Constrained analogues of tocainide as potent skeletal muscle sodium channel blockers towards the development of antimyotonic agents.
1-Benzyl-N-(2,6-dimethylphenyl)piperidine-3-carboxamide and 4-benzyl-N-(2,6-dimethylphenyl)piperazine-2-carboxamide, two conformationally restricted analogues of tocainide, were designed and synthesized as voltage-gated skeletal muscle sodium channel blockers. They showed, with respect to tocainide, a marked increase in both potency and use-dependent block.
Catalano
Alessia
A
Department of Medicinal Chemistry, University of Bari, via E. Orabona n. 4, 70125 Bari, Italy.
Carocci
Alessia
A
Corbo
Filomena
F
Franchini
Carlo
C
Muraglia
Marilena
M
Scilimati
Antonio
A
De Bellis
Michela
M
De Luca
Annamaria
A
Camerino
Diana Conte
DC
Sinicropi
Maria Stefania
MS
Tortorella
Vincenzo
V
D015394:Molecular Structure; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009222:Myotonia; D026941:Sodium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D016677:Tocainide / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D026941:Sodium Channel Blockers; D016677:Tocainide