Nitrate Esters Of Corticoid Compounds Useful As Diuretics

A method of treating a patient with heart failure by administering a therapeutically effective amount of a pharmaceutical composition comprising a nitrate ester of a corticoid compound having the formula:

• B—X1—NO2 (1)
• or their esters or salts, where B has the following structure:
• where, in place of the hydrogens H in the CH groups or two hydrogens H2 in the CH2 group shown in the general formula, there may be the following substituents:
• at position 1-2:
• there may be a double bond;
• at position 2-3:
• there may be the following substituent:
• at position 2:
• there may be Cl, Br;
• at position 3:
• there may be ↑O, —O—CH2—CH2—Cl, OH;
• at position 4-5:
• there may be a double bond;
• at position 5-6:
• there may be a double bond;
• at position 6:
• there may be Cl, F, CH3, —CHO;
• at position 7:
• there may be Cl;
• at position 9:
• there may be Cl, F;
• at position 11:
• there may be OH, CO, Cl;
• at position 16:
• there may be CH3, OH, ═CH2;
• at position 17:
• In addition to R″, the other H can be substituted with the following:
• OH, CH3, OCO(O)ua(CH2)vaCH3, or
• where ua is an integer equal to 0 or 1, va is an integer from 0 to 4;
• at positions 16-17:
• there may be the following groups:
• R and R′ are equal or different one from the other and may be hydrogen or linear or branched alkyls having from 1 to 4 carbon atoms, preferably R═R′═CH3;
• B being a corticosteroid residue;
• R″ is —(CO-L)t—(X)t1—
• where t and t1 are integers equal or different one from the other and equal to 0 or 1,
• provided that they cannot be both equal to 0 when B contains no —OH groups;
• the bivalent bridging group L is selected from:
• (CR4R5)na(O)nb(CR4R5)n′a(CO)n′b(O)n″b(CO)n″′b(CR4R5)n″a
• where na, n′a and n″a are equal or different one from the other and are integers from 0 to 6, preferably from 1 to 3;
• nb, n′ b, n″b and n″′b are equal or different one from the other and are integers equal to 0 or 1;
• R4 and R5 are equal pr different one from the other and are chosen from H, linear or branched alkyl having from 1 to 5 carbon atoms, preferably from 1 to 3;
• X is equal to X0═O, NH, NR1C where R1C is a linear or branched alkyl having from 1 to 10 C atoms;
• or equal to X2 where X2 is equal to OH, CH3, Cl, N(—CH2—CH3)2, SCH2F, SH,
• X1 is a bivalent connecting bridge chosen from:
• YO, where Y is a linear or whenever possible branched C1-C20 alkylene, preferably having from 2 to 5 carbon atoms, or an optionally substituted cycloalkylene having from 5 to 7 carbon atoms;
• Y1 selected from:
• where n3 is an integer from 0 to 3;
• where nf′ is an integer from 1 to 6, preferably from 2 to 4;
• where R1f═H, CH3 and nf is an integer from 1 to 6, preferably from 2 to 4.