Novel hexahydrospiro [piperidine-4, 1'-pyrrolo [3, 4-c] pyrroles]: highly selective small-molecule nociceptin/orphanin FQ receptor agonists

…, G Adam, AM Cesura, F Jenck, M Hennig…

文献索引：Kolczewski, Sabine; Adam, Geo; Cesura, Andrea M.; Jenck, Francois; Hennig, Michael; Oberhauser, Thomas; Poli, Sonia M.; Roessler, Felix; Roever, Stephan; Wichmann, Juergen; Dautzenberg, Frank M. Journal of Medicinal Chemistry, 2003 , vol. 46, # 2 p. 255 - 264

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被引用次数: 32

摘要

Novel hexahydrospiro [piperidine-4, 1'-pyrrolo [3, 4-c] pyrroles that act as potent and selective orphanin FQ/nociceptin (N/OFQ) receptor (NOP) agonists were identified. The best compound,(+)-5a, potently inhibited 3H-N/OFQ binding to the NOP receptor (K i= 0.49 nM) but was> 1000-fold less potent in binding to MOP, KOP, and DOP opiate receptors. Further,(+)-5a potently stimulated GTPγS binding to NOP membranes (EC50= 65 nM) and ...