Synthesis, docking studies and anti-inflammatory activity of 4,5,6,7-tetrahydro-2H-indazole derivatives |
| |
Authors: | Rosati Ornelio Curini Massimo Marcotullio Maria Carla Macchiarulo Antonio Perfumi Marina Mattioli Laura Rismondo Francesco Cravotto Giancarlo |
| |
Institution: | Dipartimento di Chimica e Tecnologia del Farmaco, Via del liceo 1, University of Perugia, 06123 Perugia (PG), Italy. ornros@unipg.it |
| |
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. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|