Discovery of potent, selective, and orally bioavailable oxadiazole-based dipeptidyl peptidase IV inhibitors

Jinyou Xu; Lan Wei; Robert J Mathvink; Scott D Edmondson; George J Eiermann; Huaibing He; Joseph F Leone; Barbara Leiting; Kathryn A Lyons; Frank Marsilio; Reshma A Patel; Sangita B Patel; Aleksandr Petrov; Giovanna Scapin; Joseph K Wu; Nancy A Thornberry; Ann E Weber

doi:10.1016/j.bmcl.2006.07.061

Discovery of potent, selective, and orally bioavailable oxadiazole-based dipeptidyl peptidase IV inhibitors

Bioorg Med Chem Lett. 2006 Oct 15;16(20):5373-7. doi: 10.1016/j.bmcl.2006.07.061. Epub 2006 Aug 17.

Authors

Jinyou Xu¹, Lan Wei, Robert J Mathvink, Scott D Edmondson, George J Eiermann, Huaibing He, Joseph F Leone, Barbara Leiting, Kathryn A Lyons, Frank Marsilio, Reshma A Patel, Sangita B Patel, Aleksandr Petrov, Giovanna Scapin, Joseph K Wu, Nancy A Thornberry, Ann E Weber

Affiliation

¹ Department of Medicinal Chemistry, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA. Jinyou_Xu@merck.com

PMID: 16919457
DOI: 10.1016/j.bmcl.2006.07.061

Abstract

A novel series of oxadiazole based amides have been shown to be potent DPP-4 inhibitors. The optimized compound 43 exhibited excellent selectivity over a variety of DPP-4 homologs.

MeSH terms

Administration, Oral
Animals
Binding Sites
Biological Availability
Dipeptidyl-Peptidase IV Inhibitors*
Dogs
Enzyme Activation / drug effects
Ether-A-Go-Go Potassium Channels / drug effects
Humans
Models, Molecular
Molecular Conformation
Oxadiazoles / administration & dosage*
Oxadiazoles / chemistry
Oxadiazoles / pharmacology*
Protease Inhibitors / administration & dosage*
Protease Inhibitors / chemistry
Protease Inhibitors / pharmacology*
Protein Conformation
Rats
Stereoisomerism
Structure-Activity Relationship

Substances

Dipeptidyl-Peptidase IV Inhibitors
Ether-A-Go-Go Potassium Channels
Oxadiazoles
Protease Inhibitors