1. Identification of 3-substituted N-benzhydryl-nortropane analogs as nociceptin receptor ligands for the management of cough and anxiety
- Author
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Geoffrey B. Varty, Shu-Wei Yang, Zheng Tan, Ahmad Fawzi, Sherry Lu, John C. Anthes, William J. Greenlee, Ginny D. Ho, Deen Tulshian, April Smith-Torhan, Hongtao Zhang, John A. Hey, Xiomara Fernandez, and Robbie L. McLeod
- Subjects
Nortropanes ,Stereochemistry ,medicine.drug_class ,Chemistry, Pharmaceutical ,Guinea Pigs ,Clinical Biochemistry ,NOP ,Administration, Oral ,Pharmaceutical Science ,Carboxamide ,Peptide ,Anxiety ,Ligands ,Biochemistry ,Chemical synthesis ,Anxiolytic ,Nociceptin Receptor ,Structure-Activity Relationship ,Drug Discovery ,medicine ,Animals ,Molecular Biology ,chemistry.chemical_classification ,Molecular Structure ,Chemistry ,Ligand ,Organic Chemistry ,Antitussive Agents ,Kinetics ,Nociceptin receptor ,Anti-Anxiety Agents ,Cough ,Antitussive Agent ,Drug Design ,Receptors, Opioid ,Molecular Medicine - Abstract
A series of nortropane analogs based on previously reported compound 1 have been synthesized and shown to bind to the nociceptin receptor with high affinity. The synthesis and structure-activity relationships around the C-3 nortropane substitution are described. From the SAR study and hPXR screening effort, compound 15 was identified to possess potent oral antitussive and anxiolytic-like activities in the guinea pig models.
- Published
- 2009
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