Nitrate esters and their use for neurological conditions

A method of mitigating cerebral damage due to ischemia in a subject, comprising administering to said subject an effective amount of a therapeutic compound such that cerebral damage is mitigated, wherein the therapeutic compound has the formula (Formula II):

• in which:
• m, n, p are integers from 0 to 10;
• R3,17 are each independently hydrogen, a nitrate group, or A;
• R1,4 are each independently hydrogen or A;
• where A is selected from:
• a substituted or unsubstituted aliphatic group (preferably a branched, or straight-chain aliphatic moiety having from 1 to 24 carbon atoms in the chain), which optionally contains O, S, NR6 and unsaturations in the chain, optionally bearing from 1 to 4 hydroxy, nitrate, amino or aryl, or heterocyclic groups;
• an unsubstituted or substituted cyclic aliphatic moiety having from 3 to 7 carbon atoms in the aliphatic ring, which optionally contains O, S, NR6 and unsaturations in the ring, optionally bearing from 1 to 4 hydroxy, nitrate, amino or aryl, or heterocyclic groups;
• an unsubstituted or substituted aliphatic moiety constituting a linkage of from 0 to 5 carbons, between R1 and R3 and/or between R17 and R4, which optionally contains O, S, NR6 and unsaturations in the linkage, and optionally bearing from 1 to 5 hydroxy, nitrate, amino or aryl, or heterocyclic groups;
• a substituted or unsubstituted aliphatic group (preferably a branched, cyclic or straight-chain aliphatic moiety having from 1 to 24 carbon atoms in the chain), containing carbonyl linkages (e.g. C═O, C═S, C═NOH), which optionally contains O, S, NR8 and unsaturations in the chain, optionally bearing from 1 to 4 hydroxy, nitrate, amino or aryl, or heterocyclic groups;
• a substituted or unsubstituted aryl group;
• a heterocyclic group;
• amino (including alkylamino, dialkylamino (including cyclic amino, diamino and triamino moieties), arylamino, diarylamino, and alkylarylamino);
• hydroxy;
• alkoxy;
• a substituted or unsubstituted aryloxy;
• R2, R5, R18, R19 are optionally hydrogen, A, or X-Y;
• where X is F, Br, Cl, NO2, CH2, CF2, O, NH, NMe, CN, NHOH, N2H3, N2H2R13, N2HR13R14, N3, S, SCN, SCN2H2(R15)2, SCN2H3(R15). SC(O)N(R15)2, SC(O)NHR15, SO3M, SH, SR7, SO2M, S(O)R8, S(O)2R9, S(O)OR8, S(O)2OR9, PO2HM, PO3HM, PO3M2, P(O)(OR15)(OR16), P(O)(OR16)(OM), P(O)(R15)(OR8), P(O)(OM)R15, CO2M, CO2H, CO2R11, C(O), C(O)R12, C(O)(OR13), PO2H, PO2M, P(O)(OR14), P(O)(R13), SO, SO2, C(O)(SR13), SR6, SSR7 or SSR5;
• Y is F, Br, Cl, CH3, CF2H, CF3, OH, NH2, NHR6, NR6R7, CN, NHOH, N2H3, N2H2R13, N2HR13R14, N3, S, SCN, SCN2H2(R15)2, SCN2H3(R15), SC(O)N(R15)2, SC(O)NHR15, SO3M, SH, SR7, SO2M, S(O)R8, S(O)2R9, S(O)OR8, S(O)2OR9, PO2HM, PO3M2, P(O)(OR15)(OR16), P(O)(OR16)(OM), P(O)(R15)(OR8), P(O)(OM)R15, CO2M, CO2H, CO2R11, C(O)R12, C(O)(OR13), C(O)(SR13), SR5, SSR7 or SSR5, or does not exist;
• R6, R7, R8, R9, R11, R12, R13, R14, R15, R16 are the same or different alkyl or acyl groups containing 1-24 carbon atoms which may contain 1-4 ONO2 substituents;
• or C1-C6 connections to R1-R4 in cyclic derivatives;
• or are each independently hydrogen, a nitrate group, or A;
• and
• M is H, Na−, K+, NH4+, N+HkR11(4-k) where k is 0-3, or other pharmaceutically acceptable counterion;
• wherein A is not substituted or unsubstituted pyridyl, and,
• when m=n=p=1, that R1, R2, R18, R19 are selected from the group consisting of H, O linkage, and C1-C2 alkyl, wherein said C1-C2 alkyl is optionally substituted with nitrate, that R3, R17 are selected from the group consisting of H, nitrate, O linkage, and C1-C2 alkyl, wherein said C1-C2 alkyl is optionally substituted with nitrate, and that R4 is not H or C1-C3 alkyl.