Synthesis and antirheumatic activity of the metabolites of esonarimod.
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.
Noguchi
Toshiya
T
Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama City, Saitama 330-8530, Japan. t.noguchi@po.rd.taisho.co.jp
Onodera
Akira
A
Tomisawa
Kazuyuki
K
Yamashita
Miyuki
M
Takeshita
Kimiyo
K
Yokomori
Sadakazu
S
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
D018501:Antirheumatic Agents; D007659:Ketones; D010666:Phenylpropionates; D013440:Sulfides; C078547:esonarimod