Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10591613 | Bioorganic & Medicinal Chemistry Letters | 2014 | 4 Pages |
Abstract
We recently reported on the discovery of AMG 232, a potent and selective piperidinone inhibitor of the MDM2-p53 interaction. AMG 232 is being evaluated in human clinical trials for cancer. Continued exploration of the N-alkyl substituent of this series, in an effort to optimize interactions with the MDM2 glycine-58 shelf region, led to the discovery of sulfonamides such as compounds 31 and 38 that have similar potency, hepatocyte stability and rat pharmacokinetic properties to AMG 232.
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Authors
Yingcai Wang, Jiang Zhu, Jiwen (Jim) Liu, Xiaoqi Chen, Jeff Mihalic, Jeffrey Deignan, Ming Yu, Daqing Sun, Frank Kayser, Lawrence R. McGee, Mei-Chu Lo, Ada Chen, Jing Zhou, Qiuping Ye, Xin Huang, Alexander M. Long, Peter Yakowec, Jonathan D. Oliner,