2. Academic Validation
  3. Improvement of the synthesis and pharmacokinetic properties of chromenotriazolopyrimidine MDM2-p53 protein-protein inhibitors

Improvement of the synthesis and pharmacokinetic properties of chromenotriazolopyrimidine MDM2-p53 protein-protein inhibitors

  • Bioorg Med Chem Lett. 2011 May 1;21(9):2752-5. doi: 10.1016/j.bmcl.2010.11.027.
Hilary P Beck 1,  Michael DeGraffenreid,  Brian Fox,  John G Allen,  Yosup Rew,  Stephen Schneider,  Anne Y Saiki,  Dongyin Yu,  Jonathan D Oliner,  Kevin Salyers,  Qiuping Ye,  Steven Olson
Affiliations

Affiliation

  • 1 Chemistry Research & Discovery, Amgen Inc., 1120 Veterans Blvd, South San Francisco, CA 94080, USA. hbeck@amgen.com
PMID: 21123063 DOI: 10.1016/j.bmcl.2010.11.027
Abstract

Human murine double minute 2 (MDM2) is a negative regulator of p53, which plays an important role in cell cycle and Apoptosis. We report several optimizations to the synthesis of the chromenotriazolopyrimidine series of MDM2-p53 protein-protein interaction inhibitors. Additionally, the in vitro and in vivo stability, pharmacokinetic properties and solubility were improved through N-substitution.

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