| Literature DB >> 25556095 |
Tina Morgan Ross1, Kathleen Battista2, Gilles C Bignan3, Doug E Brenneman4, Peter J Connolly3, Jingchun Liu5, Steven A Middleton6, Michael Orsini7, Allen B Reitz4, Dan I Rosenthal8, Malcolm K Scott3, Anil H Vaidya9.
Abstract
Small molecule (1) has been identified as a selective partial agonist of Opioid Receptor Like-1 (ORL-1) with potential utility for the treatment of anxiety and other disorders. Nociceptin (orphanin FQ) is an endogenous peptide ligand that binds to ORL-1, however it does not bind the classical δ, μ and κ opioid receptors with high affinity. The synthesis of 1 involved using a molecular diversity approach, to rapidly advance a library of compounds for biological testing. A lead selective potent partial agonist (35-fold ORL-1/Mu) progressed to ORL-1 (NOP or OP4) proof of concept testing in advanced studies. The synthetic approach and biological data for the related chemical series will be presented.Entities:
Keywords: Drug discovery; NOP receptor; Nociceptin; Opioid receptor-like receptor-1; Orphanin FQ
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Year: 2014 PMID： 25556095 DOI： 10.1016/j.bmcl.2014.12.015
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823