6533b81ffe1ef96bd127857b

RESEARCH PRODUCT

Pyrazolobenzotriazinones Derivatives as COX Inhibitors: Synthesis Biological Activity and Molecular Modeling Studies

Demetrio RaffaOnofrio MigliaraBenedetta MaggioFabiana PlesciaStella CascioferroMaria Grazia CusimanoGiuseppe TringaliCarla CannizzaroFulvio Plescia

subject

Models MolecularMolecular modelAnti-Inflammatory AgentsPharmaceutical Science2-(1H-pyrazol-1-yl)pyridines 4(3H)-Benzotriazinones docking COX-2 inhibitorsCOX-2 inhibitorschemistry.chemical_compoundAcetic acidStructure-Activity Relationship4(3H)-BenzotriazinonesDrug DiscoverymedicineStructure–activity relationshipOrganic chemistryHumansSodium nitriteSulfonamidesCyclooxygenase 2 InhibitorsTriazinesBiological activitySettore CHIM/08 - Chimica FarmaceuticachemistryDocking (molecular)CelecoxibCelecoxibSettore BIO/14 - FarmacologiaPyrazolesSelectivitymedicine.drug

description

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.

yearjournalcountryeditionlanguage
2010-01-01
10.1002/ardp.200900317http://hdl.handle.net/10447/52002