Improvement of the synthesis and pharmacokinetic properties of chromenotriazolopyrimidine MDM2-p53 protein-protein inhibitors
HP Beck, M DeGraffenreid, B Fox, JG Allen… - Bioorganic & medicinal …, 2011 - Elsevier
HP Beck, M DeGraffenreid, B Fox, JG Allen, Y Rew, S Schneider, AY Saiki, D Yu, JD Oliner…
Bioorganic & medicinal chemistry letters, 2011•ElsevierHuman 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.
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.
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.
Elsevier
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