Synthesis and structure-activity relationships of 5-phenylthiophenecarboxylic acid derivatives as antirheumatic
Toshiya Noguchi1, Masahiro Hasegawa, Kazuyuki Tomisawa
1Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., 403, Yoshino-cho, 1-chome, Kita-ku, Saitama-city, 330-8530 Saitama, Japan. t.noguchi@po.rd.taisho.co.jp
Abstract:
5-(Phenylthiophene)-3-carboxylic acid (2a), a metabolite of esonarimod (1), which was developed as a new antirheumatic drug, was considered as a lead compound for new antirheumatic drugs. A new series of 2a derivatives were synthesized and their characteristic pharmacological effects, that is their antagonistic effect toward interleukin (IL)-1 in mice and the suppressive effect against adjuvant-induced arthritis (AIA) in rats, were evaluated and compared with those of 1. The structure-activity relationships indicated that [5-(4-bromophenyl)-thiophen-3-yl]acetic acid (5d), methyl [5-(4-chlorophenyl)-thiophen-3-yl]acetate (5h), and methyl [5-(4-bromophenyl)-thiophen-3-yl]acetate (5i) suppressed AIA more potently than 1 and all of the other synthesized compounds.
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