Synthetic Approaches towards the Sulfonamide Substituted‐1,5‐Diarylimidazole‐2‐thiones as Selective Cyclooxygense‐2 inhibitors

Abstract

A new series of sulfonamide substituted 1,5‐diarylimidazole, possessing C‐2 alkylthio moiety, were synthesized for their cyclooxygense‐2 (COX‐2) inhibitory activity starting from condensation of N,N‐dibenzylaminosulfonylphenacylamine hydrochloride (2) and corresponding isothiocyanate in the presence of Et3N, followed by alkylation in the basic medium. In concomitant with these intermediates, 2‐arylamino‐5‐arylthiazole derivatives 5 were also produced. The ratio of these two products was variable with different isothiocyanates. Final debenzylation was achieved using concentrated sulfuric acid to give the title sulfonamides 8.

Hydroxycinnamic acid as a novel scaffold for the development of cyclooxygenase-2 inhibitors

“…Furthermore, due to the structural similarities between resveratrol and HCAs, both sharing the hydroxyphenylethylene moiety, the rationale for the activity of HCAs on COX-2 is strengthened, providing a solid background for the development of COX inhibitors based on the HCA scaffold. In continuation of our previous studies on biological evaluation of various synthetic derivatives as COX inhibitors [30][31][32][33] we report the COX inhibitory activity of HCA derivatives (Fig. 2B) based on p-coumaric acid (PCA), caffeic acid (CA) and 3,4,5-trihydroxycinnamic acid (THCA).…”

Recent development on COX-2 inhibitors as promising anti-inflammatory agents: The past 10 years

“…In addition, several substituted 1,5-diarylimidazole derivatives having the thioalkyl group at position 2 were reported by Navidpour et al. 34 in 2014. Of these, compound 25 showed the moderate inhibition (EIA) (IC 50 = 14.2 μmol/L) of COX-2 and displayed less selectivity (SI = 3.1) than celecoxib (IC 50 = 0.544 μmol/L; SI = 19.4).…”