Substituted γ-lactone compounds as NMDA-antagonists
First Claim
Patent Images
1. Substituted γ
- -lactone compounds of the general formula I, in whichR1 denotes an optionally at least mono-substituted aryl or heteroaryl residue, an optionally at least mono-substituted aryl or heteroaryl residue attached via a C1-6 alkylene group, an optionally at least mono-substituted, saturated, branched or unbranched aliphatic C1-10 residue, an optionally at least mono-substituted, at least partially unsaturated, branched or unbranched aliphatic C2-10 residue or an optionally at least mono-substituted, saturated or at least mono-unsaturated cycloaliphatic C3-9 residue, R2 denotes an optionally at least mono-substituted, saturated, branched or unbranched aliphatic C1-10 residue or an optionally at least mono-substituted, at least partially unsaturated, branched or unbranched aliphatic C2-10 residue, R3 denotes an optionally at least mono-substituted aryl residue, R4 denotes H, orR3 and R4 together denote an optionally at least mono-substituted, saturated or at least mono-unsaturated aliphatic C3-7 residue, with the proviso that the residue R2 in this case denotes an optionally at least mono-substituted aryl residue, an optionally at least mono-substituted, saturated, branched or unbranched aliphatic C1-10 residue or an optionally at least mono-substituted, at least partially unsaturated, branched or unbranched aliphatic C2-10 residue in the form of the racemates, diastereomers or enantiomers thereof in the form of the base thereof or of a corresponding physiologically acceptable salt, wherein the compounds of the general formula I, in which R1 denotes a 2-, 4-, 6-trichlorophenyl residue, R2 a methyl residue, R3 a phenyl residue and R4 denotes H, are excepted.
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Abstract
The invention relates to substituted γ-lactone compounds, to methods for the production thereof, to medicaments containing these compounds and to the use of these compounds for producing medicaments.
13 Citations
44 Claims
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1. Substituted γ
- -lactone compounds of the general formula I,
in which R1 denotes an optionally at least mono-substituted aryl or heteroaryl residue, an optionally at least mono-substituted aryl or heteroaryl residue attached via a C1-6 alkylene group, an optionally at least mono-substituted, saturated, branched or unbranched aliphatic C1-10 residue, an optionally at least mono-substituted, at least partially unsaturated, branched or unbranched aliphatic C2-10 residue or an optionally at least mono-substituted, saturated or at least mono-unsaturated cycloaliphatic C3-9 residue, R2 denotes an optionally at least mono-substituted, saturated, branched or unbranched aliphatic C1-10 residue or an optionally at least mono-substituted, at least partially unsaturated, branched or unbranched aliphatic C2-10 residue, R3 denotes an optionally at least mono-substituted aryl residue, R4 denotes H, or R3 and R4 together denote an optionally at least mono-substituted, saturated or at least mono-unsaturated aliphatic C3-7 residue, with the proviso that the residue R2 in this case denotes an optionally at least mono-substituted aryl residue, an optionally at least mono-substituted, saturated, branched or unbranched aliphatic C1-10 residue or an optionally at least mono-substituted, at least partially unsaturated, branched or unbranched aliphatic C2-10 residue in the form of the racemates, diastereomers or enantiomers thereof in the form of the base thereof or of a corresponding physiologically acceptable salt, wherein the compounds of the general formula I, in which R1 denotes a 2-, 4-, 6-trichlorophenyl residue, R2 a methyl residue, R3 a phenyl residue and R4 denotes H, are excepted. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44)
characterised in that at least one amine component of the general formula II, in which the residue R1 has the meaning according to claims 1 to 5, is reacted with glyoxalic acid and at least one alkene component of the general formula III, in which the residues R2 to R4 have the meaning according to claims 1 to 5, in the presence of at least one inorganic and/or organic acid in an organic solvent to yield at least one compound of the general formula I according to claims 1 to 5 and this is optionally purified using conventional methods and/or optionally isolated using conventional methods.
- -lactone compounds of the general formula I,
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7. A process according to claim 6, characterised in that the glyoxalic acid is used in the form of the monohydrate thereof or in form of an aqueous solution.
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8. A process according to claim 6, characterised in that trifluoroacetic acid is used as the organic acid.
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9. A process according to one of claim 6, characterised in that the temperature during the reaction is 0 to 100°
- C., preferably 15 to 40°
C.
- C., preferably 15 to 40°
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10. A process according to one of claim 6, characterised in that the duration of the reaction is 0.25 to 12 hours.
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11. A process for the production of substituted γ
- -lactone compounds according to claim 1, characterised in that at least one amine component of the general formula II,
in which the residue R1 has the meaning according to claim 1 is reacted with glyoxalic acid and at least one alkene component of the general formula III, in which the residues R2 to R4 have the meaning according to claim 1 in an organic solvent, optionally in the presence at least one inorganic and/or organic acid with microwave irradiation or with exposure to ultrasound, preferably with microwave irradiation, to yield at least one compound of the general formula I according to claim 1 and this is optionally purified using conventional methods and/or optionally isolated using conventinal methods.
- -lactone compounds according to claim 1, characterised in that at least one amine component of the general formula II,
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12. A process according to claim 11, characterised in that the temperature during the reaction is 40 to 70°
- C., preferably 45 to 60°
C.
- C., preferably 45 to 60°
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13. A pharmaceutical preparation containing at least one substituted γ
- -lactone compound according to claim 1 and optionally physiologically acceptable auxiliary substances.
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14. A pharmaceutical preparation according to claim 13 for combatting pain.
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15. A pharmaceutical preparation according to claim 14 for combatting chronic pain.
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16. A pharmaceutical preparation according to claim 14 for combatting neuropathic pain.
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17. A pharmaceutical preparation according to claim 13 for the treatment of neurodegenerative diseases, preferably of Alzheimer'"'"'s disease, Parkinson'"'"'s disease or Huntington'"'"'s chorea.
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18. A pharmaceutical preparation according to claim 13 for the treatment of stroke.
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19. A pharmaceutical preparation according to claim 13 for the treatment of cerebral ischaemia.
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20. A pharmaceutical preparation according to claim 13 for the treatment of cerebral infarct.
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21. A pharmaceutical preparation according to claim 13 for the treatment of cerebral oedema.
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22. A pharmaceutical preparation according to claim 13 for anxiolysis.
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23. A pharmaceutical preparation according to claim 13 for anaesthesia.
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24. A pharmaceutical preparation according to claim 13 for the treatment of schizophrenia.
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25. A pharmaceutical preparation according to claim 13 for the treatment of psychoses brought about by elevated amino acid levels.
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26. A pharmaceutical preparation according to claim 13 for the treatment of AIDS dementia.
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27. A pharmaceutical preparation according to claim 13 for the treatment of Tourette'"'"'s syndrome.
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28. A pharmaceutical preparation according to claim 13 for the treatment of inflammatory and/or allergic reactions.
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29. A pharmaceutical preparation according to claim 13 for the treatment of depression.
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30. A pharmaceutical preparation according to claim 13 for the treatment of mental health conditions.
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31. A pharmaceutical preparation according to claim 13 for the treatment of epilepsy.
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32. A pharmaceutical preparation according to claim 13 for the treatment of urinary incontinence.
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33. A pharmaceutical preparation according to claim 13 for the treatment of pruritus.
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34. A pharmaceutical preparation according to claim 13 for the treatment of tinnitus.
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35. A pharmaceutical preparation according to claim 13 for the treatment of diarrhoea.
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36. A method of treating pain comprising administering to a patient a pharmaceutically effective amount of a pharmaceutical composition comprising at least one substituted γ
- -lactone compound according to one of claim 1.
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37. A method according to claim 36, wherein the pain is chronic pain.
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38. A method according to claim 36, wherein the pain is neuropathic pain.
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39. A method of treating a neurodegenerative disease comprising administering to a patient a pharmaceutically effective amount of a pharmaceutical composition comprising at least one substituted γ
- -lactone compound according to claim 1.
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40. A method according to claim 39, wherein the neurodegenerative disease is Alzheimer'"'"'s disease.
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41. A method according to claim 39, wherein the neurodegenerative disease is Parkinson'"'"'s disease.
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42. A method according to claim 39, wherein the neurodegenerative disease is Huntington'"'"'s chorea.
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43. A method of treating migraine, stroke, cerebral ischaemia, cerebral infarct, cerebral oedema, schizophrenia, psychoses brought about by elevated amino acid levels, AIDS dementia, Tourette'"'"'s syndrome, inflammatory and/or allergic reactions;
- depression, mental health conditions, epilepsy, urinary incontinence, pruritus, tinnitus, diarrhea or anxiety comprising administering to a patient a pharmaceutically effective amount of a pharmaceutical composition comprising at least one substituted γ
-lactone compound according to claim 1.
- depression, mental health conditions, epilepsy, urinary incontinence, pruritus, tinnitus, diarrhea or anxiety comprising administering to a patient a pharmaceutically effective amount of a pharmaceutical composition comprising at least one substituted γ
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44. A method of anesthetizing comprising administering to a patient a pharmaceutically effective amount of a pharmaceutical composition comprising at least one substituted γ
- -lactone compound according to claim 1.
Specification