National Center for
3EID: Cdk2CYCLINA COMPLEXED WITH A PYRAZOLOPYRIDAZINE INHIBITOR
Synthesis and evaluation of pyrazolo[1,5-b]pyridazines as selective cyclin dependent kinase inhibitors
Bioorg. Med. Chem. Lett. (2008) 18 p.5758-5762
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 GSK3beta.