Design, synthesis and structure-activity relationships of novel imidazolo[1,2-a]pyrimid-5-ones as potent GnRH receptor antagonists.
SAR studies of lead GnRH receptor antagonists 2a and 2b reported earlier resulted in the discovery of compound 10b which showed much higher potency (K(i)=4.6 nM, compared with 2b, K(i)=230 nM) in which the 7-position of the imidazolo[1,2-a]pyrimidone core was substituted with a methyl group, and the ester at the 6-position was replaced by the 3-methoxyphenyl group.
Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 10555 Science Center Drive, San Diego, CA 92121, USA.
Timothy D
TD
Gross
Yun Fei
YF
Zhu
John
J
Saunders
Keith M
KM
Wilcoxen
Yinghong
Y
Gao
Patrick J
PJ
Connors
Zhiqiang
Z
Guo
R Scott
RS
Struthers
Greg J
GJ
Reinhart
Chen
C
Chen
D000818:Animals; D001665:Binding Sites; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D011744:Pyrimidinones; D011966:Receptors, LHRH