Pyrazolobenzotriazinone derivatives as COX inhibitors: Synthesis, biological activity, and molecular-modeling studies

Abstract

Pyrazolylbenzotriazinones are endowed with a structural analogy with the COX-2 selective inhibitor celecoxib. Considering that our research group has long been interested in the 3-pyrazolyl-substituted benzotriazinones as anti-inflammatory agents, six new pyrazolylbenzotriazinone derivatives 16a-c and 18a-c have been prepared by reacting the opportune ethyl 5-(2-aminobenzamido)- 1-(pyridin-2-yl)-1H-pyrazole-4-carboxylate or 5-(2-aminobenzamido)-1-(pyridin-2- yl)-1H-pyrazole-4-carboxyic acid with sodium nitrite in glacial acetic acid. The biological studies revealed a good pharmacological profile for some pyrazolylbenzotriazinones and, in the case of the ethyl 5-(4-oxo-1,2,3- benzotriazin-3(4H)-yl)-1-pyridin-2-yl-1H-pyrazole-4-carboxylate, a good COX-1/COX-2 selectivity. Molecular modeling studies confirmed the obtained biological results. Gastrolesivity in all those therapies associated to an inflammatory process calls for the availability of new anti-inflammatory agents. Therefore, new pyrazolylbenzotriazinones were synthesized and tested for their COX-1 and COX-2 inhibitory activities. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.