Toshiya Noguchi

Synthesis and structure-activity relationships of radicicol derivatives and WNT-5A expression inhibitory activity.

WNT-5A, a secretory glycoprotein, is related to the proliferation of dermal papilla cells. To develop a hair-growth stimulant, we have been searching for inhibitors of WNT-5A expression. We identified radicicol (1) as an active compound, and synthesized several radicicol derivatives. Among them, 6,7-dihydro-10alpha-hydroxy radicicol (31) was found to function as a new potent WNT-5A expression inhibitor with relatively low toxicity and excellent stability.

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.

Synthesis of dihydrothiophene derivatives as metabolites of esonarimod

Three compounds with a dihydrothiophene ring were synthesized as authentic samples to analyze human metabolites of Esonarimod, which has been developed as a new antirheumatic drug.

A Practical Procedure for the Synthesis of Esonarimod, (R,S)-2-Acetylthiomethyl-4- (4-methylphenyl)-4-oxobutanoic Acid, an Antirheumatic Agent. II

Abstract An efficient large-scale synthesis of Esonarimod, (R,S)-2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (1), a new antirheumatic drug, was established. A small amount of water increased the yield of the Michael addition of thioacetic acid (4) to 2-methylene-4-(4-methylphenyl)-4-oxobutanoic acid (2) to give 1. Multikilogram amounts of 1 (over 25 kg) were successfully obtained using this procedure. In addition, this procedure was repeated nine times, and reproducible results were obtained. See Ref. [1]