Dipeptidyl peptidase IV inhibitors derived from beta-aminoacylpiperidines bearing a fused thiazole, oxazole, isoxazole, or pyrazole

Bioorg Med Chem Lett. 2005 May 2;15(9):2253-8. doi: 10.1016/j.bmcl.2005.03.012.

Abstract

A series of beta-aminoacylpiperidines bearing various fused five-membered heterocyclic rings was synthesized as dipeptidyl peptidase IV inhibitors. Potent and relatively selective inhibition could be obtained, depending on choice of heterocycle, regioisomerism, and substitution. In particular, one analog (74, DPP-IV IC50=26 nM) exhibited good oral bioavailability and acceptable half-life in the rat, albeit with rather high clearance.

MeSH terms

  • Dipeptidyl Peptidase 4 / metabolism*
  • Isoxazoles
  • Oxazoles
  • Piperidines / chemical synthesis*
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Pyrazoles
  • Thiazoles

Substances

  • Isoxazoles
  • Oxazoles
  • Piperidines
  • Protease Inhibitors
  • Pyrazoles
  • Thiazoles
  • Dipeptidyl Peptidase 4