Structure-based design of novel inhibitors of the MDM2-p53 interaction.
نویسندگان
چکیده
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.
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ورودعنوان ژورنال:
- Journal of medicinal chemistry
دوره 55 11 شماره
صفحات -
تاریخ انتشار 2012