Discovery of 3-(trifluoromethyl)-1H-pyrazole-5-carboxamide activators of the M2 isoform of pyruvate kinase (PKM2)

被引：40

作者：

Xu, Yong ^{[1
]}

Liu, Xiao-Hui ^{[1
]}

Saunders, Michael ^{[1
]}

Pearce, Scott ^{[1
]}

Foulks, Jason M. ^{[1
]}

Parnell, K. Mark ^{[1
]}

Clifford, Adrianne ^{[1
]}

Nix, Rebecca N. ^{[1
]}

Bullough, Jeremy ^{[1
]}

Hendrickson, Thomas F. ^{[1
]}

Wright, Kevin ^{[1
]}

McCullar, Michael V. ^{[1
]}

Kanner, Steven B. ^{[1
]}

Ho, Koc-Kan ^{[1
]}

机构：

[1] Astex Pharmaceut Inc, Dublin, CA 94568 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 02期

关键词：

Pyruvate kinase M2; PKM2; activator; 3-(Trifluoromethyl)-1H-pyrazole-5-carboxamides; Bioisostere; Cancer metabolism; BIOLOGICAL EVALUATION; RECEPTOR ANTAGONISTS; GENE;

D O I：

10.1016/j.bmcl.2013.12.028

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Activators of the pyruvate kinase M2 (PKM2) are currently attracting significant interest as potential anticancer therapies. They may achieve a novel antiproliferation response in cancer cells through modulation of the classic 'Warburg effect' characteristic of aberrant metabolism. In this Letter, we describe the optimization of a weakly active screening hit to a structurally novel series of small molecule 3-(trifluoromethyl)-1H-pyrazole-5-carboxamides as potent PKM2 activators. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：515 / 519

页数：5

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