Organic nitrate-based compounds for the treatment of vasculopathies

Use for preparing drugs for vasculopathy treatment of compounds, or salts thereof, having the general formula:

• A-(B)b0-(C)c0-NO2 (I)
• wherein:
• c0 is an integer and is 0 or 1;
• b0 is an integer and is 0 or 1, with the proviso that c0 and b0 cannot be contemporaneously equal to zero.
• A═R—C(═O), wherein
• R is the radical of the precursor drug selected from the salicylic or acetylsalicylic acid,
• B=-TB-X2-TBI- wherein
• TB and TBI are equal or different;
• TB=X, wherein X═O, S, NR1c, R1c is H or a linear or branched alkyl having from 1 to 5 carbon atoms;
• TBI═(CO)tx or (X)txx, wherein tx and txx have the value of 0 or 1;
• with the proviso that tx=1 when txx=0, tx=0 when txx=1;
• X is as above;
• X2, bivalent radical, is such that the corresponding precursor of B-TB-X2-TBI- wherein the free valence of TB is saturated with Z, and that of TBI with OZ, Z or with —N(ZI)(ZII), wherein Z=H, C1-C10, preferably C1-C5 alkyl, linear or branched when possible, ZI, ZII equal or different have the Z values as above, depending on that TB and/or TBI═CO or X, in function of the values of t, t′, tx and txx;
• the precursor compound of B being selected from the following:
• aminoacids, selected from the following:
• L-carnosine, anserine, selenocysteine, selenome-thionine, penicillamine, N-acetylpenicillamine, cysteine, N-acetylcysteine, glutathione or its esters, preferably ethyl or isopropyl ester;
• hydroxyacids, selected from the following:
• gallic acid, ferulic acid, gentisic acid, citric acid, caffeic acid, dihydrocaffeic acid, p-cumaric acid, vanillic acid;
• aromatic and heterocyclic polyalcohols, selected from the following:
• nordihydroguaiaretic acid, quercetin, catechin, kaempferol, sulphurethyne, ascorbic acid, isoascorbic acid, hydroquinone, gossypol, reductic acid, methoxy-hydroquinone, hydroxyhydroquinone, propyl gallate, saccharose, 3,5-di-tertbutyl-4-hydroxy-benzylthio glycolate, p-cumaric alcohol, 4-hydroxy-phenylethylalcohol, coniferyl alcohol, allopurinol;
• compounds containing at least one free acid function, selected from the following:
• 3,3′-thiodipropionic acid, fumaric acid, dihydroxy-maleic acid, edetic acid;
• C is the bivalent radical -Tc—Y— wherein
• when b0=c0=1:
• Tc=(CO) when tx=0, Tc=X when txx=0, X being as above defined;
• when b0=0:
• Tc=(CO) when tx=0, Tc=X when t′=0, being X as above defined;
• when c0=0:
• tx=0, TBI═X—O—;
• Y is:
• Yp:
• 30
• wherein:
• nIX is an integer between 0 and 3, preferably 1;
• nIIX is an interger comprised between 1 and 3, preferably 1;
• RTIX, RTIX′, RTIIX, RTIIX′, equal to or different from each other are H or linear or branched C1-C4 alkyl;
• preferably RTIX, RTIX′, RTIIX, RTIIX′ are H;
• Y3 is an heterocyclic ring containing one or two nitrogen atoms, saturated, unsaturated or aromatic, having 5 or 6 atoms,
• or Y can be:
• Y0, selected from the following:
• an alkylenoxy group R′O wherein R′ is a linear or branched when possible C1-C20 alkyl, preferably having from 2 to 6 carbon atoms, or a cycloalkylene having from 5 to 7 carbon atoms, in the cycloalkylene ring one or more carbon atoms can be substituted by heteroatoms, the ring can have side chains of R′ type, R′ being as above;
• or one of the following groups:
• 31
• wherein nf′ is an integer from 1 to 6 preferably from 1 to 4;
• 32
• wherein R1f═H, CH3 and nf′ is an integer from 1 to 6;
• preferably from 1 to 4;
• or Y is YAR and is selected from the following:
• YAR1:
• 33
• wherein n3 is an integer from 0 to 3 and n3′ is an integer from 1 to 3;
• YAR2:
• 34
• wherein n3 and n3′ have the above meaning.