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Trimethyl‐4‐oxo‐4,5,6,7‐tetrahydroindazole‐1‐acetic Acid: A New Lead Compound with Selective COX‐2 Inhibitory Activity
Author(s) -
AbdelRahman Hamdy M.,
Ozadali Keriman
Publication year - 2012
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201200193
Subject(s) - acetic acid , chemistry , lead compound , cyclooxygenase , enzyme , stereochemistry , selectivity , active site , inhibitory postsynaptic potential , docking (animal) , in vitro , biochemistry , catalysis , biology , medicine , nursing , neuroscience
A novel series of 3,6,6‐trimethyl‐4‐oxo‐4,5,6,7‐tetrahydroindazole‐1‐acetic acid derivatives was designed and synthesized by a new one‐step pathway. Structure elucidation of the synthesized compounds was confirmed by various spectral and elemental analyses. The prepared compounds were evaluated for their ability to inhibit cyclooxygenase‐2 (COX‐2) and cyclooxygenase‐1 (COX‐1) enzymes in vitro . Among the synthesized compounds, the 2‐(3,6,6‐trimethyl‐4‐oxo‐4,5,6,7‐tetrahydroindazol‐1‐yl)acetic acid 4 emerged as the most potent COX‐2 inhibitor (IC 50 value: 150 nM) with the highest selectivity index (COX‐1/COX‐2 inhibition ratio: 570.6). Docking studies of compound 4 in the active site of COX‐2 recognized its potential binding mode to the enzyme. Based on the preliminary results, compound 4 was considered as a lead compound for further optimization.