Synthesis and initial structure–Activity relationships of a novel series of imidazolo[1,2- a]pyrimid-5-ones as potent GnRH receptor antagonists

• Published in: Bioorganic & medicinal chemistry letters Vol. 12; no. 16; pp. 2179 - 2183
• Main Authors: Wilcoxen, Keith M., Zhu, Yun-Fei, Connors, Patrick J., Saunders, John, Gross, Timothy D., Gao, Yinghong, Reinhart, Greg J., Struthers, R.Scott, Chen, Chen
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 19-08-2002; Elsevier
• Subjects: Binding Sites; Biological and medical sciences; Humans; Medical sciences; Molecular Structure; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Pyrimidinones - chemical synthesis; Pyrimidinones - chemistry; Pyrimidinones - pharmacology; Receptors, LHRH - antagonists & inhibitors; Structure-Activity Relationship; Angular nitrogen heterocycle; Peptide hormone; Gonadotropin RH; Non peptide compound; In vitro; Pyridine derivatives; Hypothalamic hormone; Structure activity relation; Bicyclic compound; Peptidergic receptor; Carboxamide; Benzenic compound; Antagonist; Fluorine Organic compounds; Hormone releasing factor; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(02)00370-0

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.
SAR studies of 2-arylimidazolo[1,2-
a]pyrimid-5-ones resulted in the discovery of a series of potent nonpeptide human GnRH receptor antagonists (compound
10e,
K
i=7.5
nM).