title: Synthesis and Structure-Activity Relationships of Triazaspirodecanone Derivatives as Nociceptin/Orphanin FQ Receptor Ligands.
abstract: Several spiroxatrine derivatives were synthesized and evaluated as potential NOP receptor ligands. Structural modifications of the 1,4-benzodioxane moiety of spiroxatrine have been the focus of this research project. The structure-activity relationships that emerged indicate that the presence of an H-bond donor group (hydroxyl group) is more favorable for NOP activity when it is positioned α with respect to the CH2 linked to the 1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one portion. Moreover, cis diastereoisomers of the hydroxyl derivatives4 and 22 show a moderately higher degree of stereoselectivity than trans isomers. In particular, the spiropiperidine derivative cis-4 has submicromolar agonistic activity, and it will be the reference compound for the design and synthesis of new NOP agonists.
authors.affiliation: Department of Life Sciences, University of Modena & Reggio Emilia, Via G. Campi 183, 41125, Modena, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Corrado
authors.affiliation: Department of Life Sciences, University of Modena & Reggio Emilia, Via G. Campi 183, 41125, Modena, Italy.
authors.forename: Umberto M
authors.initials: UM
authors.lastname: Battisti
authors.affiliation: Department of Life Sciences, University of Modena & Reggio Emilia, Via G. Campi 183, 41125, Modena, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sorbi
authors.affiliation: Department of Life Sciences, University of Modena & Reggio Emilia, Via G. Campi 183, 41125, Modena, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Tait
authors.affiliation: Department of Medical Sciences, Section of Pharmacology and National Institute of Neuroscience, University of Ferrara, 44121, Ferrara, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Malfacini
authors.affiliation: Department of Medical Sciences, Section of Pharmacology and National Institute of Neuroscience, University of Ferrara, 44121, Ferrara, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Camarda
authors.affiliation: Department of Medical Sciences, Section of Pharmacology and National Institute of Neuroscience, University of Ferrara, 44121, Ferrara, Italy.
authors.forename: Girolamo
authors.initials: G
authors.lastname: Calò
authors.affiliation: Department of Life Sciences, University of Modena & Reggio Emilia, Via G. Campi 183, 41125, Modena, Italy.
authors.forename: Livio
authors.initials: L
authors.lastname: Brasili
mesh_terms: D000818:Animals; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D011957:Receptors, Opioid / Q000819:agonists*; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry; D013329:Structure-Activity Relationship; D000094942:Nociceptin Receptor
chemical_list: D001372:Aza Compounds; D008024:Ligands; D011957:Receptors, Opioid; D013141:Spiro Compounds; C014826:spirodecanone; D000094942:Nociceptin Receptor; C000722283:OPRL1 protein, human
keywords: NOP ligands; ORL-1; agonists; spiroxatrine; triazaspirodecanone