Tetrahydroisoquinoline compound as potassium channel modulator and preparation and application thereof

1 . A compound having formula A or a pharmaceutically acceptable salt thereof,

wherein,

R 1 is a substituted or unsubstituted phenyl group, and the substituted means being substituted by one or more substituents selected from the group consisting of halogen, cyano, C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, —NR 8 R 9 , and ethynyl;

R 2 and R 3 are each independently hydrogen or deuterium;

R 4 and R 5 are each independently C 1-6 alkyl;

R 6 is selected from the substituted or unsubstituted group consisting of C 3-6 cycloalkyl and the substituted means being substituted by one or more substituents selected from the group consisting of halogen, C 1-6 alkyl, C 1-6 alkoxy, and halogenated C 1-6 alkyl;

n is 1 or 2;

W is C-R 7 ;

R 7 is hydrogen or halogen; and

R 8 and R 9 are each independently C 1-6 alkyl.

2 . The compound of claim 1 or the pharmaceutically acceptable salt thereof, wherein:

R 4 and R 5 are methyl;

R 6 is selected from the substituted or unsubstituted group consisting of C 3-6 cycloalkyl, and the substituted means being substituted by one or more substituents selected from halogen and C 1-6 alkyl; and

n is 1.

3 . The compound of claim 2 or the pharmaceutically acceptable salt thereof, wherein:

R 6 is selected from the group consisting of

4 . The compound of claim 3 or the pharmaceutically acceptable salt thereof, wherein:

R 6 is \

5 . A compound having formula A or a pharmaceutically acceptable salt thereof,

wherein:

R 1 is a substituted or unsubstituted phenyl group, and the substituted means being substituted by one or more substituents selected from the group consisting of halogen, cyano, C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, —NR 8 R 9 , and ethynyl;

R 2 and R 3 are each independently hydrogen or deuterium;

R 4 and R 5 are methyl;

R 6 is

n is 1;

W is C-R 7 ;

R 7 is hydrogen or halogen; and

R 8 and R 9 are each independently C 1-6 alkyl.

6 . A compound or the pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of:

7 . A method for preparing the compound of claim 1 or the pharmaceutically acceptable salt thereof comprising the following steps:

wherein:

X is selected from the group consisting of halogen, —B(OH) 2 and —OTf.

8 . A pharmaceutical composition comprising one or more pharmaceutically acceptable carriers and a therapeutically effective amount of one or more of the compounds of claim 1 or the pharmaceutically acceptable salts thereof.

9 . A medicament for the treatment of a disease sensitive to potassium ion channels, wherein the medicament comprises the compound of claim 1 or the pharmaceutically acceptable salt thereof; wherein the disease sensitive to potassium ion channels is a central nervous system disease,

selected from the group consisting of epilepsy, convulsions, inflammatory pain, neuropathic pain, depression, and anxiety disorder.

10 . A pharmaceutical composition comprising one or more pharmaceutically acceptable carriers and a therapeutically effective amount of one or more of the compounds of claim 5 or the pharmaceutically acceptable salts thereof.

11 . A pharmaceutical composition comprising one or more pharmaceutically acceptable carriers and a therapeutically effective amount of one or more of the compounds of claim 6 or the pharmaceutically acceptable salts thereof.

12 . A medicament for the treatment of a disease sensitive to potassium ion channels, wherein the medicament comprises the compound of claim 5 or the pharmaceutically acceptable salt thereof; wherein the disease sensitive to potassium ion channels is a central nervous system disease,

selected from the group consisting of epilepsy, convulsions, inflammatory pain, neuropathic pain, depression, and anxiety disorder.

13 . A medicament for the treatment of a disease sensitive to potassium ion channels, wherein the medicament comprises the compound of claim 6 or the pharmaceutically acceptable salt thereof; wherein the disease sensitive to potassium ion channels is a central nervous system disease,

selected from the group consisting of epilepsy, convulsions, inflammatory pain, neuropathic pain, depression, and anxiety disorder.