4-Amino cyclohexylglycine analogues as potent dipeptidyl peptidase IV inhibitors

Bioorg Med Chem Lett. 2004 Jan 5;14(1):43-6. doi: 10.1016/j.bmcl.2003.10.016.

Abstract

Substituted 4-amino cyclohexylglycine analogues were evaluated for DP-IV inhibitory properties. Bis-sulfonamide 15e was an extremely potent 2.6 nM inhibitor of the enzyme with excellent selectivity over all counterscreens. 2,4-difluorobenzenesulfonamide 15b and 1-naphthyl amide 16b, however, combined an acceptable in vitro profile with good pharmacokinetic properties in the rat, and 15b was orally efficacious at 3 mpk in an OGTT in lean mice.

MeSH terms

  • Animals
  • Cation Transport Proteins / metabolism
  • Dipeptidyl Peptidase 4 / metabolism*
  • Ether-A-Go-Go Potassium Channels
  • Glycine / analogs & derivatives*
  • Glycine / metabolism*
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / metabolism
  • Hypoglycemic Agents / pharmacokinetics
  • Mice
  • Potassium Channels / metabolism
  • Potassium Channels, Voltage-Gated*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / metabolism*
  • Protease Inhibitors / pharmacokinetics
  • Protein Binding / drug effects
  • Protein Binding / physiology
  • Rats

Substances

  • Cation Transport Proteins
  • Ether-A-Go-Go Potassium Channels
  • Hypoglycemic Agents
  • KCNH6 protein, human
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Protease Inhibitors
  • Dipeptidyl Peptidase 4
  • Glycine