Structure-based design of pyridopyrimidinediones as dipeptidyl peptidase IV inhibitors

Betty Lam; Zhiyuan Zhang; Jeffery A Stafford; Robert J Skene; Lihong Shi; Stephen L Gwaltney 2nd

doi:10.1016/j.bmcl.2012.08.110

Structure-based design of pyridopyrimidinediones as dipeptidyl peptidase IV inhibitors

Bioorg Med Chem Lett. 2012 Nov 1;22(21):6628-31. doi: 10.1016/j.bmcl.2012.08.110. Epub 2012 Sep 7.

Authors

Betty Lam¹, Zhiyuan Zhang, Jeffery A Stafford, Robert J Skene, Lihong Shi, Stephen L Gwaltney 2nd

Affiliation

¹ Takeda California, 10410 Science Center Drive, San Diego, CA 92121, USA. [email protected]

PMID: 23025999
DOI: 10.1016/j.bmcl.2012.08.110

Abstract

Dipeptidyl peptidase IV (DPP-4) inhibitors have been shown to enhance GLP-1 levels and thereby improve hyperglycemia in type II diabetes. From a small fragment hit, using structure-based design, we have discovered a new class of non-covalent, potent and selective DPP-4 inhibitors.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Catalytic Domain
Crystallography, X-Ray
Dipeptidyl-Peptidase IV Inhibitors / chemical synthesis
Dipeptidyl-Peptidase IV Inhibitors / chemistry*
Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
Dose-Response Relationship, Drug
Drug Design*
Enzyme Activation / drug effects
Humans
Inhibitory Concentration 50
Models, Molecular
Pyrimidinones / chemical synthesis
Pyrimidinones / chemistry*
Pyrimidinones / pharmacology*

Substances

Dipeptidyl-Peptidase IV Inhibitors
Pyrimidinones