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).
MeSH terms
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Animals
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Antirheumatic Agents / chemical synthesis*
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Antirheumatic Agents / chemistry
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Antirheumatic Agents / pharmacology*
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Arthritis, Experimental / drug therapy
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Arthritis, Experimental / pathology
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Crystallography, X-Ray
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Edema / drug therapy
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Edema / pathology
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Female
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In Vitro Techniques
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Interleukin-1 / antagonists & inhibitors
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Lipopolysaccharides
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Lymphocyte Activation / drug effects
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Mice
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Mice, Inbred C3H
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Optical Rotation
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Phenylpropionates / chemical synthesis*
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Phenylpropionates / chemistry
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Phenylpropionates / pharmacology*
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Rats
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Receptors, Interleukin-1 / biosynthesis
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Spectrophotometry, Infrared
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Stereoisomerism
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T-Lymphocytes / drug effects
Substances
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Antirheumatic Agents
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Interleukin-1
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Lipopolysaccharides
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Phenylpropionates
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Receptors, Interleukin-1
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esonarimod