title: Synthesis and antirheumatic activity of the metabolites of esonarimod.
abstract: We have developed esonarimod, (+/-)-2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid, as a new antirheumatic drug. Now we describe herein the preparation of the enantiomers of (+/-)-deacetylesonarimod, the pharmaceutically active metabolites of esonarimod, and comparison of their antirheumatic activities. No significant difference has been observed between the two enantiomers. In a pre-clinical study of esonarimod, other metabolites were detected in rat blood or urine. We also synthesized these compounds as authentic samples to analyze the human metabolites in clinical studies of esonarimod.
authors.affiliation: Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama City, Saitama 330-8530, Japan. t.noguchi@po.rd.taisho.co.jp
authors.forename: Toshiya
authors.initials: T
authors.lastname: Noguchi
authors.forename: Akira
authors.initials: A
authors.lastname: Onodera
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tomisawa
authors.forename: Miyuki
authors.initials: M
authors.lastname: Yamashita
authors.forename: Kimiyo
authors.initials: K
authors.lastname: Takeshita
authors.forename: Sadakazu
authors.initials: S
authors.lastname: Yokomori
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000097:blood / Q000138:chemical synthesis* / Q000378:metabolism* / Q000652:urine; D006801:Humans; D007659:Ketones; D010666:Phenylpropionates / Q000138:chemical synthesis / Q000378:metabolism; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013440:Sulfides
chemical_list: D018501:Antirheumatic Agents; D007659:Ketones; D010666:Phenylpropionates; D013440:Sulfides; C078547:esonarimod