Novel Pyrazole Derivatives Bearing Carbonitrile and Substituted Thiazole Moiety for Selective COX‐2 Inhibition.

In this study, a series of derivatives of pyrazole hybrid structures containing carbonitrile and substituted thiazole moiety were designed to search for selective COX‐2 inhibition. The designed target structures were synthesized with easy, practical, and efficient procedures. COX‐1/2 inhibition and cytotoxic effects of the synthesized compounds were evaluated in NIH/3T3 and MDA‐MD‐231 cell lines for inhibition concentration and selectivity index. The results showed that the compounds have an inhibitory effect with higher selectivity towards COX‐2 overall in both cell lines and moderate antiproliferative activity by targeting the breast cancer cell line MDA‐MB‐231. Among the 19 compounds synthesized (19 a–t), especially compound 19 m was found to be highly effective with COX‐2 inhibition of 5.63 μM in the NIH/3T3 cell line and 4.12 μM in the MDA‐MB‐231 cell line. Moreover, molecular docking studies showed that the compounds indeed exhibited higher affinity for the COX‐2 active site. The theoretical ADMET properties of the presented compounds were calculated, and the results showed that the compounds may have a more favorable pharmacokinetic effect profile than the selective COX‐2 inhibitor Celecoxib, thus promising COX‐2 inhibitor drug candidates for the future. [ABSTRACT FROM AUTHOR]