Claims
- 1. A method of antagonizing the biological effects of an excitatory amino acid of a subject in need of such antagonization comprising the step of administering to said subject an effective excitatory amino acid antagonizing amount of an indole-2,3-dione-3-oxime compound having the formula ##STR12## wherein R.sup.1 is hydrogen, C.sub.1-6 -alkyl which may be branched, C.sub.3-7 -cycloalkyl, benzyl, and phenyl carboxylic acid acyl, hydroxy, C.sub.1-6 -alkoxy, CH.sub.2 CO.sub.2 R' wherein R' is hydrogen or C.sub.1-6 -alkyl which may be branched, CH.sub.2 CN, CH.sub.2 CONR.sup.IV R.sup.V wherein R.sup.IV and R.sup.V independently are hydrogen or C.sub.1-6 -alkyl, or CH.sub.2 C(.dbd.NOH)NH.sub.2 ;
- R.sup.2 is hydrogen, benzyl, C.sub.1-6 -alkyl which may be branched, or C.sub.3-7 -cycloalkyl;
- R.sup.4, R.sup.5, R.sup.6, R.sup.7 independently are hydrogen, C.sub.1-6 -alkyl which may be branched, phenyl, halogen, C.sub.1-6 -alkoxy, NO.sub.2, CN, CF.sub.3, OCF.sub.3, or SO.sub.2 NR"R'" wherein R" and R'" independently are hydrogen, aralkoxy, aralkyl, or C.sub.1-6 -alkyl; or R.sup.6 and R.sup.7 together form an additional 4 to 7 membered ring which may be aromatic or partially saturated and which may be substituted with halogen, NO.sub.2, CF.sub.3, CN, OCF.sub.3, or SO.sub.2 NR"R'" wherein R" and R'" independently are hydrogen, aralkoxy, aralkyl, or C.sub.1-6 -alkyl, and R.sup.4 and R.sup.5 have the meanings set forth above.
- 2. A method according to claim 1 wherein at least one of R.sup.4, R.sup.5, R.sup.6 or R.sup.7 is NO.sub.2, CF.sub.3, CN, SO.sub.2 NR"R'", or halogen and R.sup.1, R.sup.2, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R", and R'" otherwise have the meanings set forth in claim 1.
- 3. A method according to claim 1 wherein R.sup.5 is NO.sub.2, F, CF.sub.3, OCF.sub.3, or CN.
- 4. A method of antagonizing the biological effects of an excitatory amino acid according to claim 1, wherein the compound is administered in the form of a pharmaceutical composition thereof, in which it is present together with a pharmaceutically acceptable carrier or diluent.
- 5. A method of antagonizing the biological effects of an excitatory amino acid according claim 2, wherein the compound is administered in the form of a pharmaceutical composition thereof, in which it is present together with a pharmaceutically acceptable carrier or diluent.
- 6. A pharmaceutical composition for use in antagonizing the biological effects of an excitatory amino acid of a subject in need of such antagonization comprising an effective excitatory amino acid antagonizing amount of a compound having the formula ##STR13## wherein R.sup.1 is hydrogen; R.sup.2 is hydrogen, benzyl, C.sub.1-6 -alkyl which may be branched, or C.sub.3-7 -cycloalkyl; R.sup.4, R.sup.5, R.sup.6, R.sup.7 independently are hydrogen, C.sub.1-6 -alkyl which may be branched, phenyl, halogen, C.sub.1-6 -alkoxy, NO.sub.2, CF.sub.3, OCF.sub.3, CN, or SO.sub.2 NR"R'" wherein R" and R'" independently are hydrogen, aralkoxy, aralkyl, or C.sub.1-6 -alkyl, or R.sup.6 and R.sup.7 together form an additional 4 to 7 membered ring which may be aromatic or partially saturated and which may be substituted with halogen, NO.sub.2, CF.sub.3, CN, OCF.sub.3, or SO.sub.2 NR"R'" wherein R" and R'" independently are hydrogen, aralkoxy, aralkyl, or C.sub.1-6 -alkyl, and R.sup.4 and R.sup.5 have the meanings set forth above, at least one of R.sup.4, R.sup.6 and R.sup.7 are other than hydrogen when R.sup.5 is not other than H, Cl or Br;
- or R.sup.1 is C.sub.1-6 -alkyl which may be branched, C.sub.3-7 -cycloalkyl, benzyl, phenyl, carboxylic acid acyl, hydroxy, C.sub.1-6 -alkoxy, CH.sub.2 CO.sub.2 R' wherein R' is hydrogen or C.sub.1-6 -alkyl which may be branched, CH.sub.2 CN, CH.sub.2 CONR.sup.IV R.sup.V wherein R.sup.IV and R.sup.V independently are hydrogen or C.sub.1-6 -alkyl, CH.sub.2 C(.dbd.NOH)NH.sub.2 ; R.sub.2 is hydrogen, benzyl, C.sub.1-6 -alkyl which may be branched, or C.sub.3-7 -cycloalkyl;
- R.sup.4, R.sup.5, R.sup.6, R.sup.7 independently are hydrogen, C.sub.1-6 -alkyl which may be branched, phenyl, halogen, C.sub.1-6 -alkoxy, NO.sub.2, CF.sub.3, OCF.sub.3, CN, or SO.sub.2 NR"R'" wherein R" and R'" independently are hydrogen, aralkoxy, aralkyl, or C.sub.1-6 -alkyl, or R.sup.6 and R.sup.7 together form an additional 4 to 7 membered ring which may be aromatic or partially saturated and which may be substituted with halogen, NO.sub.2, CF.sub.3, CN, OCF.sub.3, or SO.sub.2 NR"R'" wherein R" and R'" independently are hydrogen, aralkoxy, aralkyl, or C.sub.1-6 -alkyl, and R.sup.4 and R.sup.5 have the meanings set forth above, at least one of R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are other than hydrogen when R.sup.1 is methyl, at least one of R.sup.4 and R.sup.5 are other than hydrogen when R.sup.1 is phenyl, and at least one of R.sup.4 and R.sup.5 are other than hydrogen when R.sup.6 and R.sup.7 together form an additional benzene ring.
- 7. A method of antagonizing the biological effects of an excitatory amino acid of a subject in need thereof comprising the step of administering to said subject a pharmaceutical composition according to claim 6.
- 8. A compound having the formula ##STR14## wherein R.sup.1 is C.sub.1-6 -alkyl which may be branched, C.sub.3-7 -cycloalkyl, carboxylic acid acyl, hydroxy, C.sub.1-6 -alkoxy, CH.sub.2 CO.sub.2 R' wherein R' is hydrogen or C.sub.1-6 -alkyl which may be branched, CH.sub.2 CN, CH.sub.2 CONR.sup.IV R.sup.V wherein R.sup.IV and R.sup.V independently are hydrogen or C.sub.1-6 -alkyl, or CH.sub.2 C(.dbd.NOH)NH.sub.2 ;
- R.sup.2 is hydrogen, benzyl, C.sub.1-6 -alkyl which may be branched, or C.sub.3-7 -cycloalkyl;
- R.sup.5 is NO.sub.2, F, CN, OCF.sub.3, CF.sub.3, or SO.sub.2 NR"R'" wherein R" and R'" independently are hydrogen, aralkoxy, aralkyl or C.sub.1-6 -alkyl; and
- R.sup.4, R.sup.6, R.sup.7 independently are hydrogen, C.sub.1-6 -alkyl which may be branched, phenyl, halogen, C.sub.1-6 -alkoxy, NO.sub.2, OCF.sub.3, CF.sub.3, CN, or SO.sub.2 NR"R'" wherein R" and R'" independently are hydrogen, aralkoxy, aralkyl or C.sub.1-6 -alkyl, or R.sup.6 and R.sup.7 together form an additional 4 to 7 membered ring which may be aromatic or partially saturated and which may be substituted with halogen, NO.sub.2, CF.sub.3, CN, OCF.sub.3, or SO.sub.2 NR"R'" wherein R" and R'" independently are hydrogen, aralkoxy, aralkyl, or C.sub.1-6 -alkyl, and R.sup.4 has the meaning set forth above.
- 9. A compound having the formula ##STR15## wherein R.sup.1 is hydrogen,
- R.sup.2 is hydrogen, benzyl, C.sub.1-6 -alkyl which may be branched, or C.sub.3-7 -cycloalkyl;
- R.sup.5 is NO.sub.2, F, CF.sub.3, CN, OCF.sub.3, or SO.sub.2 NR"R'" wherein R" and R'" independently are hydrogen, aralkoxy, aralkyl or C.sub.1-6 -alkyl; and
- R.sup.4, R.sup.6, R.sup.7 independently are hydrogen, C.sub.1-6 -alkyl which may be branched, phenyl, halogen, C.sub.1-6 -alkoxy, NO.sub.2, CF.sub.3, OCF.sub.3, CN, or SO.sub.2 NR"R'" wherein R" and R'" independently are hydrogen, aralkoxy, aralkyl or C.sub.1-6 -alkyl, or R.sup.6 and R.sup.7 together form an additional 4 to 7 membered ring which may be aromatic or partially saturated and which may be substituted with halogen, NO.sub.2, CF.sub.3, CN, OCF.sub.3, or SO.sub.2 NR"R'" wherein R" and R'" independently are hydrogen, aralkyl, aralkoxy or C.sub.1-6 -alkyl, and R.sup.4 has the meaning set forth above; and that R.sup.5 is different from NO.sub.2 and F when R.sup.1, R.sup.4, R.sup.6 and R.sup.7 are not other than hydrogen and R.sup.2 is hydrogen or benzyl; and that R.sup.5 is different from NO.sub.2 when R.sup.1, R.sup.2, R.sup.4 and R.sup.6 are other than hydrogen and R.sup.7 is NO.sub.2.
- 10. A compound according to claim 8 or 9 wherein R.sup.4 and R.sup.5 independently are hydrogen, F, NO.sub.2, CN, CF.sub.3, OCF.sub.3, or SO.sub.2 NR"R'" wherein R" and R'" independently are hydrogen, aralkoxy, aralkyl or C.sub.1-6 -alkyl, and wherein R.sup.6 and R.sup.7 together form an additional 4 to 7 membered ring which may be aromatic or partially saturated and which may be substituted with halogen, NO.sub.2, CF.sub.3, OCF.sub.3, CN, or SO.sub.2 NR"R'" wherein R" and R'" independently are hydrogen, aralkoxy, aralkyl or C.sub.1-6 -alkyl.
- 11. A compound according to claim 10 wherein the additional ring formed by R.sup.6 and R.sup.7 is substituted with halogen, NO.sub.2, CF.sub.3, CN or SO.sub.2 NR"R'" wherein R" and R'" independently are hydrogen, aralkoxy, aralkyl or C.sub.1-6 -alkyl.
- 12. A compound of claim 9, which is 6-(N-methylsulphamoyl)-5-nitro-1H-benz[g]indole-2,3-dione-3-oxime.
- 13. A compound of claim 8, which is 5,7-dinitro-1-methyl-1H-indole-2,3-dione-3-(O-methyloxime).
- 14. A compound of claim 9, which is 5-(N-benzyloxysulphamoyl)-1H-6,7,8,9-tetrahydro-benz[g]indole-2,3-dione-3-oxime.
- 15. A method of treating a central nervous system disorder in a subject in need of such treatment, comprising the step of administering to said subject an effective amount of a compound having the formula ##STR16## wherein R.sup.1 is hydrogen, C.sub.1-6 -alkyl which may be branched, C.sub.1-6 -cycloalkyl, benzyl, phenyl carboxylic acid acyl, hydroxy, C.sub.1-6 -alkoxy, CH.sub.2 CO.sub.2 R' wherein R' is hydrogen or C.sub.1-6 -alkyl which may be branched, CH.sub.2 CN, CH.sub.2 CONR.sup.IV R.sup.V wherein R.sup.IV and R.sup.V independently are hydrogen or C.sub.1-6 -alkyl, or
- CH.sub.2 C(.dbd.NOH)NH.sub.2 ; R.sup.2 is hydrogen, benzyl, C.sub.1-6 -alkyl which may be branched, or C.sub.3-7 -cycloalkyl; R.sup.5 is NO.sub.2, F, CF.sub.3, OCF.sub.3, CN, or SO.sub.2 NR"R'" wherein R" and R'" independently are hydrogen, aralkyl, aralkoxy or C.sub.1-6 -alkyl; and R.sup.4, R.sup.6, R.sup.7 independently are hydrogen, C.sub.1-6 -alkyl which may be branched, phenyl, halogen, C.sub.1-6 -alkoxy, NO.sub.2, CN, CF.sub.3, OCF.sub.3, or SO.sub.2 NR"R'" wherein R" and R'" independently are hydrogen, aralkoxy, aralkyl or C.sub.1-6 -alkyl, or R.sup.6 and R.sup.7 together form an additional 4 to 7 membered ring which may be aromatic or partially saturated and which may be substituted with halogen, NO.sub.2, CF.sub.3, CN, OCF.sub.3, or SO.sub.2 NR"R'" wherein R" and R'" independently are hydrogen, aralkoxy, aralkyl or C.sub.1-6 -alkyl, and R.sup.4 has the meaning set forth above; and that R.sup.5 is different from NO.sub.2 and F when R.sup.1, R.sup.4, R.sup.6 and R.sup.7 are hydrogen and R.sup.2 is hydrogen or benzyl; and that R.sup.5 is different from NO.sub.2 when R.sup.1, R.sup.2, R.sup.4 and R.sup.6 are hydrogen and R.sup.7 is NO.sub.2.
- 16. The method of claim 15 wherein at least one of R.sup.4, R.sup.5, R.sup.6 or R.sup.7 is NO.sub.2, CF.sub.3, CN, OCF.sub.3, SO.sub.2 NR"R'", or halogen.
Priority Claims (6)
Number |
Date |
Country |
Kind |
6248/89 |
Dec 1989 |
DKX |
|
6470/89 |
Dec 1989 |
DKX |
|
0085/90 |
Jan 1990 |
DKX |
|
0086/90 |
Jan 1990 |
DKX |
|
0363/90 |
Feb 1990 |
DKX |
|
2093/90 |
Aug 1990 |
DKX |
|
Parent Case Info
The present application is a continuation-in-part of our prior filed co-pending application Ser. No. 07/624,409, filed Dec. 7, 1990 now abandoned.
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
3897434 |
Katner |
Jul 1975 |
|
4780477 |
Kobayashi et al. |
Oct 1988 |
|
Foreign Referenced Citations (1)
Number |
Date |
Country |
8903818 |
May 1989 |
WOX |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
624409 |
Dec 1990 |
|