A series of compounds generated by ring expansion/opening and molecular elongation/simplification of the 1,3-dioxolane scaffold were prepared and tested for binding affinity at 5-HT1AR and α1 adrenoceptors. The compounds with greater affinity were selected for further functional studies. N-((2,2-diphenyl-1,3-dioxan-5-yl)methyl)-2-(2-methoxyphenoxy)ethan-1-ammonium hydrogen oxalate (12) emerged as highly potent full agonist at the 5-HT1AR (pKi 5-HT1A = 8.8; pD2 = 9.22, %Emax = 92). The pharmacokinetic data in rats showed that the orally administered 12 has a high biodistribution in the brain compartment. Thus, 12 was further investigated in-vivo, showing an anxiolytic and antidepressant effect. Moreover, in the formalin test, 12 was able to decrease the late response to the noxious stimulus, indicating a potential use in the treatment of chronic pain.

1,3-Dioxane as a scaffold for potent and selective 5-HT1AR agonist with in-vivo anxiolytic, anti-depressant and anti-nociceptive activity / Franchini, S.; Sorbi, C.; Linciano, P.; Carnevale, G.; Tait, A.; Ronsisvalle, S.; Buccioni, M.; Del Bello, F.; Cilia, A.; Pirona, L.; Denora, N.; Iacobazzi, R. M.; Brasili, L.. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 176:(2019), pp. 310-325. [10.1016/j.ejmech.2019.05.024]

1,3-Dioxane as a scaffold for potent and selective 5-HT1AR agonist with in-vivo anxiolytic, anti-depressant and anti-nociceptive activity

Franchini S.
;
Sorbi C.;Linciano P.;Carnevale G.
Membro del Collaboration Group
;
Tait A.;Brasili L.
2019

Abstract

A series of compounds generated by ring expansion/opening and molecular elongation/simplification of the 1,3-dioxolane scaffold were prepared and tested for binding affinity at 5-HT1AR and α1 adrenoceptors. The compounds with greater affinity were selected for further functional studies. N-((2,2-diphenyl-1,3-dioxan-5-yl)methyl)-2-(2-methoxyphenoxy)ethan-1-ammonium hydrogen oxalate (12) emerged as highly potent full agonist at the 5-HT1AR (pKi 5-HT1A = 8.8; pD2 = 9.22, %Emax = 92). The pharmacokinetic data in rats showed that the orally administered 12 has a high biodistribution in the brain compartment. Thus, 12 was further investigated in-vivo, showing an anxiolytic and antidepressant effect. Moreover, in the formalin test, 12 was able to decrease the late response to the noxious stimulus, indicating a potential use in the treatment of chronic pain.
11-mag-2019
176
310
325
1,3-Dioxane as a scaffold for potent and selective 5-HT1AR agonist with in-vivo anxiolytic, anti-depressant and anti-nociceptive activity / Franchini, S.; Sorbi, C.; Linciano, P.; Carnevale, G.; Tait, A.; Ronsisvalle, S.; Buccioni, M.; Del Bello, F.; Cilia, A.; Pirona, L.; Denora, N.; Iacobazzi, R. M.; Brasili, L.. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 176:(2019), pp. 310-325. [10.1016/j.ejmech.2019.05.024]
Franchini, S.; Sorbi, C.; Linciano, P.; Carnevale, G.; Tait, A.; Ronsisvalle, S.; Buccioni, M.; Del Bello, F.; Cilia, A.; Pirona, L.; Denora, N.; Iacobazzi, R. M.; Brasili, L.
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S0223523419304337-main.pdf

accesso aperto

Descrizione: Articolo principale
Tipologia: Post-print dell'autore (bozza post referaggio)
Dimensione 1.05 MB
Formato Adobe PDF
1.05 MB Adobe PDF Visualizza/Apri
VOR_1,3-Dioxane as a scaffold.pdf

non disponibili

Tipologia: Versione dell'editore (versione pubblicata)
Dimensione 1.73 MB
Formato Adobe PDF
1.73 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento 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: http://hdl.handle.net/11380/1179862
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 13
  • ???jsp.display-item.citation.isi??? 14
social impact