Q4 · MEDICINE
Article
Author: Tarcsa, Edit ; Edmunds, Jeremy J ; Voss, Jeffrey ; Frank, Kristine E ; Argiriadi, Maria A ; Friedman, Michael ; Davis, Heather ; Stewart, Kent ; Wishart, Neil ; Woller, Kevin ; Van Epps, Stacy ; Somal, Gagandeep ; Goedken, Eric ; Aguirre, Ana ; Murtaza, Anwar ; Morytko, Michael ; George, Jonathan S ; Li, Bin ; George, Dawn M ; Wang, Lu ; Hyland, Deborah ; Fiamengo, Bryan
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.