Fluoropyrrolidine amides as dipeptidyl peptidase IV inhibitors

Bioorg Med Chem Lett. 2004 Mar 8;14(5):1265-8. doi: 10.1016/j.bmcl.2003.12.040.

Abstract

Amides derived from fluorinated pyrrolidines and 4-substituted cyclohexylglycine analogues have been prepared and evaluated as inhibitors of dipeptidyl dipeptidase IV (DP-IV). Analogues which incorporated (S)-3-fluoropyrrolidine showed good selectivity for DP-IV over quiescent cell proline dipeptidase (QPP). Compound 48 had good pharmacokinetic properties and was orally active in an oral glucose tolerance test in lean mice.

Publication types

  • Comparative Study

MeSH terms

  • Adenosine Deaminase / metabolism
  • Adenosine Deaminase Inhibitors*
  • Amides / chemistry*
  • Amides / pharmacology
  • Animals
  • Dogs
  • Fluorine / chemistry
  • Fluorine / pharmacology
  • Glycoproteins / antagonists & inhibitors*
  • Glycoproteins / metabolism
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacology
  • Pyrrolidines / chemistry*
  • Pyrrolidines / pharmacology
  • Rats

Substances

  • Adenosine Deaminase Inhibitors
  • Amides
  • Glycoproteins
  • Isoenzymes
  • Protease Inhibitors
  • Pyrrolidines
  • Fluorine
  • Adenosine Deaminase