Abstract

DESIGN, SYNTHESIS AND PHARMACOLOGICAL SCREENING OF 5-CYANO-6-(METHYLMERCAPTO)-3-(SUBSTITUTED)PHENYL-2-[(SUBSTITUTED ARYL)AMINO]-PYRIMIDIN-4(3H)-ONES AS POTENT ANTI-INFLAMMATORY AGENTS (SELECTIVE COX-2 INHIBITORS)

Vishal Chudasama*

ABSTRACT

Arachidonic acid cascade produces variety of biochemical compound called prostanoids, with potent biological activity like pain, inflammation, edema etc. Cyclooxygenase play vital role in conversion of arachidonic acid in to prostanoids, which can be blocked by NSAIDs. COX-II is the inducible isoform of COX responsible for several side effect of NSAIDs. A series of -Cyano-6-(methylmercapto)-3-(substituted)phenyl-2-[(substituted aryl)amino]-pyrimidin-4(3H)-ones were designed based on its structural similarity with celecoxib. The 3D superimposition of designed series with celecoxib found to have law r.m.s.d value 0.169 Å.. The designed series was obtained by condensation of S. N. Acetal with symmetrical S-methyl isothiourea in a high boiling dipolar aprotic solvent like DMF, containing catalytical amount of anhydrous potassiumcarbonate. All compounds were characterised by Physical and spectral analysis. All the synthesized compounds were screened for anti-inflammatory activity by Rat pae edema method (in vivo). All compound showed significant anti-inflammatory activity. The promising compound with anti-inflammatory activity comparable to celecoxib was further screened for ulcerogenic activity and COX-II selectivity. Compound had comparable law ulcer as compared to standard drug aspirin. Also compound showed COX-II selectivity.

Keywords: NSAIDs, Inflammation, Ulcer, COX, Pyrimidine.