title: Synthesis and in vitro sodium channel blocking activity evaluation of novel homochiral mexiletine analogs.
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).
authors: Dipartimento Farmaco-Chimico, Facoltà di Farmacia, Università degli Studi di Bari, Bari, Italy. carocci@farmchim.uniba.it
authors: Alessia
authors: A
authors: Carocci
authors: Alessia
authors: A
authors: Catalano
authors: Claudio
authors: C
authors: Bruno
authors: Giovanni
authors: G
authors: Lentini
authors: Carlo
authors: C
authors: Franchini
authors: Michela
authors: M
authors: De Bellis
authors: Annamaria
authors: A
authors: De Luca
authors: Diana
authors: D
authors: Conte Camerino
mesh_terms: D000818:Animals; D008801:Mexiletine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D009132:Muscles / Q000187:drug effects*; D009222:Myotonia / Q000188:drug therapy*; D026941:Sodium Channel Blockers / Q000494:pharmacology*
chemical_list: D026941:Sodium Channel Blockers; D008801:Mexiletine