Abstract
CS-600, sodium 2- (4- (2-oxocyclopentan-l-yl methyl) phenyl) propionate, which has potent anti-inflammatory and analgesic activities, showed a weak inhibitory activity to thein vitroPG synthesis with bovine seminal vesicle microsomes (IC50: 760μM) . Its main metabolite, which was produced by stereospecific reduction of the cyclopentanone moiety to hydroxy cyclopentane, exhibited a potent inhibitory activity (IC50: 9 μM) to the enzyme. The stereospecific configuration (trans-OH, SRS) was essential for the inhibitory activity. Oral administration of CS-600 to rats markedly decreased the urinary PGE2and F2α levels, suggesting that the active metabolite was produced and inhibited PG synthesisin vivo. In a culture system of 3T6 fibroblasts, CS-600 was effectively converted to the active metabolite and inhibited the PGE2production of the fibroblasts.
