Nitric oxide donors and uses thereof

1. An NO-donating compound having the general formula I:

wherein:

A is selected from the group consisting of alkyl, amine, aryl, C-amide, carbonyl, hydrazine, N-amide and any combination thereof, or absent;

X is a heteroaryl selected from the group consisting of benzodioxole, benzothiophene, diazole, dithiolane, furan, imidazole, indole, phthalazine, piperidine, pyrazine, pyrazole, pyridine, pyridinyl, pyrimidine, pyrrolidine, quinoline and thiadiazole;

B is an ethylene chain;

Y is —ONO 2 ; and

Z is methyl.

2. The NO-donating compound of claim 1 , wherein said heteroaryl is pyridine.

3. An NO-donating compound selected from the group consisting of:

3-[4-Methyl-5-(2-nitrooxy-ethyl)-thiazole-2-yl]-pyridine (Pet-12);

2-Chloro-3-[4-methyl-5-(2-nitrooxy-ethyl)-thiazol-2-yl]-6-trifluoromethyl-pyridine (Pet-18);

Diethyl-{3-[4-methyl-5-(2-nitrooxy-ethyl)-thiazol-2-yl]-pyridin-4-yl}-amine (Pet-19);

2-Methyl-5-[4-methyl-5-(2-nitrooxy-ethyl)-thiazol-2-yl]-pyridine (Pet-20);

3-[4-Methyl-5-(2-nitrooxy-ethyl)-thiazol-2-yl]-pyridine 1-oxide (Pet-21);

5-[4-Methyl-5-(2-nitrooxy-ethyl)-thiazol-2-yl]-2-trifluoromethyl-pyridine (Pet-22);

2-Methoxy-6-[4-methyl-5-(2-nitrooxy-ethyl)-thiazol-2-yl]-pyrazine (Pet-23);

Methyl-{6-[4-methyl-5-(2-nitrooxy-ethyl)-thiazol-2-yl]-pyrazin-2-yl}-amine (Pet-24);

2-Ethyl-4-[4-methyl-5-(2-nitrooxy-ethyl)-thiazol-2-yl]-pyridine 1-oxide (Pet-25);

5-[4-Methyl-5-(2-nitrooxy-ethyl)-thiazol-2-yl]-2-trifluoromethyl-pyridine 1-oxide (Pet-26);

3-(4-Amino-2-methyl-pyrimidin-5-ylmethyl)-4-methyl-5-(2-nitrooxy-ethyl)-thiazol-3-ium; chloride (Pet-68);

2-Furan-2-yl-4-methyl-5-(2-nitrooxy-ethyl)-thiazole (Pet-69);

4-Methyl-5-(2-nitrooxy-ethyl)-2-thiophen-2-yl-thiazole (Pet-71);

2-Benzo[b]thiophen-2-yl-4-methyl-5-(2-nitrooxy-ethyl)-thiazole (Pet-72);

[4-Methyl-5-(2-nitrooxy-ethyl)-thiazol-2-yl]-pyridin-3-ylmethyl-amine (Pet-80);

4-[4-Methyl-5-(2-nitrooxy-ethyl)-thiazol-2-yl]-pyridine (Pet-81);

2-(3,5-Dimethyl-pyrazol-1-yl)-4-methyl-5-(2-nitrooxy-ethyl)-thiazole (Pet-83);

5-[4-Methyl-5-(2-nitrooxy-ethyl)-thiazol-2-yl]-1H-imidazol-4-ylamine (Pet-84);

4-Methyl-5-(2-nitrooxy-ethyl)-2-thiophen-2-ylmethyl-thiazole (Pet-86);

4-Methyl-5-(2-nitrooxy-ethyl)-2-(1-thiophen-2-yl-ethyl)-thiazole (Pet-87);

[4-Methyl-5-(2-nitrooxy-ethyl)-thiazol-2-yl]-thiophen-2-yl-methanone (Pet-88);

4-Methyl-5-(2-nitrooxy-ethyl)-2-(nitrooxy-thiophen-2-yl-methyl)-thiazole (Pet-95);

2-[4-Methyl-5-(2-nitrooxy-ethyl)-thiazol-2-yl]-pyrazine (Pet-125);

2-[4-Methyl-5-(2-nitrooxy-ethyl)-thiazol-2-yl]-pyrazine 4-oxide (Pet-126);

2-[4-Methyl-5-(2-nitrooxy-ethyl)-thiazol-2-yl]-pyrazine 1,4-dioxide (Pet-127);

2-Ethyl-5-[4-methyl-5-(2-nitrooxy-ethyl)-thiazol-2-yl]-pyridine (Pet-144);

4-Methyl-5-(2-nitrooxy-ethyl)-thiazole-2-carboxylic acid N′-phthalazin-1-yl-hydrazide (Pet-153);

N-[4-methyl-5-(2-nitrooxy-ethyl)-thiazol-2-yl]-nicotinamide (Pet-154);

N-[4-methyl-5-(2-nitrooxy-ethyl)-thiazol-2-yl]-1-oxy-nicotinamide (Pet-156);

4-Methyl-5-(2-nitrooxy-ethyl)-thiazole-2-carboxylic acid pyridin-3-ylamide (Pet-170);

3-[4-Methyl-5-(2-nitrooxy-ethyl)thiazol-2-ylmethyl]-1H-indole (Pet-172);

[4-Methyl-5-(2-nitrooxy-ethyl)-2-yl]-pyridin-4-yl-amine (Pet-174); and

4-{4-[4-Methyl-5-(2-nitrooxy-ethyl)-thiazol-2-yl]-phenyl}-[1,2,3]thiadiazole (Pet-178).

4. A pharmaceutical composition comprising, as an active ingredient, the NO-donating compound of claim 1 and a pharmaceutically acceptable carrier.

5. A medical device comprising the NO-donating compound of claim 1 and a delivery system configured for delivering said NO-donating compound to a bodily site of a subject.

6. The medical device of claim 5 , wherein said NO-donating compound forms a part of a pharmaceutical composition, said pharmaceutical composition further comprising a pharmaceutically acceptable carrier.

7. The medical device of claim 5 , wherein said delivering is effected by inhalation.

8. The medical device of claim 7 , wherein said delivery system is selected from the group consisting of a metered dose inhaler, a respirator, a nebulizer inhaler, a dry powder inhaler, an electric warmer, a vaporizer, an atomizer and an aerosol generator.

9. The medical device of claim 5 , wherein said delivering is effected transdermally.

10. The medical device of claim 9 , wherein said delivery system is selected from the group consisting of an adhesive plaster and a skin patch.

11. The medical device of claim 5 , wherein said delivering is effected topically.

12. The medical device of claim 11 , wherein said delivery system is selected from the group consisting of an adhesive strip, a bandage, an adhesive plaster, a wound dressing and a skin patch.

13. The medical device of claim 5 , wherein said delivering is effected by implanting the medical device in a bodily organ.

14. The medical device of claim 13 , wherein said delivery system is selected from the group consisting of an aortic aneurysm graft device, an atrioventricular shunt, a catheter, a defibrilator, a heart valve, a hemodialysis catheter, a hemodialysis graft, an indwelling arterial catheter, an indwelling venous catheter, a needle, a pacemaker, a pacemaker lead, a patent foramen ovale septal closure device, a stent, a stent graft, a suture, a synthetic vascular graft, a thread, a tube, a vascular anastomosis clip, a vascular aneurysm occluder, a vascular clip, a vascular prosthetic filter, a vascular sheath and a drug delivery port, a venous valve and a wire.

15. The medical device of claim 13 , wherein said organ is selected from the group consisting of a pulmonary cavity, a blood vessel, an artery, a vein, a capillary, a heart, a heart cavity and a visceral organ.

16. A pharmaceutical composition comprising, as an active ingredient, the NO-donating compound of claim 3 and a pharmaceutically acceptable carrier.

17. A medical device comprising the NO-donating compound of claim 3 and a delivery system configured for delivering said NO-donating compound to a bodily site of a subject.

18. The medical device of claim 17 , wherein said NO-donating compound forms a part of a pharmaceutical composition, said pharmaceutical composition further comprising a pharmaceutically acceptable carrier.

19. The medical device of claim 17 , wherein said delivering is effected by inhalation.

20. The medical device of claim 19 , wherein said delivery system is selected from the group consisting of a metered dose inhaler, a respirator, a nebulizer inhaler, a dry powder inhaler, an electric warmer, a vaporizer, an atomizer and an aerosol generator.

21. The medical device of claim 17 , wherein said delivering is effected transdermally.

22. The medical device of claim 17 , wherein said delivering is effected topically.

23. The medical device of claim 17 , wherein said delivering is effected by implanting the medical device in a bodily organ.