Structure-activity relationships of bioisosteric replacement of the carboxylic acid in novel androgen receptor pure antagonists

  • Bioorg Med Chem. 2010 May 1;18(9):3159-68. doi: 10.1016/j.bmc.2010.03.036.
Hitoshi Yoshino  1 ,  Haruhiko Sato ,  Kazutaka Tachibana ,  Takuya Shiraishi ,  Mitsuaki Nakamura ,  Masateru Ohta ,  Nobuyuki Ishikura ,  Masahiro Nagamuta ,  Etsuro Onuma ,  Toshito Nakagawa ,  Shinichi Arai ,  Koo-Hyeon Ahn ,  Kyung-Yun Jung ,  Hiromitsu Kawata
Affiliations
  • 1. Research Division, Chugai Pharmaceutical Co., Ltd, 1-135, Komakado, Gotemba, Shizuoka 412-8513, Japan. [email protected]
PMID: 20381361 DOI: 10.1016/j.bmc.2010.03.036
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.