Pyrazolobenzotriazinones Derivatives as COX Inhibitors: Synthesis Biological Activity and Molecular Modeling Studies
- Authors: Raffa, D; Migliara, O; Maggio, B; Plescia, F; Cascioferro, SM; Cusimano, MG; Tringali, G; Cannizzaro, C; Plescia, F
- Publication year: 2010
- Type: Articolo in rivista (Articolo in rivista)
- Key words: 2-(1H-pyrazol-1-yl)pyridines, 4(3H)-Benzotriazinones, docking, COX-2 inhibitors
- OA Link: http://hdl.handle.net/10447/52002
Abstract
Pyrazolylbenzotriazinones are endowed with 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 16a, a good COX-1/COX-2 selectivity. Molecular modeling studies confirmed the obtained biological results.