A novel synthesis of 2-arylpyrrolo[1,2-a]pyrimid-7-ones and their structure-activity relationships as potent GnRH receptor antagonists.
In the process of developing GnRH receptor antagonists, a novel base-catalyzed cyclization of compounds 5a-b was discovered, which led to the formation of the 2-aryl pyrrolo[1,2-a]pyrimid-7-one core structures 6a-b. These intermediates were further modified at positions 1, 2, 4 and 6 to afford a series of potent GnRH antagonists with low nanomolar K(i) values.
Zhu
Yun-Fei
YF
Neurocrine Biosciences, Inc., 10555 Science Center Drive, San Diego, CA 92121, USA. fzhu@neurocine.com
Wilcoxen
Keith
K
Saunders
John
J
Guo
Zhiqiang
Z
Gao
Yinghong
Y
Connors
Patrick J
PJ
Gross
Timothy D
TD
Tucci
Fabio C
FC
Struthers
R Scott
RS
Reinhart
Greg J
GJ
Xie
Qiu
Q
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