Nitric oxide donating diuretic compounds, compositions and methods of use

A compound of Formula (I), or a pharmaceutically acceptable salt thereof:

• wherein the compound of Formula (I) is:
• wherein:
• X2 is —S(O)2;
• Y2 is chlorine or CF3;
• —V2—U2—W2— is:
• (i) —NH—(C(Rq)(Rr))—NRq—;
• or
• (ii) —NH—C(Rq)═N—;
• Rq and Rr at each occurrence are independently a hydrogen, a lower alkyl group, a substituted alkyl group, a benzyl group, an aryl group, an alkylaryl group, —CH2—S—CH—CH═CH2;
• —CH2—S—CF3, —CH2—S—CH2—C6H5 or K′ with the proviso that (Rq) and/or (Rr)with the carbon atom to which they are attached form a spiro ring;
• K′ is -G-Ec-(C(Re)(Rf))x—Wd—(C(Re)(Rf))y—Wi-Ej-Wg—(C(Re)(Rf))z—V4;
• K is —(W)a-Eb-(C(Re)(Rf))p1-Ec-(C(Re)(Rf))x—(W)d—(C(Re)(Rf))y—(W)i-Ej-(W)g—(C(Re)(Rf))z—V4;
• a, b, c, d, g, i and j are each independently an integer from 0 to 3;
• p1, x, y and z are each independently an integer from 0 to 10;
• G is a heterocyclic ring;
• V4 is V3, Re, —U3—V5 or V6;
• V3 is:
• R24 is —C6H4R29, —CN, —S(O)2—C6H4R29, —C(O)—N(Ra)(Ri), —NO2, —C(O)—OR25 or —S(O)2—R25;
• R25 is an aryl group, a lower alkyl group, a haloalkyl group, a hydroxyalkyl group or an arylalkyl group;
• R26 is —C(O)— or —S(O)2—;
• R29 is a hydrogen, —CN, —S(O)2—R25, —C(O)—N(Ra)(Ri), —NO2 or —C(O)—OR25;
• T′ is oxygen, sulfur or NR6;
• R6 is a hydrogen, a lower alkyl group or an aryl group;
• V6 is:
• Z5 is —CH2 or oxygen;
• Z6 is —CH or nitrogen;
• k1 is an integer from 1 to 3;
• W at each occurrence is independently —C(O)—, —C(S)—, -T3-, —(C(Re)(Rf))h—, —N(Ra)Ri, an alkyl group, an aryl group, a heterocyclic ring, an arylheterocyclic ring, —(CH2CH2O)q1— or a heterocyclic nitric oxide donor;
• E at each occurrence is independently -T3-, an alkyl group, an aryl group, —(C(Re)(Rf))h—, a heterocyclic ring, an arylheterocyclic ring, —(CH2CH2O)q1— or Y4;
• Y4 is:
• T is a —S(O)o—;
• a carbonyl or a covalent bond;
• o is an integer from 0 to 2;
• Rj and Rk are independently selected from an alkyl group, an aryl group, or Rj and Rk taken together with the nitrogen atom to which they are attached are a heterocylic ring;
• T3 at each occurrence is independently a covalent bond, a carbonyl, an oxygen, —S(O)o— or —N(Ra)Ri;
• h is an integer form 1 to 10;
• q1 is an integer from 1 to 5;
• Re and Rf 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, 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, —U3—V5, V6, —(C(Ro)(Rp))k1—U3—V5, —(C(Ro)(Rp))k1—U3—V3, —(C(Ro)(Rp))k1—U3—V6, —(C(Ro)(Rp))k1—U3—C(O)—V6, or Re and Rf 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,
• Ro and Rp 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, 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, —U3—V5, V6, or Ro and Rp 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,
• U3 is an oxygen, sulfur or —N(Ra)Ri;
• V5 is —NO or —NO2 (i.e. an oxidized nitrogen);
• k1 is an integer from 1 to 3;
• Ra is a lone pair of electrons, a hydrogen or an alkyl group;
• Ri 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, —CH2—C—(U3—V5)(Re)(Rf), a bond to an adjacent atom creating a double bond to that atom or —(N2O2—).M1+, wherein M1+ is an organic or inorganic cation;
• and
• with the proviso that the compound of Formula (I) must contain at least one group selected from a —ONO group, a —SNO group, a —NNO group, a —ONO2 group, -a SNO2 group, a —NNO2 group, a —(N2O2—).M1+ group, a heterocyclic nitric oxide donor group and a nitroxide group where the group is linked to the compound of Formula (I) through a carbon, oxygen or nitrogen atom via a bond that cannot be hydrolyzed.