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

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.
AuthorsKirk L Stevens, Michael J Reno, Jennifer B Alberti, Daniel J Price, Laurie S Kane-Carson, Victoria B Knick, Lisa M Shewchuk, Anne M Hassell, James M Veal, Stephen T Davis, Robert J Griffin, Michael R Peel
JournalBioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 18 Issue 21 Pg. 5758-62 (Nov 1 2008) ISSN: 1464-3405 [Electronic] England
PMID18835709 (Publication Type: Journal Article)
Chemical References
  • Protein Kinase Inhibitors
  • Pyridazines
  • Vascular Endothelial Growth Factor Receptor-2
  • glycogen synthase kinase 3 beta
  • Cyclin-Dependent Kinase 4
  • Glycogen Synthase Kinase 3
  • Cyclin-Dependent Kinase 4 (antagonists & inhibitors)
  • Drug Evaluation, Preclinical
  • Drug Screening Assays, Antitumor
  • Glycogen Synthase Kinase 3 (antagonists & inhibitors)
  • Models, Molecular
  • Protein Kinase Inhibitors (chemical synthesis, pharmacology)
  • Pyridazines (chemical synthesis, pharmacology)
  • Vascular Endothelial Growth Factor Receptor-2 (antagonists & inhibitors)

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