Synthesis of Some Novel 2-Azetidinones/4-Thiazolidinones Bearing 1, 3, 4- Thiadiazole Nucleus and Screening for its Anti-Imflammatory Activity

Abstract

Objective: The objective of the study was to synthesize a series of 3-chloro-4-(substituted phenyl)-1-(5-styryl-1, 3, 4-thiladiazole-2-yl) azetidin-2-one / 2-(substituted phenyl)-3-(5-styryl-1, 3, 4- thiadiazole-2-yl)-thiazolidin-4-one and screened for their possible anti-inflammatory activity by carrageenan induced paw edema in rats. Method: The synthesis of 2-amino-5-styryl-1, 3, 4-thiadiazole, an intermediate was carried out by oxidative cyclization method. In the current study, thiosemicarbazone (I) was subjected to oxidative cyclization using ferric chloride as an oxidising agent, to get 2- amino- 5- styryl -1, 3, 4-thiadiazole (II). Futhermore, compound (II) was reacted with different aromatic aldehydes in methanol to form N-(4-sustituted)- 5- styryl- 1, 3, 4-thiadiazol-2-amine (III a-h). Compound (III ah) was reacted with chloroacetyl chloride in triethylamine to form 2-azetidinone derivatives bearing 1, 3, 4-thiadiazole nucleus (IV a-h). Compound (III a-h) on cyclocondensation with mercaptoacetic acid leads to the formation of 4- thiazolidinone derivatives bearing 1, 3, 4-thiadiazole nucleus (V a-h). Results: The synthesis of the targeted compounds IVa-h and Va-h was confirmed through their MP, IR, 1H-NMR and mass spectrum studies. Compounds IVa, IVb and IVc (56.32, 61.11 and 58.24 % inhibition) exhibited significant antiinflammatory activity than that of diclofenac (65.13% inhibition). Conclusion: It may be concluded that the presence of methoxy, nitro and hydroxyl phenyl groups substituting 2- azetidinone bearing 1, 3, 4-thiadiazole showed significant anti-inflammatory activity. Keywords: Anti-inflammatory activity, diclofenac, 2-Azetidinone, 4-Thiazolidinone, 1, 3, 4-Thiadiazole, carrageenan induced paw edema.