Drugs for chronic pains

Nitrooxyderivative compounds or salts thereof having the following general formula (I):

• A-(B)b0-(C)c0-NO2 (I)
• wherein:
• c0 is an integer and is 0 or 1, preferably 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-T1-, wherein R is the radical of an analgesic drug for the chronic pain, in particular for the neuropathic pain;
• T1=(CO)t or (X)t, wherein X═O, S, NR1c, R1c is H or a linear or branched alkyl, having from 1 to 5 carbon atoms, t and t′ are integers and equal to zero or 1, with the proviso that t=1 when t′=0;
• t=0 when t′=1;
• B=-TB-X2-TBI- wherein
• TB and TBI are equal or different;
• TB=(CO) when t=0, TB=X when t′=0, X being as above;
• 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;
• and 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 valences of TB and of TBI are saturated each with OZ, with Z or with —N(ZI)(ZII), being:
• Z=H, C1-C10, preferably C1-C5 alkyl linear or branched when possible, ZI, ZII equal to or different have the values of Z 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 as above defined being selected from the following classes of compounds:
• aminoacids, selected from the following:
• L-carnosine, anserine, selenocysteine, seleno-methionine, penicillamine, N-acetylpenicillamine, cysteine, N-acetylcysteine, glutathione or esters thereof, preferably ethyl or isopropyl ester;
• hydroxyacids, selected from the following:
• gallic acid, ferulic acid, gentisic acid, citric acid, caffeic, dihydrocaffeic acid, p-cumaric acid, vanillic acid;
• aromatic and heterocyclic polyalcohols, selected from the following:
• nordihydroguaiaretic acid, quercetin, catechin, kaempferol, sulfurethyne, ascorbic acid, isoascorbic acid, hydroquinone, gossypol, reductic acid, methoxyhydroquinone, hydroxyhydroquinone, propyl gallate, saccharose, 3,5-di-tertbutyl-4-hydroxybenzylthio glycolate, p-cumaric alcohol, 4-hydroxy-phenylethyl alcohol, coniferyl alcohol, allopurinol;
• compounds containing at least one free acid function, selected from the following:
• 3,3′-thiodipropionic acid, fumaric acid, dihydroxymaleic acid, edetic acid;
• C=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 t=0, Tc X when t′=0, X being as above defined,
• when c0=0:
• tx=0, TBI=X=—O—;
• Y has one of the following meanings:
• Yp:
• 37
• wherein:
• nIX is an integer from 0 to 5, preferably 1;
• nIIX is an integer from 1 to 5 preferably 1;
• RTIX, RTIX′, X 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 a saturated, unsaturated or aromatic heterocyclic ring, having 5 or 6 atoms, containing from one to three heteroatoms, preferably from one to two, said heteroatoms being equal or different and selected from nitrogen, oxygen, sulphur;
• 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, having preferably 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 Y is selected from one of the following groups:
• 38
• wherein nf′ is an integer from 1 to 6 preferably from 1 to 4;
• 39
• wherein R1f═H, CH3 and nf is an integer from 1 to 6;
• preferably from 2 to 4;
• YAR, selected from:
• YAR1:
• 40
• wherein n3 is an integer from 0 to 5 and n3′ is an integer from 1 to 3;
• or
• YAR2:
• 41
• wherein n3 and n3′ have the above meaning.