title: Identification of an achiral analogue of J-113397 as potent nociceptin/orphanin FQ receptor antagonist.
abstract: To date, J-113397 represents the most potent and selective non peptide NOP receptor antagonist widely used in pharmacological studies. However, the synthesis, purification, and enantiomer separation of this molecule, which contains two chiral centers, is rather difficult and low-yielding. Here, we synthesized and tested a series of simplified J-113397 analogues to investigate the importance of the stereochemistry and the influence of the substituents at position 3 of the piperidine nucleus and on the nitrogen atom of the benzimidazolidinone nucleus. The compound coded as Trap-101, an achiral analogue of J-113397, combines a pharmacological profile similar to that of the parent compound with a practical, high-yielding preparation.
authors.affiliation: Department of Pharmaceutical Sciences, Biotechnology Center, University of Ferrara, 44100 Ferrara, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Trapella
authors.forename: Remo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Laura
authors.initials: L
authors.lastname: Piccagli
authors.forename: Girolamo
authors.initials: G
authors.lastname: Calo'
authors.forename: Giacomo
authors.initials: G
authors.lastname: Carra'
authors.forename: Barbara
authors.initials: B
authors.lastname: Spagnolo
authors.forename: Samantha
authors.initials: S
authors.lastname: Rubini
authors.forename: Giulia
authors.initials: G
authors.lastname: Fanton
authors.forename: Christopher
authors.initials: C
authors.lastname: Hebbes
authors.forename: John
authors.initials: J
authors.lastname: McDonald
authors.forename: David G
authors.initials: DG
authors.lastname: Lambert
authors.forename: Domenico
authors.initials: D
authors.lastname: Regoli
authors.forename: Severo
authors.initials: S
authors.lastname: Salvadori
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008958:Models, Molecular; D009292:Narcotic Antagonists; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013237:Stereoisomerism; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology; D000094942:Nociceptin Receptor
chemical_list: D001562:Benzimidazoles; C402921:J 113397; D009292:Narcotic Antagonists; D010880:Piperidines; D011957:Receptors, Opioid; D011994:Recombinant Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000094942:Nociceptin Receptor