Structure-based design and synthesis of benzimidazole derivatives as dipeptidyl peptidase IV inhibitors

Michael B Wallace; Jun Feng; Zhiyuan Zhang; Robert J Skene; Lihong Shi; Christopher L Caster; Daniel B Kassel; Rongda Xu; Stephen L Gwaltney 2nd

doi:10.1016/j.bmcl.2008.02.071

Structure-based design and synthesis of benzimidazole derivatives as dipeptidyl peptidase IV inhibitors

Bioorg Med Chem Lett. 2008 Apr 1;18(7):2362-7. doi: 10.1016/j.bmcl.2008.02.071. Epub 2008 Mar 4.

Authors

Michael B Wallace¹, Jun Feng, Zhiyuan Zhang, Robert J Skene, Lihong Shi, Christopher L Caster, Daniel B Kassel, Rongda Xu, Stephen L Gwaltney 2nd

Affiliation

¹ Takeda San Diego, Drug Discovery, 10410 Science Center Drive, San Diego, CA 92121, USA. michael.wallace@takedasd.com

PMID: 18346892
DOI: 10.1016/j.bmcl.2008.02.071

Abstract

A novel series of non-covalent, benzimidazole-based inhibitors of DPP-4 has been developed from a small fragment hit using structure-based drug design. A highly versatile synthetic route was created for the development of SAR, which led to the discovery of potent and selective inhibitors with excellent pharmaceutical properties.

Publication types

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

MeSH terms

Animals
Benzimidazoles / chemical synthesis
Benzimidazoles / pharmacology*
Crystallography, X-Ray
Dipeptidyl-Peptidase IV Inhibitors / chemical synthesis
Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
Drug Design*
Hypoglycemic Agents / chemical synthesis
Hypoglycemic Agents / pharmacology*
Models, Chemical
Rats
Structure-Activity Relationship

Substances

Benzimidazoles
Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents
benzimidazole

Associated data

PDB/3CCC