Synthesis and initial structure-activity relationships of a novel series of imidazolo[1,2-a]pyrimid-5-ones as potent GnRH receptor antagonists.
SAR studies of 2-arylimidazolo[1,2-a]pyrimid-5-ones 10a-m, which were derived from initial lead 3a, resulted in the discovery of a series of potent nonpeptide human GnRH receptor antagonists. Compounds with good potency (e.g., 10e, K(i)=7.5 nM) were prepared by introduction of a 2-(2-pyridyl)ethyl at the basic nitrogen and a 3-pentyl ester at the 6-position of the bicyclic core.
Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 10555 Science Center Drive, San Diego, CA 92121, USA. cchen@neurocrine.com
Keith M
KM
Wilcoxen
Yun Fei
YF
Zhu
Patrick J
PJ
Connors
John
J
Saunders
Timothy D
TD
Gross
Yinghong
Y
Gao
Greg J
GJ
Reinhart
R Scott
RS
Struthers
Chen
C
Chen
D001665:Binding Sites; D006801:Humans; D015394:Molecular Structure; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D011744:Pyrimidinones; D011966:Receptors, LHRH