Uracils as potent antagonists of the human gonadotropin-releasing hormone receptor without atropisomers

[Display omitted] 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=0.45nM).