JP-2025515501-A5 -

Dates

Publication Date

20260507

Application Date

20230424

Description

All patents, patent applications, websites, other publications or documents, accession numbers, and similar items cited herein are incorporated by reference in whole for all purposes, as if each individual item were specifically and individually indicated to be incorporated by reference in that manner. The present invention provides, for example, the following items: (Item 1) A method for treating a condition relating to a dysfunction of sodium ion channels in a subject requiring such treatment, wherein the subject is given a compound of formula (I), or a pharmaceutically acceptable dose of the salt thereof, administered in doses of approximately 1 mg to approximately 150 mg, in the formula, X and Y are independently CR d or N, R 1 is, A monocyclic C3-6 cycloalkyl or a 4-7 membered monocyclic heterocycline, wherein the cycloalkyl and heterocycline are optionally substituted with one or more Ra groups . R2 is a C1-4 haloalkyl, phenyl, or monocyclic C3-6 cycloalkyl that is optionally substituted with one or more Rb . R3 is hydrogen, C1-4 alkyl , or C1-4 haloalkyl , R4 is hydrogen or C1-4 alkyl , R 5 is a halo, R 6 is a C1-4 alkyl or C1-4 haloalkyl, and the C1-4 alkyl or C1-4 haloalkyl is each substituted with OR c . t is 0, 1, or 2, Ra and Rb are each independently selected from halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy , and C1-4 haloalkoxy . Rc is a C1-4 alkyl or C3-6 cycloalkyl, optionally substituted with a C3-6 cycloalkyl or C1-4 alkoxy , and R d is hydrogen or C1-4 alkyl , However, if the compound is a compound having the following formula, or or a method that does not involve a pharmaceutically acceptable salt thereof. (Item 2) The method according to item 1, wherein the compound is administered in doses of approximately 1 mg, approximately 5 mg, approximately 10 mg, approximately 15 mg, approximately 20 mg, approximately 25 mg, approximately 30 mg, approximately 35 mg, approximately 40 mg, approximately 45 mg, approximately 50 mg, approximately 55 mg, approximately 60 mg, approximately 65 mg, approximately 70 mg, approximately 75 mg, approximately 80 mg, approximately 85 mg, approximately 90 mg, approximately 95 mg, approximately 100 mg, approximately 105 mg, approximately 110 mg, approximately 115 mg, approximately 120 mg, approximately 125 mg, approximately 130 mg, approximately 135 mg, approximately 140 mg, approximately 145 mg, or approximately 150 mg. (Item 3) A method for treating a condition relating to a dysfunction of sodium ion channels in a subject requiring such treatment, wherein the subject is given a compound of formula (I), The formula includes administering a pharmaceutically acceptable dose of the salt thereof at a dose of approximately 0.25 mg/kg/day to approximately 1 mg/kg/day, wherein, X and Y are independently CR d or N, R 1 is, A monocyclic C3-6 cycloalkyl or a 4-7 member monocyclic heterocycline, wherein the cycloalkyl and heterocycline are optionally substituted with one or more Ra groups . R2 is a C1-4 haloalkyl, phenyl, or monocyclic C3-6 cycloalkyl that is optionally substituted with one or more Rb . R3 is hydrogen, C1-4 alkyl , or C1-4 haloalkyl , R4 is hydrogen or C1-4 alkyl , R 5 is a halo, R 6 is a C1-4 alkyl or C1-4 haloalkyl, and the C1-4 alkyl or C1-4 haloalkyl is each substituted with OR c . t is 0, 1, or 2, Ra and Rb are each independently selected from halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy , and C1-4 haloalkoxy . Rc is a C1-4 alkyl or C3-6 cycloalkyl, optionally substituted with a C3-6 cycloalkyl or C1-4 alkoxy , and R d is hydrogen or C1-4 alkyl , However, if the compound is a compound having the following formula, or or a method that does not involve a pharmaceutically acceptable salt thereof. (Item 4) The method according to item 3, wherein the compound is administered in doses of approximately 0.25 mg/kg/day, approximately 0.30 mg/kg/day, approximately 0.35 mg/kg/day, approximately 0.40 mg/kg/day, approximately 0.45 mg/kg/day, approximately 0.50 mg/kg/day, approximately 0.55 mg/kg/day, approximately 0.60 mg/kg/day, approximately 0.65 mg/kg/day, approximately 0.65 mg/kg/day, approximately 70 mg/kg/day, approximately 0.75 mg/kg/day, approximately 0.80 mg/kg/day, approximately 0.85 mg/kg/day, approximately 0.90 mg/kg/day, approximately 0.95 mg/kg/day, or approximately 1.0 mg/kg/day. (Item 5) The method according to any one of items 1 to 4, wherein administration of the compound results in a reduction in the severity, number, and/or frequency of seizures experienced by the subject, compared to the severity, number, and/or frequency of seizures experienced by the subject before administration of the compound. (Item 6) The method according to any one of items 1 to 5, wherein administration of the compound does not cause ataxia, lethargy, and vomiting in the subject. (Item 7) A method for reducing the severity, number, and/or frequency of seizures in a subject requiring such reduction, wherein the method comprises an effective amount of a compoun