Synthesis and biological evaluation of azobicyclo[3.3.0] octane derivatives as dipeptidyl peptidase 4 inhibitors for the treatment of type 2 diabetes.
A series of novel azobicyclo[3.3.0]octane derivatives were synthesized and evaluated as dipeptidyl peptidase 4 (DPP-4) inhibitors. The effort resulted in the discovery of inhibitor 2a, which exhibited excellent efficacies in an oral glucose tolerance test. Introduction of methyl group (2j) could prolong the inhibition of serum DPP-4 activity.
Cho
Tang Peng
TP
Shanghai Hengrui Pharmaceuticals Co., Ltd, Shanghai, China. tangpc@shhrp.com
Long
Yang Fang
YF
Gang
Lin Zhi
LZ
Yang
Wang
W
Jun
Lu He
LH
Yuan
Shen Guang
SG
Hong
Fu Jian
FJ
Lin
Wang
W
Liang
Guan Dong
GD
Lei
Zhang
Z
Jing
Luo Jing
LJ
Shen
Gong Ai
GA
Hong
She Gao
SG
Dan
Wang
W
Ying
Feng
F
Ke
Yan Pang
YP
Ying
Leng
L
Jun
Feng
F
Tai
Mong Xian
MX
D000818:Animals; D001391:Azo Compounds / Q000138:chemical synthesis; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4 / Q000097:blood / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008813:Mice, Inbred ICR; D009795:Octanes / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use*; D010599:Pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D001391:Azo Compounds; D001643:Bridged Bicyclo Compounds; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D009795:Octanes; D018819:Dipeptidyl Peptidase 4