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J Med Chem. 2014 Nov 26;57(22):9323-42. doi: 10.1021/jm501262q. Epub 2014 Nov 17.

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

Author information

1
Galapagos NV , Generaal de Wittelaan L11A3, 2800 Mechelen, Belgium.

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).

PMID:
25369270
DOI:
10.1021/jm501262q
[Indexed for MEDLINE]

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