阅读说明：本技术 作为钾通道调节剂的四氢-1h-苯氮杂卓类化合物及其制备和应用 (tetrahydro-1H-benzazepine compounds as potassium channel modulators, and preparation and application thereof ) 是由 梁波 金秋 陈焕明 张志军 华波 于 2020-05-26 设计创作，主要内容包括：本发明涉及作为钾通道调节剂的四氢-1H-苯氮杂卓类化合物及其制备和应用。具体地,本发明化合物具有式A所示结构,其中各基团和取代基的定义如说明书中所述；本发明还公开了所述化合物的制备方法及其作为钾通道调节剂的用途。(The invention relates to a tetrahydro-1H-benzazepine compound as a potassium channel regulator, and a preparation method and application thereof. Specifically, the compound has a structure shown in a formula A, wherein each group and substituent group are defined in the specification; the invention also discloses a preparation method of the compound and application of the compound as a potassium channel regulator.)

A compound of formula A or a pharmaceutically acceptable salt thereof,

wherein the content of the first and second substances,

R ₁selected from the group consisting of substituted or unsubstituted: c_6-10Aryl, 4-7 membered heteroaryl containing 1-3 heteroatoms selected from N, O or S, said substitution being with one or more substituents selected from the group consisting of: halogen, nitro, cyano, C_1-6Alkyl radical, C_3-6Cycloalkyl radical, C_1-6Alkoxy radical, C_3-6Cycloalkoxy, halo C_1-6Alkyl, halo C_1-6Alkoxy radical, C_1-6An alkylamino group;

R ₂and R₃Each independently selected from the group consisting of: hydrogen, halogen, C_1-6Alkyl radical, C _1-6Alkoxy, halo C_1-6Alkyl, halo C_1-6An alkoxy group;

R ₄selected from the group consisting of substituted or unsubstituted: c_1-6Alkyl radical, C_3-6Cycloalkyl, said substitution referring to substitution by one or more substituents selected from the group consisting of: halogen, nitro, cyano, C_1-6Alkyl radical, C_1-6Alkoxy, halo C_1-6Alkyl, halo C_1-6Alkoxy radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-6A cycloalkyl group;

m is selected from the group consisting of: 0.1, 2,3,4,5 and 6.

The compound of claim 1, or a pharmaceutically acceptable salt thereof,

R ₁is substituted C_6-10Aryl, said substitution being substituted with 1, 2,3,4 or 5 substituents selected from the group consisting of: halogen, nitro, cyano, C_1-6Alkyl radical, C_3-6Cycloalkyl radical, C_1-6Alkoxy radical, C_3-6Cycloalkoxy, halo C_1-6Alkyl, halo C_1-6Alkoxy radical, C_1-6An alkylamino group;

R ₂and R₃Each independently selected from the group consisting of: hydrogen, halogen, C_1-6Alkyl radical, C_1-6Alkoxy, halo C_1-6Alkyl, halo C_1-6An alkoxy group;

R ₄selected from the group consisting of substituted or unsubstituted: c_1-6Alkyl radical, C_3-7Cycloalkyl, said substitution being substituted with 1, 2,3,4 or 5 substituents selected from the group consisting of: halogen, nitro, cyano, C_1-6Alkyl radical, C_1-6Alkoxy, halo C_1-6Alkyl, halo C_1-6Alkoxy radical, C_2-6Alkenyl radical、C _2-6Alkynyl, C_3-6A cycloalkyl group;

m is selected from the group consisting of: 0.1, 2,3,4,5 and 6.

The compound of claim 1, or a pharmaceutically acceptable salt thereof,

R ₁is substituted C_6-10Aryl, said substitution being substituted with 1, 2,3,4 or 5 substituents selected from the group consisting of: halogen, nitro, cyano, C_1-6Alkyl radical, C_3-6Cycloalkyl radical, C_1-6Alkoxy radical, C_3-6Cycloalkoxy, halo C_1-6Alkyl, halo C_1-6Alkoxy radical, C_1-6An alkylamino group;

R ₂and R₃Each independently selected from the group consisting of: hydrogen, halogen, C_1-6Alkyl radical, C_1-6Alkoxy, halo C_1-6Alkyl, halo C_1-6An alkoxy group;

R ₄is unsubstituted C_3-7A cycloalkyl group;

m is selected from the group consisting of: 0.1, 2,3,4,5 and 6.

The compound of claim 1, or a pharmaceutically acceptable salt thereof,

R ₁is a substituted or unsubstituted 4-7 membered heteroaryl group containing 1, 2 or 3 heteroatoms selected from N, O or S, said substitution being by 1, 2,3,4 or 5 substituents selected from the group consisting of: halogen, nitro, cyano, C_1-6Alkyl radical, C_3-6Cycloalkyl radical, C_1-6Alkoxy radical, C_3-6Cycloalkoxy, halo C_1-6Alkyl, halo C_1-6Alkoxy radical, C_1-6An alkylamino group;

R ₂and R₃Each independently selected from the group consisting of: hydrogen, halogen、C _1-6Alkyl radical, C_1-6Alkoxy, halo C_1-6Alkyl, halo C_1-6An alkoxy group;

R ₄selected from the group consisting of substituted or unsubstituted: c_1-6Alkyl radical, C_3-7Cycloalkyl, said substitution being substituted with 1, 2,3,4 or 5 substituents selected from the group consisting of: halogen, nitro, cyano, C_1-6Alkyl radical, C_1-6Alkoxy, halo C_1-6Alkyl, halo C_1-6Alkoxy radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-6A cycloalkyl group;

m is selected from the group consisting of: 0.1, 2,3,4,5 and 6.

The compound of claim 1, or a pharmaceutically acceptable salt thereof,

R ₁is a substituted 4-7 membered heteroaryl group containing 1, 2 or 3 heteroatoms selected from N, O or S, said substitution being by 1, 2,3,4 or 5 substituents selected from the group consisting of: halogen, nitro, cyano, C_1-6Alkyl radical, C_3-6Cycloalkyl radical, C_1-6Alkoxy radical, C_3-6Cycloalkoxy, halo C_1-6Alkyl, halo C_1-6Alkoxy radical, C_1-6An alkylamino group;

R ₂and R₃Each independently selected from the group consisting of: hydrogen, halogen, C_1-6Alkyl radical, C_1-6Alkoxy, halo C_1-6Alkyl, halo C_1-6An alkoxy group;

R ₄selected from the group consisting of unsubstituted: c_1-6Alkyl radical, C_3-7A cycloalkyl group;

m is selected from the group consisting of: 0.1, 2,3,4,5 and 6.

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of:

a process for preparing a compound of claim 1, or a pharmaceutically acceptable salt thereof, comprising the steps of:

reacting a compound shown as a formula P with a compound shown as a formula Q to obtain a compound shown as a formula A;

wherein R is₁、R ₂、R ₃、R ₄M is as defined in claim 1;

q is selected from the group consisting of: halogen, hydroxyl.

A pharmaceutical composition comprising one or more pharmaceutically acceptable carriers and one or more compounds of claim 1 or a pharmaceutically acceptable salt thereof.

Use of a compound of claim 1, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for use selected from the group consisting of:

1) preventing and/or treating diseases associated with potassium ion channels;

2) modulating (e.g., up-regulating or down-regulating) ion flow in a potassium channel of a mammal;

3) preventing, treating and/or inhibiting a disorder or condition responsive to an abnormality (e.g., an increase or decrease) in ion flow in potassium channels.

Use according to claim 9, wherein the medicament is for the prevention and/or treatment of a condition or disorder selected from the group consisting of: a disorder or condition of the central nervous system, pain, stroke, a neurodegenerative disorder, a neuronal hyperexcitability state.