Synthesis, SAR, and X-ray structure of novel potent DPPIV inhibitors: Oxadiazolyl ketones

Synthesis of a novel series of DPPIV inhibitors with 1,2,4- and 1,3,4-oxadiazolyl ketone derivatives and its structure–activity relationships are discussed. Compound 18h showed good inhibitory activity against DPPIV and favorable pharmacokinetic properties. In vivo pharmacodynamic efficacy and co-crystal structure of compound 18h with DPPIV is also described.

Graphical abstractCompound 18h showed excellent inhibitory activity against DPPIV, good selectivity over DPPII and DPPVIII, and showed good PK, PD profile.Figure optionsDownload full-size imageDownload as PowerPoint slide