Synthesis of conformationally constrained benzoylureas as BH3-mimetics

Org Biomol Chem. 2012 Jul 21;10(27):5230-7. doi: 10.1039/c2ob25618e. Epub 2012 May 30.


The design of small molecules that mimic the BH3 domain and bind to Bcl-2 proteins has emerged as a promising approach to discovering novel anti-cancer therapeutics. We reveal the design and synthesis of conformationally constrained benzoylurea scaffolds as conformational probes. Central to helix mimicry, the intramolecular hydrogen bond in the benzoylurea plays a key role in the pre-organisation of the acyclic substrates for cyclisation via ring closing metathesis, providing efficient access to the constrained mimetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzene / chemistry*
  • Biomimetic Materials / chemical synthesis*
  • Biomimetic Materials / metabolism
  • Cyclization
  • Models, Molecular
  • Molecular Conformation
  • Protein Binding
  • Proto-Oncogene Proteins c-bcl-2 / chemistry*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Structure-Activity Relationship
  • Urea / chemical synthesis*
  • Urea / metabolism


  • Proto-Oncogene Proteins c-bcl-2
  • Urea
  • Benzene