Substituted pyrrolidine-2,4-dicarboxylic acid amides as potent dipeptidyl peptidase IV inhibitors.
A series of substituted pyrrolidine-2,4-dicarboxylic acid amides were synthesized as potential antidiabetic agents, and many of them showed good in vitro DPP-IV inhibition (IC50 = 2-250 nM) with selectivity over DPP-II, DPP8, and FAP enzymes. Selected compounds 8c and 11a showed in vivo plasma DPP-IV inhibition after oral administration in Wistar rats.
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, No. 35, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, ROC.
Ting-Yueh
TY
Tsai
Mohane Selvaraj
MS
Coumar
Tsu
T
Hsu
Hsing-Pang
HP
Hsieh
Chia-Hui
CH
Chien
Chiung-Tong
CT
Chen
Chung-Nien
CN
Chang
Yu-Kang
YK
Lo
Ssu-Hui
SH
Wu
Chung-Yu
CY
Huang
Yu-Wen
YW
Huang
Min-Hsien
MH
Wang
Hsin-Yi
HY
Wu
Hong-Jen
HJ
Lee
Xin
X
Chen
Yu-Sheng
YS
Chao
Weir-Torn
WT
Jiaang
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D003998:Dicarboxylic Acids / Q000737:chemistry*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D015195:Drug Design; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011759:Pyrrolidines / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D000577:Amides; D003998:Dicarboxylic Acids; D011480:Protease Inhibitors; D011759:Pyrrolidines; C083486:pyrrolidine-2,4-dicarboxylic acid; D018819:Dipeptidyl Peptidase 4