Discovery of Aryloxy Tetramethylcyclobutanes as Novel Androgen Receptor Antagonists
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- 作者：Chuangxing Guo ; Angelica Linton ; Susan Kephart ; Martha Ornelas ; Mason Pairish ; Javier Gonzalez ; Samantha Greasley ; Asako Nagata ; Benjamin J. Burke ; Martin Edwards ; Natilie Hosea ; Ping Kang ; Wenyue Hu ; Jon Engebretsen ; David Briere ; Manli Shi ; Hovik Gukasyan ; Paul Richardson ; Kevin Dack ; Toby Underwood ; Patrick Johnson ; Andrew Morell ; Robert Felstead ; Hidetoshi Kuruma ; Hiroaki Matsimoto ; Amina Zoubeidi ; Martin Gleave ; Gerrit Los ; Andrea N. Fanjul
- 刊名：Journal of Medicinal Chemistry
- 出版年：2011
- 出版时间：November 10, 2011
- 年：2011
- 卷：54
- 期：21
- 页码：7693-7704
- 全文大小：1211K
- 年卷期：v.54,no.21(November 10, 2011)
- ISSN：1520-4804
文摘
An aryloxy tetramethylcyclobutane was identified as a novel template for androgen receptor (AR) antagonists via cell-based high-throughput screening. Follow-up to the initial 鈥渉it鈥?established 5 as a viable lead. Further optimization to achieve full AR antagonism led to the discovery of 26 and 30, both of which demonstrated excellent in vivo tumor growth inhibition upon oral administration in a castration-resistant prostate cancer (CRPC) animal model.