5-pyridine-3-mercapto-1, 2, 4-triazole (1) A solution of pyridine potassium dithiocarbazinate (1.5 mol) in water (5 ml) and hydrazine hydrate ( 1.5 mol) was refluxed for 10 h. The colour of the reaction mixture changed to green with the evolution of hydrogen sulfide gas. The reaction mixture was cooled at room temperature and diluted with water (100 ml). n acidification with concentrated HCl the required triazole (1) was precipitated, which was filtered, washed thoroughly with cooled water and recrystallized from acetone to furnish compound 1. Yield 95%; m.p C. I (KBr, ν max in cm -1 ): 3380 (H 2 ), 3132 (aromatic CH), 2585 (SH), 1612 (C=C of aromatic ring), 1608 (C=), 1281 (-). 1 HM (CDCl 3 + DMS-d 6 ) δ in ppm: (s, 1H, SH exchangeable with D 2 ), (m, 4H, Ar-H), 5.72 (s, 2H, H 2 exchangeable with D 2 ). MS: [M] + at m/z Anal. Calcd. for C 7 H 7 5 S: C, 43.51; H, 3.65;, 36.24: Found: C, 43.45; H, 3.94;, 36.49%. 2

3 SYTHESIS AD ATIBACTEIAL ACTIVITY F SME EW PYIDIYL/QUIAZLIYL/AZETIDIYL/THIAZLIDIYL C H 2 H 2. H 2 CHH 2 CS 2 /KH H 2 H 2. H 2 CH 3 CH (1) H 2 SH CH SH (2a-g) CH ClCH 2 CCl SCH 2 CCl CH (3a-g) H 2 Br = 4-H & 3-CH 3, 2,4-Cl, 2,6-Cl, 2,4-Br, 2,6-Br, 2-H, 4-(CH 3 ) 2 SCH 2 CH CH (4a-g) Br ClCH 2 CCl/Et 3 HSCH/Anhy.ZnCl 2 SCH 2 CH H C Cl (5a-g) Br SCH 2 CH H C S (6a-g) Br SCHEME-1 3

4 SYTHESIS AD ATIBACTEIAL ACTIVITY F SME EW PYIDIYL/QUIAZLIYL/AZETIDIYL/THIAZLIDIYL General procedure for synthesis of 4- (substitutedbenzylideneamino)-5-(pyridin-4-yl)-4h- 3-mercapto-1,2,4-triazoles (2a-2g) A solution of compound (1) (0.5 mol) and various substituted aromatic aldehydes (0.5 mol) in 40 ml of ethanol along with glacial acetic acid (2-3 drops) were refluxed for 2 h. The completion of the reaction checked by TLC. The reaction mixtures were cooled, filtered and washed with ethanol, dried and recrystallization with DMF, water to yield compound 2a-2g. 4-(4-hydroxy-3-methoxybenzylideneamino)-5- (pyridin-4-yl)-4h-3-mercapto-1,2,4-triazole (2a) Yield 93% (Acetone); m.p C. I (KBr, ν max in cm -1 ): 3451 (H), 3133 (aromatic CH), 2581 (SH), 1645 (C=), 1612 (C=C of aromatic ring), 1592 (=CH), 1492 (-), 1453 (C-), 1224 (CH 3 ). 1 HM (CDCl 3 ) δ in ppm: (s, 1H, H exchangeable with D 2 ), (s, 1H, SH exchangeable with D 2 ), 8.86 (s, 1H, =CH), (m, 7H, Ar-H), 3.36 (s, 3H, CH 3 ). MS: [M] + at m/z Anal. Calcd. for C 15 H S: C, 55.03; H, 4.00.;, 21.39: Found: C, 55.21; H, 4.25;, 21.30% 4-(2,4-dichlorobenzylideneamino)-5-(pyridin-4-yl)- 4H-3-mercapto-1,2,4-triazole (2b) Yield 91% (Methanol); m.p C. I (KBr, ν max in cm -1 ): 3132 (aromatic CH), 2581 (SH), 1647 (C=), 1614 (C=C of aromatic ring), 1592 (=CH), 1493 (-), 1454 (C-), 760 (C-Cl). 1 HM (CDCl 3 ) δ in ppm: (s, 1H, SH exchangeable with D 2 ), 8.87 (s, 1H, =CH), (m, 7H, Ar-H). MS: [M] + at m/z Anal. Calcd. for C 14 H 9 Cl 2 5 S: C, 48.01; H, 2.59;, 20.00: Found: C, 48.32; H, 2.79;, 2.25% 4-(2,6-dichlorobenzylideneamino)-5-(pyridine-4-yl)- 4H-3-mercapto-1,2,4-triazole (2c) Yield 90% (Acetone); m.p C. I (KBr, ν max in cm -1 ): 3132 (aromatic CH), 2581 (SH), 1647 (C=), 1614 (C=C of aromatic ring), 1591 (=CH), 1493 (-), 1455 (C-), 760 (C-Cl). 1 HM (CDCl 3 ) δ in ppm: (s, 1H, SH exchangeable with D 2 ), 8.86 (s, 1H, =CH), (m, 7H, Ar-H). MS: [M] + at m/z Anal. Calcd. for C 14 H 9 Cl 2 5 S: C, 48.01; H, 2.59;, 20.00: Found: C, 48.23; H, 2.77;, 20.26% 4-(2,4-dibromobenzylideneamino)-5-(pyridin-4-yl)- 4H-3-mercapto-1,2,4-triazole (2d) Yield 87% (Petrolium ether); m.p C. I (KBr, ν max in cm -1 ): 3133 (aromatic CH), 2583 (SH), 1648 (C=), 1616 (C=C of aromatic ring), 1591 (=CH), 1494 (-), 1454 (C-), 610 (C-Br). 1 HM (CDCl 3 ) δ in ppm: (s, 1H, SH exchangeable with D 2 ), 8.88 (s, 1H, =CH), (m, 7H, Ar-H). MS: [M] + at m/z Anal. Calcd. for C 14 H 9 Br 2 5 S: C, 38.29; H, 2.07;, 15.95: Found: C, 38.55; H, 2.26;, 15.76% 4-(2,6-dibromobenzylideneamino)-5-(pyridin-4-yl)- 4H-3-mercapto-1,2,4-triazole (2e) Yield 86% (Ethanol); m.p C. I (KBr, ν max in cm -1 ): 3132 (aromatic CH), 2584 (SH), 1647 (C=), 1614 (C=C of aromatic ring), 1592 (=CH), 1493 (-), 1457(C-), 611 (C-Br). 1 HM (CDCl 3 ) δ in ppm: (s, 1H, SH exchangeable with D 2 ), 8.86 (s, 1H, =CH), (m, 7H, Ar-H). MS: [M] + at m/z Anal. Calcd. for C 14 H 9 Br 2 5 S: C, 38.29; H, 2.07;, 15.95: Found: C, 38.55; H, 2.26;, 15.76% 4-(4-hydroxybenzylideneamino)-5-(pyridin-4-yl)- 4H-3-mercapto-1,2,4-triazole (2f) Yield 84% (Methanol); m.p C. I (KBr, ν max in cm -1 ): 3450(H), 3134 (aromatic CH), 2581 (SH), 4

5 SYTHESIS AD ATIBACTEIAL ACTIVITY F SME EW PYIDIYL/QUIAZLIYL/AZETIDIYL/THIAZLIDIYL 1647 (C=), 1614 (C=C of aromatic ring), 1591 (=CH), 1495 (-), 1455 (C-). 1 HM (CDCl 3 ) δ in ppm: (s, 1H, H exchangeable with D 2 ), (s, 1H, SH exchangeable with D 2 ), 8.87 (s,1h, =CH), (m, 8H, Ar-H). MS: [M] + at m/z Anal. Calcd. for C 14 H 11 5 S: C, 56.55; H, 3.73;, 23.55: Found: C, 56.84; H, 3.54;, 23.76% 4-(4-(dimethylamino)benzylideneamino)-5-(pyridin- 4-yl)-4H-3-mercapto-1,2,4-triazole (2g) Yield 83% (DMF-water); m.p C. I (KBr, ν max in cm -1 ): 3132 (aromatic CH), 2585 (SH), 1648 (C=), 1614(C=C of aromatic ring), 1592 (=CH), 1493 (-), 1453 (C-). 1 HM (CDCl 3 ) δ in ppm: (s, 1H, SH exchangeable with D 2 ), 8.87 (s, 1H, =CH), (m, 8H, Ar-H), 2.32 (s, 6H, (CH 3 ) 2 ). MS: [M] + at m/z Anal. Calcd. for C 16 H 16 6 S: C, 59.24; H, 4.97;, 25.91: Found: C, 59.46; H, 4.75;, 25.75% General procedure for synthesis of 4- (substitutedbenzylideneamino)-5-(pyridin-4-yl)-3- thioacetylchlorid-1,2,4-triazoles (3a-3g) A mixture of compounds 2a-2g (0.1 mol) in dry diethylether (10 ml) and triethylamine (0.03 mol), choroacetyl chloride (0.15 mol) was added dropwise with stirring between C. After completion of addition the stirring was continued at room temperature. The reaction mixtures were then kept for 46 to 50 h at room temperature. Finally, the reaction mixtures were added to ice cold water to obtain the final product. It was dried and purified by recrystallization from appropriate solvents to obtained compounds 3a-3g. Yield 81% (Acetone); m.p C. I (KBr, ν max in cm -1 ): 3451(H), 3132 (aromatic CH), 1647 (C=), 1614 (C=C of aromatic ring), 1592 (=CH), 1493 (-), 1455 (C-), 1226 (CH 3 ), 682 (C-S-C). 1 HM (CDCl 3 ) δ in ppm: (s, 1H, H exchangeable with D 2 ), 8.85 (s, 1H, =CH), (m, 7H, Ar-H), 4.45 (s, 2H, S-CH 2 -C), 3.38 (s, 3H, CH 3 ). MS: [M] + at m/z Anal. Calcd. for C 17 H 14 Cl 5 3 S: C, 50.56; H, 3.49;, 17.34: Found: C, 50.87; H, 3.68;, 17.55% 4-(2,4-dichlorobenzylideneamino)-5-(pyridin-4-yl)- 3-thioacetylchlorid-1,2,4-triazole (3b) Yield 80% (Petroleum ether); m.p C. I (KBr, ν max in cm -1 ): 3135 (aromatic CH), 1649 (C=), 1615 (C=C of aromatic ring), 1595 (=CH), 1490 (-), 1454 (C-), 682 (C-S-C), 762 (C-Cl). 1 HM (CDCl 3 ) δ in ppm: 8.86 (s, 1H, =CH), (m, 7H, Ar-H), 4.47 (s, 2H, S-CH 2 -C). MS: [M] + at m/z Anal. Calcd. for C 16 H 10 Cl 3 5 S: C, 45.04; H, 2.36;, 16.41: Found: C, 45.25; H, 2.65;, 16.76% 4-(2,6-dichlorobenzylideneamino)-5-(pyridin-4-yl)- 3-thioacetylchlorid-1,2,4-triazole (3c) Yield 79% (Ethanol); m.p C. I (KBr, ν max in cm -1 ): 3132 (aromatic CH), 1647 (C=), 1614 (C=C of aromatic ring), 1592 (=CH), 1493 (-), 1455 (C-), 681 (C-S-C), 760 (C-Cl). 1 HM (CDCl 3 ) δ in ppm: 8.88 (s, 1H, =CH), (m, 7H, Ar- H), 4.45 (s, 2H, S-CH 2 -C). MS: [M] + at m/z Anal. Calcd. for C 16 H 10 Cl 3 5 S: C, 45.04; H, 2.36;, 16.41: Found: C, 45.25; H, 2.65;, 16.76% 4-(2,4-dibromobenzylideneamino)-5-(pyridin-4-yl)- 3-thioacetylchlorid-1,2,4-triazole (3d) Yield 77% (DMF-water); m.p C. I (KBr, ν max in cm -1 ): 3135 (aromatic CH), 1646 (C=), 1617 (C=C of aromatic ring), 1591 (=CH), 1492 (-), 1458 (C-), 682(C-S-C), 612 (C-Br). 1 HM (CDCl 3 ) δ in ppm: 8.86 (s, 1H, =CH), (m, 7H, Ar-H), 4.47 (s, 2H, S-CH 2 -C). MS: [M] + at m/z Anal. Calcd. for 5

6 SYTHESIS AD ATIBACTEIAL ACTIVITY F SME EW PYIDIYL/QUIAZLIYL/AZETIDIYL/THIAZLIDIYL C 16 H 10 Br 2 Cl 5 S: C, 37.27; H, 1.95;, 13.58: Found: C, 37.56; H, 1.76;, 13.69% 4-(2,6-dibromobenzylideneamino)-5-(pyridin-4-yl)- 3-thioacetylchlorid-1,2,4-triazole (3e) Yield 76% (Methanol); m.p C. I (KBr, ν max in cm -1 ): 3132 (aromatic CH), 1645 (C=), 1615 (C=C of aromatic ring), 1591 (=CH), 1495 (-), 1455 (C-), 681 (C-S-C), 611 (C-Br). 1 HM (CDCl 3 ) δ in ppm: 8.87 (s, 1H, =CH), (m, 7H, Ar-H), 4.46 (s, 2H, S-CH 2 -C). MS: [M] + at m/z Anal. Calcd. for C 16 H 10 Br 2 Cl 5 S: C, 37.27; H, 1.95;, 13.58: Found: C, 37.56; H, 1.76;, 13.69% 4-(2-hydroxybenzylideneamino)-5-(pyridin-4-yl)-3- thioacetylchlorid-1,2,4-triazole (3f) Yield 74% (Acetone); m.p C. I (KBr, ν max in cm -1 ): 3445 (H), 3135 (aromatic CH), 1648 (C=), 1614 (C=C of aromatic ring), 1595 (=CH), 1492 (-), 1457 (C-), 683 (C-S-C). 1 HM (CDCl 3 ) δ in ppm: 12.21(s, 1H, H exchangeable with D 2 ), 8.86 (s, 1H, =CH), (m, 8H, Ar-H), 4.46 (s, 2H, S-CH 2 -C). MS: [M] + at m/z Anal. Calcd. for C 16 H 12 Cl 5 2 S: C,51.41; H, 3.24;, 18.73: Found: C, 51.75; H, 3.46;, 18.54% 4-(4-(dimethylamino)benzylideneamino)-5-(pyridin- 4-yl)-3-thioacetylchlorid-1,2,4-triazole (3g) Yield 73% (DMF-water); m.p C. I (KBr, ν max in cm -1 ): 3134 (aromatic CH), 1646 (C=), 1615 (C=C of aromatic ring), 1591 (=CH), 1492 (-), 1455 (C-), 681 (C-S-C). 1 HM (CDCl 3 ) δ in ppm: 8.85 (s, 1H, =CH), (m, 8H, Ar-H), 4.47 (s, 2H, S-CH 2 -C), 3.06 (s, 6H, (CH 3 ) 2 ). MS: [M] + at m/z Anal. Calcd. for C 18 H 17 Cl 6 S: C, 53.93; H, 4.27;, 20.96: Found: C, 53.64; H, 4.58;, 20.58% General procedure for synthesis of (6-bromo-2- methyl-4-oxoquinazolin-3(4h)-yl)-2-(4- (substitutedbenzylideneamino)-5-(pyridin-4-yl)-3- thio)acetamido-1,2,4-triazoles (4a-4g) A mixture of 4-(substituted benzylideneamino)-5-(pyridin-4-yl)-4h-3-yl thioacetylchlorid- 1,2,4-triazoles (3a-3g) (0.05 mol) and 6-bromo-2-methyl-4-oxoquinazolin (0.05 mol) in ethanol (100 ml) was refluxed for 12 h. The solids thus obtained were filtered, dried and recrystallized from appropriate solvens to yielded compounds 4a- 4g. Yield (70%) (Petroleum ether); m.p C. I (KBr, ν max in cm -1 ): 3453 (H), 3136 (aromatic CH), 2885 (CH 3 ), 1680 (C=.amide), 1645 (C=), 1614 (C=C of aromatic ring), 1593 (=CH), 1492 (-), 1455 (C-), 1224, (CH 3 ), 680 (C-S-C). 1 HM (CDCl 3 ) δ in ppm : (s, 1H, H exchangeable with D 2 ), 8.86 (s, 1H, =CH), (m, 10H, Ar-H), 6.95 (s, 1H, H exchangeable with D 2 ), 4.46 (s, 2H, S-CH 2 -C), 3.83 (s, 3H, CH 3 ), 2.17 (s, 3H, CH 3 ). MS: [M] + at m/z Anal. Calcd. for C 26 H 21 Br 8 4 S: C, 50.25; H, 3.41;, 18.03: Found: C, 50.36; H, 3.80;, 18.25% -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2- (4-(2,4-dichlorobenzylideneamino)-5-(pyridin-3-yl)- 3-thio)acetamido-1,2,4-triazole (4b) Yield 68% (Acetone); m.p C. I (KBr, ν max in cm -1 ) : 3132 (aromatic CH), 2885 (CH 3 ), 1680 (C=.amide), 1645 (C=), 1617 (C=C of aromatic ring), 1594 (=CH), 1491 (-), 1457 (C-), 761 (C-Cl), 681 (C-S-C), 611 (C-Br). 1 HM (CDCl 3 ) δ in ppm : 8.87 (s, 1H, =CH), (m, 10H, Ar-H), 6.96 (s, 1H, H exchangeable with D 2 ), 4.47 (s, 2H, S-CH 2 -C), 2.17 (s, 3H, CH 3 ). MS: [M] + at m/z Anal. Calcd. for 6

7 SYTHESIS AD ATIBACTEIAL ACTIVITY F SME EW PYIDIYL/QUIAZLIYL/AZETIDIYL/THIAZLIDIYL C 25 H 17 BrCl S: C, 46.60; H, 2.66;, 17.39: Found: C, 46.79; H, 2.85;, 17.69% -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2- (4-(2,6-dichlorobenzylideneamino)-5-(pyridin-4-yl)- 3-thio)acetamido-1,2,4-triazole (4c) Yield 69% (DMF-water); m.p C. I (KBr, ν max in cm -1 ): 3135 (aromatic CH), 2886 (CH 3 ), 1683 (C=.amide), 1646 (C=), 1615 (C=C of aromatic ring), 1591 (=CH), 1492 (-), 1455 (C-), 763 (C-Cl), 682 (C-S-C), 611 (C-Br). 1 HM (CDCl 3 ) δ in ppm : 8.85 (s, 1H, =CH), (m, 10H, Ar-H), 6.98 (s, 1H, H exchangeable with D 2 ),4.46 (s, 2H, S-CH 2 -C), 2.16 (s, 3H, CH 3 ). MS: [M] + at m/z Anal. Calcd. for C 25 H 17 BrCl S: C, 46.60; H, 2.66;, 17.39: Found: C, 46.79; H, 2.85;, 17.69% -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2- (4-(2,4-dibromobenzylideneamino)-5-(pyridin-4-yl)- 3-thio)acetamido-1,2,4-triazole (4d) Yield 65% (Petroleum ether); m.p C. I (KBr, ν max in cm -1 : 3132 (aromatic CH), 2884 (CH 3 ), 1682 (C=.amide), 1648 (C=), 1615 (C=C of aromatic ring), 1591 (=CH), 1492 (-), 1455 (C- ), 761 (C-Cl), 681 (C-S-C), 611 (C-Br). 1 HM (CDCl 3 ) δ in ppm : 8.86 (s, 1H, =CH), (m, 10H, Ar-H), 6.99 (s, 1H, H exchangeable with D 2 ), 4.47(s, 2H, S-CH 2 -C), 2.17 (s, 3H, CH 3 ). MS: [M] + at m/z Anal. Calcd. for C 25 H 17 Br S: C, 40.95; H, 2.34;, 15.28: Found: C, 40.74; H, 2.65;, 15.47% -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2- (4-(2,6-dibromobenzylideneamino)-5-(pyridin-4-yl)- 3-thio)acetamido-1,2,4-triazole (4e) Yield 63% (Methanol); m.p C. I (KBr, ν max in cm -1 ): 3132 (aromatic CH), 2885 (CH 3 ), 1680 (C=.amide), 1645 (C=), 1615 (C=C of aromatic ring), 1591 (=CH), 1492 (-), 1455 (C-), 761 (C-Cl), 681 (C-S-C), 611 (C-Br). 1 HM (CDCl 3 ) δ in ppm : 8.87 (s, 1H, =CH), (m, 10H, Ar-H), 6.98 (s, 1H, H exchangeable with D 2 ), 4.49 (s, 2H, S-CH 2 -C), 2.17 (s, 3H, CH 3 ). MS: [M] + at m/z Anal. Calcd. for C 25 H 17 Br S: C, 40.95; H, 2.34;, 15.28: Found: C, 40.74; H, 2.65;, % -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2- (4-(2-hyroxybenzylideneamino)-5-(pyridin-4-yl)-3- thio)acetamido-1,2,4-triazole (4f) Yield 62% (Ethanol); m.p.: C. I (KBr, ν max in cm -1 ): 3446 (H), 3135 (aromatic CH), 2887 (CH 3 ), 1683 (C=.amide), 1645 (C=), 1614 (C=C of aromatic ring), 1593 (=CH), 1493 (-), 1456 (C-), 680 (C-S-C), 610 (C-Br). 1 HM (CDCl 3 ) δ in ppm : (s, 1H, H exchangeable with D 2 ), 9.57 (s, 1H, =CH), (m, 11H, Ar-H), 6.97 (s, 1H, H exchangeable with D 2 ), 4.46 (s, 2H, S- CH 2 -C), 2.18 (s, 3H, CH 3 ). MS: [M] + at m/z Anal. Calcd. for C 25 H 19 Br 8 3 S: C, 50.77; H, 3.24;, 18.95: Found: C, 50.94; H, 3.55;, 18.77% -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2- (4-(4(dimethylamino)benzylideneamino)-5-(pyridin- 4-yl)-3-thio)acetamido-1,2,4-triazole (4g) Yield 60% (Acetone); m.p C. I (KBr, ν max in cm -1 ): 3134 (aromatic CH), 2885 (CH 3 ), 1683 (C=.amide), 1648 (C=), 1615 (C=C of aromatic ring), 1591 (=CH), 1492 (-), 1455 (C-), 681 (C-S-C), 611 (C-Br). 1 HM (CDCl 3 ) δ in ppm : 8.88 (s, 1H, =CH), (m, 11H, Ar-H), 6.99 (s, 1H, H exchangeable with D 2 ), 4.49 (s, 2H, S- CH 2 -C), 2.23 (s, 6H, (CH 3 ) 2 ), 2.19 (s, 3H, CH 3 ). MS: [M] + at m/z Anal. Calcd. for C 27 H 24 Br 9 2 S: C, 52.43; H, 3.91;, 20.38: Found: C, 52.74; H, 3.75;, 20.47% 7

8 SYTHESIS AD ATIBACTEIAL ACTIVITY F SME EW PYIDIYL/QUIAZLIYL/AZETIDIYL/THIAZLIDIYL -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2- (4-(3-chloro-2-(substitutedphenyl)-4-oxoazetidin-1- yl)-5-(pyridin-4-yl)-3-thio)acetamido-1,2,4-triazoles (5a-5g) A mixture of (6-bromo-2-methyl-4-oxoquinazolin- 3(4H)-yl)-2-(4-(substituted benzylideneamino)-5- (pyridin-4-yl)-4h-3-ylthio)acetamido-1,2,4-triazoles (4a-4g) (0.01 mole) in dry dioxan (10 ml) and triethylamine (0.005 mole) was taking in round bottom flask. The reactions were stirred on an ice bath and when temperature dropped below C, then choroacetylchloride (0.015 mole) was added dropwise with stirring and reaction mixtures were refluxed for 10 h and then kept a side for 50 h. Finally, the reaction mixtures were added to ice cold water to obtain the final product. It was dried and purified by recrystallization from appropriate solvents to furnish compounds 5a-5g. -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2- (4-(3-chloro-2-(4-hydroxy-3-methoxyphenyl)-4- oxoazetidin-1-yl)-5-(pyridin-4-yl)-3-thio)acetamido- 1,2,4-triazole (5a) Yield (69%) (Methanol); m.p C. I (KBr, ν max in cm -1 ): 3456 (H), 2887 (CH 3 ), 1685 (C=.amide), 1648 (C=), 1617 (C=C of aromatic ring), 1591 (=CH), 1495 (-), 1453 (C-), 680 (C-S-C), 760 (CH-Cl), 612 (C-Br). 1 HM (CDCl 3 ) δ in ppm : (s, 1H, H exchangeable with D 2 ), (m, 10H, Ar-H), 6.98 (s, 1H, H exchangeable with D 2 ), 6.68 (d, 1H, -CH of oxoazetidine), 4.74 (d, 1H, CH-Cl of oxoazetidine), 4.46 (s, 2H, S-CH 2 -C), 3.39 (s, 3H, CH 3 ), 2.17 (s, 3H, CH 3 ). MS: [M] + at m/z Anal. Calcd. for C 28 H 22 BrCl 8 5 S: C, 48.18; H, 3.18;, 16.05: Found: C, 48.39; H, 3.25;, 16.35% -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2- (4-(3-chloro-2-(2,4-dichlorophenyl)-4-oxoazetidin- 1-yl)-5-(pyridin-4-yl)-3-thio)acetamido-1,2,4- triazole (5b) Yield 77% (DMF-water); m.p C. I (KBr, ν max in cm -1 ): 2885 (CH 3 ), 1680 (C=.amide), 1645 (C=), 1615 (C=C of aromatic ring), 1591 (=CH), 1492 (-), 1455 (C-), 761 (CH-Cl), 611 (C-Br). 1 HM (CDCl 3 ) δ in ppm : (m, 10H, Ar- H), 6.98 (s, 1H, H exchangeable with D 2 ), 6.68 (d,1h, -CH of oxoazetidine), 4.72 (d, 1H, CH-Cl of oxoazetidine), 4.45 (s, 2H, S-CH 2 -C), 2.19 (s, 3H, CH 3 ). MS: [M] + at m/z Anal. Calcd. for C 27 H 18 BrCl S: C, 44.99; H, 2.52;, 15.55: Found: C, 44.87; H, 2.75;, 15.84% -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2- (4-(3-chloro-2-(2,6-dichlorophenyl)-4-oxoazetidin- 1-yl)-5-(pyridin-4-yl)-3-thio)acetamido-1,2,4- triazole (5c) Yield 76% (Ethanol); m.p C. I (KBr, ν max in cm -1 ): 2883 (CH 3 ), 1685 (C=.amide), 1649 (C=), 1617 (C=C of aromatic ring), 1594 (=CH), 1495 (-), 1459 (C-), 763 (CH-Cl), 613 (C-Br). 1 HM (CDCl 3 ) δ in ppm : (m, 10H, Ar- H), 6.97 (s, 1H, H), 6.69 (d,1h, -CH of oxoazetidine), 4.75 (d,1h, CH-Cl of oxoazetidine), 4.47 (s, 2H, S-CH 2 -C), 2.18 (s, 3H, CH 3 ). MS: [M] + at m/z Anal. Calcd. for C 27 H 18 BrCl S: C, 44.99; H, 2.52;, 15.55: Found: C, 44.88; H, 2.74;, 15.83% -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2- (4-(3-chloro-2-(2,4-dibromophenyl)-4-oxoazetidin- 1-yl)-5-(pyridin-4-yl)-3-thio)acetamido-1,2,4- triazole (5d) Yield 60% (Methanol); m.p C. I (KBr, ν max in cm -1 ): 2885 (CH 3 ), 1680 (C=.amide), 1645 (C=), 1615 (C=C of aromatic ring), 1591 (=CH), 1492 (-), 1455 (C-), 761 (CH-Cl), 611 (C-Br). 1 HM (CDCl 3 ) δ in ppm : (m, 10H, Ar- 8

9 SYTHESIS AD ATIBACTEIAL ACTIVITY F SME EW PYIDIYL/QUIAZLIYL/AZETIDIYL/THIAZLIDIYL H), 6.99 (s, 1H, H exchangeable with D 2 ), 6.68 (d, 1H, -CH of oxoazetidine), 4.74 (d, 1H, CH-Cl of oxoazetidine), 4.46 (s, 2H, S-CH 2 -C), 2.16 (s, 3H, CH 3 ). MS: [M] + at m/z Anal. Calcd. for C 27 H 18 Br 3 Cl 8 3 S: C, 40.05; H, 2.24;, 13.84: Found: C, 40.24; H, 2.55;, 13.56% -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2- (4-(3-chloro-2-(2,6-dibromophenyl)-4-oxoazetidin- 1-yl)-5-(pyridin-4-yl)-3-thio)acetamido-1,2,4- triazole (5e) Yield 62% (Petroleum ether); m.p C. I (KBr, ν max in cm -1 ): 2889 (CH 3 ), 1683 (C=.amide), 1646 (C=), 1617 (C=C of aromatic ring), 1595 (=CH), 1496 (-), 1458 (C-), 764 (CH-Cl), 611 (C-Br). 1 HM (CDCl 3 ) δ in ppm : (m, 10H, Ar-H), 6.99 (s, 1H, H exchangeable with D 2 ), 6.69 (d,1h, -CH of oxoazetidine), 4.73 (d, 1H, CH-Cl of oxoazetidine), 4.47 (s, 2H, S-CH 2 -C), 2.16 (s, 3H, CH 3 ). MS: [M] + at m/z Anal. Calcd. for C 27 H 18 Br 3 Cl 8 3 S: C, 40.05; H, 2.24;, 13.84: Found: C, 40.26; H, 2.47;, 13.59% -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2- (4-(3-chloro-2-(2-hydroxyphenyl)-4-oxoazetidin-1- yl)-5-(pyridin-4-yl)-3-thio)acetamido-1,2,4-triazole (5f) Yield 69% (Ethanol); m.p C. I (KBr, ν max in cm -1 ): 3481 (H), 2885 (CH 3 ), 1680 (C=.amide), 1645 (C=), 1615 (C=C of aromatic ring), 1591 (=CH), 1492 (-), 1455 (C-), 761 (CH-Cl), 611 (C-Br). 1 HM (CDCl 3 ) δ in ppm : (s, 1H, H exchangeable with D 2 ), (m, 11H, Ar-H), 6.97(s, 1H, H exchangeable with D 2 ), 6.69 (d,1h, -CH of oxoazetidine), 4.74 (d,1h, CH-Cl of oxoazetidine), 4.45 (s, 2H, S-CH 2 - C), 2.19 (s, 3H, CH 3 ). MS: [M] + at m/z Anal. Calcd. for C 27 H 20 BrCl 8 4 S: C, 48.55; H, 3.02;, 16.78: Found: C, 48.78; H, 3.25;, 16.97% -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2- (4-(3-chloro-2-(4-(dimethylamino)phenyl)-4- oxoazetidin-1-yl)-5-(pyridin-3-yl)-3-thio)acetamido- 1,2,4-triazole (5g) Yield 68% (Acetone); m.p C. I (KBr, ν max in cm -1 ): 2885 (CH 3 ), 1680 (C=.amide), 1645 (C=), 1615 (C=C of aromatic ring), 1593(=CH), 1496 (-), 1458 (C-), 763 (CH-Cl), 614 (C-Br). 1 HM (CDCl 3 ) δ in ppm : (m, 11H, Ar- H), 6.98 (s, 1H, H exchangeable with D 2 ), 6.67 (d,1h, -CH of oxoazetidine), 4.75 (d, 1H, CH-Cl of oxoazetidine), 4.47 (s, 2H, S-CH 2 -C), 2.24 (s, 6H, (CH 3 ) 2 ), 2.18 (s, 3H, CH 3 ). MS: [M] + at m/z Anal. Calcd. for C 29 H 25 BrCl 9 3 S: C, 50.12; H, 3.63;, 18.14: Found: C, 50.35; H, 3.96;, 18.45% -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2- (4-(2-(substitutedphenyl)-4-oxothiazolidin-3-yl)-5- (pyridin-4-yl)-3-thio)acetamido-1,2,4-triazoles (6a- 6g) To a ethanolic solution (60 ml) of (6-bromo-2- methyl-4-oxoquinazolin-3(4h)-yl)-2-(4-(substituted benzylideneamino)-5-(pyridin-4-yl)-4h-3- ylthio)acetamido-1,2,4-triazoles (4a-4g) (0.01 mol), thioglycolic acid (0.02 mol) was added in the presence of anhydrous zinc chloride. The reaction mixtures were refluxed for 15 h. The excess of solvent was distilled off and the reaction mixtures were poured into ice water, filtered, washed with water and recrystallized from appropriate solvents to yield compounds 6a-6g. Yield (64%) (DMF-water); m.p C. I (KBr, ν max in cm -1 ): 3455 (H), 2885 (CH 3 ), 1680 (C=.amide), 1645 (C=), 1615 (C=C of aromatic ring), 1622 (C= cyclized), 1591 (=CH), 1492 (-), 1455 (C-), 1227 (CH 3 ), 9

10 SYTHESIS AD ATIBACTEIAL ACTIVITY F SME EW PYIDIYL/QUIAZLIYL/AZETIDIYL/THIAZLIDIYL 761 (CH-Cl), 683 (C-S-C), 611 (C-Br). 1 HM (CDCl 3 ) δ in ppm: (s,1h, H exchangeable with D 2 ), (m, 10H, Ar-H), 6.98 (s, 1H, H exchangeable with D 2 ), 6.69 (d,1h, -CH of oxothiazolidine), 3.73 (s, 2H, CH 2 of oxothiazoidine), 4.47 (s, 2H, S-CH 2 -C), 3.82 (s, 1H, CH 3 ), 2.18 (s, 3H, CH 3 ). MS: [M] + at m/z Anal. Calcd. for C 28 H 23 Br 8 5 S 2 : C, 48.35; H, 3.33;, 16.11:Found: C, 48.46; H, 3.70;, 16.32% -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2- (4-(2-(2,4-dichlorophenyl)-4-oxothiazolidin-3-yl)-5- (pyridin-4-yl)-3-thio)acetamido-1,2,4-triazole (6b) Yield 63% (Ethanol-water); m.p.: C. I (KBr, ν max in cm -1 ): 2889 (CH 3 ), 1686 (C=.amide), 1648 (C=), 1617 (C=C of aromatic ring), 1625(C= cyclized) 1595 (=CH), 1495 (- ), 1457 (C-), 763 (C-Cl), 685 (C-S-C), 610 (C- Br). 1 HM (CDCl 3 ) δ in ppm : (m, 10H, Ar-H), 6.99 (s, 1H, H exchangeable with D 2 ), 6.70 (s, 1H, -CH of oxothiazolidine), 4.46 (s, 2H, S-CH 2 -), 3.74 (s, 2H, CH 2 of oxothiazolidine), 2.18 (s, 3H, CH 3 ). MS: [M] + at m/z Anal. Calcd. for C 27 H 19 BrCl S 2 : C, 45.14; H, 2.67;, 15.60: Found: C, 45.35; H, 2.86;, 15.35% -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2- (4-(2-(2,6-dichlorophenyl)-4-oxothiazolidin-3-yl)-5- (pyridin-4-yl)-3-thio)acetamido-1,2,4-triazole (6c) Yield 62% (Petroleum ether); m.p C. I (KBr, ν max in cm -1 ): 2885 (CH 3 ), 1680 (C=.amide), 1645 (C=), 1615 (C=C of aromatic ring), 1626 (C= cyclized), 1591 (=CH), 1492 (-), 1455 (C-), 761 (C-Cl), 683 (C-S-C), 611 (C-Br). 1 HM (CDCl 3 ) δ in ppm : (m, 10H, Ar-H), 6.98 (s, 1H, H exchangeable with D 2 ), 6.71 (s,1h, - CH of oxothiazolidine), 4.47 (s, 2H, S-CH 2 -C), 3.75 (s, 2H, CH 2 of oxothiazolidine), 2.17 (s, 3H, CH 3 ). MS: [M] + at m/z Anal. Calcd. for C 27 H 19 BrCl S 2 : C, 45.14; H, 2.67;, 15.60: Found: C, 45.38; H, 2.89;, 15.45% -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2- (4-(2-(2,4-dibromophenyl)-4-oxothiazolidin-3-yl)-5- (pyridin-4-yl)-3-thio)acetamido-1,2,4-triazole (6d) Yield 60% (Methanol); m.p C. I (KBr, ν max in cm -1 ): 2890 (CH 3 ), 1686 (C=.amide), 1643 (C=), 1614 (C=C of aromatic ring), 1621 (C= cyclized), 1597 (=CH), 1490 (-), 1452 (C-), 685 (C-S-C), 613 (C-Br). 1 HM (CDCl 3 ) δ in ppm : (m, 10H, Ar-H), 6.98 (s, 1H, H exchangeable with D 2 ), 6.73 (s,1h, -CH of oxothiazolidine), 4.45 (s, 2H, S-CH 2 -C), 3.84 (s, 2H, CH 2 of oxothiazolidine), 2.18 (s, 3H, CH 3 ). MS: [M] + at m/z Anal. Calcd. for C 27 H 19 Br S 2 : C, 40.17; H, 2.37;, 13.88: Found: C, 40.35; H, 2.68;, 13.59% -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2- (4-(2-(2,6-dibromophenyl)-4-oxothiazolidin-3-yl)-5- (pyridin-4-yl)-3-thio)acetamido-1,2,4-triazole (6e) Yield 59% (Acetone); m.p C. I (KBr, ν max in cm -1 ): 2885 (CH 3 ), 1680 (C=.amide), 1645 (C=), 1615 (C=C of aromatic ring), 1623(C= cyclized), 1591 (=CH), 1492 (-), 1455 (C-), 683 (C-S-C), 611 (C-Br). 1 HM (CDCl 3 ) δ in ppm : (m, 10H, Ar-H), 6.99 (s, 1H, H exchangeable with D 2 ), 6.70 (s, 1H, -CH of oxothiazolidine), 4.47 (s, 2H, S-CH 2 -C), 3.85 (s, 2H, CH 2 of oxothiazolidine), 2.17 (s, 3H, CH 3 ). MS: [M] + at m/z Anal. Calcd. for C 27 H 19 Br S 2 : C, 40.17; H, 2.37;, 13.88: Found: C, 40.36; H, 2.67;, 13.58% -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2- (4-(2-(2-hydroxyphenyl)-4-oxothiazolidin-3-yl)-5- (pyridin-4-yl)-3-thio)acetamido-1,2,4-triazole (6f) 10

11 SYTHESIS AD ATIBACTEIAL ACTIVITY F SME EW PYIDIYL/QUIAZLIYL/AZETIDIYL/THIAZLIDIYL Yield 61% (Ethanol); m.p C. I (KBr, ν max in cm -1 ): 3484 (H), 2885 (CH 3 ), 1680 (C=.amide), 1645 (C=), 1615 (C=C of aromatic ring), 1625(C= cyclized), 1591 (=CH), 1493 (- ), 1455 (C-), 683 (C-S-C). 1 HM (CDCl 3 ) δ in ppm : (s,1h, H exchangeable with D 2 ), (m, 11H, Ar-H), 6.97 (s, 1H, H exchangeable with D 2 ), 6.72 (s,1h, -CH of oxothiazolidine), 4.46 (s, 2H, S-CH 2 -C), 3.83 (s, 2H, CH 2 of oxothiazolidine), 2.18 (s, 3H, CH 3 ). MS: [M] + at m/z Anal. Calcd. for C 27 H 21 Br 8 4 S 2 : C, 48.73; H, 3.18;, 16.84: Found: C, 48.95; H, 3.37;, 16.54% -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2- (4-(2-(4-(dimethylamino)phenyl)-4-oxothiazolidin- 3-yl)-5-(pyridin-4-yl)-3-thio)acetamido-1,2,4- triazole (6g) Yield 59% (DMF-water); m.p C. I (KBr, ν max in cm -1 ): 2886 (CH 3 ), 1682 (C=.amide), 1645 (C=), 1615 (C=C of aromatic ring), 1620 (C= cyclized), 1591 (=CH), 1495 (-), 1457 (C-), 682 (C-S-C). 1 HM (CDCl 3 ) δ in ppm : (m, 11H, Ar-H), 6.99 (s, 1H, H exchangeable with D 2 ), 6.73 (s,1h,-ch of oxothiazolidine), 4.48(s, 2H, S-CH 2 -C), 3.84 (s, 2H, CH 2 of oxothiazolidine), 2.21 (s, 6H, (CH 3 ) 2 ), 2.14 (s, 3H, CH 3 ). MS: [M] + at m/z Anal. Calcd. for C 29 H 26 Br 9 3 S 2 : C, 50.29; H, 3.78;, 18.20: Found: C, 50.45; H, 3.99;, 18.46% ESULTS AD DISCUSSI All the synthesized compounds were screened for their antibacterial activities at a dose of 50 mg/kg i.p. and pharmacological data of these compounds have been reported in Table 1. Compound 1 exhibited zone of inhibition diameter of 6mm against S.aureus and 5mm against P. vulgaris 11 respectively. The characteristic feature of the compounds 2a-2g is the presence of azomethine (=CH-) linkage. Among compounds 2a-2g, compound 2a was devoid of antibacterial activity and compounds 2b, 2c 2d, 2e 2f and 2g have shown mild antibacterial activity. The 3-mercapto acetyl chloride of trazoles (3a 3g) associated with mild to moderate anti bacterial activity. These compounds exhibited i.e mm zone of inhibition against S. aureus, E. coli, P. vulgaris, K. pneumoniae. The addition of 6-bromo-2- methyl-4-oxoquinozoline with substituted triazoles yielded compounds 4a-4g. The compounds 4a-4g were found to possess moderate antibacterial activity. Compound 4b exhibited zone of inhibition 17mm against S. aureus, 15mm against P. vulgaris and 18mm against K. pneumoniae antibacterial activity. Compounds 4a-4g have shown better antibacterial activity than compounds 3a-3g. Cyclization of compounds 4a-4g into 5a-5g. Among azetidinones 5a-5g, compound 5b exhibited promising antibacterial activity. Compound 5b showed better antibacterial activity against S.aureus (21mm), E.coli (22mm), K. pneumoniae (20mm). Cyclization of compounds 4a-4g into 6a-6g. Among the compounds 6a-6g, compounds 6b and 6c showed better antibacterial activity than standard drug against S.aureus, E.coli and P.vulgaris. The compound 6e was found to exhibited equipotent antibacterial activity to that standard drugs. Compounds 6a, 6d, 6f and 6g showed good antibacterial activity. These compounds exhibited mm zone of inhibition against S. aureus, E. coli P. vulgaris, K. pneumoniae. The synthesized compounds were also tested for approximate lethal dose ALD 50 and were found to exhibit a higher value of ALD 50 i.e. more than 1000mg/kg i.p. except compound 6b, 6c which

12 SYTHESIS AD ATIBACTEIAL ACTIVITY F SME EW PYIDIYL/QUIAZLIYL/AZETIDIYL/THIAZLIDIYL exhibited ALD 50 of more than 2000mg/kg i.p. (maximum dose tested). As these compounds have Table 1a shown high value of ALD 50 thus indicating good safety margin. Antibacterial activity of the compounds: 4-amino-5-pyridin-3-mercapto-1,2,4-triazole (1),4-(4-hydroxy-3- methoxy benzylideneamino)-5-(pyridin-4-yl)-4h-3-mercapto-1,2,4-triazoles (2a-g). SH SH H 2 1 2(a-g) ALD 50 Compound Bacterial growth inhibition (diameter) Mg/kg i.p o. S. aureus E. coli P. vulgaris K. pneumoniae 1 6mm _ 5mm _ >1000 2a 4-H, 3-CH 3 >1000 2b 2,4-Cl 10mm 8mm 7mm _ >1000 2c 2,6-Cl 9mm _ 8mm 6mm >1000 2d 2,4-Br _ 7mm >

13 SYTHESIS AD ATIBACTEIAL ACTIVITY F SME EW PYIDIYL/QUIAZLIYL/AZETIDIYL/THIAZLIDIYL 2e 2,6-Br 5mm _ >1000 2f 2-H 6mm _ >1000 2g (CH 3 ) 2 6mm _ 7mm 5mm >1000 Ampicllin 20mm 18mm 18mm 14mm Gattifloxacin 25mm 22mm 20mm 21mm Table1b Antibacterial activity of the compounds: 4-(4-hydroxy-3-methoxy benzylideneamino)-5-(pyridin-4-yl)-4h-3- ylthioacetyl chloride-1,2,4-triazoles (3a-g), -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2-(4-(4- hydroxy-3-methoxybenzylidineamino)-5-(pyridin-4-yl)-4h-3-ylthio)acetamide-1,2,4-triazoles (4a-g). SCH 2 CCl CH SCH 2 CH CH Br (3a-g) (4a-g) ALD 50 Bacterial growth inhibition (diameter) Mg/kg i.p Compound o. S. aureus E. coli P. vulgaris K. pneumoniae 3a 4-H, 3-CH 3 10mm _ 8mm _ >

14 SYTHESIS AD ATIBACTEIAL ACTIVITY F SME EW PYIDIYL/QUIAZLIYL/AZETIDIYL/THIAZLIDIYL 3b 2,4-Cl 13mm 12mm >1000 3c 2,6-Cl _ 10mm >1000 3d 2,4-Br _ 11mm >1000 3e 2,6-Br 10mm _ 7mm _ >1000 3f 2-H 8mm _ 9mm 7mm >1000 3g (CH 3 ) 2 7mm _ 9mm _ >1000 4a 4-H, 3-CH 3 _ 12mm >1000 4b 2,4-Cl 17mm _ 15mm 18mm >1000 4c 2,6-Cl 15mm 14mm _ 13mm >1000 4d 2,4-Br _ 13mm 12mm _ >1000 4e 2,6-Br _ 12mm _ 11mm >1000 4f 2-H 11mm _ 10mm 9mm >1000 4g (CH 3 ) _ 11mm >1000 Ampicillin 20mm 18mm 18mm 14mm Gattifloxacin 25mm 22mm 20mm 21mm 14

15 SYTHESIS AD ATIBACTEIAL ACTIVITY F SME EW PYIDIYL/QUIAZLIYL/AZETIDIYL/THIAZLIDIYL Table1c Antibacterial activity of the compounds: -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2-(4-(3-chloro-2- (4-hydroxy-3-methoxyphenyl)-4-oxoazetidin-1-yl)-5-(pyridin-4-yl)-4H-3-ylthio)acetamide-1,2,4-triazoles (5ag), -(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)-2-(4-(2-(4-hydroxy-3-methoxyphenyl)-4-oxothiazolidin- 3-yl)-5-(pyridin-4-yl)-4H-3-ylthio)acetamide-1,2,4-triazoles (6a-g). H C SCH 2 CH Br H C SCH 2 CH Br Cl S (5a-g) (6a-g) ALD 50 Bacterial growth inhibition (diameter) Mg/kg i.p Compound o. S. aureus E.coli P. vulgaris K. pneumoniae 5a 4-H, 3-CH 3-18mm 16mm - >1000 5b 2,4-Cl 21mm 22mm - 20mm >1000 5c 2,6-Cl 20mm 16mm - 17mm >1000 5d 2,4-Br 18mm 18mm 16mm - >1000 5e 2,6-Br 18mm - 15mm 17mm >

16 SYTHESIS AD ATIBACTEIAL ACTIVITY F SME EW PYIDIYL/QUIAZLIYL/AZETIDIYL/THIAZLIDIYL 5f 2-H 15mm 17mm - 12mm >1000 5g (CH 3 ) 2-16mm - 14mm >1000 6a 4-H, 3-CH 3 22mm - 20mm 21mm >1000 6b 2,4-Cl 26mm - 24mm - >2000 6c 2,6-Cl 27mm 23mm 21mm - >1000 6d 2,4-Br - 19mm - 20mm >1000 6e 2,6-Br 20mm - 20mm 21mm >1000 6f 2-H 21mm 18mm - - >1000 6g (CH 3 ) 2 18mm 19mm - - >1000 Ampicillin 20mm 18mm 18mm 14mm Gattifloxacin 25mm 22mm 20mm 21mm CCLUSIS While considering all the newly synthesized compounds of this series we may concluded that: 1. 2,4/2,6-di chlorophenyl substituted triazole derivatives showed more efficacy 2. Incorporation of azetidinones moieties are beneficial to antibacterial activities. 3 Compounds 6b and 6c are the most potent antibacterial compound of this series in comparision to used standard drugs viz. Ampicillin, Gattifloxacine. 4 Compounds 6a-6g containing thiazolidinones exhibited better antibacterial activity than rest of the compounds of this series. 16 EFEECE 1..A. Phillips, E.E. Udo, M.E. Abdel-Hamid,. Varghese; Synthesis and antibacterial activity of novel 5-(4-methyl-1H-1,2,3-triazole)methyl oxazolidinones; Eur. J. Med. Chem., 44(B) (2009) S.D. Srivastava, T.. awat; Synthesis of new benzotriazole derivatives: antimicrobial and anticonvulsant agents; Indian J. Chem., 38B (1999) H.G. Jin, X.Y. Sun, K.Y. Chai, H.. Piao, S.Z. quan; Anticonvulsant and toxicity evaluation of some 7-alkoxy-4,5-dihydro-[1,2,4-]triazolo[4,3-

17 SYTHESIS AD ATIBACTEIAL ACTIVITY F SME EW PYIDIYL/QUIAZLIYL/AZETIDIYL/THIAZLIDIYL a]quinazolinone-1 (2H)-one; bioorg. Med. Chem., 20 (2006), Y. Dundar, B. Cakir, E. Kupeli, M.F. Sahin,. oyanalpan; Synthesis of some new 1- Acylthiosemicarbazides and 1,2,4-triazol-5- thiones and their analgesic and anti- Inflammatory activities; Turk J. Chem., 31 (2007) A. A.-M. Abdel-Aziz, H.I. El-Subbagh,T. Kunieda; Lewis acid-promoted transformation of 2-alkoxypyridines into 2-aminopyridines and their antibacterial activity. Part2: emarkably facile C- bond formation; Bioorganic & Med. Chem., 13 (2005) S.B. Holla, M.T. Padmaja, M.K. Shivananda, P.M. Akbarali; Synthesis and antibacterial activity of nitro furylvinyl quinazolinones. Indian J. Chem., 37B (1998) D.K. Shukla, S.D. Srivastava; Synthesis of some new 5-[2-{1,2,3-benzotriazol-1-yl-methyl}-1 - (4-substituted aryl-3-chloro-2-oxoazetidine)]- ameno-1,3,4-thiadiazoles:antifungal and antibacterial agents; Indian J. of Chem., 47B, (2008), S. Bhusare, B.A. Shinde, P.. Pawar P, B.Y. Vibhute; Synthesis and antimicrobial activity of heterocyclic schif bases, 4-thiazolidinones and 2-azetidinones; Indian J. Pharm. Sci., 3 (2004) Chuinckshank, J.P. Dugid,.H.A. Swain; Medical Microbiology, 2 (1975). 10. Q.E. Smith; Pharmacological Screening Tests Progressive, Medicinal Chemistry Butterworths, London, 1 (1960)