Structure–activity relationships of bioisosteric replacement of the carboxylic acid in novel androgen receptor pure antagonists
详细信息 查看全文
- 作者：Hitoshi Yoshino ; Haruhiko Sato ; Kazutaka Tachibana ; Takuya Shiraishi ; Mitsuaki Nakamura ; Masateru Ohta ; Nobuyuki Ishikura ; Masahiro Nagamuta ; Etsuro Onuma ; Toshito Nakagawa ; Shinichi Arai ; Koo-Hyeon A
- 关键词：Androgen receptor ; Pure antagonist ; Prostate cancer ; Bioisostere ; Sulfonamide
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2010
- 出版时间：1 May 2010
- 年：2010
- 卷：18
- 期：9
- 页码：3159-3168
- 全文大小：656 K
文摘
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.