Investigation of the 4-O-alkylamine substituent of non-peptide quinolone GnRH receptor antagonists.
Bioorg Med Chem Lett
; 9(17): 2621-4, 1999 Sep 06.
Article
in En
| MEDLINE
| ID: mdl-10498221
ABSTRACT
Synthesis and in vitro activity of the enantiomers of quinolone GnRH antagonist (+/-)-1 are reported. Chiral amino alcohols were prepared from the appropriate cyclic D- or L-amino acids by the Amdt-Eistert homologation followed by reduction of the resulting esters. Incorporation of these pharmacophores was achieved via a novel Mitsunobu alkylation of 4-hydroxyquinolones. The key amine pharmacophore for binding to the rat GnRH receptor was most active in the S-configuration. Ring size was not important for potency with 4, 5, 6, and 7-membered ring amines exhibiting similar potency.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Quinolones
/
Receptors, LHRH
Limits:
Animals
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
1999
Document type:
Article
Affiliation country: