Pyrazolobenzotriazinone derivatives as COX inhibitors: synthesis, biological activity, and molecular-modeling studies.
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.
Department of Pharmaceutical Chemistry and Technology, University of Palermo, Italy. demraffa@unipa.it
Demetrio
D
Raffa
Onofrio
O
Migliara
Benedetta
B
Maggio
Fabiana
F
Plescia
Stella
S
Cascioferro
Maria Grazia
MG
Cusimano
Giuseppe
G
Tringali
Carla
C
Cannizzaro
Fulvio
F
Plescia
D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D011720:Pyrazoles; D013329:Structure-Activity Relationship; D013449:Sulfonamides; D014227:Triazines / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D014227:Triazines; D000068579:Celecoxib