title: Structure-activity studies on the nociceptin/orphanin FQ receptor antagonist 1-benzyl-N-{3-[spiroisobenzofuran-1(3H),4'-piperidin-1-yl]propyl} pyrrolidine-2-carboxamide.
abstract: Twelve derivatives of the nociceptin/orphanin FQ (N/OFQ) receptor (NOP) antagonist 1-benzyl-N-{3-[spiroisobenzofuran-1(3H),4'-piperidin-1-yl]propyl} pyrrolidine-2-carboxamide (Comp 24) were synthesized and tested in binding experiments performed on CHO(hNOP) cell membranes. Among them, a novel interesting NOP receptor antagonist (compound 35) was identified by blending chemical moieties taken from different NOP receptor ligands. In vitro in various assays, Compound 35 consistently behaved as a pure, highly potent (pA(2) in the range 8.0-9.9), competitive and NOP selective antagonist. However compound 35 was found inactive when challenged against N/OFQ in vivo in the mouse tail withdrawal assay. Thus, the usefulness of the novel NOP ligand compound 35 is limited to in vitro investigations.
authors.affiliation: Department of Pharmaceutical Sciences and Biotechnology Center, University of Ferrara, via Fossato di Mortara 19, 44100 Ferrara, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Trapella
authors.forename: Carmela
authors.initials: C
authors.lastname: Fischetti
authors.forename: Michela
authors.initials: M
authors.lastname: Pela'
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lazzari
authors.forename: Remo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Girolamo
authors.initials: G
authors.lastname: Calo'
authors.forename: Anna
authors.initials: A
authors.lastname: Rizzi
authors.forename: Valeria
authors.initials: V
authors.lastname: Camarda
authors.forename: David G
authors.initials: DG
authors.lastname: Lambert
authors.forename: John
authors.initials: J
authors.lastname: McDonald
authors.forename: Domenico
authors.initials: D
authors.lastname: Regoli
authors.forename: Severo
authors.initials: S
authors.lastname: Salvadori
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004558:Electric Stimulation; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000187:drug effects; D008297:Male; D051379:Mice; D009292:Narcotic Antagonists; D010880:Piperidines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000378:metabolism*; D013141:Spiro Compounds / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000187:drug effects; D000094942:Nociceptin Receptor
chemical_list: C543193:1-benzyl-N-(3-(spiroisobenzofuran-1(3H),4'-piperidin-1-yl)propyl)pyrrolidine-2-carboxamide; D009292:Narcotic Antagonists; D010880:Piperidines; D011957:Receptors, Opioid; D013141:Spiro Compounds; D000094942:Nociceptin Receptor