Synthesis and evaluation of structurally constrained imidazolidin derivatives as potent dipeptidyl peptidase IV inhibitors.
To find potent and selective inhibitors of dipeptidyl peptidase IV (DPP-IV), we synthesized a series of 2-cyanopyrrolidine derivatives with constrained imidazolidin ring and tested their activities against DPP-IV. Most of them exhibited submicromolar inhibitory activities against DPP-IV. The most potent compound among these is (S)-1-(2-(2-(3-(3,4-dimethoxyphenyl)-2-oxoimidazolidin-1-yl)ethyl-amino)acetyl)pyrrolidine-2-carbonitrile (6n), which is a 2 nM DPP-IV inhibitor.
West China School of Pharmacy, Sichuan University, Chengdu, PR China.
Liutang
L
Wang
Bin
B
Zhang
Jianxin
J
Ji
Bogang
B
Li
Jufang
J
Yan
Weiyu
W
Zhang
Yong
Y
Wu
Xuechao
X
Wang
D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D048288:Imidazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D011759:Pyrrolidines / Q000737:chemistry
D054873:Dipeptidyl-Peptidase IV Inhibitors; D048288:Imidazolines; D011759:Pyrrolidines; C032519:pyrrolidine