Discovery of potent and selective phenylalanine based dipeptidyl peptidase IV inhibitors

Jinyou Xu; Lan Wei; Robert Mathvink; Jiafang He; You-Jung Park; Huaibing He; Barbara Leiting; Kathryn A Lyons; Frank Marsilio; Reshma A Patel; Joseph K Wu; Nancy A Thornberry; Ann E Weber

doi:10.1016/j.bmcl.2005.03.055

Discovery of potent and selective phenylalanine based dipeptidyl peptidase IV inhibitors

Bioorg Med Chem Lett. 2005 May 16;15(10):2533-6. doi: 10.1016/j.bmcl.2005.03.055.

Authors

Jinyou Xu¹, Lan Wei, Robert Mathvink, Jiafang He, You-Jung Park, Huaibing He, Barbara Leiting, Kathryn A Lyons, Frank Marsilio, Reshma A Patel, 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.

PMID: 15863311
DOI: 10.1016/j.bmcl.2005.03.055

Abstract

anti-Substituted beta-methylphenylalanine derived amides have been shown to be potent DPP-IV inhibitors exhibiting excellent selectivity over both DPP8 and DPP9. These are among the most potent compounds reported to date lacking an electrophilic trap. The most potent compound among these is 5-oxo-1,2,4-oxadiazole 44, which is a 3 nM DPP-IV inhibitor.

MeSH terms

Dipeptidyl Peptidase 4 / drug effects*
Phenylalanine / chemistry
Phenylalanine / pharmacology*
Protease Inhibitors / chemistry
Protease Inhibitors / pharmacology*

Substances

Protease Inhibitors
Phenylalanine
Dipeptidyl Peptidase 4