Discovery of C-(1-aryl-cyclohexyl)-methylamines as selective, orally available inhibitors of dipeptidyl peptidase IV.
Bioorg Med Chem Lett
; 24(3): 731-6, 2014 Feb 01.
Article
in En
| MEDLINE
| ID: mdl-24439847
ABSTRACT
The successful launches of dipeptidyl peptidase IV (DPP IV) inhibitors as oral anti-diabetics warrant and spur the further quest for additional chemical entities in this promising class of therapeutics. Numerous pharmaceutical companies have pursued their proprietary candidates towards the clinic, resulting in a large body of published chemical structures associated with DPP IV. Herein, we report the discovery of a novel chemotype for DPP IV inhibition based on the C-(1-aryl-cyclohexyl)-methylamine scaffold and its optimization to compounds which selectively inhibit DPP IV at low-nM potency and exhibit an excellent oral pharmacokinetic profile in the rat.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Dipeptidyl Peptidase 4
/
Dipeptidyl-Peptidase IV Inhibitors
/
Drug Discovery
/
Methylamines
Limits:
Animals
/
Humans
Language:
En
Year:
2014
Type:
Article