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 a 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 derivatives 4 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.

Synthesis and Structure-Activity Relationships of Triazaspirodecanone Derivatives as Nociceptin/Orphanin FQ Receptor Ligands / Corrado, Sandra; Battisti, Umberto M.; Sorbi, Claudia; Tait, Annalisa; Malfacini, Davide; Camarda, Valeria; Calò, Girolamo; Brasili, Livio. - In: CHEMICAL BIOLOGY & DRUG DESIGN. - ISSN 1747-0277. - STAMPA. - 86:4(2015), pp. 447-458. [10.1111/cbdd.12505]

Synthesis and Structure-Activity Relationships of Triazaspirodecanone Derivatives as Nociceptin/Orphanin FQ Receptor Ligands

SORBI, Claudia;TAIT, Annalisa;BRASILI, Livio
2015

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 a 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 derivatives 4 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.
2015
20-gen-2015
86
4
447
458
Synthesis and Structure-Activity Relationships of Triazaspirodecanone Derivatives as Nociceptin/Orphanin FQ Receptor Ligands / Corrado, Sandra; Battisti, Umberto M.; Sorbi, Claudia; Tait, Annalisa; Malfacini, Davide; Camarda, Valeria; Calò, Girolamo; Brasili, Livio. - In: CHEMICAL BIOLOGY & DRUG DESIGN. - ISSN 1747-0277. - STAMPA. - 86:4(2015), pp. 447-458. [10.1111/cbdd.12505]
Corrado, Sandra; Battisti, Umberto M.; Sorbi, Claudia; Tait, Annalisa; Malfacini, Davide; Camarda, Valeria; Calò, Girolamo; Brasili, Livio...espandi
File in questo prodotto:
File Dimensione Formato  
cbdd12505_published online version_def.pdf

Accesso riservato

Descrizione: Articolo principale
Tipologia: Versione pubblicata dall'editore
Dimensione 1.73 MB
Formato Adobe PDF
1.73 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1062705
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 7
  • ???jsp.display-item.citation.isi??? 7
social impact