Novel potent antagonists of human neuropeptide Y Y5 receptors. Part 2: substituted benzo[ a]cycloheptene derivatives

• Published in: Bioorganic & medicinal chemistry letters Vol. 12; no. 5; pp. 757 - 761
• Main Authors: Itani, Hiromichi, Ito, Harunobu, Sakata, Yoshihiko, Hatakeyama, Yoshifumi, Oohashi, Hiroko, Satoh, Yoshinari
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 11-03-2002; Elsevier
• Subjects: Benzoic Acid - chemistry; Biological and medical sciences; Cycloheptanes - chemical synthesis; Cycloheptanes - chemistry; Cycloheptanes - pharmacology; Medical sciences; Models, Molecular; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Receptors, Neuropeptide Y - antagonists & inhibitors; Structure-Activity Relationship; Human; Sulfonamide; Benzocycloheptene derivatives; Non peptide compound; Selectivity; Condensed benzenic compound; In vitro; Y5 neuropeptide Y receptor; Diamine; Structure activity relation; Piperidine derivatives; Bicyclic compound; Peptidergic receptor; Affinity; Aromatic compound; Antagonist; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(02)00002-1

Novel benzo[
a]cycloheptene derivatives were prepared for the purpose of searching new neuropeptide Y-Y5 (NPY-Y5) receptor antagonists. The structure–activity relationships are described and compound
2o (FR226928) showed the most potent affinity for Y5 receptor of all we prepared and was found to have higher potency and better selectivity for Y5 over Y1 receptor affinities when compared with the known lead compound
1.
Novel substituted benzo[
a]cycloheptene derivatives were prepared and
FR226928 showed high affinity for the NPY-Y5 receptors.