Claims
- 1. A compound of Formula I:
- 2. The compound of claim 1 of Formula I wherein one of four substituents of R1, R2, R3 and R4 must be C1-C3-alkylthio group or C1-C3-alkoxy group, the other substituents are independently H, R13O—, R13 S—, halogen (F, Cl, Br), or C1-C3-alkyl;
R2 and R3 taken together can be —SCH2S—, —SCH2O—, or —OCH2S—; R9 is
R15R6NCO—, R15R16NCS—, R15R16N(CR17)—, R17OCO—, R5CO—, or H; R10 and R11 are independently H, H2N—, or CH3CONH—; and pharmaceutically acceptable salts thereof.
- 3. The compound of claim 2 further comprising a pharmaceutically acceptable carrier.
- 4. The compound of claim 3 in a dosage form comprising a therapeutically effective amount of the compound for treating a disorder in a patient associated with excessive activation of the α-amino-3-hydroxy-5-methyl-4-isooxazoleproprionic acid (AMPA) subtype of the ionotropic excitatory amino acid (EAA) receptors.
- 5. The compound of claim 2 of Formula I selected from the group consisting of
1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-acetyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-acetyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-methylcarbamoyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-ethylcarbamoyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-propylcarbamoyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-butylcarbamoyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-3,5-dihydro-4-methyl-3-acetyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-3,5-dihydro-4-methyl-3-methylcarbamoyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-3,5-dihydro-4-methyl-3-ethylcarbamoyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-3,5-dihydro-4-methyl-3-propylcarbamoyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-3,5-dihydro-4-methyl-3-butylcarbamoyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-acetyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-methylcarbamoyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-ethylcarbamoyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-propylcarbamoyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-butylcarbamoyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-7-amino-3,5-dihydro-4-methyl-3-acetyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-7-amino-3,5-dihydro-4-methyl-3-methylcarbamoyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-7-amino-3,5-dihydro-4-methyl-3-ethylcarbamoyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-7-amino-3,5-dihydro-4-methyl-3-propylcarbamoyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-7-amino-3,5-dihydro-4-methyl-3-butylcarbamoyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-acetyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-methylcarbamoyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-ethylcarbamoyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-propylcarbamoyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-butylcarbamoyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-3,5-dihydro-4-methyl-3-acetyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-3,5-dihydro-4-methyl-3-methylcarbamoyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-3,5-dihydro-4-methyl-3-ethylcarbamoyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-3,5-dihydro-4-methyl-3-propylcarbamoyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-3,5-dihydro-4-methyl-3-butylcarbamoyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-acetyl-8-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-methylcarbamoyl-8-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-ethylcarbamoyl-8-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-propylcarbamoyl-8-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-butylcarbamoyl-8-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-7-amino-3,5-dihydro-4-methyl-3-acetyl-8-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-7-amino-3,5-dihydro-4-methyl-3-methylcarbamoyl-8-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-7-amino-3,5-dihydro-4-methyl-3-ethylcarbamoyl-8-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-7-amino-3,5-dihydro-4-methyl-3-propylcarbamoyl-8-methylthio-5H-2,3-benzodiazepine, and 1-(4-Aminophenyl)-7-amino-3,5-dihydro-4-methyl-3-butylcarbamoyl-8-methylthio-5H-2,3-benzodiazepine.
- 6. The compound of claim 5 further comprising a pharmaceutically acceptable carrier.
- 7. The compound of claim 6 in a dosage form comprising a therapeutically effective amount of the compound for treating a disorder in a patient associated with excessive activation of the α-amino-3-hydroxy-5-methyl-4-isooxazoleproprionic acid (AMPA) subtype of the ionotropic excitatory amino acid (EAA) receptors.
- 8. The compound of claim 1 further comprising a pharmaceutically acceptable carrier.
- 9. The compound of claim 8 in a dosage form comprising a therapeutically effective amount of the compound for treating a disorder in a patient associated with excessive activation of the α-amino-3-hydroxy-5-methyl-4-isooxazoleproprionic acid (AMPA) subtype of the ionotropic excitatory amino acid (EAA) receptors.
- 10. A method for treating a patient having a disorder associated with excessive activation of the α-amino-3-hydroxy-5-methyl-4-isooxazoleproprionic acid (AMPA) subtype of the ionotropic excitatory amino acid (EAA) receptors, the method comprising administering to the patient, in an effective amount to alleviate the symptoms of the disorder, a compound of Formula I:
- 11. The method of claim 10 wherein, in the compound of Formula I, one of four substituents of R1, R2, R3 and R4 must be C1-C3-alkylthio group or C1-C3-alkoxy group, the other substituents are independently H, R13O—, R13S—, halogen (F, Cl, Br), or C1-C3-alkyl;
R2 and R3 taken together can be —SCH2S—, —SCH2O—, or —OCH2S—; R9 is
R15R16NCO—, R15R16NCS—, R15 R16N(CR17)—, R17OCO—, R15CO—, or H; R10 and R11 are independently H, H2N—, or CH3CONH—; and pharmaceutically acceptable salts thereof.
- 12. The method of claim 11 wherein the disorder is selected from the group consisting of neurological, neuropsychological, neuropsychiatric, neurodegenerative, neuropsychopharmacological and functional disorders.
- 13. The method of claim 11 wherein the compound of Formula I is selected from the group consisting of
1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-acetyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-acetyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-methylcarbamoyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-ethylcarbamoyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-propylcarbamoyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-butylcarbamoyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-3,5-dihydro-4-methyl-3-acetyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-3,5-dihydro-4-methyl-3-methylcarbamoyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-3,5-dihydro-4-methyl-3-ethylcarbamoyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-3,5-dihydro-4-methyl-3-propylcarbamoyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-3,5-dihydro-4-methyl-3-butylcarbamoyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-acetyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-methylcarbamoyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-ethylcarbamoyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-propylcarbamoyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-butylcarbamoyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-7-amino-3,5-dihydro-4-methyl-3-acetyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-7-amino-3,5-dihydro-4-methyl-3-methylcarbamoyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-7-amino-3,5-dihydro-4-methyl-3-ethylcarbamoyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-7-amino-3,5-dihydro-4-methyl-3-propylcarbamoyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-7-amino-3,5-dihydro-4-methyl-3-butylcarbamoyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-acetyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-methylcarbamoyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-ethylcarbamoyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-propylcarbamoyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-butylcarbamoyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-3,5-dihydro-4-methyl-3-acetyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-3,5-dihydro-4-methyl-3-methylcarbamoyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-3,5-dihydro-4-methyl-3-ethylcarbamoyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-3,5-dihydro-4-methyl-3-propylcarbamoyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-3,5-dihydro-4-methyl-3-butylcarbamoyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-acetyl-8-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-methylcarbamoyl-8-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-ethylcarbamoyl-8-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-propylcarbamoyl-8-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-3,5-dihydro-4-methyl-3-butylcarbamoyl-8-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-7-amino-3,5-dihydro-4-methyl-3-acetyl-8-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-7-amino-3,5-dihydro-4-methyl-3-methylcarbamoyl-8-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-7-amino-3,5-dihydro-4-methyl-3-ethylcarbamoyl-8-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-7-amino-3,5-dihydro-4-methyl-3-propylcarbamoyl-8-methylthio-5H-2,3-benzodiazepine, and 1-(4-Aminophenyl)-7-amino-3,5-dihydro-4-methyl-3-butylcarbamoyl-8-methylthio-5H-2,3-benzodiazepine.
- 14. The method of claim 13 wherein the disorder is selected from the group consisting of neurological, neuropsychological, neuropsychiatric, neurodegenerative, neuropsychopharmacological and functional disorders.
- 15. The method of claim 10 wherein the disorder is selected from the group consisting of neurological, neuropsychological, neuropsychiatric, neurodegenerative, neuropsychopharmacological and functional disorders.
- 16. A compound of Formula II:
- 17. The compound of claim 16 of Formula II wherein one of four substitutents of R1, R2, R3 and R4 must be C1-C3-alkylthio or C1-C3-alkoxy group, the other substituents are independently H, R13O—, R13S—, halogen (F, Cl, Br), or C1-C3-alkyl;
R2 and R3 taken together can be —SCH2S—, —SCH2O—, or —OCH2S—; R20 and R21 are independently H, H2N—, or CH3CONH—; and pharmaceutically acceptable salts thereof.
- 18. The compound of claim 17 further comprising a pharmaceutically acceptable carrier.
- 19. The compound of claim 18 in a dosage form comprising a therapeutically effective amount of the compound for treating a disorder in a patient associated with excessive activation of the α-amino-3-hydroxy-5-methyl-4-isooxazoleproprionic acid (AMPA) subtype of the ionotropic excitatory amino acid (EAA) receptors.
- 20. The compound of claim 17 of Formula II selected from the group consisting of
1-(4-Aminophenyl)-4-methyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-4-methyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-4-methyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-7-amino-4-methyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-4-methyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-4-methyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-4-methyl-8-methylthio-5H-2,3-benzodiazepine, and 1-(4-Aminophenyl)-7-amino-4-methyl-8-methylthio-5H-2,3-benzodiazepine.
- 21. The compound of claim 20 further comprising a pharmaceutically acceptable carrier.
- 22. The compound of claim 21 in a dosage form comprising a therapeutically effective amount of the compound for treating a disorder in a patient associated with excessive activation of the α-amino-3-hydroxy-5-methyl-4-isooxazoleproprionic acid (AMPA) subtype of the ionotropic excitatory amino acid (EAA) receptors.
- 23. The compound of claim 16 further comprising a pharmaceutically acceptable carrier.
- 24. The compound of claim 23 in a dosage form comprising a therapeutically effective amount of the compound for treating a disorder in a patient associated with excessive activation of the α-amino-3-hydroxy-5-methyl-4-isooxazoleproprionic acid (AMPA) subtype of the ionotropic excitatory amino acid (EAA) receptors.
- 25. A method for treating a patient having a disorder associated with excessive activation of the α-amino-3-hydroxy-5-methyl-4-isooxazoleproprionic acid (AMPA) subtype of the ionotropic excitatory amino acid (EAA) receptors, the method comprising administering to the patient, in an effective amount to alleviate the symptoms of the disorder, a compound of Formula II:
- 26. The method of claim 25 wherein, in the compound of Formula II, one of four substitutents of R1, R2, R3 and R4 must be C1-C3-alkylthio or C1-C3-alkoxy group, the other substituents are independently H, R13O—, R13S—, halogen (F, Cl, Br), or C1-C3-alkyl;
R2 and R3 taken together can be —SCH2S—, —SCH2O—, or —OCH2S—; R20 and R21 are independently H, H2N—, or CH3CONH—; and pharmaceutically acceptable salts thereof.
- 27. The method of claim 26 wherein the disorder is selected from the group consisting of neurological, neuropsychological, neuropsychiatric, neurodegenerative, neuropsychopharmacological and functional disorders.
- 28. The method of claim 26 wherein the compound of Formula II is selected from the group consisting of
1-(4-Aminophenyl)-4-methyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-4-methyl-7-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-4-methyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-7-amino-4-methyl-8-methoxy-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-4-methyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-8-amino-4-methyl-7-methylthio-5H-2,3-benzodiazepine, 1-(4-Aminophenyl)-4-methyl-8-methylthio-5H-2,3-benzodiazepine, and 1-(4-Aminophenyl)-7-amino-4-methyl-8-methylthio-5H-2,3-benzodiazepine.
- 29. The method of claim 28 wherein the disorder is selected from the group sting of neurological, neuropsychological, neuropsychiatric, neurodegenerative, psychopharmacological and functional disorders.
- 30. The method of claim 25 wherein the disorder is selected from the group sting of neurological, neuropsychological, neuropsychiatric, neurodegenerative, psychopharmacological and functional disorders.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] Priority is claimed to U.S. provisional application Serial No. 60/212,238, filed Jun. 16, 2000, the teachings f which are incorporated herein
Provisional Applications (1)
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Number |
Date |
Country |
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60212238 |
Jun 2000 |
US |