Development of novel NK3 receptor antagonists with reduced environmental impact.
Bioorg Med Chem
; 24(16): 3494-500, 2016 08 15.
Article
in En
| MEDLINE
| ID: mdl-27298001
ABSTRACT
The neurokinin B (NKB)-neurokinin-3 receptor (NK3R) signaling positively regulates the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. The NK3R-selective antagonists may suppress the reproductive functions of mammals. For development of novel NK3R antagonists with reduced environmental toxicity, a structure-activity relationship study of an NK3R antagonist, talnetant, was carried out. Among several talnetant derivatives with labile functional groups in the natural environment, 3-mercaptoquinoline 2f exhibited a comparable biological activity to that of the parent talnetant. Additionally, compound 2f was converted into the disulfide 3f or isothiazolone 8 by air-oxidation, both of which showed no binding affinity to NK3R.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Receptors, Neurokinin-3
Limits:
Animals
/
Humans
Language:
En
Journal:
Bioorg Med Chem
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2016
Type:
Article
Affiliation country:
Japan