Structure-based design and synthesis of benzimidazole derivatives as dipeptidyl peptidase IV inhibitors.
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.
Wallace
Michael B
MB
Takeda San Diego, Drug Discovery, 10410 Science Center Drive, San Diego, CA 92121, USA. michael.wallace@takedasd.com
Feng
Jun
J
Zhang
Zhiyuan
Z
Skene
Robert J
RJ
Shi
Lihong
L
Caster
Christopher L
CL
Kassel
Daniel B
DB
Xu
Rongda
R
Gwaltney
Stephen L
SL
D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D015195:Drug Design; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D008956:Models, Chemical; D051381:Rats; D013329:Structure-Activity Relationship
D001562:Benzimidazoles; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; C031000:benzimidazole