title: Structure-activity relationships of bioisosteric replacement of the carboxylic acid in novel androgen receptor pure antagonists.
abstract: A series of 5,5-dimethylthiohydantoin derivatives were synthesized and evaluated for androgen receptor pure antagonistic activities for the treatment of hormone refractory prostate cancer. CH4933468 (32d) with a sulfonamide side chain not only exhibited antagonistic activity with no agonistic activity in the reporter gene assay but also inhibited the growth of bicalutamide-resistant cell lines. This compound also inhibited tumor growth of the LNCaP xenograft in mice dose-dependently.
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd, 1-135, Komakado, Gotemba, Shizuoka 412-8513, Japan. yoshinohts@chugai-pharm.co.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yoshino
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sato
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Tachibana
authors.forename: Takuya
authors.initials: T
authors.lastname: Shiraishi
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Nakamura
authors.forename: Masateru
authors.initials: M
authors.lastname: Ohta
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ishikura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nagamuta
authors.forename: Etsuro
authors.initials: E
authors.lastname: Onuma
authors.forename: Toshito
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Arai
authors.forename: Koo-Hyeon
authors.initials: KH
authors.lastname: Ahn
authors.forename: Kyung-Yun
authors.initials: KY
authors.lastname: Jung
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kawata
mesh_terms: D000726:Androgen Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D016513:Mice, SCID; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D013867:Thiohydantoins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; C551969:CH4933468; D002264:Carboxylic Acids; D009570:Nitriles; D013449:Sulfonamides; D013867:Thiohydantoins