Design, optimization, and in vivo evaluation of a series of pyridine derivatives with dual NK1 antagonism and SERT inhibition for the treatment of depression.
Bioorg Med Chem Lett
; 23(2): 407-11, 2013 Jan 15.
Article
in En
| MEDLINE
| ID: mdl-23253443
ABSTRACT
A series of substituted pyridines, ether linked to a phenylpiperidine core were optimized for dual NK(1)/SERT affinity. Optimization based on NK(1)/SERT binding affinities, and minimization of off-target ion channel activity lead to the discovery of compound 44. In vivo evaluation of 44 in the gerbil forced swim test (a depression model), and ex-vivo NK(1)/SERT receptor occupancy data support the potential of a dual acting compound for the treatment of depression.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyridines
/
Serotonin Antagonists
/
Drug Design
/
Depression
/
Neurokinin-1 Receptor Antagonists
Limits:
Animals
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2013
Document type:
Article
Affiliation country:
United States