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

A series of β-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.

Graphical abstractA series of β-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 the choice of heterocycle, regioisomerism, and substitution.Figure optionsDownload full-size imageDownload as PowerPoint slide