Synthesis and evaluation of pyrazolo [1, 5-b] pyridazines as selective cyclin dependent kinase inhibitors

…, MJ Reno, JB Alberti, DJ Price, LS Kane-Carson…

Index: Stevens, Kirk L.; Reno, Michael J.; Alberti, Jennifer B.; Price, Daniel J.; Kane-Carson, Laurie S.; Knick, Victoria B.; Shewchuk, Lisa M.; Hassell, Anne M.; Veal, James M.; Davis, Stephen T.; Griffin, Robert J.; Peel, Michael R. Bioorganic and Medicinal Chemistry Letters, 2008 , vol. 18, # 21 p. 5758 - 5762

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Citation Number: 18

Abstract

A novel series of pyrazolo [1, 5-b] pyridazines have been synthesized and identified as cyclin dependant kinase inhibitors potentially useful for the treatment of solid tumors. Modification of the hinge-binding amine or the C (2)-and C (6)-substitutions on the pyrazolopyridazine core provided potent inhibitors of CDK4 and demonstrated enzyme selectivity against VEGFR-2 and GSK3β.