| Literature DB >> 22524527 |
Yosup Rew1, Daqing Sun, Felix Gonzalez-Lopez De Turiso, Michael D Bartberger, Hilary P Beck, Jude Canon, Ada Chen, David Chow, Jeffrey Deignan, Brian M Fox, Darin Gustin, Xin Huang, Min Jiang, Xianyun Jiao, Lixia Jin, Frank Kayser, David J Kopecky, Yihong Li, Mei-Chu Lo, Alexander M Long, Klaus Michelsen, Jonathan D Oliner, Tao Osgood, Mark Ragains, Anne Y Saiki, Steve Schneider, Maria Toteva, Peter Yakowec, Xuelei Yan, Qiuping Ye, Dongyin Yu, Xiaoning Zhao, Jing Zhou, Julio C Medina, Steven H Olson.
Abstract
Structure-based rational design led to the discovery of novel inhibitors of the MDM2-p53 protein-protein interaction. The affinity of these compounds for MDM2 was improved through conformational control of both the piperidinone ring and the appended N-alkyl substituent. Optimization afforded 29 (AM-8553), a potent and selective MDM2 inhibitor with excellent pharmacokinetic properties and in vivo efficacy.Entities:
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Year: 2012 PMID： 22524527 DOI： 10.1021/jm300354j
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446