Uracils as potent antagonists of the human gonadotropin-releasing hormone receptor without atropisomers.
Uracil derivatives were designed and synthesized to avoid atropisomers observed in the 6-methyluracils as antagonists of the human GnRH receptor. Optimization at the 1- and 5-positions of the uracil resulted in potent compounds such as 24 (Ki=0.45 nM).
Guo
Zhiqiang
Z
Department of Medicinal Chemistry, Neurocrine Biosciences, Inc. 12790 El Camino Real, San Diego, CA 92130, USA.
Chen
Yongsheng
Y
Huang
Charles Q
CQ
Gross
Timothy D
TD
Pontillo
Joseph
J
Rowbottom
Martin W
MW
Saunders
John
J
Struthers
Scott
S
Tucci
Fabio C
FC
Xie
Qiu
Q
Wade
Warren
W
Zhu
Yun-Fei
YF
Wu
Dongpei
D
Chen
Chen
C
D006801:Humans; D007536:Isomerism; D015394:Molecular Structure; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors*; D014498:Uracil / Q000737:chemistry / Q000494:pharmacology*; D014961:X-Ray Diffraction
D011966:Receptors, LHRH; D014498:Uracil