title: Structure-based design and synthesis of benzimidazole derivatives as dipeptidyl peptidase IV inhibitors.
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.
authors.affiliation: Takeda San Diego, Drug Discovery, 10410 Science Center Drive, San Diego, CA 92121, USA. michael.wallace@takedasd.com
authors.forename: Michael B
authors.initials: MB
authors.lastname: Wallace
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Skene
authors.forename: Lihong
authors.initials: L
authors.lastname: Shi
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Caster
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Kassel
authors.forename: Rongda
authors.initials: R
authors.lastname: Xu
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Gwaltney
mesh_terms: 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
chemical_list: D001562:Benzimidazoles; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; C031000:benzimidazole