Identification and initial structure-activity relationships of a novel non-peptide quinolone GnRH receptor antagonist

Screening of the Merck sample collection for non-peptide compounds with bin ding affinity for the rat GnRH receptor led to the identification of the su bstituted quinolone (1) as a lead compound in the search for a non-peptide GnRH receptor antagonist. Substantial improvements in potency (similar to 3 00 fold) were achieved by addition of an alkyl amine at the 4-position, a 3 ,5-dimethylphenyl group at the 3-position and 6-nitro-7-chloro-substitution of the 1H-quinolone core. (C) 1999 Elsevier Science Ltd. All rights reserv ed.