Abstract

DESIGN, SYNTHESIS AND PHARMACOLOGICAL SCREENING OF A 5-CYANO-6-METHYLMERCAPTO-2,4-DI[(SUBSTITUTED ARYL)AMINO]PYRIMIDINES AS POTENT ANTI-INFLAMMATORY AGENTS (SELECTIVE COX-II INHIBITORS)

Vishal Chudasama*

Abstract

The design, synthesis, and development of novel non-steroidal anti-inflammatory drugs (NSAIDs) with better activity and lower side effects are respectable area of research. Novel Pyrimidine derivatives were designed and synthesized, and their respective chemical structures were deduced using various spectral tools (IR, 1H NMR and MS). The compounds were synthesized via Dimroth rearrangement reaction. The reaction involves nucleophilic attack by amine of S,N acetal at the amidine carbon of methylisothiourea ether with concomitant loss of methyl mercaptan. The resultant guanidine intermediate undergoes intramolecular cyclisation to afford the condensed 4-iminopyrimidine, the designed series. The anti-inflammatory activity of all synthesized compounds was investigated applying the Carrageenan-induced paw edema model against Celecoxib as positive control. Percentage inhibition of edema indicated that compounds were exhibiting a significant anti-inflammatory activity. Ulcerogenic potency of most potent compound among all was evaluated using: Development of hemorrhages and ulcer after treatment with drug technique. Further same compound was screened for COX-I binding capacity using Inhibition of RBC aggregation method. The selected compound showed law ulcerogenic potency as compared to Aspirin and had law COX-I binding capacity, which help us to postulate our compounds to be selective COX-II inhibitors.

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