title: Discovery of potent dipeptidyl peptidase IV inhibitors derived from β-aminoamides bearing substituted [1,2,3]-triazolopiperidines for the treatment of type 2 diabetes.
abstract: A series of novel [1,2,3]-triazolopiperidine derivatives 5a-5y were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes, most of the compounds exhibited excellent in vitro potency (IC(50)<50n M) against DPP-4. Among these, compound 5d with potent in vitro activity against DPP-4 and good pharmacokinetic profiles exhibited pronounced in vivo efficacy in an oral glucose tolerance test (OGTT) in ICR mice. On the base of these properties, compound 5d was selected as a potential new candidate for the treatment of type 2 diabetes.
authors.affiliation: Department of Medicinal Chemistry, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Shan
authors.forename: Min
authors.initials: M
authors.lastname: Peng
authors.forename: Houxing
authors.initials: H
authors.lastname: Fan
authors.forename: Qingtao
authors.initials: Q
authors.lastname: Lu
authors.forename: Peng
authors.initials: P
authors.lastname: Lu
authors.forename: Chuansheng
authors.initials: C
authors.lastname: Zhao
authors.forename: Yilang
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000577:Amides / Q000737:chemistry*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000302:isolation & purification / Q000627:therapeutic use*; D055808:Drug Discovery; D020128:Inhibitory Concentration 50; D051379:Mice; D008813:Mice, Inbred ICR; D010880:Piperidines / Q000302:isolation & purification / Q000627:therapeutic use*
chemical_list: D000577:Amides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D010880:Piperidines