Preparation and antirheumatic activity of optically active 2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (KE-298).
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).
Kameo
K
K
Research Center, Taisho Pharmaceutical Co., Ltd, Saitama, Japan.
Takeshita
K
K
Yasuda
Y
Y
Matsumoto
K
K
Tomisawa
K
K
D000818:Animals; D018501:Antirheumatic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000473:pathology; D018360:Crystallography, X-Ray; D004487:Edema / Q000188:drug therapy / Q000473:pathology; D005260:Female; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D009904:Optical Rotation; D010666:Phenylpropionates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism; D013601:T-Lymphocytes / Q000187:drug effects
D018501:Antirheumatic Agents; D007375:Interleukin-1; D008070:Lipopolysaccharides; D010666:Phenylpropionates; D017472:Receptors, Interleukin-1; C078547:esonarimod