Discovery of novel urea-diarylpyrazole hybrids as dual COX-2/sEH inhibitors with improved anti-inflammatory activity and highly reduced cardiovascular risks.

Herein we describe our efforts to develop novel anti-inflammatory/analgesic agents devoid of known cardiovascular drawbacks. In doing so, two 1,5-diarylpyrazole series of urea linked (9a-f) and amide linked (11a-f) compounds were synthesized and evaluated in vitro as dual COX-2/sEH inhibitors using recombinant enzyme assays. The in vivo anti-inflammatory and analgesic activities were then examined using reported animal models.

Design, synthesis and analgesic/anti-inflammatory evaluation of novel diarylthiazole and diarylimidazole derivatives towards selective COX-1 inhibitors with better gastric profile.

The inhibition of gastric cyclooxygenase 1 (COX-1) enzyme was believed to be the major cause of non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastric ulcer. Recent studies disproved this belief and showed that the gastric tissues vulnerability is not solely connected to COX-1 inhibition. This work aimed at exploring and rationalizing the differential analgesic and anti-inflammatory activities of novel selective COX-1 inhibitors with improved gastric profile.