1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: identification of a potent Aurora kinase inhibitor with a favorable antitumor kinase inhibition profile

J Med Chem. 2006 Nov 30;49(24):7247-51. doi: 10.1021/jm060897w.


The optimization of a series of 5-phenylacetyl 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives toward the inhibition of Aurora kinases led to the identification of compound 9d. This is a potent inhibitor of Aurora kinases that also shows low nanomolar potency against additional anticancer kinase targets. Based on its high antiproliferative activity on different cancer cell lines, favorable chemico-physical and pharmacokinetic properties, and high efficacy in in vivo tumor models, compound 9d was ultimately selected for further development.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Aurora Kinases
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Male
  • Mice
  • Models, Molecular
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors*
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / pharmacokinetics
  • Pyrazoles / pharmacology
  • Pyrroles / chemical synthesis*
  • Pyrroles / pharmacokinetics
  • Pyrroles / pharmacology
  • Solubility
  • Structure-Activity Relationship


  • Antineoplastic Agents
  • Pyrazoles
  • Pyrroles
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases