Composition for inhibiting sodium leak channel (NALCN), comprising n-benzhydryl quinuclidine derivatives

A method for treating a disease resulting from abnormality of sodium leak channels, comprising:

• administering, to an individual with the disease resulting from abnormality of sodium leak channels, a pharmaceutical composition comprising as an active ingredient N-benzhydryl quinuclidine, a N-benzhydryl quinuclidine derivative represented by the following Formula 1, or a pharmaceutically acceptable salt thereof;
• and
• detecting and measuring a change of an electrical current through the sodium leak channel to confirm inhibition of the sodium leak channel,
• wherein in the following Formula 1, R is an unsubstituted or substituted benzyl group,
• wherein the disease is one or more diseases selected from the group consisting of infantile neuroaxonal dystrophy (INAD), neurodevelopmental autosomal syndromes with severe hypotonia, speech impairment, cognitive delay, cervical dystonia, pancreatic cancer, non-small cell lung cancer, glioblastoma, 13q deletion syndrome, restless legs syndrome, and autism:
• and
• wherein the abnormality of sodium leak channels is caused by a mutation of a gene encoding the sodium leak channel.

A method for inhibiting a sodium leak channel, comprising:

• treating a cell comprising a mutation of a gene encoding the sodium leak channel or an with a pharmaceutical composition comprising as an active ingredient N-benzhydryl quinuclidine, a N-benzhydryl quinuclidine derivative represented by the following Formula 1, or a pharmaceutically acceptable salt thereof;
• and
• detecting and measuring a change of an electrical current through the sodium leak channel in the cell:
• wherein R is
• wherein R1 is hydrogen, halogen, C1-4 alkyl, C1-4 haloalkyl, or C1-4 alkoxy, and R2 is hydrogen, halogen, or C1-4 haloalkyl, and
• wherein the N-benzhydryl quinuclidine, a N-benzhydryl quinuclidine derivative or a pharmaceutically acceptable salt thereof inhibits the sodium leak channel.