Discovery of Pyrroloaminopyrazoles as Novel PAK Inhibitors
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- 作者：Chuangxing Guo ; Indrawan McAlpine ; Junhu Zhang ; Daniel D. Knighton ; Susan Kephart ; M. Catherine Johnson ; Haitao Li ; Djamal Bouzida ; Anle Yang ; Liming Dong ; Joseph Marakovits ; Jayashree Tikhe ; Paul Richardson ; Lisa C. Guo ; Robert Kania ; Martin P. Edwards ; Eugenia Kraynov ; James Christensen ; Joseph Piraino ; Joseph Lee ; Eleanor Dagostino ; Christine Del-Carmen ; Ya-Li Deng ; Tod Smeal ; Brion W. Murray
- 刊名：Journal of Medicinal Chemistry
- 出版年：2012
- 出版时间：May 24, 2012
- 年：2012
- 卷：55
- 期：10
- 页码：4728-4739
- 全文大小：575K
- 年卷期：v.55,no.10(May 24, 2012)
- ISSN：1520-4804
文摘
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.