Inhibition of prostaglandin biosynthesis by clidanac and related compounds: structural and conformational requirements for PG synthetase inhibition.
J Pharm Pharmacol, 1981/1;33(1):29-32.
PMID: 6114148
Impact factor: 4.81
Abstract
The inhibition of prostaglandin (PG) biosynthesis by clidanac (6-chloro-5-cyclohexyl-1-indancarboxylic acid, TAI-284), its metabolites and some analogues has been examined using various microsomal preparations as enzyme source. Clidanac and some analogues were among the most potent inhibitors. The (+)-isomer of clidanac was shown to be 1000 times more potent than the (-)-isomer in inhibiting PG synthetase activity. The cis-3'-hydroxyl metabolite which retains anti-inflammatory activity comparable to that of clidanac had much less inhibitory activity. Structure-activity studies with clidanac analogues showed that the position of halogen substitution in 1-indancarboxylic acid is of considerable significance for the conformational requirement for binding to the enzyme.
MeSH terms
Animals; Anti-Inflammatory Agents; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Guinea Pigs; Indans; Indenes; Male; Molecular Conformation; Prostaglandin Antagonists; Prostaglandins; Rabbits; Rats; Stereoisomerism; Structure-Activity Relationship
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