Designing Bifunctional Nop Receptor-Mu Opioid Receptor Ligands from Nop Receptor-Selective Scaffolds. Part I


Zaveri, N. T., Jiang, F., Olsen, C., Polgar, W. E., & Toll, L. (2013). Designing bifunctional NOP receptor-mu opioid receptor ligands from NOP receptor-selective scaffolds. Part I. Bioorganic & Medicinal Chemistry Letters, 23(11), 3308-3313. doi: 10.1016/j.bmcl.2013.03.101


The nociceptin receptor (NOP) and its endogenous agonist, nociceptin/orphanin FQ (N/OFQ), members of the opioid receptor and peptide families respectively, modulate the pharmacological effects of classical opioids, particularly opioid-induced reward and nociception. We hypothesized that compounds containing both NOP and opioid receptor activity in a single molecule may have useful pharmacological profiles as non-addicting analgesics or as drug abuse medications. We report here our forays into the structure–activity relationships for discovering ‘bifunctional’ NOP–mu opioid receptor (MOP) ligands, starting from our NOP-selective scaffolds. This initial SAR suggests pharmacophoric elements that may be modified to modulate/increase opioid affinity, while maintaining high affinity for the NOP receptor, to result in potent bifunctional small-molecule NOP/MOP ligands.

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