Novel trans-2-aryl-cyclopropylamine analogues as potent and selective dipeptidyl peptidase IV inhibitors.
A series of trans-2-aryl-cyclopropylamine derived compounds were synthesized and evaluated their biological activities against DPP-IV. The structure-activity relationships (SAR) led to the discovery of novel series of DPP-IV inhibitors, having IC(50) values of <100 nM with excellent selectivity over the closely related enzymes, DPP8, DPP-II and FAP. The studies identified a potent and selective DPP-IV inhibitor 24b, which exhibited the ability to both significantly inhibit plasma DPP-IV activity in rats and improve glucose tolerance in lean mice and diet induced obese mice.
Tsai
Ting-Yueh
TY
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, No. 35, Keyan Rd., Zhunan Town, Miaoli Country 350, Taiwan, ROC.
Hsu
Tsu
T
Chen
Chiung-Tong
CT
Cheng
Jai-Hong
JH
Yeh
Teng-Kuang
TK
Chen
Xin
X
Huang
Chung-Yu
CY
Chang
Chung-Nien
CN
Yeh
Kai-Chia
KC
Hsieh
Su-Huei
SH
Chien
Chia-Hui
CH
Chang
Yi-Wei
YW
Huang
Chih-Hsiang
CH
Huang
Yu-Wen
YW
Huang
Chen-Lung
CL
Wu
Ssu-Hui
SH
Wang
Min-Hsien
MH
Lu
Cheng-Tai
CT
Chao
Yu-Sheng
YS
Jiaang
Weir-Torn
WT
D000818:Animals; D003521:Cyclopropanes / Q000737:chemistry* / Q000494:pharmacology*; D018819:Dipeptidyl Peptidase 4 / Q000097:blood; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005951:Glucose Tolerance Test; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
D003521:Cyclopropanes; D054873:Dipeptidyl-Peptidase IV Inhibitors; D011480:Protease Inhibitors; C067351:cyclopropylamine; D018819:Dipeptidyl Peptidase 4