Bicyclic cyanothiazolidines as novel dipeptidyl peptidase 4 inhibitors.
The synthesis and biochemical evaluation of novel cyanothiazolidine inhibitors of dipeptidyl peptidase 4 (DPP4) is described. Their main structural feature is a constrained bicyclic core that prevents the intramolecular formation of inactive cyclic species. The inhibitors show good to moderate biochemical potency against DPP4 and display distinct selectivity profiles towards DPP7, DPP8 and DPP9 depending on their substitution.
Betancort
Juan M
JM
Phenomix Corporation, 5871 Oberlin Drive, Suite 200, San Diego, CA 92121, USA. juan.betancort@phenomixcorp.com
Winn
David T
DT
Liu
Ruzhang
R
Xu
Quansheng
Q
Liu
Junjuan
J
Liao
Wensheng
W
Chen
Shu-Hui
SH
Carney
David
D
Hanway
Denise
D
Schmeits
James
J
Li
Xinqiang
X
Gordon
Eric
E
Campbell
David A
DA
D053961:Azabicyclo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D002384:Catalysis; D003920:Diabetes Mellitus / Q000188:drug therapy; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011759:Pyrrolidines / Q000737:chemistry; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry; D053778:Thiazolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013997:Time Factors
D053961:Azabicyclo Compounds; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004791:Enzyme Inhibitors; D009570:Nitriles; D011759:Pyrrolidines; D013844:Thiazoles; D053778:Thiazolidines