Optimization of a series of 2,4-diaminopyridines as neuropeptide Y Y1 receptor antagonists with reduced hERG activity.
Bioorg Med Chem Lett
; 19(15): 4325-9, 2009 Aug 01.
Article
in En
| MEDLINE
| ID: mdl-19487123
The synthesis and evaluation of a series of 2,4-diaminopyridine-based neuropeptide Y Y1 (NPY Y1) receptor antagonists are described. Compound 1 was previously reported by our laboratory to be a potent and selective Y1 antagonist; however, 1 was also found to have potent hERG inhibitory activity. The main focus of this communication is structure-activity relationship development aimed at eliminating the hERG activity of 1. This resulted in the identification of compound 3d as a potent and selective NPY Y1 antagonist with reduced hERG liability.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
4-Aminopyridine
/
Receptors, Neuropeptide Y
/
Ether-A-Go-Go Potassium Channels
Limits:
Animals
/
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2009
Document type:
Article
Affiliation country:
Country of publication: