Design and synthesis of novel amide AKT1 inhibitors with selectivity over CDK2

Bioorg Med Chem Lett. 2011 Sep 15;21(18):5191-6. doi: 10.1016/j.bmcl.2011.07.056. Epub 2011 Jul 23.

Abstract

Through the analysis of X-ray crystallographic information and previous SAR studies, a novel series of protein kinase B (PKB/AKT) inhibitors was developed. The compounds showed nanomolar inhibition of AKT1 and were selective against cyclin-dependent kinase 2 (CDK2).

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry
  • Amides / pharmacology*
  • Chemistry Techniques, Synthetic
  • Crystallography, X-Ray
  • Cyclin-Dependent Kinase 2 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 2 / metabolism
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Amides
  • Enzyme Inhibitors
  • Proto-Oncogene Proteins c-akt
  • Cyclin-Dependent Kinase 2