Controlled HNO release through intramolecular cyclization-elimination

1. A compound of formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

n is an integer selected from the group consisting of 1, 2, and 3;

X 1 is selected from the group consisting of O and NR 1 ;

R and R 1 are each independently selected from the group consisting of H, unsubstituted or substituted linear alkyl, unsubstituted or substituted branched alkyl, and unsubstituted or substituted aryl;

X 2 is a leaving group selected from the group consisting of halogen and L-Y;

L is a bond, —SO 2 —, or —O—;

Y is W, alkyl, monocyclic cycloalkyl, bicyclic cycloalkyl, tricyclic cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which are unsubstituted or substituted with one or more substituent groups selected from W;

W is a substituent group selected from the group consisting of unsubstituted or substituted linear alkyl, unsubstituted or substituted branched alkyl, alkoxyl, perhaloalkyl, hydroxyl, hydroxyalkyl, alkylsulfonyl, alkylsulfanyl, alkylsulfinyl, N-hydroxylsulfonamidyl, carboxyl, carbonyl, carbamoyl, alkylcarbamoyl, halogen, amino, dialkylamino, cycloalkoxyl, cycloalkylsulfanyl, arylsulfanyl, arylsulfinyl, nitro, nitrile, amide, haloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted aryloxyl, cycloalkyl, aralkyloxyl, —SO 3 H, acyl, —COR 2 , —COOR 2 , —CONR 2 R 3 , — CH(C(O)R 2 ) 2 , —SO 2 R 2 , and —COX 3 ;

X 3 is halogen; and

R 2 and R 3 are independently unsubstituted alkyl or aryl, or R 2 and R 3 are taken together to form an unsubstituted or substituted cycloalkyl or an unsubstituted or substituted heterocycloalkyl.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) has the following structure:

wherein:

m is an integer selected from the group consisting of 0, 1, 2, 3, 4, and 5; and

each Y 1 is independently selected from the group consisting of unsubstituted or substituted linear alkyl, unsubstituted or substituted branched alkyl, alkoxyl, perhaloalkyl, hydroxyl, hydroxyalkyl, alkylsulfonyl, alkylsulfanyl, alkylsulfinyl, N-hydroxylsulfonamidyl, carboxyl, carbonyl, carbamoyl, alkylcarbamoyl, halogen, amino, dialkylamino, cycloalkoxyl, cycloalkylsulfanyl, arylsulfanyl, arylsulfinyl, nitro, nitrile, amide, haloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted aryloxyl, cycloalkyl, aralkyloxyl, —SO 3 H, and acyl.

3. The compound of claim 2 or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) has the following structure:

4. The compound of claim 3 or a pharmaceutically acceptable salt thereof, wherein R is selected from the group consisting of methyl, iso-propyl, benzyl, and phenyl.

5. The compound of claim 3 or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from the group consisting of methyl, ethyl, sec-butyl, and benzyl.

6. The compound of claim 3 or a pharmaceutically acceptable salt thereof, wherein n is 1 or 2.

7. The compound of claim 3 or a pharmaceutically acceptable salt thereof, wherein n is 1.

8. The compound of claim 2 or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) has the following structure:

9. The compound of claim 8 or a pharmaceutically acceptable salt thereof, wherein R is selected from the group consisting of methyl, iso-propyl, tert-butyl, benzyl, phenyl, 4-chlorophenyl, and 4-methoxyphenol.

10. The compound of claim 2 or a pharmaceutically acceptable salt thereof, wherein n is 1 or 2.

11. The compound of claim 2 or a pharmaceutically acceptable salt thereof, wherein n is 1.

12. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein n is 1 or 2.

13. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein n is 1.

14. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

15. A kit comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof.

16. The kit of claim 15 , further comprising instructions for use in treating a disease or condition that is responsive to nitroxyl therapy.

17. A compound of the structure

or a pharmaceutically acceptable salt thereof wherein:

R is methyl and R′ is methyl;

R is benzyl and R′ is methyl;

R is iso-propyl and R′ is methyl;

R is phenyl and R′ is methyl;

R is methyl and R′ is ethyl;

R is methyl and R′ is benzyl; or

R is methyl and R′ is sec-butyl.

18. A compound which is:

2-bromo-benzenesulfonamidyl-2-(methylamino)-ethyl carbonate hydrochloride;

2-bromo-benzenesulfonamidyl-2-(benzylamino)-ethyl carbonate hydrochloride;

2-bromo-benzenesulfonamidyl-2-(iso-propylamino)-ethyl carbonate hydrochloride;

2-bromo-benzenesulfonamidyl-2-(tert-butylamino)-ethyl carbonate hydrochloride;

2-bromo-benzenesulfonamidyl-2-(phenylamino)-ethyl carbonate hydrochloride;

2-bromo-benzenesulfonamidyl-2-(4-methoxy-phenylamino)-ethyl carbonate hydrochloride;

2-bromo-benzenesulfonamidyl-2-(4-chloro-phenylamino)-ethyl carbonate hydrochloride;

2-bromo-benzenesulfonamidyl-3-(iso-propylamino)-propyl carbonate hydrochloride; or

a pharmaceutically acceptable salt thereof.