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Discovery of a series of novel 5H-pyrrolo[2,3-b]pyrazine-2-phenyl ethers, as potent JAK3 kinase inhibitors.

Abstract：

:We report the discovery of a novel series of ATP-competitive Janus kinase 3 (JAK3) inhibitors based on the 5H-pyrrolo[2,3-b]pyrazine scaffold. The initial leads in this series, compounds 1a and 1h, showed promising potencies, but a lack of selectivity against other isoforms in the JAK family. Computational and crystallographic analysis suggested that the phenyl ether moiety possessed a favorable vector to achieve selectivity. Exploration of this vector resulted in the identification of 12b and 12d, as potent JAK3 inhibitors, demonstrating improved JAK family and kinase selectivity.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Jaime-Figueroa S,De Vicente J,Hermann J,Jahangir A,Jin S,Kuglstatter A,Lynch SM,Menke J,Niu L,Patel V,Shao A,Soth M,Vu MD,Yee C

doi

10.1016/j.bmcl.2013.03.015

subject

Has Abstract

pub_date

2013-05-01 00:00:00

pages

2522-6

issue

9

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(13)00331-4

journal_volume

23

pub_type

杂志文章

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