Synthesis and Pharmacological Evaluation of Novel Arylpiperazine Derivatives as Nonsteroidal Androgen Receptor Antagonists

Isao Kinoyama; Nobuaki Taniguchi; Toru Yoden; Hiroshi Koutoku; Takashi Furutani; Masafumi Kudoh; Minoru Okada

doi:10.1248/cpb.52.1330

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Synthesis and Pharmacological Evaluation of Novel Arylpiperazine Derivatives as Nonsteroidal Androgen Receptor Antagonists

Isao Kinoyama, Nobuaki Taniguchi, Toru Yoden, Hiroshi Koutoku, Takashi Furutani, Masafumi Kudoh, Minoru Okada

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Keywords: androgen receptor, antagonist, antiandrogen, prostate cancer

JOURNAL FREE ACCESS

2004 Volume 52 Issue 11 Pages 1330-1333

DOI https://doi.org/10.1248/cpb.52.1330

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Abstract

The search for novel antiandrogens by high-throughput screening (HTS) of the Yamanouchi chemical library led to the discovery of the lead compound (5), which possesses an arylmorpholine moiety. Through the optimization of the lead compound (5), we have found a series of novel arylpiperazine derivatives. Among them, 4-[4-cyano-(3-trifluoromethyl)phenyl]-N-(4-fluorophenyl)piperazine-1-carboxamide (22; YM-92088) exhibited a potent AR antagonistic activity with an IC₅₀ value of 0.47 μM in the reporter assay, which is more potent than bicalutamide (4) which has an IC₅₀ value of 0.89 μM.

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