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Published on: June 23, 2019
Discovery of pyrroloaminopyrazoles as novel PAK inhibitors
Chuangxing Guo1, Indrawan McAlpine, Junhu Zhang
1Pfizer Global Research and Development, 10770 Science Center Drive, San Diego, California 92121, United States. alexguo01@gmail.com
Abstract:
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.
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