Tetrahydroisoquinoline amide substituted phenyl pyrazoles as selective Bcl-2 inhibitors

Bioorg Med Chem Lett. 2009 Jan 1;19(1):230-3. doi: 10.1016/j.bmcl.2008.10.113. Epub 2008 Oct 31.

Abstract

Anti-apoptotic Bcl-2 protects cells from apoptosis by binding to pro-apoptotic members of the Bcl-2 family thereby playing a role in tumour survival in response to chemo- or radiation therapy. We describe a series of phenyl pyrazoles that have high affinity for Bcl-2 and rationalise the observed SAR by means of an X-ray crystal structure.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Crystallography, X-Ray
  • Molecular Structure
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / pharmacology
  • Structure-Activity Relationship
  • Tetrahydroisoquinolines / chemistry*
  • Tetrahydroisoquinolines / pharmacology

Substances

  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Pyrazoles
  • Tetrahydroisoquinolines