1-[2-[(5-Cyanopyridin-2-yl)amino]ethylamino]acetyl-2-(S)-pyrrolidinecarbonitrile: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties

J Med Chem. 2002 Jun 6;45(12):2362-5. doi: 10.1021/jm025522z.

Abstract

Dipeptidyl peptidase IV (DPP-IV) inhibition has the potential to become a valuable therapy for type 2 diabetes. We report the first use of solid-phase synthesis in the discovery of a new DPP-IV inhibitor class and a solution-phase synthesis that is practical up to the multikilogram scale. One compound, NVP-DPP728 (2), is profiled as a potent, selective, and short-acting DPP-IV inhibitor that has excellent oral bioavailability and potent antihyperglycemic activity.

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Caco-2 Cells
  • Dipeptidyl Peptidase 4 / metabolism*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Glucose Tolerance Test
  • Humans
  • Hypolipidemic Agents / chemical synthesis*
  • Hypolipidemic Agents / pharmacology
  • Macaca fascicularis
  • Male
  • Nitriles / chemical synthesis*
  • Nitriles / pharmacology
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / pharmacology
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship

Substances

  • 1-(((2-((5-cyanopyridin-2-yl)amino)ethyl)amino)acetyl)-2-cyano-(S)-pyrrolidine
  • Enzyme Inhibitors
  • Hypolipidemic Agents
  • Nitriles
  • Protease Inhibitors
  • Pyrrolidines
  • Dipeptidyl Peptidase 4