Design, synthesis and biological evaluation of novel imidazolone derivatives as dipeptidyl peptidase 4 inhibitors.
A series of novel imidazolone derivatives were designed and synthesized via a rational drug design strategy. These compounds were obtained from 3-substituted imidazolidine-2,4-dione through alkylation, formylation, dehydration, and amination. The structures were characterized by (1)H NMR, (13)C NMR, and MS. All target compounds were screened for their DPP-4 inhibitory activity in vitro. The results revealed that some imidazolone derivatives showed potent DPP-4 inhibition. Compound 5b had an IC50 value of 2.21 µM inhibitory activity against DPP-4. As a promising lead compound, compound 5b with DPP-4 binding mode was further studied by docking analysis. The expected interaction mode was obtained.
ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. lt601@zju.edu.cn.
Yang
Y
Liu
Chaoyi
C
Jiang
Haoshu
H
Wu
Peng
P
Wu
Meimei
M
Si
Yongzhou
Y
Hu
Tao
T
Liu
D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013552:Swine
D054873:Dipeptidyl-Peptidase IV Inhibitors; D007093:Imidazoles; C117197:imidazolone