Methods and compositions for mitigating pain
AssigneeQueen's University at Kingston
InventorsGregory R. J. Thatcher, Brian M. Bennett, James N. Reynolds, Khem Jhamandas
Life of this patent
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Abstract
Methods and therapeutic compounds for treating pain, mitigating inflammation, effecting analgesia and/or effecting sedation in a subject are described. A subject is administered an effective amount of a therapeutic compound which is a nitrate ester. Novel pharmaceutical compositions are also described.
Claims26
A method for reducing anxiety, aiding sleep, or inducing sleep in a subject in need thereof, comprising administering to the subject an effective amount of a therapeutic compound, wherein said therapeutic compound is of the formula (Ia):
- , in which
- F2 is a nitrate group or an organic radical which may be joined in a cyclic ring system with G2, and which may contain inorganic counterions;
- E is a methylene group;
- G1 is a methylene group or does not exist;
- F1 is H;
- and
- G2 is joined with F2 to form a cyclic system or is RN—ZN;
- wherein RN is an organic radical possessing a heteroaryl group containing a P or S atom, where said P or S is positioned β, γ, or δ to a nitrate group;
- and ZN is WNmm—XNnn—YNoo;
- wherein
- mm, nn, oo are 0 or 1 and WN, XN, YN are NH, NRNN, CO, O, or CH2;
- wherein
- RNN is a C1–C12 alkyl group.
A method for reducing anxiety, aiding sleep, or inducing sleep in a subject in need thereof, comprising administering to said subject an effective amount of a therapeutic compound, wherein said therapeutic compound is of the formula (Ic):
- in which
- E is (R1R2C)m and G2—G1—CF1F2— is R19—(R3R4C)p—(R17R18C)n—;
- wherein
- each of m, n, and p is an integer from 0 to 10;
- R3 and R17 are each independently hydrogen, a nitrate group, or A;
- and
- R1 and R4 are each independently hydrogen, or A;
- where A is selected from a substituted or unsubstituted aliphatic group comprising a branched or straight-chain aliphatic moiety having from 1 to 24 carbon atoms in the chain, which optionally may contain O, S, NR6, or an unsaturation in the chain, optionally bearing from 1 to 4 hydroxy, nitrate, amino, aryl, or heterocyclic groups;
- an unsubstituted or substituted cyclic aliphatic moiety having from 3 to 7 carbon atoms in the aliphatic ring, which optionally may contain O, S, NR6, or an unsaturation in the ring, optionally bearing from 1 to 4 hydroxy, nitrate, amino, 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 may contain O, S, NR6, or an unsaturation in the linkage, and optionally bearing from 1 to 4 hydroxy, nitrate, amino, aryl, or heterocyclic groups;
- a substituted or unsubstituted aliphatic group comprising a branched, cyclic or straight-chain aliphatic moiety having from 1 to 24 carbon atoms in the chain, containing linkages selected from the group consisting of C═O, C═S, and C═NOH, which optionally may contain O, S, NR6, or an unsaturation in the chain, optionally bearing from 1 to 4 hydroxy, nitrate, amino, aryl, or heterocyclic groups;
- a substituted or unsubstituted aryl group;
- a substituted or unsubstituted heterocyclic group;
- an amino group selected from alkylamino, dialkylamino, cyclic amino, diamino, triamino, arylamino, diarylamino, and alkylarylamino moieties;
- hydroxy;
- alkoxy;
- and a substituted or unsubstituted aryloxy;
- wherein
- 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), SR5, 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;
- each of R2, R5, R18, and R19 is, independently, hydrogen, A, or X—Y;
- each of R6, R7, R8, R9, R11, R12, R13, R14, R15, R16 is, independently, an alkyl or acyl group containing 1–24 carbon atoms, which may contain 1–4 ONO2 substituents;
- a C1–C6 connection to R1–R4 in a cyclic derivative, which may contain 1–4 ONO2 substituents;
- a hydrogen, a nitrate group, or A;
- M is H, Na+, K+, NH4+, or N+HkR11(4-k), where k is 0–3;
- or other pharmaceutically acceptable counterion;
- and with the proviso that when m=n=p=1 and R19, R2, R18, R1═H and R17, R3 are nitrate groups, R4 is not H.
A method of reducing anxiety, aiding sleep, or inducing sleep in a subject in need thereof, comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of:
A method of reducing anxiety, aiding sleep, or inducing sleep in a subject in need thereof, comprising administering to said subject an effective amount of a therapeutic compound selected from the group consisting of:
A method of reducing anxiety, aiding sleep, or inducing sleep in a subject in need thereof, comprising administering to said subject an effective amount of a therapeutic compound having the formula IVk:
A method of reducing anxiety, aiding sleep, or inducing sleep in a subject in need thereof, comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of:
A method of reducing anxiety, aiding sleep, or inducing sleep in a subject in need thereof, comprising administering to said subject an effective amount of a therapeutic compound having the formula IVr:
A method of providing sedation or anesthesia in a subject in need thereof, comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of:
A method of providing sedation or anesthesia in a subject in need thereof, comprising administering to said subject an effective amount of a therapeutic compound selected from the group consisting of:
A method of providing sedation or anesthesia in a subject in need thereof, comprising administering to said subject an effective amount of a therapeutic compound selected from the group consisting of:
Dependencies are inferred from the claim text.