Investigation of the 4-O-alkylamine substituent of non-peptide quinolone GnRH receptor antagonists

Bioorg Med Chem Lett. 1999 Sep 6;9(17):2621-4. doi: 10.1016/s0960-894x(99)00447-3.


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.

MeSH terms

  • Animals
  • Protein Binding
  • Quinolones / chemical synthesis*
  • Quinolones / metabolism
  • Quinolones / pharmacology
  • Rats
  • Receptors, LHRH / antagonists & inhibitors*
  • Receptors, LHRH / metabolism
  • Stereoisomerism


  • Quinolones
  • Receptors, LHRH