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.
Gross
Timothy D
TD
Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 10555 Science Center Drive, San Diego, CA 92121, USA.
Zhu
Yun Fei
YF
Saunders
John
J
Wilcoxen
Keith M
KM
Gao
Yinghong
Y
Connors
Patrick J
PJ
Guo
Zhiqiang
Z
Struthers
R Scott
RS
Reinhart
Greg J
GJ
Chen
Chen
C
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