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
  • 1. Chemistry Research & Discovery, Amgen Inc., 1120 Veterans Blvd, South San Francisco, CA 94080, USA. [email protected]
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.

Products