Studies on the synthesis and cox inhibitory activities of some 6-(thiazole-4-yl)-2-oxo-3h-benzoxazole derivatives

The aim of this thesis dissertation is to perform the synthesis of compounds which may have dual COX-2 and Tx synthase inhibitory activities, therefore minimizing side effects such as the cardiovascular problems currently associated with COX-2 inhibitors and to evaluate in vitro COX inhibitory activities of the synthesized compounds. The compounds were designed by inspiration from 1,3-diaryl heterocyclic COX-2 inhibitors and tromboxane synthase inhibitors. These compounds carry thiazole as a central heterocyclic ring substituted with 2- oxo-3H-benzoxazole and substitue phenyl moiety at meta positions. The derivatives that bear acetic acid or ester function at position 3 of 2-oxo-3Hbenzoxazole and -F, -Cl, -OCH3 substituted phenyl ring at o- or ppositions have been synthesized. After structure elucidation of compounds by means of IR, 1HNMR and elementary analysis, the COX-1 and COX-2 inhibitory activities were screened at 10 ?M concentration. Ethyl 6-[2-(4-florophenyl)-1,3-thiazole-4-yl]-2-oxo-3Hbenzoxazole- 3-yl]acetate (Compound 10), ethyl 6-[2-(4-chlorophenyl)-1,3- thiazole-4-yl]-2-oxo-3H-benzoxazole-3-yl]acetate (Compound 11) and ethyl 6-[2-(4-methoxyphenyl)-1,3-thiazole-4-yl]-2-oxo-3H-benzoxazole-3- yl]acetate (Compound 12) have shown selective COX-1 inhibitory activities. For inhibitory activities, the ester residue and para substitue phenyl ring with electron withdrawing groups are seem to be important. Key Words: 1,3-diaryl heterocyclic COX-2 inhibitors, 2-oxo- 3H-benzoxazole, thiazole, Tx synthase inhibitors