Sodium channel blockers

1. A method of promoting mucus clearance in mucosal surfaces, comprising administering to a subject an effective amount of a compound represented by formula (I):

wherein

X is halogen;

Y is —N(R 2 ) 2 ;

R 1 is hydrogen;

each R 2 is hydrogen

R 3 is hydrogen;

R 4 is a group represented by formula (A):

wherein

each R L is, independently, —R 7 , —(CH 2 ) n —OR 8 , —O—(CH 2 ) m —OR 8 , —(CH 2 ) n —NR 7 R 10 , —O—(CH 2 ) m —NR 7 R 10 , —(CH 2 ) n (CHOR 8 )(CHOR 8 ) n —CH 2 OR 8 , —O—(CH 2 ) m (CHOR 8 )(CHOR 8 ) n —CH 2 OR 8 , —(CH 2 CH 2 O) m —R 8 , —O—(CH 2 CH 2 O) m —R 8 , —(CH 2 CH 2 O) m —CH 2 CH 2 NR 7 R 10 , —O—(CH 2 CH 2 O) m —CH 2 CH 2 NR 7 R 10 , —(CH 2 ) n —C(═O)NR 7 R 10 , —O—(CH 2 ) m —C(═O)NR 7 R 10 , —(CH 2 ) n -(Z) g —R 7 , —O—(CH 2 ) m —(Z) g —R 7 , —(CH 2 ) n —NR 10 —CH 2 (CHOR 8 )(CHOR 8 ) n —CH 2 OR 8 , —O—(CH 2 ) m —NR 10 —CH 2 (CHOR 8 )(CHOR 8 ) n —CH 2 OR 8 , —(CH 2 ) n —CO 2 R 7 , —O—(CH 2 ) m —CO 2 R 7 , —OSO 3 H, —O-glucuronide, —O-glucose,

each o is, independently, an integer from 0 to 10;

each p is an integer from 0 to 10;

with the proviso that the sum of o and p in each contiguous chain is from 2 to 4;

each x represents a single bond;

each R 5 is —(CH 2 ) m —OR 8 , —O—(CH 2 ) m —OR 8 , —(CH 2 ) n —NR 7 R 10 , —O—(CH 2 ) m —NR 7 R 10 , —(CH 2 ) n (CHOR 8 )(CHOR 8 ) n —CH 2 OR 8 , —O—(CH 2 ) m (CHOR 8 )(CHOR 8 ) n —CH 2 OR 8 , —(CH 2 CH 2 O) m —R 8 , —O—(CH 2 CH 2 O) m —R 8 , —(CH 2 CH 2 O) m —CH 2 CH 2 NR 7 R 10 , —O—(CH 2 CH 2 O) m —CH 2 CH 2 NR 7 R 10 , —(CH 2 ) n —C(═O)NR 7 R 10 , —O—(CH 2 ) m —C(═O)NR 7 R 10 , —(CH 2 ) n —(Z) g —R 7 , —O—(CH 2 ) m —(Z) g —R 7 , —(CH 2 ) n —NR 10 —CH 2 (CHOR 8 )(CHOR 8 ) n —CH 2 OR 8 , —O—(CH 2 ) m —NR 10 —CH 2 (CHOR 8 )(CHOR 8 ) n —CH 2 OR 8 , —(CH 2 ) n —CO 2 R 7 , —O—(CH 2 ) n —CO 2 R 7 —OSO 3 H, —O-glucuronide, —O-glucose,

each R 6 is, independently, —R 7 , —OR 11 , —N(R 7 ) 2 , —(CH 2 ) m —OR 8 , —O—(CH 2 ) m —OR 8 , —(CH 2 ) n —NR 7 R 10 , —O—(CH 2 ) m —NR 7 R 10 , —(CH 2 ) n (CHOR 8 )(CHOR 8 ) n —CH 2 OR 8 , —O—(CH 2 ) m (CHOR 8 )(CHOR 8 ) n —CH 2 OR 8 , —(CH 2 CH 2 O) m —R 8 , —O—(CH 2 CH 2 O) m —R 8 , —(CH 2 CH 2 O) m —CH 2 CH 2 NR 7 R 10 , —O—(CH 2 CH 2 O) m —CH 2 CH 2 NR 7 R 10 , —(CH 2 ) n —C(═O)NR 7 R 10 , —O—(CH 2 ) m —C(═O)NR 7 R 10 , —(CH 2 ) n —(Z) g —R 7 , —O—(CH 2 ) m —(Z) g —R 7 , —(CH 2 ) n —NR 10 —CH 2 (CHOR 8 )(CHOR 8 ) n —CH 2 OR 8 , —O—(CH 2 ) m —NR 10 —CH 2 (CHOR 8 )(CHOR 8 ) n —CH 2 OR 8 , —(CH 2 ) n —CO 2 R 7 , —O—(CH 2 ) m —CO 2 R 7 , —OSO 3 H, —O-glucuronide, —O-glucose,

wherein when two R 6 are —OR 11 , and are located adjacent to each other on a phenyl ring, the alkyl moieties of the two R 6 may be bonded together to form a methylenedioxy group;

each R 7 is, independently, hydrogen or (C 1 -C 7 ) alkyl;

each R 8 is, independently, hydrogen, (C 1 -C 7 ) alkyl, —C(═O)—R 11 , glucuronide, 2-tetrahydropyranyl, or

each R 9 is, independently, —CO 2 R 7 , —CON(R 7 ) 2 , —SO 2 CH 3 , or —C(═O)R 7 ;

each R 10 is, independently, —H, —SO 2 CH 3 , —CO 2 R 7 , —C(═O)NR 7 R 9 , —C(═O)R 7 , or —CH 2 —(CHOH)—CH 2 OH;

each Z is, independently, CHOH, C(═O), CHNR 7 R 10 , C═NR 10 , or NR 10 ;

each R 11 is, independently, (C 1 -C 7 ) alkyl;

each g is, independently, an integer from 1 to 6;

each m is, independently, an integer from 1 to 7;

each n is, independently, an integer from 0 to 7;

each Q is, independently, C—R 5 or C—R 6 , or a nitrogen atom, wherein one Q in is a nitrogen atom;

or a pharmaceutically acceptable salt thereof, and

inclusive of all enantiomers, diastereomers, and racemic mixtures thereof.

2. The method of claim 1 , wherein Y is —NH 2 , R 2 is hydrogen, R 1 is hydrogen, X is chlorine, and R 3 is hydrogen.

3. The method of claim 2 , wherein each R L is hydrogen, o is 4, p is 0 and x represents a single bond.

4. The method of claim 3 , wherein each R 6 is hydrogen.

5. The method of claim 4 , wherein R 5 is —O—(CH 2 ) m —OR 8 .

6. The method of claim 4 , wherein R 5 is —(CH 2 ) n —NR 7 R 10 or —O—(CH 2 ) m —NR 7 R 10 .

7. The method of claim 4 , wherein R 5 is selected from: —(CH 2 ) n (CHOR 8 )(CHOR 8 ) n —CH 2 OR 8 , —(CH 2 CH 2 O) m —R 8 , and —(CH 2 CH 2 O) m —CH 2 CH 2 NR 7 R 10 .

8. The method of claim 4 , wherein R 5 is —O— (CH 2 ) m (CHOR 8 )(CHOR 8 ) n —CH 2 OR 8 .

9. The method of claim 4 , wherein R 5 is —O—(CH 2 CH 2 O) m —R 8 .

10. The method of claim 4 , wherein R 5 is —O— (CH 2 CH 2 O) m —CH 2 CH 2 NR 7 R 10 .

11. The method of claim 4 , wherein R 5 is —(CH 2 ) n —C(═O)NR 7 R 10 or —O—(CH 2 ) m —C(═O)NR 7 R 10 .

12. The method of claim 4 , wherein R 5 is —(CH 2 ) n —(Z) g —R 7 .

13. The method of claim 4 , wherein R 5 is —O—(CH 2 ) m —(Z) g —R 7 .

14. The method of claim 4 , wherein R 5 is —(CH 2 ) n —NR 10 —CH 2 (CHOR 8 )(CHOR 8 ) n —CH 2 OR 8 .

15. The method of claim 4 , wherein R 5 is —O—(CH 2 ) m —NR 10 —CH 2 (CHOR 8 )(CHOR 8 ) n —CH 2 OR 8 .

16. The method of claim 14 , wherein R 5 is —O—(CH 2 ) m —CO 2 R 7 .

17. The method of claim 4 , wherein R 5 is selected from —OSO 3 H, —O-glucuronide, —O-glucose,

18. The method of claim 4 , wherein R 5 is

19. The method of claim 1 , wherein R 5 is selected from: —O—(CH 2 ) m —OR 8 , —(CH 2 ) n —NR 7 R 10 , —O—(CH 2 ) m —NR 7 R 10 , —(CH 2 ) n (CHOR 8 )(CHOR 8 ) n —CH 2 OR 8 , —O—(CH 2 ) m (CHOR 8 )(CHOR 8 ) n —CH 2 OR 8 , —(CH 2 CH 2 O) m —R 8 , —O—(CH 2 CH 2 O) m —R 8 , —(CH 2 CH 2 O) m —CH 2 CH 2 NR 7 R 10 , —O—(CH 2 CH 2 O) m —CH 2 CH 2 NR 7 R 10 , —(CH 2 ) n —C(═O)NR 7 R 10 , —O—(CH 2 ) m —C(═O)NR 7 R 10 , —(CH 2 ) n —(Z) g —R 7 , —O—(CH 2 ) m —(Z) g —R 7 , —(CH 2 ) n —NR 10 —CH 2 (CHOR 8 )(CHOR 8 ) n —CH 2 OR 8 , —O—(CH 2 ) m —NR 10 —CH 2 (CHOR 8 )CHOR 8 ) n —CH 2 OR 8 , —O—(CH 2 ) m —CO 2 R 7 , —OSO 3 H, —O-glucuronide, —O-glucose,

20. The method of claim 1 , which is in the form of a pharmaceutically acceptable salt.

21. The method according to claim 1 wherein the subject is human.