Document Report Card

Basic Information

ID: ALA4118146

Journal: Bioorg Med Chem Lett

Title: Design, synthesis and evaluation of substituted piperidine based KCNQ openers as novel antiepileptic agents.

Authors: Yang S, Lu D, Ouyang P.

Abstract: Epilepsy is a kind of disease with complicated pathogenesis. KCNQ (Kv7) is a voltage dependent potassium channel that is mostly associated with epilepsy and thus becomes an important target in the treatment of epilepsy. In this paper, a series of substituted piperidine derivatives targeting KCNQ were designed and synthesized by using scaffold hopping and active substructure hybridization. Compounds were evaluated by fluorescence-based thallium influx assay, Rb+ flow assay and electrophysiological patch-clamp assay. Results showed that some compounds possessed more potent potassium channel opening activity than Retigabine. More significantly, compound 11 was found to have good pharmacokinetic profiles in vivo.

CiteXplore: 29706422

DOI: 10.1016/j.bmcl.2018.04.040