Discovery of potent and selective small molecule NPY Y5 receptor antagonists

• Published in: Bioorganic & medicinal chemistry letters Vol. 12; no. 13; pp. 1767 - 1769
• Main Authors: Islam, Imadul, Dhanoa, Dale, Finn, John, Du, Ping, Walker, Mary W, Salon, John A, Zhang, Jack, Gluchowski, Charles
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 08-07-2002; Elsevier
• Subjects: Animals; Biological and medical sciences; COS Cells; Histidine - chemistry; Humans; Medical sciences; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Models, Molecular; Mutagenesis, Site-Directed; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Protein Structure, Secondary; Radioligand Assay; Receptors, Neuropeptide Y - antagonists & inhibitors; Receptors, Neuropeptide Y - chemistry; Receptors, Neuropeptide Y - metabolism; Stereoisomerism; Structure-Activity Relationship; Sulfonamides - chemistry; Sulfonamides - metabolism; Sulfonamides - pharmacology; Sulfonamide; Non peptide compound; Condensed benzenic compound; In vitro; Modeling; Naphthalene derivatives; Y5 neuropeptide Y receptor; Structure activity relation; Molecular model; Bicyclic compound; Peptidergic receptor; Antagonist; Chemical synthesis; Secondary amine
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(02)00287-1

The discovery of a new class of sulfonamide NPY Y5 receptor antagonists is described. Optimization of this series led to the identification of compounds with high affinity for the hY5 subtype and excellent selectivity over the other NPY receptor subtypes. The SAR for this series was examined and a model for understanding the ligand–receptor interactions was developed.
The discovery of a new class of sulfonamide NPY Y5 receptor antagonists is described. Optimization of this series led to the identification of compounds with high affinity for the hY5 subtype and excellent selectivity over the other NPY receptor subtypes. The SAR for this series was examined and a model for understanding the ligand–receptor interactions was developed.