Aryl[a]pyrrolo[3,4-c]carbazoles as selective cyclin D1-CDK4 inhibitors

Bioorg Med Chem Lett. 2003 Nov 3;13(21):3835-9. doi: 10.1016/s0960-894x(03)00791-1.

Abstract

The synthesis of new analogues of Arcyriaflavin A in which one indole ring is replaced by an aryl or heteroaryl ring is described. These new series of aryl[a]pyrrolo[3,4-c]carbazoles were evaluated as inhibitors of Cyclin D1-CDK4. A potent and selective D1-CDK4 inhibitor, 7a (D1-CDK4 IC(50)=45 nM), has been identified. The potency, selectivity profile against other kinases, and structure-activity relationship (SAR) trends of this class of compounds are discussed.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology*
  • Carbazoles / chemical synthesis*
  • Carbazoles / chemistry*
  • Carbazoles / pharmacology*
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Cyclin D1 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Humans
  • Proto-Oncogene Proteins*
  • Pyrroles / chemical synthesis*
  • Pyrroles / pharmacology*

Substances

  • Antineoplastic Agents
  • Carbazoles
  • Proto-Oncogene Proteins
  • Pyrroles
  • arcyriaflavin A
  • Cyclin D1
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases