Potent antagonists of gonadotropin releasing hormone receptors derived from quinolone-6-carboxamides

• Published in: Bioorganic & medicinal chemistry letters Vol. 10; no. 5; pp. 443 - 447
• Main Authors: Walsh, Thomas F, Toupence, Richard B, Young, Jonathan R, Huang, Song X, Ujjainwalla, Feroze, DeVita, Robert J, Goulet, Mark T, Wyvratt, Matthew J, Fisher, Michael H, Lo, Jane-Ling, Ren, Ning, Yudkovitz, Joel B, Yang, Yi Tien, Cheng, Kang, Smith, Roy G
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 06-03-2000; Elsevier
• Subjects: Amides - chemical synthesis; Amides - pharmacology; Animals; Biological and medical sciences; CHO Cells; Cricetinae; Hormones. Endocrine system; Humans; Luteinizing Hormone - metabolism; Medical sciences; Pharmacology. Drug treatments; Phosphatidylinositols - metabolism; Quinolones - chemical synthesis; Quinolones - pharmacology; Rats; Receptors, LHRH - antagonists & inhibitors; Stereoisomerism; Structure-Activity Relationship; Human; Rat; Nitrogen heterocycle; Rodentia; Lactam; Gonadotropin RH; Quinoline derivatives; In vitro; Hypothalamic hormone; Vertebrata; Mammalia; Structure activity relation; Ammonium compound; Animal; Chlorine Organic compounds; Bicyclic compound; Organic amide; Aromatic compound; Antagonist; Hormone releasing factor; Chemical synthesis; Quinolone derivatives
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(00)00024-X

SAR studies which focused upon the C-6 position of a recently described series of quinolone gonadotropin releasing hormone antagonists are reported. Synthetic access to diverse quinolone-6-carboxamides was achieved via the palladium-catalyzed amino-carbonylation reactions of iodide
4
with various amines. Amides related to
9y were especially potent, functional antagonists of rat and human GnRH receptors.