☆ 4.7 Article

Discovery of Pyrroloaminopyrazoles as Novel PAK Inhibitors

JOURNAL OF MEDICINAL CHEMISTRY (2012)

Journal

JOURNAL OF MEDICINAL CHEMISTRY

Volume 55, Issue 10, Pages 4728-4739

Publisher

AMER CHEMICAL SOC

DOI: 10.1021/jm300204j

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Chemistry, Medicinal

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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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