Claims
- 1. A compound of general formula 1 wherein:R1 and R2, which are identical or different, are each hydrogen or F; R3 is hydrogen or methyl; R4 is hydrogen R5 and R6 are each methyl; X is NH2, NH-(methyl), N(methyl)2, NH—COH, or NH—COMe; and A is —CH(Methyl)-O—CH2—, —(CH2)2—O—CH2—, or the racemates thereof, the enantiomers thereof, the diastereomers thereof, and mixtures thereof, and the pharmacologically acceptable acid addition salts thereof.
- 2. The compound of general formula 1 according to claim 1, wherein:R3 is methyl, the racemates thereof, the enantiomers thereof, the diastereomers thereof, and mixtures thereof, and the pharmacologically acceptable acid addition salts thereof.
- 3. The compound of general formula 1 according to claim 1, wherein:R3 is hydrogen; and A is —CH(methyl)-O—CH2—, the racemates thereof, the enantiomers thereof, the diastereomers thereof, and mixtures thereof, and the pharmacologically acceptable acid addition salts thereof.
- 4. A compound of general formula 1 wherein:R1 and R1, which are identical or different, are each hydrogen or F; R3 is hydrogen or methyl; R5 is hydrogen; R4 and R6 are each methyl; is NH2, NH-(methyl), N(methyl)2, NH—COH, or NH—COMe; and A is —CH(Methyl)-O—CH2—, —(CH2)2—O—CH2—, or the racemates thereof, the enantiomers thereof, the diastereomers thereof, and mixtures thereof, and the pharmacologically acceptable acid addition salts thereof.
- 5. The compound of general formula 1 according to claim 4, wherein:R3 is methyl; the racemates thereof, the enantiomers thereof, the diastereomers thereof, and mixtures thereof, and the pharmacologically acceptable acid addition salts thereof.
- 6. The compound of general formula 1 according to claim 4, wherein:R3 is hydrogen, the racemates thereof, the enantiomers thereof, the diastereomers thereof, and mixtures thereof, and the pharmacologically acceptable acid addition salts thereof.
- 7. The compound of general formula 1 according to claim 6, wherein:A is —CH(methyl)-O—CH2—, the racemates thereof, the enantiomers thereof, the diastereomers thereof, and mixtures thereof, and the pharmacologically acceptable acid addition salts thereof.
- 8. A pharmaceutical preparation comprising:(a) a compound of formula 1 according to one of claims 1-7; and (b) one or more conventional excipients or carriers.
- 9. A method of blocking the voltage-dependent sodium channel in a host by administering a compound of formula 1 according to one of claims 1-7 to a host.
- 10. A method of treating arrhythmias, spasms, cardiac and cerebral ischaemia, pain, and neurodegenerative diseases, the method comprising administering to a host a therapeutically acceptable amount of a compound of formula 1 according to one of claims 1-7.
- 11. A method of treating epilepsy, hypoglycaemia, hypoxia, anoxia, brain trauma, brain oedema, cerebral stroke, perinatal asphyxia, degeneration of the cerebellum, amyotrophic lateral sclerosis, Huntington's disease, Alzheimer's disease, Parkinson's disease, cyclophrenia, hypotonia, cardiac infarct, cardiac rhythm disorders, angina pectoris, chronic pain, neuropathic pain, or local anesthesia, the method comprising administering to a host a therapeutically acceptable amount of a compound of formula 1 according to one of claims 1-7.
- 12. A method for preparing a compound of general formula 1 wherein:R1 and R2, which may be identical or different, are each hydrogen, C1-C6-alkyl, C1-C6-alkyloxy, OH, F, Cl, or Br; R3 is hydrogen, F, Cl, Br, methyl, ethyl, OH, or methoxy; R4, R5, and R6, which may be identical or different, are each hydrogen, methyl, or ethyl; is NH2; A is —(CH2)3—, —CH2—CH2—O—, —CH2—O—CH2—, —(CH2)4—, —CH(C1-C6-alkyl)-O—CH2—, —(CH2)2—O—CH213 , —(CH2)3—O—, —(CH2)5—, —CH2—O—(CH2)313 , 13 (CH2)2—O—(CH2)2—, —(CH2)3—O—CH2—, —(CH2)4—O—, —CH2—O—CH2—CH2—O—, the racemates thereof, the enantiomers thereof, the diastereomers thereof, and mixtures thereof, and the pharmacologically acceptable acid addition salts thereof, the method comprising reacting a compound of general formula 3 wherein the groups R1, R2, R3, R4, R5, R6, and A have the meanings given above, with a source of nitrogen in an aromatic solvent with palladium catalysis.
- 13. A compound of general formula 3 wherein:R1 and R2, which may be identical or different, are each hydrogen, C1-C6-alkyl, C1-C6-alkyloxy, OH, F, Cl, or Br; R3 is hydrogen, F, Cl, Br, methyl, ethyl, OH, or methoxy; R4, R5, and R6, which may be identical or different, are each hydrogen, methyl, or ethyl; X is NH2, NH-(C1-C6-alkyl), N(C1-C6-alkyl)2, the two C1-C6-alkyl groups of which may be identical or different, NH—COH, NH—CO(C1-C6-alkyl), or F; A is —(CH2)3—, —CH2—CH2—O—, —CH2—O—CH2—, —(CH2)4—, —CH(C1-C6-alkyl)-O—CH2—, —(CH2)2—O—CH213 , —(CH2)3—O—, —(CH2)5—, —CH2—O—(CH2)3—, —(CH2)2—O—(CH2)2—, —(CH2)3—O—CH2—, —(CH2)4—O—, —CH2—O—CH2—CH2—O—, the racemates thereof, the enantiomers thereof, the diastereomers thereof, and mixtures thereof, and the pharmacologically acceptable acid addition salts thereof.
- 14. A method for preparing a compound of general formula 1 wherein:R1 and R2, which may be identical or different, are each hydrogen, C1-C6-alkyl, C1-C6-alkyloxy, OH, F, Cl, or Br; R3 is hydrogen, F, Cl, Br, methyl, ethyl, OH, or methoxy; R4, R5, and R6, which may be identical or different, are each hydrogen, methyl, or ethyl; X is NH-(C1-C6-alkyl), N(C1-C6-alkyl)2, the two C1-C6-alkyl groups of which may be identical or different, NH—COH, NH—CO(C1-C6-alkyl), or F; A is —(CH2)3—, —CH2—CH2—O—, —CH2—O—CH2—, —(CH2)4—, —CH(C1-C6-alkyl)-O—CH2—, —(CH2)2—O—CH213 , —(CH2)3—O—, —(CH2)5—, —CH2—O—(CH2)3—, —(CH2)2—O—(CH2)2—, —(CH2)3—O—CH2—, —(CH2)4—O—, —CH2—O—CH2—CH2—O—, the racemates thereof, the enantiomers thereof, the diastereomers thereof, and mixtures thereof, and the pharmacologically acceptable acid addition salts thereof, the method comprising: reacting a compound of formula 1, wherein the groups R1, R2, R3, R4, R5, R6, and A have the meanings given above and X is NH2: (a) with a base and an alkylating agent, in a polar organic solvent, to obtain the compound of general formula 1, wherein X is NH-(C1-C6-alkyl) or N(C1-C6-alkyl)2; or (b) with aldehydes or ketones, with cooling, in the presence of acids, to obtain a Schiff base or an iminium salt and subsequently reducing the Schiff base or the iminium salt obtained with metal hydrides to obtain the compound of general formula 1, wherein X is NH-(C1-C6-alkyl) or N(C1-C6-alkyl)2; or (c) with an acid chloride or anhydride, in the presence of a base, to obtain the compound of general formula 1, wherein X is NHCO(C1-C6-alkyl); or (d) with an acid chloride or anhydride, in the presence of a base, to obtain the compound of general formula 1, wherein X is NHCO(C1-C6-alkyl), and subsequently reducing the compound of general formula 1, wherein X is NHCO(C1-C6-alkyl), with a metal hydride, using a Lewis acids as a catalyst, to obtain the compound of general formula 1, wherein X is NH-(C1-C6-alkyl) or N(C1-C6-alkyl)2; or (e) with formic acid at elevated temperature to obtain the compound of general formula 1, wherein X is NHCOH; or (f) by diazotization and subsequent decoction with BF4− to obtain the compound of formula 1, wherein X is F.
Priority Claims (1)
| Number |
Date |
Country |
Kind |
| 199 57 156 |
Nov 1999 |
DE |
|
RELATED APPLICATION
This application claims the benefit of U.S. Provisional Application Ser. No. 60/169,864, filed Dec. 9, 1999.
US Referenced Citations (2)
| Number |
Name |
Date |
Kind |
|
5607941 |
Merz et al. |
Mar 1997 |
A |
|
5731318 |
Carter et al. |
Mar 1998 |
A |
Foreign Referenced Citations (4)
| Number |
Date |
Country |
| 2072814 |
Jan 1993 |
CA |
| 0521422 |
Jan 1993 |
EP |
| WO 9914199 |
Sep 1999 |
WO |
| WO 0050421 |
Aug 2000 |
WO |
Provisional Applications (1)
|
Number |
Date |
Country |
|
60/169864 |
Dec 1999 |
US |
Patent Grant
6355652
