Studies on The Synthesis of 5-Chloro-6-(Substitue Thiazole-4-yl)-2-Oxo-3H-Benzoxazole derivatives and on identification of their COX inhibitory activities

The aim of this study is to synthesize 18 new 1,3-diaryl heterocyclic compounds starting from 5-chloro-2-oxo-3H-benzoxazole and to prove their structure and to evaluate their COX-1 and COX-2 inhibitory activities. The synthesized compounds are originated from 5-chloro-6-(2- substitue phenyl-1,3-thiazole-4-yl)-2-oxo-3H-benzoxazole and [5-chloro-6-(2- substitue phenyl-1,3-thiazole-4-yl)-2-oxo-3H-benzoxazole-3-yl] acetic acid and the ester forms of these acids. The synthesized 1,3-diaryl compounds possess thiazole ring as central heterocyclic ring and possess 5-chloro-2-oxo-3H-benzoxazole and 2 or 4 substitue phenyl as diaryl substitutions. The third position of 5-chloro-2-oxo- 3H-benzoxazole is substitued with acetic acid or ester moiety and the phenyl ring is substitued with small groups such as fluorine, chlorine and methoxy. Based on the literature, the synthesized compounds are considered to have selective COX-2 inhibitory activity. The compounds possessing acetic acid moiety are expected to have TXA2 synthase activity as well as selective COX-2 inhibitory activity. Complete structural assignments of all compounds were established by 1H-NMR and IR spectroscopic data and the results of these data are supported with elementary analysis. The activities of the compounds for possible COX-1 and COX-2 inhibitory activity were performed by enzyme immunoassay method at 10 ?M concenration. Ethyl {5-chloro-6-[2-(2-florophenyl)-1,3-thiazole-4-yl]-2-oxo-3Hbenzoxazole- 3-yl}acetate (Compound 11) have been found out considerable for evaluating the increase in selective COX-2 inhibition and {5-chloro-6-[2-(4- methoxyphenyl)-1,3-thiazole-4-yl]-2-oxo-3H-benzoxazole-3-yl}acetic acid (Compound 16) have been found out considerable for evaluating the increase in COX-1 and COX-2 inhibitory activity. Key words: 1,3-diaryl heterocyclic compounds, selective COX-2 inhibition, 5-chloro-2-oxo-3H- benzoxazole.