Pyrazolone derivatives as nitroxyl donors

1. A compound of formula (Ia)

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is (C 1 -C 6 )alkyl or unsubstituted phenyl;

R 2 is phenyl wherein said phenyl is unsubstituted or substituted with 1, 2, 3, 4, or 5 substituent(s) independently selected from halo, (C 1 -C 6 )alkyl, (C 1 -C 4 )haloalkyl, (C 1 -C 4 )perhaloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 4 )haloalkoxy, (C 1 -C 4 )perhaloalkoxy, (C 1 -C 6 )alkylsulfanyl, (C 1 -C 4 )haloalkylsulfanyl, (C 1 -C 4 )perhaloalkylsulfanyl, (C 1 -C 6 )alkylsulfinyl, (C 1 -C 6 )alkylsulfonyl, (C 3 -C 6 )cycloalkylsulfonyl, (C 1 -C 4 )haloalkylsulfinyl, (C 1 -C 4 )haloalkylsulfonyl, (C 1 -C 4 )perhaloalkylsulfinyl, (C 1 -C 4 )perhaloalkylsulfonyl, —S(O) 2 —NH 2 , N—(C 1 -C 6 )alkylaminosulfonyl, and N,N-di(C 1 -C 6 )alkylaminosulfonyl; and

R 3 is (C 1 -C 6 )alkyl or —C(═NOR 9 )R 10 wherein R 9 and R 10 are independently selected from (C 1 -C 6 )alkyl.

2. The compound of claim 1 , wherein R 1 is (C 1 -C 6 )alkyl unsubstituted or substituted with C(═O)OH.

3. The compound of claim 1 , wherein R 1 is unsubstituted phenyl.

4. The compound of claim 1 , wherein R 2 is phenyl substituted with 1, 2, or 3 substituent(s) independently selected from halo, (C 1 -C 6 )alkyl, (C 1 -C 4 )perhaloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 4 )haloalkoxy, (C 1 -C 4 )perhaloalkoxy, (C 1 -C 6 )alkylsulfanyl, (C 1 -C 6 )alkylsulfinyl, (C 1 -C 6 )alkylsulfonyl, (C 1 -C 4 )haloalkylsulfinyl, (C 1 -C 4 )haloalkylsulfonyl, (C 1 -C 4 )perhaloalkylsulfinyl, (C 1 -C 4 )perhaloalkylsulfonyl, —S(O) 2 —NH 2 , or N,N-di(C 1 -C 6 )alkylaminosulfonyl.

5. The compound of claim 1 , wherein R 2 is unsubstituted phenyl.

6. The compound of claim 1 , wherein R 3 is (C 1 -C 6 )alkyl.

7. The compound of claim 1 , wherein R 3 is —C(═NOR 9 )R 10 .

8. The compound of claim 1 , wherein, R 3 is —C(═NOR 9 )R 10 wherein each of R 9 and R 10 is methyl.

9. A pharmaceutical composition comprising the compound of claim 1 and at least one pharmaceutically acceptable excipient.

10. The pharmaceutical composition of claim 9 , wherein the pharmaceutical composition is suitable for oral administration.

11. The pharmaceutical composition of claim 9 , wherein the pharmaceutical composition is formulated for administration in solid form.

12. The pharmaceutical composition of claim 9 , wherein the at least one pharmaceutically acceptable excipient is selected from lactose, microcrystalline cellulose, croscarmellose, or any mixture thereof.

13. A method of treating a cardiovascular disease, comprising administering an effective amount of the compound of claim 1 or a pharmaceutical composition of claim 9 to a patient in need thereof.

14. The method of claim 13 , wherein the cardiovascular disease is heart failure.

15. The method of claim 13 , wherein the cardiovascular disease is acute decompensated heart failure.

16. The method of claim 13 , wherein the compound or the pharmaceutical composition is administered orally.

17. A compound of formula (Ib)

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is (C 1 -C 6 )alkyl or unsubstituted phenyl;

R 2 is (C 1 -C 6 )alkyl, (C 1 -C 4 )haloalkyl, or (C 1 -C 4 )perhaloalkyl;

R 3 is (5- or 6-membered)heteroaryl or phenyl wherein said heteroaryl and phenyl are unsubstituted or substituted with 1, 2, 3, 4, or 5 substituent(s) independently selected from halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, phenyl, —C(═O)NR 4 R 5 , (C 1 -C 6 )alkylsulfinyl, (C 1 -C 6 )alkylsulfonyl, and N,N-di(C 1 -C 6 )alkylaminosulfonyl; and

R 4 and R 5 are independently H or (C 1 -C 6 )alkyl.

18. The compound of claim 17 , wherein R 1 is (C 1 -C 6 )alkyl.

19. The compound of claim 17 , wherein R 2 is methyl.

20. The compound of claim 17 , wherein R 3 is phenyl substituted with halo or (C 1 -C 6 )alkylsulfonyl.

21. The compound of claim 17 , wherein:

R 1 is (C 1 -C 6 )alkyl or unsubstituted phenyl;

R 2 is (C 1 -C 6 )alkyl, (C 1 -C 4 )haloalkyl, or (C 1 -C 4 )perhaloalkyl; and

R 3 is phenyl wherein said phenyl is unsubstituted or substituted with 1, 2, 3, 4, or 5 substituent(s) independently selected from halo, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkylsulfinyl and (C 1 -C 6 )alkylsulfonyl.

22. The compound of claim 17 , wherein R 1 is unsubstituted phenyl.

23. The compound of claim 17 , wherein R 3 is unsubstituted phenyl.

24. A pharmaceutical composition comprising the compound of claim 17 and at least one pharmaceutically acceptable excipient.

25. A compound of formula (Ic)

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is (C 1 -C 6 )alkyl or phenyl, wherein said phenyl is unsubstituted or substituted with 1, 2, or 3 substituent(s) independently selected from halo;

R 2 is (C 1 -C 6 )alkoxy, phenylsulfanyl, phenylsulfonyl, phenylsulfinyl or (C 3 -C 6 )cycloalkyl; and

R 3 is (C 1 -C 6 )alkyl or —C(═NOR 9 )R 10 wherein R 9 and R 10 are independently selected from (C 1 -C 6 )alkyl.

26. The compound of claim 25 , wherein R 1 is (C 1 -C 6 )alkyl.

27. The compound of claim 25 , wherein R 1 is unsubstituted phenyl.

28. The compound of claim 25 , wherein R 2 is cyclopropyl.

29. The compound of claim 25 , wherein R 3 is —C(═NOR 9 )R 10 wherein each of R 9 and R 10 is methyl.

30. The compound of claim 25 , wherein:

R 1 is (C 1 -C 6 )alkyl or phenyl, wherein said phenyl is unsubstituted or substituted with 1, 2, or 3 substituent(s) independently selected from halo;

R 2 is (C 3 -C 6 )cycloalkyl; and

R 3 is —C(═NOR 9 )R 10 wherein R 9 and R 10 are independently selected from (C 1 -C 6 )alkyl.

31. The compound of claim 25 , wherein R 1 is phenyl substituted with 1, 2, or 3 substituent(s) independently selected from halo.

32. A pharmaceutical composition comprising the compound of claim 25 and at least one pharmaceutically acceptable excipient.

33. A compound selected from:

5-(4-chlorophenyl)-4-(hydroxyamino)-2,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one,

5-(2-chlorophenyl)-4-(hydroxyamino)-2,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one,

5-(2-fluorophenyl)-4-(hydroxyamino)-2,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one,

4-(hydroxyamino)-2,4-dimethyl-5-(4-(trifluoromethyl)phenyl)-2,4-dihydro-3H-pyrazol-3-one,

5-(4-fluorophenyl)-4-(hydroxyamino)-2,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one,

4-(hydroxyamino)-2,5-dimethyl-4-phenyl-2,4-dihydro-3H-pyrazol-3-one,

5-(3,5-dimethylphenyl)-4-(hydroxyamino)-2,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one,

5-(2-chlorophenyl)-4-(hydroxyamino)-2-iso-propyl-4-methyl-2,4-dihydro-3H-pyrazol-3-one,

5-(3,5-dichlorophenyl)-4-(hydroxyamino)-2,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one,

4-(hydroxyamino)-2,4-dimethyl-5-(4-(methylsulfinyl)phenyl)-2,4-dihydro-3H-pyrazol-3-one,

5-(2-chloro-4-fluorophenyl)-4-(hydroxyamino)-2,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one,

4-(hydroxyamino)-2,4-dimethyl-5-(4-(methylsulfonyl)phenyl)-2,4-dihydro-3H-pyrazol-3-one,

4-(hydroxyamino)-2,4-dimethyl-5-phenyl-2,4-dihydro-3H-pyrazol-3-one,

2-(4-bromophenyl)-4-(hydroxyamino)-5-iso-propyl-4-(1-(methoxyimino)ethyl)-2,4-dihydro-3H-pyrazol-3-one,

5-(3-fluoro-4-methoxyphenyl)-4-(hydroxyamino)-2,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one,

5-cyclopropyl-4-(hydroxyamino)-4-(1-(methoxyimino)ethyl)-2-methyl-2,4-dihydro-3H-pyrazol-3-one,

4-(hydroxyamino)-2,4-dimethyl-5-(2-(methylsulfinyl)phenyl)-2,4-dihydro-3H-pyrazol-3-one,

4-(hydroxyamino)-2,4-dimethyl-5-(3-(trifluoromethyl)phenyl)-2,4-dihydro-3H-pyrazol-3-one,

5-(tert-butyl)-4-(hydroxyamino)-4-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one,

4-(hydroxyamino)-5-methyl-2,4-diphenyl-2,4-dihydro-3H-pyrazol-3-one,

4-(hydroxyamino)-4-methyl-2,5-diphenyl-2,4-dihydro-3H-pyrazol-3-one,

5-(2-fluorophenyl)-4-(hydroxyamino)-2-iso-propyl-4-methyl-2,4-dihydro-3H-pyrazol-3-one,

4-(4-fluorophenyl)-4-(hydroxyamino)-2,5-dimethyl-2,4-dihydro-3H-pyrazol-3-one,

5-(tert-butyl)-4-(hydroxyamino)-2-iso-propyl-4-(1-(methoxyimino)ethyl)-2,4-dihydro-3H-pyrazol-3-one,

5-(2-fluorophenyl)-4-(hydroxyamino)-4-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one,

4-(hydroxyamino)-1-isopropyl-3-methyl-4-phenyl-1H-pyrazol-5(4H)-one,

4-ethyl-5-(2-fluorophenyl)-4-(hydroxyamino)-2-methyl-2,4-dihydro-3H-pyrazol-3-one,

4-(hydroxyamino)-2-iso-propyl-4-methyl-5-(4-(methylsulfonyl)phenyl)-2,4-dihydro-3H-pyrazol-3-one,

4-(hydroxyamino)-2,4-dimethyl-5-(4-((trifluoromethyl)sulfonyl)phenyl)-2,4-dihydro-3H-pyrazol-3-one,

4-(hydroxyamino)-2,4-dimethyl-5-(4-((trifluoromethyl)sulfinyl)phenyl)-2,4-dihydro-3H-pyrazol-3-one,

4-(hydroxyamino)-2,4-dimethyl-5-(4-(methylthio)phenyl)-2,4-dihydro-3H-pyrazol-3-one,

4-(hydroxyamino)-2,5-dimethyl-4-(4-(methylsulfonyl)phenyl)-2,4-dihydro-3H-pyrazol-3-one,

5-(3-fluoro-4-(methylsulfinyl)phenyl)-4-(hydroxyamino)-2,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one,

4-(hydroxyamino)-2,4-dimethyl-5-(3-methyl-4-(methylsulfinyl)phenyl)-2,4-dihydro-3H-pyrazol-3-one,

5-(3-fluoro-4-(methylsulfonyl)phenyl)-4-(hydroxyamino)-2,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one,

4-(hydroxyamino)-2,4-dimethyl-5-(3-methyl-4-(methylsulfonyl)phenyl)-2,4-dihydro-3H-pyrazol-3-one,

4-(hydroxyamino)-4-(1-(methoxyimino)ethyl)-2-methyl-5-(4-(methylsulfonyl)-phenyl)-2,4-dihydro-3H-pyrazol-3-one,

4-(hydroxyamino)-4-(4-methoxyphenyl)-1,3-dimethyl-1H-pyrazol-5(4H)-one,

5-(3,5-difluoro-4-(methylsulfonyl)phenyl)-4-(hydroxyamino)-2,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one,

4-(hydroxyamino)-4-(1-(methoxyimino)ethyl)-2-methyl-5-phenyl-2,4-dihydro-3H-pyrazol-3-one,

4-(hydroxyamino)-2,4-dimethyl-5-(3-(methylsulfonyl)phenyl)-2,4-dihydro-3H-pyrazol-3-one,

4-(4-(hydroxyamino)-1,4-dimethyl-5-oxo-4,5-dihydro-1H-pyrazol-3-yl)-N,N-dimethylbenzenesulfonamide,

4-(hydroxyamino)-1,4-dimethyl-3-(o-tolyl)-1H-pyrazol-5(4H)-one,

4-(hydroxyamino)-4-(1-(methoxyimino)ethyl)-1-methyl-3-(4-(trifluoromethyl)phenyl)-1H-pyrazol-5(4H)-one,

4-(hydroxyamino)-3-(4-methoxyphenyl)-1,4-dimethyl-1H-pyrazol-5(4H)-one,

3-(3-chlorophenyl)-4-(hydroxyamino)-1,4-dimethyl-1H-pyrazol-5(4H)-one,

4-(hydroxyamino)-3-(2-methoxyphenyl)-1,4-dimethyl-1H-pyrazol-5(4H)-one,

4-(hydroxyamino)-1,4-dimethyl-3-(2-(trifluoromethoxy)phenyl)-1H-pyrazol-5(4H)-one,

3-(2,3-dichlorophenyl)-4-(hydroxyamino)-1,4-dimethyl-1H-pyrazol-5(4H)-one,

3-(2,4-dichlorophenyl)-4-(hydroxyamino)-1,4-dimethyl-1H-pyrazol-5(4H)-one,

4-(hydroxyamino)-1,4-dimethyl-3-(4-(trifluoromethoxy)phenyl)-1H-pyrazol-5(4H)-one,

4-(hydroxyamino)-1,4-dimethyl-3-(2-(trifluoromethyl)phenyl)-1H-pyrazol-5(4H)-one,

4-(hydroxyamino)-4-methyl-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5(4H)-one,

3-(2-ethoxy-4-fluorophenyl)-4-(hydroxyamino)-1,4-dimethyl-1H-pyrazol-5(4H)-one,

3-(4-fluorophenyl)-4-(hydroxyamino)-4-(1-(methoxyimino)ethyl)-1-methyl-1H-pyrazol-5(4H)-one,

4-(hydroxyamino)-1,3-dimethyl-4-(4-(methylsulfinyl)phenyl)-1H-pyrazol-5(4H)-one,

4-(4-chlorophenyl)-4-(hydroxyamino)-1,3-dimethyl-1H-pyrazol-5(4H)-one,

4-(hydroxyamino)-1,4-dimethyl-3-(4-((trifluoromethyl)thio)phenyl)-1H-pyrazol-5(4H)-one,

4-(3-bromo-4-methoxyphenyl)-4-(hydroxyamino)-1,3-dimethyl-1H-pyrazol-5(4H)-one,

3-(3,5-bis(trifluoromethyl)phenyl)-4-(hydroxyamino)-1,4-dimethyl-1H-pyrazol-5(4H)-one,

3-(3-Chloro-4-methanesulfonylphenyl)-4-(hydroxyamino)-1,4-dimethyl-4,5-dihydro-1H-pyrazol-5-one,

methyl 4-[4-(hydroxyamino)-1,4 dimethyl-5-oxo-4,5-dihydro-1H-pyrazol-3-yl]benzoate,

2,2,2-trifluoro-N-({4-[4-(hydroxyamino)-1,4-dimethyl-5-oxo-4,5-dihydro-1H-pyrazol-3-yl]phenyl}(methyl)oxo-λ 6 -sulfanylidene) acetamide,

4-(3,4-dimethoxyphenyl)-4-(hydroxyamino)-1,3-dimethyl-4,5-dihydro-1H-pyrazol-5-one,

4-[4-(hydroxyamino)-1,4-dimethyl-5-oxo-4,5-dihydro-1H-pyrazol-3-yl]benzoic acid,

4-(hydroxyamino)-3-{4-[imino(methyl)oxo-λ 6 -sulfanyl]phenyl}-1,4-dimethyl-4,5-dihydro-1H-pyrazol-5-one,

4-(hydroxyamino)-4-(4-methoxy-3-methylphenyl)-1,3-dimethyl-4,5-dihydro-1H-pyrazol-5-one,

4-(hydroxyamino)-3-(4-methanesulfonyl-3-methoxyphenyl)-1,4-dimethyl-4,5-dihydro-1H-pyrazol-5-one,

4-(hydroxyamino)-1,4-dimethyl-3-[4-(propane-2-sulfonyl)phenyl]-4,5-dihydro-1H-pyrazol-5-one,

4-(hydroxyamino)-3-(4-methanesulfonyl-3,5-dimethylphenyl)-1,4-dimethyl-4,5-dihydro-1H-pyrazol-5-one,

4-(hydroxyamino)-1,4-dimethyl-3-[4-(morpholine-4-sulfonyl)phenyl]-4,5-dihydro-1H-pyrazol-5-one,

4-(hydroxyamino)-1,4-dimethyl-3-[4-(morpholine-4-carbonyl)phenyl]-4,5-dihydro-1H-pyrazol-5-one,

4-(hydroxyamino)-3-[4-methanesulfonyl-3-(morpholin-4-yl)phenyl]-1,4-dimethyl-4,5-dihydro-1H-pyrazol-5-one,

4-(hydroxyamino)-3-{4-methanesulfonyl-3-[(2-methoxyethyl)(methyl)amino]phenyl}-1,4-dimethyl-4,5-dihydro-1H-pyrazol-5-one,

4-[4-(hydroxyamino)-1,4-dimethyl-5-oxo-4,5-dihydro-1H-pyrazol-3-yl]-N,N-dimethylbenzamide,

3-[4-(4,4-difluoropiperidine-1-carbonyl)phenyl]-4-(hydroxyamino)-1,4-dimethyl-4,5-dihydro-1H-pyrazol-5-one,

3-[4-(ethanesulfonyl)phenyl]-4-(hydroxyamino)-1,4-dimethyl-4,5-dihydro-1H-pyrazol-5-one,

3-[3-(dimethylamino)-4-methanesulfonylphenyl]-4-(hydroxyamino)-1,4-dimethyl-4,5-dihydro-1H-pyrazol-5-one,

4-(hydroxyamino)-3-[4-methanesulfonyl-3-(4-methylpiperazin-1-yl)phenyl]-1,4-dimethyl-4,5-dihydro-1H-pyrazol-5-one,

3-[4-(benzenesulfonyl)phenyl]-4-(hydroxyamino)-1,4-dimethyl-4,5-dihydro-1H-pyrazol-5-one,

4-[4-(hydroxyamino)-1,4-dimethyl-5-oxo-4,5-dihydro-1H-pyrazol-3-yl]-N-(2-methoxyethyl)-N-methylbenzene-1-sulfonamide,

3-(4-tert-butylphenyl)-4-(hydroxyamino)-1,4-dimethyl-4,5-dihydro-1H-pyrazol-5-one,

4-[4-(hydroxyamino)-1,4-dimethyl-5-oxo-4,5-dihydro-1H-pyrazol-3-yl]benzamide,

4-(hydroxyamino)-3-[4-methanesulfonyl-3-(piperazin-1-yl)phenyl]-1,4-dimethyl-4,5-dihydro-1H-pyrazol-5-one,

2-({4-[4-(hydroxyamino)-1,4-dimethyl-5-oxo-4,5-dihydro-1H-pyrazol-3-yl]phenyl}formamido)propanoic acid,

2-({4-[4-(hydroxyamino)-1,4-dimethyl-5-oxo-4,5-dihydro-1H-pyrazol-3-yl]phenyl}formamido)acetic acid,

4-(3-fluorophenyl)-4-(hydroxyamino)-1,3-dimethyl-4,5-dihydro-1H-pyrazol-5-one,

4-(hydroxyamino)-3-[4-methanesulfonyl-3-(trifluoromethyl)phenyl]-1,4-dimethyl-4,5-dihydro-1H-pyrazol-5-one,

4-(hydroxyamino)-1,3-dimethyl-4-(3-methylphenyl)-4,5-dihydro-1H-pyrazol-5-one,

4-(3-chlorophenyl)-4-(hydroxyamino)-1,3-dimethyl-4,5-dihydro-1H-pyrazol-5-one,

4-(hydroxyamino)-4-(3-methoxyphenyl)-1,3-dimethyl-4,5-dihydro-1H-pyrazol-5-one,

4-[4-(hydroxyamino)-1,4-dimethyl-5-oxo-4,5-dihydro-1H-pyrazol-3-yl]-N-methanesulfonylbenzamide,

3-(3,4-dimethanesulfonylphenyl)-4-(hydroxyamino)-1,4-dimethyl-4,5-dihydro-1H-pyrazol-5-one,

4-(hydroxyamino)-4-[1-(methoxyimino)ethyl]-3-(4-methoxyphenyl)-1-methyl-4,5-dihydro-1H-pyrazol-5-one,

3-(4-bromophenyl)-4-(hydroxyamino)-1,4-dimethyl-4,5-dihydro-1H-pyrazol-5-one,

4-(hydroxyamino)-1-methyl-3,4-diphenyl-4,5-dihydro-1H-pyrazol-5-one,

3-ethoxy-4-(hydroxyamino)-4-[1-(methoxyimino)ethyl]-1-phenyl-4,5-dihydro-1H-pyrazol-5-one,

1-(4-bromophenyl)-3-ethoxy-4-(hydroxyamino)-4-[1-(methoxyimino)ethyl]-4,5-dihydro-1H-pyrazol-5-one,

3-tert-butyl-4-(hydroxyamino)-1-methyl-4-phenyl-4,5-dihydro-1H-pyrazol-5-one,

3-{4-[(4,4-difluoropiperidin-1-yl)sulfonyl]phenyl}-4-(hydroxyamino)-1,4-dimethyl-4,5-dihydro-1H-pyrazol-5-one,

4-(hydroxyamino)-3-methoxy-4-[1-(methoxyimino)ethyl]-1-phenyl-4,5-dihydro-1H-pyrazol-5-one,

4-(hydroxyamino)-3-{4-[imino(oxo)propan-2-yl-λ 6 -sulfanyl]phenyl}-1,4-dimethyl-4,5-dihydro-1H-pyrazol-5-one,

4-[4-(hydroxyamino)-4-[1-(methoxyimino)ethyl]-1-methyl-5-oxo-4,5-dihydro-1H-pyrazol-3-yl]-N,N-dimethylbenzene-1-sulfonamide,

4-[3-tert-butyl-4-(hydroxyamino)-1-methyl-5-oxo-4,5-dihydro-1H-pyrazol-4-yl]-N,N-dimethylbenzene-1-sulfonamide,

4-[4-(hydroxyamino)-4-[1-(methoxyimino)ethyl]-1-methyl-5-oxo-4,5-dihydro-1H-pyrazol-3-yl]-N,N-dimethylbenzamide,

4-[3-tert-butyl-4-(hydroxyamino)-1-methyl-5-oxo-4,5-dihydro-1H-pyrazol-4-yl]-N,N-dimethylbenzamide,

4-[1-[(benzyloxy)imino]ethyl]-3-ethoxy-4-(hydroxyamino)-1-methyl-4,5-dihydro-1H-pyrazol-5-one,

3-ethoxy-4-(hydroxyamino)-4-[1-(methoxyimino)ethyl]-1-methyl-4,5-dihydro-1H-pyrazol-5-one,

3-ethoxy-4-(hydroxyamino)-4-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one,

4-(hydroxyamino)-4-[1 (methoxyimino)ethyl]-1-phenyl-3-(phenylsulfanyl)-4,5-dihydro-1H-pyrazol-5-one,

3-(benzenesulfonyl)-4-(hydroxyamino)-4-[1-(methoxyimino)ethyl]-1-phenyl-4,5-dihydro-1H-pyrazol-5-one,

3-(benzenesulfinyl)-4-(hydroxyamino)4-[1-(methoxyimino)ethyl]-1-phenyl-4,5-dihydro 1H-pyrazol-5-one,

4-(hydroxyamino)-1,3-dimethyl-4-(5-phenyl-1,2,4-oxadiazol-3-yl)-4,5-dihydro-1H-pyrazol-5-one,

4-[4-(hydroxyamino)-4-methyl-5-oxo-4,5-dihydro-1H-pyrazol-3-yl]-N,N-dimethylbenzene-1-sulfonamide,

4-(hydroxyamino)-3-(4-methanesulfonylphenyl)-4-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one,

4-(hydroxyamino)-3-(4-methanesulfonylphenyl)-4-methyl-1-(pyrazin-2-yl)-4,5-dihydro-1H-pyrazol-5-one and

2-(4-(hydroxyamino)-4-methyl-3-(4-(methylsulfonyl)phenyl)-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)acetic acid.

34. The compound of claim 33 , which is 5-(4-chlorophenyl)-4-(hydroxyamino)-2,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one.

35. The compound of claim 33 , which is 4-(hydroxyamino)-2,4-dimethyl-5-(4-(methylsulfonyl)phenyl)-2,4-dihydro-3H-pyrazol-3-one.

36. The compound of claim 33 , which is 5-(2-fluorophenyl)-4-(hydroxyamino)-2,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one.

37. The compound of claim 33 , which is 4-(hydroxyamino)-2,4-dimethyl-5-(4-(trifluoromethyl)phenyl)-2,4-dihydro-3H-pyrazol-3-one.

38. The compound of claim 33 , which is 4-(hydroxyamino)-2-iso-propyl-4-methyl-5-(4-(methylsulfonyl)phenyl)-2,4-dihydro-3H-pyrazol-3-one.

39. The compound of claim 33 , which is 5-(2-fluorophenyl)-4-(hydroxyamino)-2-iso-propyl-4-methyl-2,4-dihydro-3H-pyrazol-3-one.

40. A compound of formula (Ia)

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is (C 1 -C 6 )alkyl substituted with C(═O)OH or unsubstituted (5- or 6-membered)heteroaryl;

R 2 is phenyl wherein said phenyl is unsubstituted or substituted with 1, 2, 3, 4, or 5 substituent(s) independently selected from halo, (C 1 -C 6 )alkyl, (C 1 -C 4 )haloalkyl, (C 1 -C 4 )perhaloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 4 )haloalkoxy, (C 1 -C 4 )perhaloalkoxy, —C(═O)OH, —C(═O)O(C 1 -C 6 )alkyl, —C(═O)NR 4 R 5 , —C(═O)—(C 5 -C 7 )heterocycloalkyl, (C 5 -C 7 )heterocycloalkyl, (C 1 -C 6 )alkylsulfanyl, (C 1 -C 4 )haloalkylsulfanyl, (C 1 -C 4 )perhaloalkylsulfanyl, (C 1 -C 6 )alkylsulfinyl, (C 1 -C 6 )alkylsulfonyl, (C 3 -C 6 )cycloalkylsulfonyl, (C 1 -C 4 )haloalkylsulfinyl, (C 1 -C 4 )haloalkylsulfonyl, (C 1 -C 4 )perhaloalkylsulfinyl, (C 1 -C 4 )perhaloalkylsulfonyl, —S(O) 2 —NH 2 , —S(O) 2 —NR 6 R 7 , —S(O) 2 -phenyl, —S(O) 2 —(C 5 -C 7 )heterocycloalkyl, —S(═O)(═NR 8 )(C 1 -C 6 )alkyl, —NR 4 R 5 , N—(C 1 -C 6 )alkylaminosulfonyl, or N,N-di(C 1 -C 6 )alkylaminosulfonyl, wherein said (C 5 -C 7 )heterocycloalkyl is unsubstituted or substituted with 1 or 2 substituent(s) independently selected from halo or (C 1 -C 6 )alkyl;

R 4 and R 6 are independently H or (C 1 -C 6 )alkyl ;

R 5 is H, (C 1 -C 6 )alkyl or (C 1 -C 6 )alkylsulfonyl, wherein said alkyl is unsubstituted or substituted with C(═O) OH or wherein a methylene group of said alkyl is optionally replaced with an oxygen atom;

R 7 is H or (C 1 -C 6 )alkyl, wherein a methylene group of said alkyl is optionally replaced with an oxygen atom;

R 8 is H, —(C═O)(C 1 -C 6 )alkyl or —(C═O)(C 1 -C 4 )perhaloalkyl; and

R 3 is (C 1 -C 6 )alkyl or —C(═NOR 9 )R 10 wherein R 9 and R 10 are independently selected from (C 1 -C 6 )alkyl.

41. The compound of claim 40 , wherein R 2 is phenyl substituted with 1, 2, or 3 substituent(s) independently selected from halo, (C 1 -C 6 )alkyl, (C 1 -C 4 )perhaloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 4 )haloalkoxy, (C 1 -C 4 )perhaloalkoxy, —C(═O)OH, —C(═O)O(C 1 -C 6 )alkyl, —C(═O)NR 4 R 5 , —C(═O)—(C 5 -C 7 )heterocycloalkyl, (C 5 -C 7 )heterocycloalkyl, (C 1 -C 6 )alkylsulfanyl, (C 1 -C 6 )alkylsulfinyl, (C 1 -C 6 )alkylsulfonyl, (C 1 -C 4 )haloalkylsulfinyl, (C 1 -C 4 )haloalkylsulfonyl, (C 1 -C 4 )perhaloalkylsulfinyl, (C 1 -C 4 )perhaloalkylsulfonyl, —S(O) 2 —NR 6 R 7 , —S(O) 2 -phenyl, —S(O) 2 -(C 5 -C 7 )heterocycloalkyl, —S(═O)(═NR 8 )(C 1 -C 6 )alkyl, —NR 4 R 5 , or N,N-di(C 1 -C 6 )alkylaminosulfonyl, wherein said (C 5 -C 7 )heterocycloalkyl is unsubstituted or substituted with 1 or 2 substituent(s) independently selected from halo or (C 1 -C 6 )alkyl.

42. The compound of claim 40 , wherein R 1 is (C 1 -C 6 )alkyl substituted with C(═O)OH.

43. The compound of claim 40 , wherein R 3 is (C 1 -C 6 )alkyl.

44. The compound of claim 40 , wherein R 2 is unsubstituted phenyl.

45. The compound of claim 40 , wherein R 3 is —C(═NOR 9 )R 10 .

46. The compound of claim 40 , wherein, R 3 is —C(═NOR 9 )R 10 wherein each of R 9 and R 10 is methyl.

47. A pharmaceutical composition comprising the compound of claim 40 and at least one pharmaceutically acceptable excipient.

48. A method of treating a cardiovascular disease, comprising administering an effective amount of the compound of claim 40 or a pharmaceutical composition of claim 47 to a patient in need thereof.