High-throughput synthesis optimization of sulfonamide NPY Y5 antagonists

• Published in: Bioorganic & medicinal chemistry letters Vol. 12; no. 13; pp. 1771 - 1774
• Main Authors: Finn, John, Pelham, David, Walker, Mary W., Gluchowski, Charles
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 08-07-2002; Elsevier
• Subjects: Amines - chemistry; Animals; Biological and medical sciences; Cell Membrane - metabolism; COS Cells; Drug Design; Humans; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Protein Binding; Radioligand Assay; Receptors, Neuropeptide Y - antagonists & inhibitors; Receptors, Neuropeptide Y - chemistry; Receptors, Neuropeptide Y - metabolism; Structure-Activity Relationship; Sulfonamides - chemical synthesis; Sulfonamides - chemistry; Sulfonamides - metabolism; Sulfonamides - pharmacology; Urea - analogs & derivatives; Urea - chemistry; Sulfonamide; Combinatorial chemistry; In vitro; Y5 neuropeptide Y receptor; Screening; Structure activity relation; Chemical compound library; Carboxamide; Ureas; Aromatic compound; Antagonist; Chemical synthesis; Secondary amine
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(02)00288-3

A series of sulfonamide neuropeptide Y Y5 antagonists was optimized by preparation of sets of analogues using high-throughput synthesis and purification techniques. Testing of these compounds for their ability to bind to the human NPY Y5 receptor revealed separate SAR trends for sulfonamide amides versus sulfonamide ureas versus sulfonamide amines. By understanding these SAR trends, potent compounds were identified in all three series.
A series of sulfonamide neuropeptide Y Y5 antagonists was optimized by preparation of sets of analogues using high-throughput synthesis and purification techniques.