Discovery and optimization of chromenotriazolopyrimidines as potent inhibitors of the mouse double minute 2− tumor protein 53 protein− protein interaction

…, MD Bartberger, K Michelsen, R Hungate…

Index: Allen, John G.; Bourbeau, Matthew P.; Wohlhieter, G. Erich; Bartberger, Michael D.; Michelsen, Klaus; Hungate, Randall; Gadwood, Robert C.; Gaston, Rick D.; Evans, Bruce; Mann, Larry W.; Matison, Michael E.; Schneider, Stephen; Huang, Xin; Yu, Dongyin; Andrews, Paul S.; Reichelt, Andreas; Long, Alexander M.; Yakowec, Peter; Yang, Evelyn Y.; Lee, Tani Ann; Oliner, Jonathan D. Journal of Medicinal Chemistry, 2009 , vol. 52, # 22 p. 7044 - 7053

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Citation Number: 107

Abstract

Tumor protein 53 (p53) is a critical regulator of cell cycle and apoptosis that is frequently disabled in human tumors. In many tumor types, p53 is deleted or mutated, but in others p53 is inactivated by overexpression or amplification of its negative regulator mouse double minute 2 (MDM2). A high-throughput screening effort identified 6, 7-bis (4-bromophenyl)-7, 12-dihydro-6 H-chromeno [4, 3-d][1, 2, 4] triazolo [1, 5-a] pyrimidine as a potent inhibitor of ...