- Design and evaluation of 3,6-di(hetero)aryl imidazo[1,2-a]pyrazines as inhibitors of checkpoint and other kinases
-
A range of 3,6-di(hetero)arylimidazo[1,2-a]pyrazine ATP-competitive inhibitors of CHK1 were developed by scaffold hopping from a weakly active screening hit. Efficient synthetic routes for parallel synthesis were developed to prepare analogues with improved potency and ligand efficiency against CHK1. Kinase profiling showed that the imidazo[1,2-a]pyrazines could inhibit other kinases, including CHK2 and ABL, with equivalent or better potency depending on the pendant substitution. These 3,6-di(hetero)aryl imidazo[1,2-a]pyrazines appear to represent a general kinase inhibitor scaffold.
- Matthews, Thomas P.,McHardy, Tatiana,Klair, Suki,Boxall, Kathy,Fisher, Martin,Cherry, Michael,Allen, Charlotte E.,Addison, Glynn J.,Ellard, John,Aherne, G. Wynne,Westwood, Isaac M.,Montfort, Rob van,Garrett, Michelle D.,Reader, John C.,Collins, Ian
-
scheme or table
p. 4045 - 4049
(2010/08/19)
-