Prodrugs of ion channel modulating compounds and uses thereof

1. A prodrug represented by an ion channel modulating compound attached to a prodrug moiety, wherein the ion channel modulating compound is a compound of formula (IA), or a pharmaceutically acceptable salt, a stereoisomers or a stereoisomeric mixture thereof:

wherein, R 7 , R 8 and R 9 are independently selected from hydrogen, hydroxy and C 1 -C 6 alkoxy, with the proviso that R 7 , R 8 and R 9 cannot all be hydrogen;

wherein the prodrug moiety is selected from the group consisting of:

wherein:

each n is an integer from 1 to 10;

R′ and R″ are independently selected from hydrogen and C 1 -C 6 alkyl;

each R is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl and substituted alkynyl;

R′″ is alkylene; and

each X′ is independently selected from O, NH, S or CH 2 ; and

wherein at least one valency of the compound of formula (IA) is substituted with a bond to the prodrug moiety.

2. The prodrug of claim 1 , wherein the ion channel modulating compound of formula (IA) is selected from the group consisting of the following:

(1R,2R)/(1S,2S)-2-[(3R)/(3S)-Hydroxypyrrolidinyl]-1-(3,4-dimethoxyphenethoxy)-cyclohexane;

(1R,2R)/(1S,2S)-2-[(3R)-hydroxypyrrolidinyl]-1-(3,4-dimethoxyphenethoxy)-cyclohexane;

(1R,2R)/(1S,2S)-2-[(3S)-hydroxypyrrolidinyl]-1-(3,4-dimethoxyphenethoxy)-cyclohexane;

(1R,2R)-2-[(3R)-hydroxypyrrolidinyl]-1-(3,4-dimethoxyphenethoxy)-cyclohexane;

(1R,2R)-2-[(3S)-hydroxypyrrolidinyl]-1-(3,4-dimethoxyphenethoxy)-cyclohexane;

(1R,2S)-2-[(3R)-hydroxypyrrolidinyl]-1-(3,4-dimethoxyphenethoxy)-cyclohexane;

(1R,2S)-2-[(3S)-hydroxypyrrolidinyl]-1-(3,4-dimethoxyphenethoxy)-cyclohexane;

(1S,2R)-2-[(3R)-hydroxypyrrolidinyl]-1-(3,4-dimethoxyphenethoxy)-cyclohexane;

(1S,2R)-2-[(3S)-hydroxypyrrolidinyl]-1-(3,4-dimethoxyphenethoxy)-cyclohexane;

(1S,2S)-2-[(3R)-hydroxypyrrolidinyl]-1-(3,4-dimethoxyphenethoxy)-cyclohexane;

(1S,2S)-2-[(3S)-hydroxypyrrolidinyl]-1-(3,4-dimethoxyphenethoxy)-cyclohexane; and

(1R,2S)/(1S,2R)-2-[(3R)/(3S)-hydroxypyrrolidinyl]-1-(3,4-dimethoxyphenethoxy)-cyclohexane.

3. A pharmaceutical composition comprising a prodrug of claim 1 and a pharmaceutically acceptable excipient.

4. The prodrug of claim 1 of the formula (PRO-A), formula (PRO-A-Za) or formula (PRO-A-Zb):

or a pharmaceutically acceptable salt thereof;

wherein Z′, Za and Zb are independently selected from:

wherein:

each n is an integer from 1 to 10;

R′ and R″ are independently selected from hydrogen and C 1 -C 6 alkyl;

each R is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl and substituted alkynyl;

R′″ is alkylene; and

each R′″ is independently selected from O, NH, S or CH 2 .

5. The prodrug of claim 4 selected from:

or a pharmaceutically acceptable salt thereof.

6. The prodrug of claim 4 of formula (PRO-A):

or a pharmaceutically acceptable salt thereof;

wherein Z′ is

wherein:

n is an integer from 1 to 10; and

each R is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl and substituted alkynyl.

7. The prodrug of claim 6 having the formula (PRO-A8):

or a pharmaceutically acceptable salt thereof.

8. The prodrug of claim 4 of formula (PRO-A-Za):

or a pharmaceutically acceptable salt thereof;

wherein Za is

wherein:

n is an integer from 1 to 10; and

each R is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl and substituted alkynyl.

9. The prodrug of claim 7 of formula (PRO-A-Za1):

or a pharmaceutically acceptable salt thereof.