文章基本信息

标题：Relationship between the Metabolic Chiral Inversion and Chemical Structure of 4-Phenyl-4-oxobutanoic Acids, Derivatives of Anti-rheumatic Agent KE-298
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作者：Hideo YOSHIDA ; Yoshiro KOHNO ; Hiromi ENDO 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1997
卷号：20
期号：1
页码：94-96
DOI：10.1248/bpb.20.94
出版社：The Pharmaceutical Society of Japan
摘要：The relationship between metabolic chiral inversion and chemical structure of various 4-phenyl-4-oxobutanoic acids (4-OBA), derivatives of anti-rheumatic agent KE-298 [2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid], was investigated in rats. Chiral inversion occurred with the thio-alkyl group, whereas the thio-acyl group played no role in the inversion of 4-OBA. A 2-methylene moiety was required for the inversion. When the 4-carbonyl moiety was removed, chiral inversion was significantly decreased, which provided an affinity for the intramitochondrial medium chain fatty acid CoA ligase. In addition, the distance between the chiral center and the carbonyl moiety was also an important factor for chiral inversion. While a sulfur atom was not indispensable for the chiral inversion, the existence of the sulfur atom influenced its affinity to the long chain fatty acid CoA ligase.
关键词：stereoselectivity;chiral inversion;CoA ligase;anti-rheumatic agent;immunomodulator;rat