Quinine analogs as non-peptide calcitonin gene-related peptide (CGRP) receptor antagonists

• Published in: Bioorganic & medicinal chemistry letters Vol. 7; no. 20; pp. 2673 - 2676
• Main Authors: Daines, Robert A., Sham, Kelvin K.C., Taggart, Jack J., Kingsbury, William D., Chan, James, Breen, Ann, Disa, Jyoti, Aiyar, Nambi
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 21.10.1997; Elsevier
• Subjects: Biological and medical sciences; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Human; Arene; Quinuclidine derivatives; Angular nitrogen heterocycle; Nitrogen heterocycle; Quinoline derivatives; Non peptide compound; Calcitonine gene related peptide; In vitro; Structure activity relation; Bicyclic compound; Peptidergic receptor; Aromatic compound; Antagonist; Recombinant protein; Secondary alcohol; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(97)10046-4

A high-throughput screen identified quinine analog 1 as an antagonist of the human calcitonin generelated peptide (hCGRP) receptor. Thus, compound 1 displaces [ 125I]-CGRP from the hCGRP receptor and inhibits CGRP-mediated cAMP production with IC 50 values of 5.9 ± 1.2 μM and 26 ± 5 μM, respectively. A limited structure-activity study of 1 is described. Compound 1, identified in a high-throughput screen, displaces [ 125I]-CGRP from the hCGRP receptor and inhibits CGRP-mediated cAMP production with IC 50 values of 5.9 ± 1.2 μM and 26 ± 5 μM, respectively. A limited structure - activity study of 1 is described.