Studies on the synthesis and COX inhibitory effects of some 5-chloro-6-(thiazole-4-YL)-2-oxo-3H-benzothiazole derivatives

The aim of this master thesis is perform the synthesis of compounds which may possess both COX-2 and TxA2 inhibitory activities and determine in vitro COX-2 selective inhibitory activities of these compounds by in vitro enzyme immunoassay method. In this study, twelve compounds which bear a central thiazole ring and have 1,3 diaryl structure were designed and synthesized. Since the six of the designed compounds have the structural features needed to achieve TxA2 inhibitory activity, these six compounds were also expected to have antiplatelet activity. The designed compounds carry 5-chloro-2-oxo-3H-benzothiazole and phenyl moiety at meta positions of the central thiazole ring. Derivatives carrying F, Cl, OCH3 groups at positions meta or para of phenyl ring have synthesized. The structure of the compounds have been elucidated by IR, 1H-NMR and elementary analysis data. The test for the COX-1 and COX-2 enzyme inhibitory activity has been performed at 10 ?M concentration. Two of the compounds which have the structure [5- chloro-6-[2-(2-chlorophenyl)-1,3-thiazole-4-yl]-2-oxo-3Hbenzothiazole- 3-yl]acetic acid (Compound 8) and [5-chloro-6-[2-(4- florophenyl)-1,3-thiazole-4-yl]-2-oxo-3H-benzothiazole-3-yl]acetic acid (Compound 12) attracts attention. First one exhibits increased COX-1 and COX-2 inhibitory activity and second one exhibits increased COX-2 selective inhibitory activity. Key Words: Thiazole, 5-chloro-2-oxo-3H-benzothiazole, COX-2 selective inhibitors, TxA2 inhibitory activity