Preparation and antirheumatic activity of optically active 2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (KE-298).

ABSTRACT

2-Acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanonic acid (KE-298) is an antirheumatic agent. To elucidate the effects of optically active KE-298, we resolved the racemic acid and obtained the two optical isomers. (+)-KE-298 was converted to the 4-bromobenzyl ester derivative and the absolute structure was confirmed as (S) by X-ray crystallographic analysis. The pharmacological activities of the optical isomers and racemic KE-298 were compared by using the characteristic tests for KE-298. Though (+)-KE-298 showed a stronger suppressive effect on rat adjuvant arthritis than (-)-KE-298, no difference between the two isomers was detected in in vitro tests (enhancing effect on lymphocyte transformation, IL-1 antagonistic effect).