Discovery of 5-(2-amino-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-N-(tert-butyl)pyridine-3-sulfonamide (CZC24758), as a potent, orally bioavailable and selective inhibitor of PI3K for the treatment of inflammatory disease

被引：23

作者：

Sunose, Mihiro ^{[1
]}

Bell, Kathryn ^{[1
]}

Ellard, Katie ^{[1
]}

Bergamini, Giovanna ^{[2
]}

Neubauer, Gitte ^{[2
]}

Werner, Thilo ^{[2
]}

Ramsden, Nigel ^{[1
]}

机构：

[1] Cellzome Ltd, Saffron Walden CB10 1XL, England

[2] Cellzome AG, D-69117 Heidelberg, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 14期

关键词：

PI3K gamma; Inflammation; Triazolopyridine; Collagen induced arthritis; Rheumatoid arthritis; PHOSPHOINOSITIDE 3-KINASE PATHWAY; RHEUMATOID-ARTHRITIS; PI3K-GAMMA; CANCER; ACTIVATION; ISOFORM; KINASE; GAMMA;

D O I：

10.1016/j.bmcl.2012.05.090

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Herein, we disclose the discovery of a series of 7-substituted triazolopyridines which culminated in the identification of 14 (CZC24758), a potent, orally bioavailable small-molecule inhibitor of PI3K gamma, an attractive drug target for inflammatory and autoimmune disorders. Compound 14 has excellent selectivity across the kinome, demonstrates good potency in cell based assays and furthermore exhibits in vivo efficacy in a collagen induced arthritis model in mouse after oral dosing. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：4613 / 4618

页数：6

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