Design and structure-activity relationships of 2-alkyl-3-aminomethyl-6-(3-methoxyphenyl)-7-methyl-8-(2-fluorobenzyl)imidazolo[1,2-a]pyrimid-5-ones as potent GnRH receptor antagonists.
SAR studies of 7-phenylpyrrolo[1,2-a]pyrimid-4-ones 1 and 2, and 2-phenylimidazolo[1,2-a]pyrimidines 3 and 4, as nonpeptide human GnRH receptor antagonists, lead us to believe that the aromatic ring at position-2 of 4 is no longer crucial for the binding once an aryl group is incorporated at postion-6. We report here the use of a 2-alkyl group on the imidazolo[1,2-a]pyrimidone core to generate potent GnRH receptor antagonists. This discovery enabled us to obtain smaller but equally potent GnRH receptor antagonists.
Zhu
Yun-Fei
YF
Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 10555 Science Center Drive, San Diego, California 92121, USA.
Guo
Zhiqiang
Z
Gross
Timothy D
TD
Gao
Yinghong
Y
Connors
Patrick J
PJ
Struthers
R Scott
RS
Xie
Qiu
Q
Tucci
Fabio C
FC
Reinhart
Greg J
GJ
Wu
Dongpei
D
Saunders
John
J
Chen
Chen
C
D015195:Drug Design; D006801:Humans; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D011744:Pyrimidinones; D011966:Receptors, LHRH