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Triazolopyridines as selective JAK1 inhibitors: from hit identification to GLPG0634.

Abstract：

:Janus kinases (JAK1, JAK2, JAK3, and TYK2) are involved in the signaling of multiple cytokines important in cellular function. Blockade of the JAK-STAT pathway with a small molecule has been shown to provide therapeutic immunomodulation. Having identified JAK1 as a possible new target for arthritis at Galapagos, the compound library was screened against JAK1, resulting in the identification of a triazolopyridine-based series of inhibitors represented by 3. Optimization within this chemical series led to identification of GLPG0634 (65, filgotinib), a selective JAK1 inhibitor currently in phase 2B development for RA and phase 2A development for Crohn's disease (CD).

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Menet CJ,Fletcher SR,Van Lommen G,Geney R,Blanc J,Smits K,Jouannigot N,Deprez P,van der Aar EM,Clement-Lacroix P,Lepescheux L,Galien R,Vayssiere B,Nelles L,Christophe T,Brys R,Uhring M,Ciesielski F,Van Rompaey L

doi

10.1021/jm501262q

subject

Has Abstract

pub_date

2014-11-26 00:00:00

pages

9323-42

issue

22

eissn

0022-2623

issn

1520-4804

journal_volume

57

pub_type

杂志文章

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