Discovery of pyrroloaminopyrazoles as novel PAK inhibitors

…, D Bouzida, A Yang, L Dong, J Marakovits…

文献索引：Guo, Chuangxing; McAlpine, Indrawan; Zhang, Junhu; Knighton, Daniel D.; Kephart, Susan; Johnson, M. Catherine; Li, Haitao; Bouzida, Djamal; Yang, Anle; Dong, Liming; Marakovits, Joseph; Tikhe, Jayashree; Richardson, Paul; Guo, Lisa C.; Kania, Robert; Edwards, Martin P.; Kraynov, Eugenia; Christensen, James; Piraino, Joseph; Lee, Joseph; Dagostino, Eleanor; Del-Carmen, Christine; Deng, Ya-Li; Smeal, Tod; Murray, Brion W. Journal of Medicinal Chemistry, 2012 , vol. 55, # 10 p. 4728 - 4739

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被引用次数: 31

摘要

The P21-activated kinases (PAK) are emerging antitumor therapeutic targets. In this paper, we describe the discovery of potent PAK inhibitors guided by structure-based drug design. In addition, the efflux of the pyrrolopyrazole series was effectively reduced by applying multiple medicinal chemistry strategies, leading to a series of PAK inhibitors that are orally active in inhibiting tumor growth in vivo.