title: Synthesis, docking studies and anti-inflammatory activity of 4,5,6,7-tetrahydro-2H-indazole derivatives.
abstract: A regioselective synthesis of 2,3-disubstituted tetrahydro-2H-indazols, mediated by alpha-zirconium sulfophenylphosphonate-methanephosphonate, was reported. Docking studies into the catalytic site of COX-2 were used to identify potential anti-inflammatory lead compounds. Two lead derivatives were chosen endowed with good binding energies and good ADME profiling. The biological in vivo evaluation of these compounds in two different experimental models (Freund's adjuvant-induced arthritis and carrageenan-induced oedema) proved the presence of anti-inflammatory activity. Noteworthy, both compounds evidenced the lack of any gastric injury even at high doses in gastric ulcerogenic assays.
authors: Dipartimento di Chimica e Tecnologia del Farmaco, Via del liceo 1, University of Perugia, 06123 Perugia (PG), Italy. ornros@unipg.it
authors: Ornelio
authors: O
authors: Rosati
authors: Massimo
authors: M
authors: Curini
authors: Maria Carla
authors: MC
authors: Marcotullio
authors: Antonio
authors: A
authors: Macchiarulo
authors: Marina
authors: M
authors: Perfumi
authors: Laura
authors: L
authors: Mattioli
authors: Francesco
authors: F
authors: Rismondo
authors: Giancarlo
authors: G
authors: Cravotto
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000473:pathology; D002351:Carrageenan; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005528:Foot / Q000473:pathology; D005620:Freund's Adjuvant; D007191:Indazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D007191:Indazoles; D007202:Indicators and Reagents; D002351:Carrageenan; D005620:Freund's Adjuvant