Premium
Pyrazolobenzotriazinone Derivatives as COX Inhibitors: Synthesis, Biological Activity, and Molecular‐Modeling Studies
Author(s) -
Raffa Demetrio,
Migliara Onofrio,
Maggio Benedetta,
Plescia Fabiana,
Cascioferro Stella,
Cusimano Maria Grazia,
Tringali Giuseppe,
Cannizzaro Carla,
Plescia Fulvio
Publication year - 2010
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200900317
Subject(s) - pyrazole , chemistry , carboxylate , acetic acid , molecular model , biological activity , stereochemistry , sodium nitrite , selectivity , chemical synthesis , biochemistry , organic chemistry , in vitro , catalysis
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)‐1 H ‐pyrazole‐4‐carboxylate or 5‐(2‐aminobenzamido)‐1‐(pyridin‐2‐yl)‐1 H ‐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(4 H )‐yl)‐1‐pyridin‐2‐yl‐1 H ‐pyrazole‐4‐carboxylate, a good COX‐1/COX‐2 selectivity. Molecular modeling studies confirmed the obtained biological results.