title: Synthesis and pharmacological evaluation of novel arylpiperazine derivatives as nonsteroidal androgen receptor antagonists.
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 IC(50) value of 0.47 microM in the reporter assay, which is more potent than bicalutamide (4) which has an IC(50) value of 0.89 microM.
authors.affiliation: Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. kinoyama@yamanouchi.co.jp
authors.forename: Isao
authors.initials: I
authors.lastname: Kinoyama
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Taniguchi
authors.forename: Toru
authors.initials: T
authors.lastname: Yoden
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Koutoku
authors.forename: Takashi
authors.initials: T
authors.lastname: Furutani
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kudoh
authors.forename: Minoru
authors.initials: M
authors.lastname: Okada
mesh_terms: D059002:Androgen Receptor Antagonists; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000096:biosynthesis
chemical_list: D059002:Androgen Receptor Antagonists; D010879:Piperazines; D011944:Receptors, Androgen