Tripeptidyl-peptidase II (TPP II) inhibitory activity of (S)-2,3-dihydro-2-(1H-imidazol-2-yl)-1H-indoles, a systematic SAR evaluation. Part 2

Bioorg Med Chem Lett. 2003 Dec 15;13(24):4467-71. doi: 10.1016/j.bmcl.2003.09.014.

Abstract

We have systematically explored the structure-activity relationship (SAR) for a series of compounds 2 as inhibitors of tripeptidyl-peptidase II (TPP II), a serine protease responsible for the degradation of cholecystokinin-8 (CCK-8). This SAR evaluation of the core structure 2 suggest a fairly restrictive pharmacophore for such related structures, but has yielded a limited set of compounds (2b, 2c, 2d, 2s, and 2t) with potent TPP II inhibitory activity (IC(50) 4-11 nM).

MeSH terms

  • Aminopeptidases
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Imidazoles / chemistry
  • Imidazoles / pharmacology
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Kinetics
  • Models, Molecular
  • Molecular Structure
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Serine Endopeptidases / metabolism*
  • Structure-Activity Relationship

Substances

  • Imidazoles
  • Indoles
  • Protease Inhibitors
  • Aminopeptidases
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • tripeptidyl-peptidase 2
  • Serine Endopeptidases