Structure activity optimization of 6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazines as Jak1 kinase inhibitors

被引：15

作者：

Friedman, Michael ^{[1
]}

Frank, Kristine E. ^{[2
]}

Aguirre, Ana ^{[2
]}

Argiriadi, Maria A. ^{[1
]}

Davis, Heather ^{[1
]}

Edmunds, Jeremy J. ^{[1
]}

George, Dawn M. ^{[1
]}

George, Jonathan S. ^{[1
]}

Goedken, Eric ^{[1
]}

Fiamengo, Bryan ^{[3
]}

Hyland, Deborah ^{[1
]}

Li, Bin ^{[1
]}

Murtaza, Anwar ^{[4
]}

Morytko, Michael ^{[1
]}

Somal, Gagandeep ^{[1
]}

Stewart, Kent ^{[2
]}

Tarcsa, Edit ^{[1
]}

Van Epps, Stacy ^{[1
]}

Voss, Jeffrey ^{[1
]}

Wang, Lu ^{[1
]}

Woller, Kevin ^{[2
]}

Wishart, Neil ^{[1
]}

机构：

[1] Abbvie Biores Ctr, Worcester, MA 01605 USA

[2] Abbvie, N Chicago, IL 60064 USA

[3] Materia Inc, Pasadena, CA 91107 USA

[4] Merck Res Labs, Boston, MA 02115 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 20期

关键词：

Tricyclic pyrrolopyrazines; 6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazines; Jak inhibitors; Jak selectivity; RHEUMATOID-ARTHRITIS; JANUS KINASES; CP-690,550; TOFACITINIB; PLACEBO; DESIGN;

D O I：

10.1016/j.bmcl.2015.09.020

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Previous work investigating tricyclic pyrrolopyrazines as kinase cores led to the discovery that 1-cyclohexyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (12) had Jak inhibitory activity. Herein we describe our initial efforts to develop orally bioavailable analogs of 12 with improved selectivity of Jak1 over Jak2. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：4399 / 4404

页数：6

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