Cinnamic acids and mono-substituted benzoic acids as useful capping groups for the preparation of hNK2 receptor antagonists

Bioorg Med Chem Lett. 2008 Aug 15;18(16):4705-7. doi: 10.1016/j.bmcl.2008.06.102. Epub 2008 Jul 4.


NK(2) antagonists have been reported to be potentially useful for the treatment of a number of chronic diseases, such as asthma, irritable bowel syndrome, cystitis, and depression. Starting from an in-house prepared library of capped dipeptides, we have identified a series of molecules with subnanomolar binding affinity for the hNK(2) receptor. These molecules are composed by three well-defined regions: a planar aromatic acyl system as N-terminal capping group, a rigid and quite lipophilic core, and a flexible and relatively hydrophilic C-terminal capping group. Here we report how we were able to manipulate the N-terminal capping group to obtain significant in vivo activity after i.v. and i.d. administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoates / chemistry*
  • Caco-2 Cells
  • Chemistry, Pharmaceutical / methods*
  • Cinnamates / chemistry*
  • Colon / drug effects
  • Drug Design
  • Guinea Pigs
  • Humans
  • Models, Chemical
  • Models, Statistical
  • Peptides / chemistry
  • Protein Structure, Tertiary
  • Receptors, Neurokinin-2 / antagonists & inhibitors*


  • Benzoates
  • Cinnamates
  • Peptides
  • Receptors, Neurokinin-2
  • cinnamic acid