The design and synthesis of a novel quinolizidine template for potent opioid and opioid receptor-like (ORL1, NOP) receptor ligands

• Published in: Bioorganic & medicinal chemistry letters 2004-01, Vol.14 (1), p.181-185
• Main Authors: Jong, Ling, Zaveri, Nurulain, Toll, Lawrence
• Format: Article
• Language: English
• Subjects: Analgesics, Opioid - metabolism; Analgesics, Opioid - pharmacology; Biological and medical sciences; Drug Design; Ligands; Medical sciences; Narcotic Antagonists - metabolism; Narcotic Antagonists - pharmacology; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Protein Binding - drug effects; Protein Binding - physiology; Quinolizines - chemical synthesis; Quinolizines - metabolism; Receptors, Opioid - agonists; Receptors, Opioid - metabolism; Structure-Activity Relationship
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2003.09.068

A new class of high affinity opioid and opioid receptor-like receptor (ORL1 receptor, NOP receptor) ligands has been designed by conformational restriction of piperidine-based NOP receptor ligands, resulting in a novel quinolizidine scaffold. Different modifications of the pendant functional groups on the scaffold provide differential activities at the opioid and NOP receptors. While the conformational rigidity will provide an improved understanding of the NOP and opioid receptor binding pockets, these compounds also provide a new template for the design of novel opiate and NOP ligands. The design and synthesis of a novel scaffold for potent ORL1 and opioid ligands is described.