Discovery of 3-aminopiperidines as potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitors

Substituted 3-aminopiperidines 3 were evaluated as DPP-4 inhibitors. The inhibitors showed good DPP-4 potency with superb selectivity over other peptidases (QPP, DPP8, and DPP9). Selected DPP-4 inhibitors were further evaluated for their hERG potassium channel, L-type calcium channel, Cyp2D6, and ph...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2007-08, Vol.17 (16), p.4579-4583
Main Authors: Cox, Jason M., Harper, Bart, Mastracchio, Anthony, Leiting, Barbara, Sinha Roy, Ranabir, Patel, Reshma A., Wu, Joseph K., Lyons, Kathryn A., He, Huaibing, Xu, Shiyao, Zhu, Bing, Thornberry, Nancy A., Weber, Ann E., Edmondson, Scott D.
Format: Article
Language:English
Subjects:
Aminopiperidine
Animals
Area Under Curve
Biological and medical sciences
Biological Availability
Dipeptidyl peptidase IV
Dipeptidyl-Peptidase IV Inhibitors
DPP-4
DPP8
DPP9
Half-Life
Humans
Hypoglycemic Agents - chemistry
Hypoglycemic Agents - pharmacology
Medical sciences
Miscellaneous
Molecular Structure
Pharmacology. Drug treatments
Piperidines - blood
Piperidines - chemistry
Piperidines - pharmacology
QPP
Rats
Structure-Activity Relationship
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Substituted 3-aminopiperidines 3 were evaluated as DPP-4 inhibitors. The inhibitors showed good DPP-4 potency with superb selectivity over other peptidases (QPP, DPP8, and DPP9). Selected DPP-4 inhibitors were further evaluated for their hERG potassium channel, L-type calcium channel, Cyp2D6, and pharmacokinetic profiles. Substituted 3-aminopiperidines 3 were evaluated as DPP-4 inhibitors. The inhibitors showed good DPP-4 potency with superb selectivity over other peptidases (QPP, DPP8, and DPP9). Selected DPP-4 inhibitors were further evaluated for their hERG potassium channel, calcium channel, Cyp2D6, and pharmacokinetic profiles.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2007.05.087