Initial structure-activity relationship studies of a novel series of pyrrolo[1,2-a]pyrimid-7-ones as GnRH receptor antagonists.
Initial SAR studies on 1-aminomethyl-2-aryl-3-cyano-pyrrolo[1,2-a]pyrimid-7-one-6-carboxylates as human GnRH receptor antagonists were discussed. 2-(2-Methylaminoethyl)pyridine was discovered to be a key feature for generating active compounds. The best compound from the series had 25 nM (K(i)) binding affinity to human GnRH receptor.
Zhu
Yun-Fei
YF
Neurocrine Biosciences, Inc., 10555 Science Center Drive, San Diego, CA 92121, USA. fzhu@neurocrine.com
Struthers
R Scott
RS
Connors
Patrick J
PJ
Gao
Yinghong
Y
Gross
Timothy D
TD
Saunders
John
J
Wilcoxen
Keith
K
Reinhart
Greg J
GJ
Ling
Nicholas
N
Chen
Chen
C
D000818:Animals; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; D011744:Pyrimidinones; D011758:Pyrroles; D011966:Receptors, LHRH