Cardiovascular Compounds Comprising Nitric Oxide Enhancing Groups, Compositions and Methods of Use

1 . A compound of Formula (I), (II), (III), (IV), (V), (VI), (VII) or a pharmaceutically acceptable salt thereof:

wherein the compound of Formula (I) is:

wherein:

X 3 is:

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

(9) —C(O)—U 3 D 1 ;

(10) —C(O)—CH 2 —NH(D 1 );

(11) —S(O) 2 —N(D 1 )-C(O)—C 6 H 5 ;

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

(13) —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)

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 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:

R 32 is a hydrogen, an alkyl or an aryl;

R 33 is —(CH 2 ) 2 —OD 1 or

R 34 is a hydrogen, a lower alkyl, a lower haloalkyl, an aryl or an arylalkyl;

R 35 is a hydrogen or a lower alkyl;

R 36 is an alkoxy, -D 6 an amino group or —N(R 13 )(R 13 );

R 40 is a hydrogen, a lower alkyl, an alkoxyalkyl or —(C(R g )R h )) k —V 4 ;

R 41 is a hydrogen or a lower alkyl;

R 42 is a lower alkyl or —(C(R g )R h )) k —V 4 ;

R 43 and R 44 taken together are:

Z 5 is —CH 2 or oxygen;

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 ) a1 -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 —V 4 ;

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;

V 4 is V 3 , R e , —U 3 —V 5 or V 6 ;

V 3 is:

R 24 is —C 6 H 4 R 37 , —CN, —S(O) 2 —C 6 H 4 R 37 , —C(O)—N(R a )(R i ), —NO 2 , —C(O)—OR 25 or —S(O) 2 —R 25 ;

R 25 is an aryl group, a lower alkyl group, a haloalkyl group, a hydroxyalkyl group or an arylalkyl group;

R 26 is —C(O)— or —S(O) 2 —;

R 37 is a hydrogen, —CN, —S(O) 2 —R 25 , —C(O)—N(R a )(R i ), —NO 2 or —C(O)—OR 25 ;

T′ is oxygen, sulfur or NR 6 ;

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

V 6 is:

Z 6 is —CH or nitrogen;

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

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, —(CH 2 CH 2 O) q1 — or Y 4 ;

Y 4 is:

T is a —S(O) o —; a carbonyl or a covalent bond;

o is an integer from 0 to 2;

R j and R k are independently selected from an alkyl group, an aryl group, or R j and R k taken together with the nitrogen atom to which they are attached are a heterocylic ring;

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 arylalkylthioalkyl, 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, an 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, —U 3 —V 5 , V 6 , —(C(R o )(R p )) k1 —U 3 —V 5 , —(C(R o )(R p )) k1 —U 3 —V 3 , —(C(R o )(R p )) k1 —U 3 —V 6 , —(C(R o )(R p )) k1 —U 3 —C(O)—V 6 , 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, an imine, a hydrazone, a bridged cycloalkyl group,

R o and R p 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 arylalkylthioalkyl, 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, an 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, —U 3 —V 5 , V 6 , or R o and R p 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, an imine, a hydrazone a bridged cycloalkyl group,

U 3 is an oxygen, sulfur or —N(R a )R i ;

V 5 is —NO or —NO 2 (i.e. an oxidized nitrogen);

k 1 is an integer from 1 to 3;

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, an arylsulphonyloxy, a sulfonamido, a carboxamido, a carboxylic ester, an aminoalkyl, an aminoaryl, —CH 2 —C—(U 3 —V 5 )(R e )(R f ), a bond to an adjacent atom creating a double bond to that atom or —(N 2 O 2 —).M 1 + , wherein M 1 + is an organic or inorganic cation; and

with the proviso that the compound of Formula (I) must contain at least one nitric oxide enhancing group linked to the compound of Formula (I) through an oxygen atom, a nitrogen atom or a sulfur atom via a bond or moiety that can be hydrolyzed;

wherein the compound of Formula (E) 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 nitric oxide enhancing group linked to the compound of Formula (II) through an oxygen atom, a nitrogen atom or a sulfur atom via a bond or moiety that can be hydrolyzed;

wherein 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 nitric oxide enhancing group linked to the compound of Formula (III) through an oxygen atom, a nitrogen atom or a sulfur atom via a bond or moiety that can be hydrolyzed;

wherein the compound of Formula (IV) is:

wherein:

X 3 and Y 3 are as defined herein; and

with the proviso that the compounds of Formula (IV) must contain at least one nitric oxide enhancing group linked to the compound of Formula (IV) through an oxygen atom, a nitrogen atom or a sulfur atom via a bond or moiety that can be hydrolyzed;

wherein the compound of Formula (V) is:

wherein:

X 3 and Y 3 are as defined herein; and

with the proviso that the compounds of Formula (V) must contain at least one nitric oxide enhancing group linked to the compound of Formula (V) through an oxygen atom, a nitrogen atom or a sulfur atom via a bond or moiety that can be hydrolyzed;

wherein the compound of Formula (VI) is:

wherein:

X 3 and Y 3 are as defined herein; and

with the proviso that the compounds of Formula (VI) must contain at least one nitric oxide enhancing group linked to the compound of Formula (VI) through an oxygen atom, a nitrogen atom or a sulfur atom via a bond or moiety that can be hydrolyzed;

wherein the compound of Formula (VII) is:

wherein:

R 47 is a lower alkyl group;

X 3 and Y 3 as defined herein; and

with the proviso that the compounds of Formula (VII) must contain at least one nitric oxide enhancing group linked to the compound of Formula (VII) through an oxygen atom, a nitrogen atom or a sulfur atom via a bond or moiety that can be hydrolyzed;

wherein the compound of Formula (VIII) is:

wherein:

X 3 and Y 3 are as defined herein; and

with the proviso that the compounds of Formula (VIII) must contain at least one nitric oxide enhancing group linked to the compound of Formula (VIII) through an oxygen atom, a nitrogen atom or a sulfur atom via a bond or moiety that can be hydrolyzed.

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 nitric oxide enhancing abitesartan, a nitric oxide enhancing candesartan, a nitric oxide enhancing candesartan cilexetil, a nitric oxide enhancing elisartan analogue, a nitric oxide enhancing embusartan, a nitric oxide enhancing enoltasosartan, a nitric oxide enhancing fonsartan, a nitric oxide enhancing forasartan, a nitric oxide enhancing glycyllosartan, a nitric oxide enhancing irbesartan, a nitric oxide enhancing losartan, a nitric oxide enhancing olmesartan, a nitric oxide enhancing milfasartan, a nitric oxide enhancing pomisartan, a nitric oxide enhancing ripisartan, a nitric oxide enhancing tasosartan, a nitric oxide enhancing telmisartan, a nitric oxide enhancing valsartan, a nitric oxide enhancing CL-329167, a nitric oxide enhancing analogue related to EMD 66684, a nitric oxide enhancing EXP 3134, a nitric oxide enhancing MK 996, a nitric oxide enhancing SR-47436, a nitric oxide enhancing YM 358, or a nitric oxide enhancing 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-OP, 165113-37-1P, 165113-38-2P, 165113-39-3P, 16511340-6P, 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-OP, 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 nitric oxide enhancing eprosartan; the compound of Formula (III) is a nitric oxide enhancing saprisartan, a nitric oxide enhancing zalasartan, the compound of Formula (IV) is a nitric oxide enhancing BMS 180560; the compound of Formula (V) is a nitric oxide enhancing KW 3433; the compound of Formula (VI) is a nitric oxide enhancing GA 0056; and the compound of Formula (VII) is a nitric oxide enhancing L 158,809; and pharmaceutically acceptable salts thereof.

4 . The compound of claim 1 , wherein the compound of Formula (I) is a nitric oxide enhancing abitesartan of Formula (IX), a nitric oxide enhancing candesartan cilexetil of Formula (X), a nitric oxide enhancing elisartan analogue of Formula (XI), a nitric oxide enhancing embusartan of Formula (XII), a nitric oxide enhancing enoltasosartan of Formula (XIII), a nitric oxide enhancing fonsartan of Formula (XIV), a nitric oxide enhancing forasartan of Formula (XV), a nitric oxide enhancing glycyllosartan of Formula (XVI), a nitric oxide enhancing irbesartan of Formula (XVII), a nitric oxide enhancing losartan of Formula (XVIII), a nitric oxide enhancing olmesartan metabolite of Formula (XIX), a nitric oxide enhancing milfasartan of Formula (XX), a nitric oxide enhancing pomisartan of Formula (XXI), a nitric oxide enhancing ripisartan of Formula (XXII), a nitric oxide enhancing tasosartan of Formula (XXIII), a nitric oxide enhancing telmisartan of Formula (XXIV), a nitric oxide enhancing valsartan of Formula (XXV); a nitric oxide enhancing EMD 66684 of Formula (XXVI); a nitric oxide enhancing EXP 3134 of Formula (XXVII); a nitric oxide enhancing MK-996 of Formula (XXVII); the compound of Formula (II) is a nitric oxide enhancing of eprosartan of Formula (XXIX); and the compound of Formula (II) is a nitric oxide enhancing analogue related to saprisartan of Formula (XXX), a nitric oxide enhancing zolasartan of Formula (XXXI), or a pharmaceutically acceptable salt thereof,

wherein 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 (XXI) is:

and the compound of Formula (XXIII) is:

and the compound of Formula (XXIV) is:

and the compound of Formula (XXV) is:

and the compound of Formula (XXVI) is:

and the compound of Formula (XXVII) is:

and the compound of Formula (XXVIII) is:

and the compound of Formula (XXIX) is:

and the compound of Formula (XXX) is:

and the compound of Formula (XXXI) is:

wherein

T′ is oxygen, sulfur or NR 6 ;

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

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;

wherein

R m -R n taken together are a hydrogen atom; or

R m is:

(i) —C—(O)—;

(ii) —C—(O)—NR 6 ;

(iii) —C(O)—O—;

(iv) —C(O)—S;

(v) —CH 2 —O—;

(vi) —CH(CH 3 )—O—;

(vii) —N—C(O)—S—;

(viii) —N—C(O)—CH 2 —;

(ix) —N—C(O)—O—;

(x) a covalent bond;

(xi) —(C—(R e )(R f )) 2-5 —; or

(xii) —(C—(R e )(R f )) 2-5 -T′-C(O)—;

R n is:

a hydrogen or:

R 24 is —C 6 H 4 R 37 , —CN, —S(O) 2 —C 6 H 4 R 37 , —C(O)—N(R a )(R i ), —NO 2 , —C(O)—OR 25 or —S(O) 2 —R 25 ;

R 25 is an aryl group, a lower alkyl group, a haloalkyl group, a hydroxyalkyl group or an arylalkyl group;

R 26 is —C(O)— or —S(O) 2 —;

R 37 is a hydrogen, —CN, —S(O) 2 —R 25 , —C(O)—N(R a )(R i ), —NO 2 or —C(O)—OR 25 ;

T′ is oxygen, sulfur or NR 6 ;

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

R j and R k are independently selected from an alkyl group, an aryl group, or R j and R k taken together with the nitrogen atom to which they are attached are a heterocylic ring; and

with the proviso that the compounds of Formula (IX) to Formula (XXXI) must contain at least one nitric oxide enhancing group linked to the compound through an oxygen atom, a nitrogen atom or a sulfur atom via a bond or moiety that can be hydrolyzed.

5 . The compound of claim 1 , wherein the Formula (I) is a nitric oxide enhancing abitesartan of Formula (XXXII), a nitric oxide enhancing candesartan cilexetil of Formula (XXXIII), a nitric oxide enhancing elisartan analogue of Formula (XXXIV), a nitric oxide enhancing embusartan of Formula (XXXV), a nitric oxide enhancing enoltasosartan of Formula (XXXVI), a nitric oxide enhancing fonsartan of Formula (XXXVII), a nitric oxide enhancing forasartan of Formula (XXXVIII), a nitric oxide enhancing glycyllosartan of Formula (XXXIX), a nitric oxide enhancing irbesartan of Formula (XL), a nitric oxide enhancing losartan of Formula (XLI), a nitric oxide enhancing olmesartan metabolite of Formula (XLII), a nitric oxide enhancing milfasartan of Formula (XLIII), a nitric oxide enhancing pomisartan of Formula (XLIV), a nitric oxide enhancing ripisartan of Formula (XLV), a nitric oxide enhancing tasosartan of Formula (XLVI), a nitric oxide enhancing telmisartan of Formula (XLVII), a nitric oxide enhancing valsartan of Formula (XLVIII); a nitric oxide enhancing analogue related to EMD 66684 of Formula (XLIX); a nitric oxide enhancing EXP 3134 of Formula (L); a nitric oxide enhancing MK-996 of Formula (LI); the compound of Formula (II) is a nitric oxide enhancing eprosartan of Formula (LII); and compound of Formula (III) is a nitric oxide enhancing analogue related to saprisartan of Formula (LIII), a nitric oxide enhancing zolasartan of Formula (LIV), or a pharmaceutically acceptable salt thereof,

wherein the compound of Formula (XXXII) is:

and the compound of Formula (XXXIIII) is:

and the compound of Formula (XXXIV) is:

and the compound of Formula (XXXV) is:

and the compound of Formula (XXXVI) is:

and the compound of Formula (XXVII) is:

and the compound of Formula (XXXVIII) is:

and the compound of Formula (XXXIX) is:

and the compound of Formula (XL) is:

and the compound of Formula (XLI) is:

and the compound of Formula (XLII) is:

and the compound of Formula (XLIII) is:

and the compound of Formula (XLIV) is:

and the compound of Formula (XLV) is:

and the compound of Formula (XLVI) is:

and the compound of Formula (XLVII) is:

and the compound of Formula (XLVIII) is:

and the compound of Formula (LIX) is:

and the compound of Formula (L) is:

and the compound of Formula (LI) is:

and the compound of Formula (LII) is:

and the compound of Formula (LIII) is:

and the compound of Formula (LIV) is:

wherein:

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

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 45 is:

R 48 is —S(O) 2 —C 6 H 5 ; —CN, —C(O)—NH 2 or —C(O)OCH 3 , and

R 49 is a hydrogen or chlorine;

R 65 is a hydrogen or a methyl group; R 46 is:

wherein:

R 66 is —(CH 2 ) 2 —O—C(O)—CH 3 or —(CH 2 ) 2 —NH—C(O)—CH 3 ;

R 67 is —CN, —C(O)—NH 2 or —C(O)—OCH 3 ;

R 49 and R 65 are as defined herein; and

with the proviso that the compounds of Formula (XXXII) to (LIV) must contain at least one nitric oxide enhancing group linked to the compound through an oxygen atom, a nitrogen atom or a sulfur atom via a bond or moiety that can be hydrolyzed.

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

7 . The method of claim 6 , wherein the cardiovascular disease is 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 complications 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 events, post-angioplasty restenosis, coronary plaque inflammation, hypercholesterolemia, embolism, stroke, shock, arrhythmia, atrial fibrillation or atrial flutter, thrombotic occlusion and reclusion cerebrovascular incidents, left ventricular dysfunction and hypertrophy,

8 . The method of claim 7 , wherein the cardiovascular disease is hypertension, heart failure and/or diastolic dysfunction.

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

10 . The method of claim 9 , wherein the renovascular disease is renal failure, renal insufficiency, renal deterioration associated with severe hypertension or renovascular hypertension.

11 . A method for treating diabetes; treating diseases resulting from oxidative stress; treating endothelial dysfunctions; treating a disease caused by endothelial dysfunctions; treating cirrhosis; treating pre-eclampsia; treating osteoporosis; treating nephropathy; treating a peripheral vascular disease; treating portal hypertension; treating an ophthalmic disorder; treating metabolic syndrome; or treating hyperlipidemia in a patient in need thereof comprising administering to the patient an effective amount of the composition of claim 2 .

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

13 . The composition of claim 12 , wherein the therapeutic agent is an aldosterone antagonist, an α-adrenergic receptor agonist, an α-adrenergic receptor antagonist, an angiotensin II antagonist, an angiotensin-converting enzyme inhibitor, an antidiabetic compound, an anti-hyperlipidemic compound, an antimicrobial compound, an antioxidant, an antithrombotic and vasodilator compound, a β-adrenergic antagonist, a calcium channel blocker, a carbonic anhydrase inhibitor, a digitali, a diuretic, an endothelin antagonist, a hydralazine compound, a H 2 receptor antagonist, an neutral endopeptidase inhibitor, a nonsteroidal antiinflammatory compound, a phosphodiesterase inhibitor, a potassium channel blocker, a platelet reducing agent, a prostaglandin, a proton pump inhibitor, a renin inhibitor, a selective cyclooxygenase-2 inhibitor, a steroid, or a combination of two or more thereof.

14 . The composition of claim 13 , 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 (ACE) inhibitor, a β-adrenergic antagonist, a calcium channel blocker, a diuretic, a hydralazine compound and a renin inhibitor.

15 . The composition of claim 14 , wherein the aldosterone antagonist is eplerenone or spironolactone; the angiotensin II antagonist is candesartan, 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, ramipril; the α-adrenergic antagonist is bisoprolol fumarate, carvedilol, metoprolol tartrate, propranolol hydrochloride or timolol maleate; the calcium channel blockers is amlodipine, diltiazem, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine, nitrendipine, verapamil; the diuretic is amiloride hydrochloride, chlorthalidone, hydrochlorothiazide or triamterene; the hydralazine compound is hydralazine hydrochloride; and the renin inhibitor is aliskiren, ciprokiren, ditekiren, enalkrein, medullipin, remikiren, terlkiren, tonin or zankiren.

16 . The composition of claim 12 , wherein the nitric oxide enhancing 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, a furoxan or a nitroxide.

17 . The method of claims 6 , 9 or 11 , further comprising administering (i) at least one therapeutic agent; (ii) at least one nitric oxide enhancing compound (iii) at least one therapeutic agent and at least one nitric oxide enhancing compound.

18 . The method of claim 17 , wherein the therapeutic agent is an aldosterone antagonist, an α-adrenergic receptor agonist, an α-adrenergic receptor antagonist, an angiotensin II antagonist, an angiotensin-converting enzyme inhibitor, an antidiabetic compound, an anti-hyperlipidemic compound, an antimicrobial compound, an antioxidant, an antithrombotic and vasodilator compound, a β-adrenergic antagonist, a calcium channel blocker, a carbonic anhydrase inhibitor, a digitali, a diuretic, an endothelin antagonist, a hydralazine compound, a H 2 receptor antagonist, an neutral endopeptidase inhibitor, a nonsteroidal antiinflammatory compound, a phosphodiesterase inhibitor, a potassium channel blocker, a platelet reducing agent, a prostaglandin, a proton pump inhibitor, a renin inhibitor, a selective cyclooxygenase-2 inhibitor, a steroid, or a combination of two or more thereof.

19 . The method of claim 17 , 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, a furoxan or a nitroxide.

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

21 . The kit of claim 20 , further comprising further comprising (i) at least one therapeutic agent; (ii) at least one nitric oxide enhancing compound; or (iii) at least one therapeutic agent and at least one nitric oxide enhancing compound.

22 . The kit of claim 21 , wherein the (i) at least one therapeutic agent; (ii) at least one nitric oxide enhancing compound; or (iii) at least one therapeutic agent and at least one nitric oxide enhancing compound are in the form of separate components in the kit.