18 research outputs found
Aziridine Ring Opening for the Synthesis of Sphingolipid Analogues: Inhibitors of Sphingolipid-Metabolizing Enzymes
Identification and Electrophysiological Evaluation of 2-Methylbenzamide Derivatives as Na v
Identification and Electrophysiological Evaluation of 2‑Methylbenzamide Derivatives as Na<sub>v</sub>1.1 Modulators
Voltage-gated sodium channels (Na<sub>v</sub>) are crucial to the
initiation and propagation of action potentials (APs) in electrically
excitable cells, and during the past decades they have received considerable
attention due to their therapeutic potential. Here, we report for
the first time the synthesis and the electrophysiological evaluation
of 16 ligands based on a 2-methylbenzamide scaffold that have been
identified as Na<sub>v</sub>1.1 modulators. Among these compounds, <i>N</i>,<i>N</i>′-(1,3-phenylene)ÂbisÂ(2-methylbenzamide)
(<b>3a</b>) has been selected and evaluated in ex-vivo experiments
in order to estimate the activation impact of such a compound profile.
It appears that <b>3a</b> increases the Na<sub>v</sub>1.1 channel
activity although its overall impact remains moderate. Altogether,
our preliminary results provide new insights into the development
of small molecule activators targeting specifically Na<sub>v</sub>1.1 channels to design potential drugs for treating CNS diseases