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

Michael Friedman,Kristine E Frank,Ana L Aguirre,Maria A Argiriadi,Heather M Davis,J J Edmunds,Dawn M George,J George,Eric R Goedken,Bryan A Fiamengo,Deborah Hyland, Bin Li,Anwar Murtaza,Michael J Morytko, Gagandeep Somal,Kent D Stewart,Edit Tarcsa,Stacy Van Epps,Jeffrey W Voss,Lu Wang,Kevin Woller,Neil Wishart

Bioorganic & Medicinal Chemistry Letters（2015）

Cited 14|Views45
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Abstract
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.
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Tricyclic pyrrolopyrazines,6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazines,Jak inhibitors,Jak selectivity
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