Diastereoselective synthesis and configuration-dependent activity of (3-substituted-cycloalkyl)glycine pyrrolidides and thiazolidides as dipeptidyl peptidase IV inhibitors

Bioorg Med Chem Lett. 2004 Feb 23;14(4):859-63. doi: 10.1016/j.bmcl.2003.12.013.

Abstract

A diastereoselective synthesis was used to prepare a series of (3-substituted-cyclopentyl and -cyclohexyl)glycine pyrrolidides and thiazolidides. The three chiral centers were generated in an unambiguous, stereochemically defined manner. Inhibitory activity was dependent on the configuration at each stereocenter and on the nature of the 3-substituent. In the cyclopentylglycine pyrrolidide series, high potency against dipeptidyl peptidase IV and good selectivity could be achieved.

MeSH terms

  • Dipeptidyl Peptidase 4 / drug effects*
  • Dipeptidyl Peptidase 4 / metabolism*
  • Molecular Conformation
  • Molecular Structure
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / pharmacology
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / pharmacology
  • Stereoisomerism
  • Thiazoles / chemical synthesis*
  • Thiazoles / pharmacology

Substances

  • Protease Inhibitors
  • Pyrrolidines
  • Thiazoles
  • Dipeptidyl Peptidase 4