Synthesis of 2-substituted-4-aryl-6-phenylpyridazin-3(2H)-ones as potential anti-inflammatory and analgesic agents with cardioprotective and ulcerogenic sparing effects

Several new 2-substituted-4-aryl-6-phenylpyridazin-3(2H)-ones were synthesized and evaluated for in vivo anti-inflammatory and analgesic activities and possible in vitro COX-2 selectivity. To critically evaluate the possibility of deleterious effects of newly synthesized agents on normal hemostasis, anti-platelet activity and whole blood clotting time were also assessed. The structures of the synthesized compounds were confirmed on the basis of spectral data and elemental analysis. The present study has led to the identification of 4-(4-methoxyphenyl)-2-(2-(4-phenylpiperazin-1-yl)-2-oxoethyl)-6-phenylpyridazin-3(2H)-one (17) as an ideal anti-inflammatory agent with good affinity and remarkable selectivity for COX-2 enzyme without any ulcerogenic and cardiovascular side effects. In addition, at lower doses all the pyridazinone derivatives do not seem to affect normal hemostatic balance.