New chiral mexiletine analogs were synthesized in their optically active forms and evaluated in vitro as use-dependent blockers of skeletal muscle sodium channels. Tests carried out on sodium currents of single muscle fibers of Rana esculenta demonstrated that all of them exerted a higher use-dependent block than mexiletine. The most potent analog, (S)-3-(2,6-dimethylphenoxy)-1-phenylpropan-1-amine (S)-(5), was six-fold more potent than (R)-Mex in producing a tonic block. As observed with mexiletine, the newly synthesized compounds exhibit modest enantioselective behavior, that is more evident in 3-(2,6-dimethylphenoxy)butan-1-amine (3).

Synthesis and in vitro sodium channel blocking activity evaluation of novel homochiral mexiletine analogs

CAROCCI, ALESSIA;CATALANO, ALESSIA;LENTINI, Giovanni;FRANCHINI, Carlo;DE BELLIS, MICHELA;DE LUCA, Annamaria;CONTE, Diana
2010-01-01

Abstract

New chiral mexiletine analogs were synthesized in their optically active forms and evaluated in vitro as use-dependent blockers of skeletal muscle sodium channels. Tests carried out on sodium currents of single muscle fibers of Rana esculenta demonstrated that all of them exerted a higher use-dependent block than mexiletine. The most potent analog, (S)-3-(2,6-dimethylphenoxy)-1-phenylpropan-1-amine (S)-(5), was six-fold more potent than (R)-Mex in producing a tonic block. As observed with mexiletine, the newly synthesized compounds exhibit modest enantioselective behavior, that is more evident in 3-(2,6-dimethylphenoxy)butan-1-amine (3).
File in questo prodotto:
File Dimensione Formato  
Chirality2010.pdf

non disponibili

Tipologia: Documento in Post-print
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 184.53 kB
Formato Adobe PDF
184.53 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11586/121805
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 25
  • ???jsp.display-item.citation.isi??? 22
social impact