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ID: ALA1770142

Journal: Bioorg Med Chem Lett

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

Authors: Beck HP, DeGraffenreid M, Fox B, Allen JG, Rew Y, Schneider S, Saiki AY, Yu D, Oliner JD, Salyers K, Ye Q, Olson S.

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.

CiteXplore: 21123063

DOI: 10.1016/j.bmcl.2010.11.027