Diazeniumdiolate cyclopentyl derivatives

1. A compound having the formula I:

or a pharmaceutically acceptable salt thereof, wherein

R 1 is hydrogen, —OH, —O—C 1-6 alkyl, ═O, or halogen;

R 2 is

hydrogen,

—C(O)OR 8 ,

—C 6 H 5 C(O)OR 8 ,

—(CH 2 ) 1-2 OH,

—CR 9 R 10 OH,

—C(O)O(CH 2 ) 0-2 aryl,

—C(O)NR 9 R 10 ,

—C(O)SO 2 NR 9 R 10 ,

—C 6 H 5 OR 9 ,

—W—C(O)OR 8 ,

—W—OR 9 ,

—Y, or

—P(O)(OR 9 )(OR 10 );

R 3 is hydrogen or —C 1-6 alkyl;

R 4 is hydrogen, —OH, or —C(O)OR 9 ;

R 5 is hydrogen or deuterium;

R 6 and R 7 are independently —C 1-6 alkyl, fluoro-substituted-C 1-6 alkyl, deutero-substituted —C 1-6 alkyl or —(CH 2 ) 1-2 R 11 , wherein any carbon atom of the fluoro-substituted —C 1-6 alkyl is mono- or di-substituted with fluoro, and any carbon atom of the deutero-substituted —C 1-6 alkyl is mono- or di-substituted with fluoro;

R 8 , in each instance in which it occurs, hydrogen, —C 1-6 alkyl, or —(CH 2 ) 2 N + (CH 3 ) 3 ;

R 9 and R 10 , in each instance in which they occur, are independently —C 1-6 alkyl;

R 11 is —OH, —O—C 1-6 alkyl, —OCD3, —OC(O)OC 1-6 alkyl, —NH 2 , —C 6 H 5 , —N 3 , or W;

W is an unsubstituted 5- or 6-membered heteroaryl ring having 1, 2, or 3 nitrogen atoms, or a substituted 5- or 6-membered heteroaryl ring having 1, 2, or 3 nitrogen atoms that is mono- or di-substituted at any carbon atom with R 6 or R 7 ;

Y is a 5- or 6-membered heterocyclic ring having 1, 2, 3 or 4 heteroatoms which are N, O or S, or stereoisomers thereof, or pharmaceutically acceptable salts thereof, or pharmaceutically acceptable salts of stereoisomers thereof.

2. A compound of claim 1 , wherein the compound has the formula Ia:

or a pharmaceutically acceptable salt thereof.

3. A compound of claim 1 , wherein R 1 is hydrogen, —OH, —OCH 3 , ═O, or F, or a pharmaceutically acceptable salt thereof.

4. A compound of claim 1 , wherein R 2 is

—C(O)OR 8 ,

—C 6 H 5 C(O)OR 8 ,

—(CH 2 ) 1-2 OH,

—C(O)O(CH 2 ) 0-2 aryl,

—C 6 H 5 OR 9 , or

—P(O)(OR 9 )(OR 10 ),

or a pharmaceutically acceptable salt thereof.

5. A compound of claim 4 , wherein R 2 is

—C(O)OH,

—C(O)OCH 3 ,

—C(O)OCH 2 CH 3 ,

—C(O)OC 6 H 5 ,

—C(O)OCH 2 CH 2 N(CH 3 ) 3 ,

—C 6 H 5 C(O)OCH 2 CH 3 ,

—C 6 H 5 C(O)OH,

—CH 2 OH,

—C(O)OCH 2 C 6 H 5 ,

—C 6 H 5 OCH 3 , or

—P(O)(OCH 2 CH 3 ) 2

or a pharmaceutically acceptable salt thereof.

6. A compound of claim 4 , wherein R 3 is hydrogen or —CH 3 , or a pharmaceutically acceptable salt thereof.

7. A compound of claim 6 , wherein R 3 is hydrogen, or a pharmaceutically acceptable salt thereof.

8. A compound of claim 7 , wherein R 4 is hydrogen, —OH, or —C(O)OCH 2 CH 3 , or a pharmaceutically acceptable salt thereof.

9. A compound of claim 8 , wherein R 4 is hydrogen, or a pharmaceutically acceptable salt thereof.

10. A compound of claim 1 , wherein R 5 is hydrogen, or a pharmaceutically acceptable salt thereof.

11. A compound of claim 1 , wherein R 6 is

—CH 3 ,

—CH(CH 3 ) 2 ,

—CH 2 CH 3 ,

—(CH 2 ) 3 CH 3 ,

—(CH 2 ) 2 CH(CH 3 ) 2 ,

—(CH 2 ) 2 OH,

—(CH 2 ) 2 OCH 3 ,

—(CH 2 ) 2 OCD 3 ,

—(CH 2 ) 2 OC(O)OC(CH 3 ) 3 ,

—NH 2

—CH 2 CH 2 CH 3 ,

—CH 2 CH 2 N + 3 , or

or a pharmaceutically acceptable salt thereof.

12. A compound of claim 1 , wherein R 7 is —C(CH 3 ) 3 or —CH 2 C 6 H 5 , or a pharmaceutically acceptable salt thereof.

13. A compound of claim 12 , wherein R 7 is —C(CH 3 ) 3 , or a pharmaceutically acceptable salt thereof.

14. A compound of claim 1 , which is

(1R,3R)-3-({[(1Z)-2-tert-butyl-2-ethyl-1-oxido-1λ 5 -diazan-1-ylidene]amino}oxy)cyclopentanecarboxylic acid,

ethyl (1R,3R)-3-({[(1Z)-2-tert-butyl-2-ethyl-1-oxido-1λ 5 -diazan-1-ylidene]amino}oxy)cyclopentanecarboxylate,

(1S,3S)-3-({[(1Z)-2-tert-butyl-2-ethyl-1-oxido-1λ 5 -diazan-1-ylidene]amino}oxy)cyclopentanecarboxylic acid,

(1R,3R)-3-({[(1Z)-2-tert-butyl-2-methyl-1-oxido-1λ 5 -diazan-1-ylidene]amino}oxy)cyclopentanecarboxylic acid,

(1S,3S)-3-({[(1Z)-2-tert-butyl-2-methyl-1-oxido-1λ 5 -diazan-1-ylidene]amino}oxy)cyclopentanecarboxylic acid,

(1R,3R)-3-({[(1Z)-2-tert-butyl-2-(2-methoxyethyl)-1-oxido-1λ 5 -diazan-1-ylidene]amino}oxy)cyclopentanecarboxylic acid,

2-{tert-butyl[(Z)-{[(1R,3R)-3-(4-methoxyphenyl)cyclopentyl]oxy}-NNO-azoxy]amino}ethanol,

N-(2-methoxyethyl)-N—[(Z)-{[(1R,3R)-3-(4-methoxyphenyl)cyclopentyl]oxy}-NNO-azoxy]-2-methylpropan-2-amine,

(1R,3R)-3-({[(1Z)-2-tert-butyl-2-{2-[( 2 H 3 )methyloxy]ethyl}-1-oxido-1λ 5 -diazan-1-ylidene]amino}oxy)cyclopentanecarboxylic acid,

(1R,3R)-3-({[(1Z)-2-tert-butyl-2-propyl-1-oxido-1λ 5 -diazan-1-ylidene]amino}oxy)cyclopentanecarboxylic acid,

(1R,3R)-3-({[(1Z)-2-tert-butyl-2-butyl-1-oxido-1λ 5 -diazan-1-ylidene]amino}oxy)cyclopentanecarboxylic acid,

(1R,3R)-3-({[(1Z)-2-tert-butyl-2-(3-methylbutyl)-1-oxido-1λ 5 -diazan-1-ylidene]amino}oxy)cyclopentanecarboxylic acid,

(1S,3R)-3-({[(1Z)-2-tert-butyl-2-methyl-1-oxido-1λ 5 -diazan-1-ylidene]amino}oxy)cyclopentanecarboxylic acid,

(1S,3R)-3-({[(1Z)-2-tert-butyl-2-propyl-1-oxido-1λ 5 -diazan-1-ylidene]amino}oxy)cyclopentanecarboxylic acid,

(1S,3R)-3-({[(1Z)-2-tert-butyl-2-butyl-1-oxido-1λ 5 -diazan-1-ylidene]amino}oxy)cyclopentanecarboxylic acid,

(1S,3R)-3-({[(1Z)-2-tert-butyl-2-(2-methoxyethyl)-1-oxido-1λ 5 -diazan-1-ylidene]amino}oxy)cyclopentanecarboxylic acid,

(1S,3R)-3-({[(1Z)-2-{2-[(tert-butoxycarbonyl)oxy]ethyl}-2-tert-butyl-1-oxido-1λ 5 -diazan-1-ylidene]amino}oxy)cyclopentanecarboxylic acid,

(1S,3R)-3-({[(1Z)-2-(2-aminoethyl)-2-tert-butyl-1-oxido-1λ 5 -diazan-1-ylidene]amino}oxy)cyclopentanecarboxylic acid,

(1S,3R)-3-[({(1Z)-2-tert-butyl-1-oxido-2-[2-(1H-1,2,3-triazol-1-yl)ethyl]-1λ 5 -diazan-1-ylidene}amino)oxy]cyclopentanecarboxylic acid,

(1R,3S)-3-({[(1Z)-2-tert-butyl-2-ethyl-1-oxido-1λ 5 -diazan-1-ylidene]amino}oxy)cyclopentanecarboxylic acid,

(1S,3R)-3-({[(1Z)-2-tert-butyl-2-ethyl-1-oxido-1λ 5 -diazan-1-ylidene]amino}oxy)cyclopentanecarboxylic acid,

(1RS,3SR,4RS)-3-({[(1Z)-2-tert-butyl-2-methyl-1-oxido-1λ 5 -diazan-1-ylidene]amino}oxy)-4-fluorocyclopentanecarboxylic acid,

(1RS,3RS,4RS)-3-({[(1Z)-2-tert-butyl-2-methyl-1-oxido-1λ 5 -diazan-1-ylidene]amino}oxy)-4-methoxycyclopentanecarboxylic acid,

(1RS,3RS)-3-({[(1Z)-2-tert-butyl-2-methyl-1-oxido-1λ 5 -diazan-1-ylidene]amino}oxy)-1-methylcyclopentanecarboxylic acid, and

(1RS,3SR)-3-({[(1Z)-2-tert-butyl-2-ethyl-1-oxido-1λ 5 -diazan-1-ylidene]amino}oxy)-1-methylcyclopentanecarboxylic acid,

or a pharmaceutically acceptable salt thereof.

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

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

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

18. A method for treating hypertension in a patient which comprises administering to the patient a therapeutically effective amount of the composition of claim 15 .