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.

journal_name

Bioorg Med Chem

authors

Rosati O,Curini M,Marcotullio MC,Macchiarulo A,Perfumi M,Mattioli L,Rismondo F,Cravotto G

doi

10.1016/j.bmc.2007.03.006

subject

Has Abstract

pub_date

2007-05-15 00:00:00

pages

3463-73

issue

10

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(07)00192-7

journal_volume

15

pub_type

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