Discovery of Aryloxy Tetramethylcyclobutanes as Novel Androgen Receptor Antagonists
Journal of Medicinal Chemistry2011Vol. 54(21), pp. 7693–7704
Citations Over TimeTop 10% of 2011 papers
Chuangxing Guo, Angelica Linton, Susan E. Kephart, Martha A. Ornelas, Mason Pairish, Javier González, S.E. Greasley, Asako Nagata, Benjamin J. Burke, Martin P. Edwards, Natilie Hosea, Ping Kang, Wenyue Hu, Jon Engebretsen, David M. Briere, Manli Shi, Hovik Gukasyan, Paul Richardson, Kevin N. Dack, Toby J. Underwood, Patrick S. Johnson, Andrew Morell, Robert Felstead, Hidetoshi Kuruma, Hiroaki Matsimoto, Amina Zoubeidi, Martin Gleave, Gerrit Los, Andrea Fanjul
Abstract
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 "hit" 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.
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