Nitrosated And Nitrosylated Cardiovascular Compounds, Compositions And Methods Of Use

1 . A compound of Formula (I), (II) or (III), or a pharmaceutically acceptable salt thereof,

wherein the compound of Formula (I) is:

wherein:

X 3 is:

(7) —N(D 1 )-C(O)—N(D 1 )-CH 2 —CH 2 —CH 3 ;

(8) —C(O)—U 3 D 1 ;

(9) —C(O)—CH 2 —NH(D 1 );

(10) —S(O) 2 —N(D 1 )-C(O)—C 6 H 5 ;

(11) —S(O) 2 —N(D 1 )—C(O)—ND 1 -CH 2 —CH 2 —CH 3 ; or

(12) —S(O) 2 —N(D 1 )-OD 1 ;

D 4 is D 1 , —C(O)—CH 2 —NH(D 1 ) or —C(C 6 H 5 ) 3 ;

Z 3 is a carbon, —CH or a nitrogen atom;

R 10 is a fluorine or a hydrogen atom;

Y 3 is:

Z 4 is C—R 29 or a nitrogen;

R 11 is:

(1) —CH 2 —OD 1 ;

(2) —C(O)—U 3 D 1 ;

(3) —C(O)—O—CH(CH 3 )—O—C(O)—OR 13 ; or

(4) —CH 2 —N(D 1 )-C(O)—OR 13 ;

R 12 is a chlorine, —SCH 3 or a haloalkyl;

R 13 is a lower alkyl or K;

R 14 is a lower alkyl or a cycloalkyl;

R 15 is:

(1) hydrogen;

(2) a lower alkyl;

(3)

(4)

(5) —C(O)—U 3 D 1 ;

R 16 is a hydrogen, a lower alkyl, an alkoxy, —OD 1 , a cyano, —C(O)—U 3 D 1 , NH(D 1 ) or an alkylcarbonyl;

R 17 is an aryl or a cycloalkyl;

R 18 at each occurrence is independently selected from a lower alkyl, an alkoxyalkyl, an alkylcarboxylic acid, an hydroxyalkyl, an arylalkoxy, an arylalkyl or an aryl;

R 19 is a hydrogen or —C(O)—U 3 D 1 ;

R 20 is a hydrogen, a lower alkyl or —C(O)—U 3 D 1 ;

R 21 is:

R 22 is a hydrogen, —C(O)—U 3 D 1 or

R 23 is a lower alkyl or an alkoxyalkyl;

R 24 is a hydrogen, an alkyl or an aryl;

R 25 is —(CH 2 ) 2 —OD 1 or

R 26 is a hydrogen, a lower alkyl, a lower haloalkyl, an aryl or an arylalkyl;

R 27 is a lower alkyl, an aryl an arylalkyl or —(CH 2 ) k —C(O)U 3 D 1 ;

R 28 is —OD 1 , —S(O) 2 —N(D 1 )H, —N(D 1 )H, —C(O)—U 3 D 1 or CH 2 —OD 1 ;

R 29 is a hydrogen, a lower alkyl or —C(O)U 3 D 1 ;

R 30 is a lower alkyl or a haloalkyl;

R 31 is:

o 1 is an integer from 0 to 3;

k is an integer from 1 to 3;

D 1 is a hydrogen, V 3 or K;

K is (W 3 ) a -E b -(C(R e )(R f )) p1 -E c -(C(R e )(R f )) x —(W 3 ) d —(C(R e )(R f )) y —(W 3 ) i -E j -(W 3 ) g —(C(R e )(R f )) z —U 3 —V 3 ;

V 3 is —NO or —NO 2 ;

a, b, c, d, g, i and j are each independently an integer from 0 to 3;

p 1 , x, y and z are each independently an integer from 0 to 10;

W 3 at each occurrence is independently —C(O)—, —C(S)—, -T 3 -, —(C(R e )(R f )) h —, an alkyl group, an aryl group, a heterocyclic ring, an arylheterocyclic ring, or —(CH 2 CH 2 O) q1 —;

E at each occurrence is independently -T 3 -, an alkyl group, an aryl group, —(C(R e )(R f )) h —, a heterocyclic ring, an arylheterocyclic ring, or —(CH 2 CH 2 O) q1 —;

T 3 at each occurrence is independently a covalent bond, a carbonyl, an oxygen, —S(O) o — or —N(R a )R i ;

h is an integer form 1 to 10;

q 1 is an integer from 1 to 5;

R e and R f are each independently a hydrogen, an alkyl, a cycloalkoxy, a halogen, a hydroxy, an hydroxyalkyl, an alkoxyalkyl, an arylheterocyclic ring, an alkylaryl, an alkylcycloalkyl, an alkylheterocyclic ring, a cycloalkylalkyl, a cycloalkylthio, an arylalklythio, an arylalklythioalkyl, an alkylthioalkyl a cycloalkenyl, an heterocyclicalkyl, an alkoxy, a haloalkoxy, an amino, an alkylamino, a dialkylamino, an arylamino, a diarylamino, an alkylarylamino, an alkoxyhaloalkyl, a sulfonic acid, a sulfonic ester, an alkylsulfonic acid, an arylsulfonic acid, an arylalkoxy, an alkylthio, an arylthio, a cyano an aminoalkyl, an aminoaryl, an aryl, an arylalkyl, an alkylaryl, a carboxamido, a alkylcarboxamido, an arylcarboxamido, an amidyl, a carboxyl, a carbamoyl, an alkylcarboxylic acid, an arylcarboxylic acid, an alkylcarbonyl, an arylcarbonyl, an ester, a carboxylic ester, an alkylcarboxylic ester, an arylcarboxylic ester, a sulfonamido, an alkylsulfonamido, an arylsulfonamido, an alkylsulfonyl, an alkylsulfonyloxy, an arylsulfonyl, arylsulphonyloxy, a sulfonic ester, an alkyl ester, an aryl ester, a urea, a phosphoryl, a nitro, K or R e and R f taken together with the carbons to which they are attached form a carbonyl, a methanthial, a heterocyclic ring, a cycloalkyl group, an aryl group, an oxime, a hydrazone or a bridged cycloalkyl group;

U 3 at each occurrence is independently an oxygen, —S(O) o — or —N(R a )R i ;

o is an integer from 0 to 2;

R a is a lone pair of electrons, a hydrogen or an alkyl group;

R i is a hydrogen, an alkyl, an aryl, an alkylcarboxylic acid, an arylcarboxylic acid, an alkylcarboxylic ester, an arylcarboxylic ester, an alkylcarboxamido, an arylcarboxamido, an alkylaryl, an alkylsulfinyl, an alkylsulfonyl, an alkylsulfonyloxy, an arylsulfinyl, an arylsulfonyl, arylsulphonyloxy, a sulfonamido, a carboxamido, a carboxylic ester, an aminoalkyl, an aminoaryl, —CH 2 —C(U 3 —V 3 )(R e )(R f ), a bond to an adjacent atom creating a double bond to that atom, —(N 2 O 2 —) − .M 1 + , wherein M 1 + is an organic or inorganic cation; and

with the proviso that the compounds of Formula (I) must contain at least one NO group, and/or at least one NO 2 group; wherein the at least one NO group and/or the at least one NO 2 group is linked to the compound through an oxygen atom, a nitrogen atom or a sulfur atom; and

the compound of Formula (II) is:

wherein:

U 3 and D 1 are as defined herein; and

with the proviso that the compounds of Formula (II) must contain at least one NO group, and/or at least one NO 2 group; wherein the at least one NO group and/or the at least one NO 2 group is linked to the compound through an oxygen atom, a nitrogen atom or a sulfur atom; and

the compound of Formula (III) is:

wherein:

X 3 and Y 3 are as defined herein; and

with the proviso that the compounds of Formula (III) must contain at least one NO group, and/or at least one NO 2 group; wherein the at least one NO group and/or the at least one NO 2 group is linked to the compounds through an oxygen atom, a nitrogen atom or a sulfur atom.

2 . A composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.

3 . The compound of claim 1 , wherein the compound of Formula (I) is a nitrosated abitesartan, a nitrosylated abitesartan, a nitrosated and nitrosylated abitesartan, a nitrosated candesartan, a nitrosylated candesartan, a nitrosated and nitrosylated candesartan, a nitrosated elisartan, a nitrosylated elisartan, a nitrosated and nitrosylated elisartan, a nitrosated embusartan, a nitrosylated embusartan, a nitrosated and nitrosylated embusartan, a nitrosated enoltasosartan, a nitrosylated enoltasosartan, a nitrosated and nitrosylated enoltasosartan, a nitrosated fonsartan, a nitrosylated fonsartan, a nitrosated and nitrosylated fonsartan, a nitrosated forasartan, a nitrosylated forasartan, a nitrosated and nitrosylated forasartan, a nitrosated glycyllosartan, a nitrosylated glycyllosartan, a nitrosated and nitrosylated glycyllosartan, a nitrosated irbesartan, a nitrosylated irbesartan, a nitrosated and nitrosylated irbesartan, a nitrosated losartan, a nitrosylated losartan, a nitrosated and nitrosylated losartan, a nitrosated olmesartan, a nitrosylated olmesartan, a nitrosated and nitrosylated olmesartan, a nitrosated milfasartan, a nitrosylated milfasartan, a nitrosated and nitrosylated milfasartan, a nitrosated ripisartan, a nitrosylated ripisartan, a nitrosated and nitrosylated ripisartan, a nitrosated tasosartan, a nitrosylated tasosartan, a nitrosated and nitrosylated tasosartan, a nitrosated telmisartan, a nitrosylated telmisartan, a nitrosated and nitrosylated telmisartan, a nitrosated valsartan, a nitrosylated valsartan, a nitrosated and nitrosylated valsartan, a nitrosated SR-47436, a nitrosylated SR-47436, a nitrosated and nitrosylated SR-47436, or a nitrosated, or a nitrosylated, or a nitrosated and nitrosylated compound of any of the following compounds of ACS registry number 124750-92-1, 133240-46-7, 135070-05-2, 139958-16-0, 145160-84-5, 147403-03-0, 153806-29-2, 439904-54-8P, 439904-55-9P, 439904-56-0P, 439904-57-1P, 439904-58-2P, 155918-60-8P, 155918-61-9P, 272438-16-1P, 272446-75-0P, 223926-77-0P, 169281-89-4, 439904-65-1P, 165113-01-9P, 165113-02-0P, 165113-03-1P, 165113-03-2P, 165113-05-3P, 165113-06-4P, 165113-07-5P, 165113-08-6P, 165113-09-7P, 165113-10-0P, 165113-11-1P, 165113-12-2P, 165113-17-7P, 165113-18-8P, 165113-19-9P, 165113-20-2P, 165113-13-3P, 165113-14-4P, 165113-15-5P, 165113-16-6P, 165113-21-3P, 165113-22-4P, 165113-23-5P, 165113-24-6P, 165113-25-7P, 165113-26-8P, 165113-27-9P, 165113-28-0P, 165113-29-1P, 165113-30-4P, 165113-31-5P, 165113-32-6P, 165113-33-7P, 165113-34-8P, 165113-35-9P, 165113-36-0P, 165113-37-1P, 165113-38-2P, 165113-39-3P, 165113-40-6P, 165113-41-7P, 165113-42-8P, 165113-43-9P, 165113-44-0P, 165113-45-1P, 165113-46-2P, 165113-47-3P, 165113-48-4P, 165113-49-5P, 165113-50-8P, 165113-51-9P, 165113-52-0P, 165113-53-1P, 165113-54-2P, 165113-55-3P, 165113-56-4P, 165113-57-5P, 165113-58-6P, 165113-59-7P, 165113-60-0P, 165113-61-1P, 165113-62-2P, 165113-63-3P, 165113-64-4P, 165113-65-5P, 165113-66-6P, 165113-67-7P, 165113-68-8P, 165113-69-9P, 165113-70-2P, 165113-71-3P, 165113-72-4P, 165113-73-5P, 165113-74-6P, 114798-27-5, 114798-28-6, 114798-29-7, 124749-82-2, 114798-28-6, 124749-84-4, 124750-88-5, 124750-91-0, 124750-93-2, 161946-65-2P, 161947-47-3P, 161947-48-4P, 161947-51-9P, 161947-52-0P, 161947-55-3P, 161947-56-4P, 161947-60-0P, 161947-61-1P, 161947-68-8P, 161947-69-9P, 161947-70-2P, 161947-71-3P, 161947-72-4P, 161947-74-6P, 161947-75-7P, 161947-81-5P, 161947-82-6P, 161947-83-7P, 161947-84-8P, 161947-85-9P, 161947-86-0P, 161947-87-1P, 161947-88-2P, 161947-89-3P, 161947-90-6P, 161947-91-7P, 161947-92-8P, 161947-93-9P, 161947-94-0P, 161947-95-1P, 161947-96-2P, 161947-97-3P, 161947-98-4P, 161947-99-5P, 161948-00-1P, 161948-01-2P, 161948-02-3P, 168686-32-6P, 167301-42-0P, 166813-82-7P, 166961-56-4P, 166961-58-6P, 158872-96-9P, 158872-97-0P, 158807-14-8P, 158807-15-9P, 158807-16-0P, 158807-17-1P, 158807-18-2P, 158807-19-3P, 158807-20-6P, 155884-08-5P, 154749-99-2, 167371-59-7P, 244126-99-6P, 177848-35-0P and 141309-82-2P; the compound of Formula (II) is a nitrosated eprosartan, a nitrosylated eprosartan, a nitrosated and nitrosylated eprosartan; the compound of Formula (III) is a nitrosated saprisartan, a nitrosylated saprisartan, a nitrosated and nitrosylated saprisartan, a nitrosated zalasartan, a nitrosylated zalasartan, a nitrosated and nitrosylated zalasartan, or pharmaceutically acceptable salts thereof.

4 . The compound of claim 1 , wherein K is:

(1) —Y—(CR 4 R 4 ′) p -T-(CR 4 R 4 ′) p —ONO 2 ;

(2)

wherein T is ortho, meta or para;

(3)

(4) —Y—(CR 4 C 4 ′) p —V—B-T-(CR 4 R 4 ′) p —ONO 2 ;

(5) —Y—(CR 4 R 4 ′) p -T-C(O)—(CR 4 R 4 ′) o —(CH 2 )—ONO 2 ;

(6) —Y—(CR 4 R 4 ′) p —C(Z)-(CH 2 ) q -T-(CR 4 R 4 ′) q —(CH 2 )—ONO 2 ;

(7) —Y—(CR 4 R 4 ′) p -T-(CH 2 ) q —V—(CR 4 R 4 ′) q —(CH 2 )—ONO 2 ;

(8) —Y—(CR 4 R 4 ′) p —V—(CH 2 ) q —V—(CR 4 R 4 ′) q —(CH 2 )—ONO 2 ;

(9) —Y—(CR 4 R 4 ′) o —(W) q —(CR 4 R 4 ′) n —(CH 2 )—ONO 2 ;

(10) —NR j —O—(CH 2 ) o —V—(CR 4 ′) q —(CH 2 )—ONO 2 ;

(11) —NR j —O—(CH 2 ) o —(W) q —(CR 4 R 4 ′) q —(CH 2 )—ONO 2 ;

(12) —O—NR j —(CH 2 ) o —(W) q —(CR 4 R 4 ′) q —(CH 2 )—ONO 2 ;

(13) —Y—(CH 2 ) o —(W) q —(CH 2 ) o —V—(CR 4 R 4 ′) o -Q′-(CR 4 R 4 ′) o —(CH 2 )—ONO 2 ;

(14) —Y—(CR 4 R 4 ′) p —V—(CH 2 ) o —(W) q —(CR 4 R 4 ′) q —(CH 2 )—ONO 2 ;

(15) —O—NR j —(CH 2 ) o —V—(CR 4 R 4 ′) q —(CH 2 )—ONO 2 ;

(16) —Y—(CR 4 R 4 ′) o -Q′-(CR 4 R 4 ′) o —V—(CR 4 R 4 ′) o —(CH 2 )—ONO 2 ;

(17) —Y—(CR 4 R 4 ′) o -Q′-(CR 4 R 4 ′) o —(W) q —(CR 4 R 4 ′) o —(CH 2 )—ONO 2 ;

(18) —Y—(CR 4 R 4 ′) p -T-(CR 4 R 4 ′) p -Q′-(CR 4 R 4 ′) o —(CH 2 )—ONO 2 ;

(19) —Y—(CR 4 R 4 ′) q —C(Z)-(CR 4 R 4 ′) o —(CH 2 )—ONO 2 ;

(20) —Y—(CR 4 R 4 ′) p -Q′-(CR 4 R 4 ′) o —(CH 2 )—ONO 2 ;

(21) —Y—(CR 4 R 4 ′) q —P(O)MM′;

(22) —Y—(CR 4 R 4 ′) o -Q′-(CR 4 R 4 ′) o —(CH 2 )—ONO 2 ;

(23) —Y—(CR 4 R 4 ′) o -Q′-(CR 4 R 4 ′) o -T-(CR 4 R 4 ′) o —(CH 2 )—ONO 2 ;

(24) —Y—(CR 4 R 4 ′) q —(W) q —(CR 4 R 4 ′) o -Q′-(CR 4 R 4 ′) o —(CH 2 )—ONO 2 ;

(25) —Y—(CR 4 R 4 ′) q —V—(CR 4 R 4 ′) o -Q′-(CR 4 R 4 ′) n —(CH 2 )—ONO 2 ;

(26) —Y—(CR 4 R 4 ′) p -(T) o -(W) q —(CR 4 R 4 ′) o —(CH 2 )—ONO 2 ;

(27) —Y—(CR 4 R 4 ′) p —(W) q -(T) o -(CR 4 R 4 ′) o —(CH 2 )—ONO 2 ;

(28) —Y—(CR 4 R 4 ′) q —C(Z)-V—(CR 4 R 4 ′) q —(CH 2 )—ONO 2 ;

(29) —Y—(CR 4 R 4 ′) o —C(R 4 )(ONO 2 )—(CR 4 R 4 ′) q -(T) o -(W) q -(T) o -(CR 4 R 4 ′) o —R 5 ;

(30) —Y—(CR 4 R 4 ′) o —V—(CR 4 R 4 ′) o -Q′-(CR 4 R 4 ′)—(CH 2 )—ONO 2 ;

(31) —Y—(CR 4 R 4 ′) q —C(Z)-Q′-(CR 4 R 4 ′) o —(CH 2 )—ONO 2 ;

(32) —Y—(CR 4 R 4 ′) p —V—(CR 4 R 4 ′) p —(CH 2 )—ONO 2 ;

(33) —Y—(CR 4 R 4 ′) p —V—(CH 2 ) q -(T) o -(CR 4 R 4 ′) q —(CH 2 )—ONO 2 ;

(34) —Y—(CR 4 R 4 ′) p -(T) o -Q′-(T) o -(CR 4 R 4 ′) q —(CH 2 )—ONO 2 ;

(35) —Y—(CR 4 R 4 ′) q —C(Z)-(CR 4 R 4 ′) q —V—(CR 4 R 4 ′) o -Q′-(CR 4 R 4 ′) o —(CH 2 )—ONO 2 ;

(36) —Y—(CR 4 R 4 ′) q —C(Z)-(CR 4 R 4 ′) q —(W) q —(CR 4 R 4 ′) o -Q′-(CR 4 R 4 ′) o —(CH 2 )—ONO 2 ;

(37) —NR j —O—(CH 2 ) o —V—(CR 4 R 4 ′) o -Q′-(CH 2 )—ONO 2 ;

(38) —NR j —O—(CH 2 ) o —(W) q —(CR 4 R 4 ′) o -Q′-(CH 2 )—ONO 2 ;

(39) —O—NR j —(CH 2 ) o —(W) q —(CR 4 R 4 ′) o -Q′-(CH 2 )—ONO 2 ;

(40) —O—NR j —(CH 2 ) o —V—(CR 4 R 4 ′) o -Q′-(CH 2 )—ONO 2 ;

(41) —NR j —NR j —(CR 4 R 4 ′) p —(W) q -(T) o -(CR 4 R 4 ′) o —(CH 2 )—ONO 2 ; or

(42) —Y—(CR 4 R 4 ′) o -Q′-(CR 4 R 4 ′) o —ONO 2 ; or

(43) —Y—(CR 4 R 4 ′) o —V—(CR 4 R 4 ′) o -Q-(CR 4 R 4 ′) o —ONO 2 ;

R 4 and R 4 ′ at each occurrence are independently a hydrogen, lower alkyl group, —OH, —CH 2 OH, —ONO 2 , —NO 2 or —CH 2 ONO 2 ; or R 4 and R 4 ′ taken together with the carbon atom to which they are attached are a cycloalkyl group or a heterocyclic ring;

V is —C(O)-T-, -T-C(O)—, -T-C(O)-T or T-C(O)—C(O)-T;

W is a covalent bond or a carbonyl group;

T at each occurrence is independently an oxygen, (S(O) o ) o or NR j ;

R j is a hydrogen, an alkyl group, an aryl group, a heterocyclic ring, an alkylcarbonyl group, an alkylaryl group, an alkylsulfinyl group, an alkylsulfonyl group, an arylsulfinyl group, an arylsulfonyl group, a sulfonamido group, a N-alkylsulfonamido group, a N,N-diarylsulfonamido group, a N-arylsulfonamido group, a N-alkyl-N-arylsulfonamido group, a carboxamido group or a hydroxyl group;

p at each occurrence is independently an integer from 1 to 6;

q at each occurrence is independently an integer from 1 to 3;

o at each occurrence is independently an integer from 0 to 2;

Y is independently a covalent bond, a carbonyl, an oxygen, —S(O) o — or —NR j ;

B is either phenyl or (CH 2 ) o ;

Q′ is a cycloalkyl group, a heterocyclic ring or an aryl group;

Z is (═O), (═N—OR 5 ), (═N—NR 5 R′ 5 ) or (═CR 5 R′ 5 );

M and M′ are each independently —O − H 3 N + —(CR 4 R′ 4 ) q —CH 2 ONO 2 or -T-(CR 4 R′ 4 ) o —CH 2 ONO 2 ; and

R 5 and R 5 ′ at each occurrence are independently a hydrogen, a hydroxyl group, an alkyl group, an aryl group, an alkylsulfonyl group, an arylsulfonyl group, a carboxylic ester, an alkylcarbonyl group, an arylcarbonyl group, a carboxamido group, an alkoxyalkyl group, an alkoxyaryl group, a cycloalkyl group or a heterocyclic ring.

5 . The compound of claim 1 , wherein K is:

Y′ a covalent bond, a carbonyl, an oxygen, —S(O) o — or —NR 6 ;

T′ is oxygen, sulfur or NR 6 ;

X 5 is oxygen, (S(O) o ) o or NR 6 ;

R 6 is a hydrogen, a lower alkyl group, an aryl group;

R 7 is a lower alkyl group or an aryl group;

R 8 at each occurrence is independently is a hydrogen, a hydroxyl group, a lower alkyl group, an aryl group, —NO 2 , —CH 2 —ONO 2 or —CH 2 —OH;

n′ and m′ are each independently an integer from 0 to 10; and

o is an integer from 0 to 2.

6 . The compound of claim 1 , wherein the compound of Formula (I) is compound of Formula (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII) or (XIX); the compound of Formula (II) is a compound of Formula (XX), and the compound of Formula (III) is a compound of Formula (XXI) or (XXII); or a pharmaceutically acceptable salt thereof,

wherein the compound of Formula (IV) is:

and the compound of Formula (V) is:

and the compound of Formula (VI) is:

and the compound of Formula (VII) is:

and the compound of Formula (VIII) is:

and the compound of Formula (IX) is:

and the compound of Formula (X) is:

and the compound of Formula (XI) is:

and the compound of Formula (XII) is:

and the compound of Formula (XIII) is:

and the compound of Formula (XIV) is:

and the compound of Formula (XV) is:

and the compound of Formula (XVI) is:

and the compound of Formula (XVII) is:

and the compound of Formula (XVIII) is:

and the compound of Formula (XIX) is:

and the compound of Formula (XX) is:

and the compound of Formula (XXI) is:

and the compound of Formula (XXII) is:

wherein

T′ is oxygen, sulfur or NR 6 ;

nBu is the lower alkyl group CH 3 —CH 2 —CH 2 —CH 2 —;

nPr is the lower alkyl group CH 3 —CH 2 —CH 2 —;

iPr is the lower alkyl group (CH 3 ) 2 —CH—;

OEt is the alkoxy group —OCH 2 —CH 3 ;

R 6 is a hydrogen, a lower alkyl group, an aryl group;

R m -R n taken together can be a hydrogen atom; or

R n is:

a hydrogen or

wherein:

R 9 is a lower alkyl group;

T′ is oxygen, sulfur or NR 6 ;

R 6 is a hydrogen, a lower alkyl group, an aryl group; and

with the proviso that the compounds of Formula (IV) to Formula (XXII) must contain at least one —NO 2 group.

7 . A method for treating a cardiovascular disease in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 2 .

8 . The method of claim 7 , wherein the cardiovascular disease is congestive heart failure, restenosis, hypertension, diastolic dysfunction, a coronary artery disease, myocardial infarction, cerebral infarction, atherosclerosis, atherogenesis, cerebrovascular disease, angina, aneurysm, ischemic heart disease, cerebral ischemia, myocardial ischemia, thrombosis, platelet aggregation, platelet adhesion, smooth muscle cell proliferation, a vascular or non-vascular complication associated with the use of a medical device, a wound associated with the use of a medical device, vascular or non-vascular wall damage, peripheral vascular disease, neointimal hyperplasia following percutaneous transluminal coronary angiograph, vascular grafting, coronary artery bypass surgery, a thromboembolic event, post-angioplasty restenosis, coronary plaque inflammation, hypercholesterolemia, embolism, stroke, shock, arrhythmia, atrial fibrillation or atrial flutter, or thrombotic occlusion and reclusion cerebrovascular incident.

9 . The method of claim 8 , wherein the cardiovascular disease is congestive heart failure, hypertension or diastolic dysfunction.

10 . A method for treating a renovascular disease in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 2 .

11 . The method of claim 10 , wherein the renovascular disease is renal failure or renal insufficiency.

12 . A method for treating a disease resulting from oxidative stress; treating an endothelial dysfunction; treating a disease caused by endothelial dysfunction; treating cirrhosis; treating pre-eclampsia; treating osteoporosis; or treating nephropathy in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 2 .

13 . The composition of claim 2 , further comprising (i) at least one therapeutic agent; (ii) at least one nitric oxide donor compound; or (iii) at least one therapeutic agent and at least one nitric oxide donor compound.

14 . The composition of claim 13 , wherein the therapeutic agent is an aldosterone antagonist, an alpha-adrenergic receptor antagonist, an angiotensin II antagonist, an angiotensin-converting enzyme inhibitor, an antidiabetic compound, an anti-hyperlipidemic compound, an antioxidant, an antithrombotic and vasodilator compound, a β-adrenergic antagonist, a calcium channel blocker, a digitalis, a diuretic, an endothelin antagonist, a hydralazine compound, a H 2 receptor antagonist, a neutral endopeptidase inhibitor, a nonsteroidal antiinflammatory compound, a phosphodiesterase inhibitor, a potassium channel blocker, a platelet reducing agent, a proton pump inhibitor, a renin inhibitor, a selective cyclooxygenase-2 inhibitor, or a combination of two or more thereof.

15 . The composition of claim 14 , wherein the therapeutic agent is at least one compound selected from the group consisting of an aldosterone antagonist, an angiotensin II antagonist, an angiotensin-converting enzyme inhibitor, a β-adrenergic antagonist, a diuretic and a hydralazine compound.

16 . The composition of claim 15 , wherein the aldosterone antagonist is eplerenone or spironolactone; the angiotensin II antagonist is candesartan cilexetil, eprosartan mesylate, irbesartan, losartan potassium, medoxomil, telmisartan, trandolapril, trandolaprilat or valsartan; the angiotensin-converting enzyme inhibitor is benazepril hydrochloride, captopril, enalapril maleate, fosinopril sodium, lisinopril, moexipril hydrochloride, quinapril hydrochloride; the β-adrenergic antagonist is bisoprolol fumarate, carvedilol, metoprolol tartrate, propranolol hydrochloride or timolol maleate; the diuretic is amiloride hydrochloride, chlorthalidone, hydrochlorothiazide or triamterene; and the hydralazine compound is hydralazine hydrochloride.

17 . The composition of claim 13 , wherein the nitric oxide donor compound is selected from the group consisting of a S-nitrosothiol, a nitrite, a nitrate, a S-nitrothiol, a sydnonimine, a NONOate, a N-nitrosoamine, a N-hydroxyl nitrosamine, a nitrosimine, a diazetine dioxide, an oxatriazole 5-imine, an oxime, a hydroxylamine, a N-hydroxyguanidine, a hydroxyurea or a furoxan.

18 . The method of claim 7 , 10 or 12 , further comprising administering (i) at least one therapeutic agent; (ii) at least one nitric oxide donor compound; or (iii) at least one therapeutic agent and at least one nitric oxide donor compound.

19 . The method of claim 18 , wherein the therapeutic agent is an aldosterone antagonist, an alpha-adrenergic receptor antagonist, an angiotensin II antagonist, an angiotensin-converting enzyme inhibitor, an antidiabetic compound, an anti-hyperlipidemic compound, an antioxidant, an antithrombotic and vasodilator compound, a β-adrenergic antagonist, a calcium channel blocker, a digitalis, a diuretic, an endothelin antagonist, a hydralazine compound, a H 2 receptor antagonist, a neutral endopeptidase inhibitor, a nonsteroidal antiinflammatory compound, a phosphodiesterase inhibitor, a potassium channel blocker, a platelet reducing agent, a proton pump inhibitor, a renin inhibitor, a selective cyclooxygenase-2 inhibitor, or a combination of two or more thereof.

20 . The method of claim 19 , wherein the therapeutic agent is at least one compound selected from the group consisting of an aldosterone antagonist, an angiotensin II antagonist, an angiotensin-converting enzyme inhibitor, a β-adrenergic antagonist, a diuretic and a hydralazine compound.

21 . The method of claim 20 , wherein the aldosterone antagonist is eplerenone or spironolactone; the angiotensin II antagonist is candesartan cilexetil, eprosartan mesylate, irbesartan, losartan potassium, medoxomil, telmisartan, trandolapril, trandolaprilat or valsartan; the angiotensin-converting enzyme inhibitor is benazepril hydrochloride, captopril, enalapril maleate, fosinopril sodium, lisinopril, moexipril hydrochloride or quinapril hydrochloride; the β-adrenergic antagonist is bisoprolol fumarate, carvedilol, metoprolol tartrate, propranolol hydrochloride or timolol maleate; the diuretic is amiloride hydrochloride, chlorthalidone, hydrochlorothiazide or triamterene; and the hydralazine compound is hydralazine hydrochloride.

22 . The method of claim 18 , wherein the nitric oxide donor compound is selected from the group consisting of a S-nitrosothiol, a nitrite, a nitrate, a S-nitrothiol, a sydnonimine, a NONOate, a N-nitrosoamine, a N-hydroxyl nitrosamine, a nitrosimine, a diazetine dioxide, an oxatriazole 5-imine, an oxime, a hydroxylamine, a N-hydroxyguanidine, a hydroxyurea or a furoxan.

23 . A kit comprising at least one compound of claim 1 .

24 . The kit of claim 23 , further comprising further comprising (i) at least one therapeutic agent; (ii) at least one nitric oxide donor compound; or (iii) at least one therapeutic agent and at least one nitric oxide donor compound.

25 . The kit of claim 24 , wherein the (i) at least one therapeutic agent; (ii) at least one nitric oxide donor compound; or (iii) at least one therapeutic agent and at least one nitric oxide donor compound are in the form of separate components in the kit.