title: The highly potent and selective dipeptidyl peptidase IV inhibitors bearing a thienopyrimidine scaffold effectively treat type 2 diabetes.
abstract: New dipeptidyl peptidase IV inhibitors were designed based on Alogliptin using a scaffold-hopping strategy. All of the compounds constructed on a thienopyrimidine scaffold demonstrated good inhibition and selectivity for DPP-IV. Compound 10d exhibited subnanomolar (IC(50)=0.33nM) DPP-IV inhibitory activity, good in vivo efficacy and an acceptable pharmacokinetic profile. A pharmacokinetic-driven optimization of 10d may lead to a new class of clinical candidate DPP-IV inhibitors.
authors.affiliation: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kai Yuan Avenue, Guangzhou Science Park, Guangzhou 510530, China.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Deng
authors.forename: Li
authors.initials: L
authors.lastname: Peng
authors.forename: Guicheng
authors.initials: G
authors.lastname: Zhang
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Lan
authors.forename: Chufang
authors.initials: C
authors.lastname: Li
authors.forename: Fuxin
authors.initials: F
authors.lastname: Chen
authors.forename: Yayao
authors.initials: Y
authors.lastname: Zhou
authors.forename: Zuoxian
authors.initials: Z
authors.lastname: Lin
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Renke
authors.initials: R
authors.lastname: Dai
authors.forename: Hongjiang
authors.initials: H
authors.lastname: Xu
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
authors.forename: Xiquan
authors.initials: X
authors.lastname: Zhang
authors.forename: Wenhui
authors.initials: W
authors.lastname: Hu
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D004285:Dogs; D055808:Drug Discovery; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D010880:Piperidines / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D014498:Uracil / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D010880:Piperidines; D011743:Pyrimidines; C476003:thienopyrimidine; D014498:Uracil; D018819:Dipeptidyl Peptidase 4; C520853:alogliptin