Discovery and SAR of spirochromane Akt inhibitors

Bioorg Med Chem Lett. 2011 Apr 15;21(8):2410-4. doi: 10.1016/j.bmcl.2011.02.073. Epub 2011 Feb 18.


A novel series of spirochromane pan-Akt inhibitors is reported. SAR optimization furnished compounds with improved enzyme potencies and excellent selectivity over the related AGC kinase PKA. Attempted replacement of the phenol hinge binder provided compounds with excellent Akt enzyme and cell activities but greatly diminished selectivity over PKA.

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • Drug Evaluation, Preclinical
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Structure-Activity Relationship


  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-akt