Alkyl substituted indoloquinoxalines
Novel substituted indoloquinoxalines of formula (I wherein R 1 is hydrogen or represents one or more similar or different substituents in the positions 7 to 10 selected from the group halogen, lower alkyl/alkoxy, hydroxy, trifluoromethyl, trichloromethyl, trifluoromethoxy, R 2 represents similar or different C 1 -C 4 alkyl substituents, X is CO or CH 2 , Y is OH, NH 2 , NH—(CH 2 ) n —R 3 wherein R 3 represents lower alkyl, OH, NH 2 , NHR 4 or NR 5 R 6 wherein R 4 , R 5 and R 6 independently are lower alkyl or cyclo-alkyl and n is an integer of from 2 to 4, with the provision that when X is CH 2 , Y is OH or NH—(CH 2 ) n —OH, and pharmacologically acceptable salts thereof are described. The compounds are useful as drugs for preventing and/or treating autoimmune diseases.
1. A method for the treatment of an autoimmune disease selected from rheumatoid arthritis and multiple sclerosis, comprising
administering to a patient in need thereof an autoimmune-effective amount of a compound of formula (I)
wherein
R 1 is hydrogen or represents one or more similar or different substituents in the positions 7 to 10 selected from the group halogen, lower alkyl/alkoxy, hydroxy, trifluoromethyl, trichloromethyl, trifluoromethoxy,
R 2 represents similar or different C 1 -C 4 alkyl substituents,
X is CO or CH 2 ,
Y is OH, NH 2 , NH—(CH 2 ) n —R 3 wherein R 3 represents lower alkyl, OH, NH 2 , NHR 4 or NR 5 R 6 wherein R 4 , R 5 and R 6 independently are lower alkyl or cyclo-alkyl and n is an integer of from 2 to 4,
with the provision that when X is CH 2 , Y is OH or NH—(CH 2 ) n —OH,
or a pharmacologically acceptable salt thereof.
2. A method according to claim 1 , wherein said patient is a patient suffering from rheumatoid arthritis.
3. A method according to claim 1 , wherein said patient is a patient suffering from multiple sclerosis.
4. A method according to claim 1 wherein, in said compound, X is CO and Y is OH or NH 2 and R 1 is a halogen atom.
5. A method according to claim 1 wherein, in said compound, X is CO and Y is NH—CH 2 —CH 2 —R 3 wherein R 3 is NH 2 or N(CH 3 ) 2 wherein R 1 is a chloro or fluoro atom.
6. A method according to claim 1 wherein, in said compound, X is CO and Y is NH—CH 2 —CH 2 —R 3 wherein R 3 is NH 2 or N(CH 3 ) 2 .
7. A method according to claim 1 wherein, in said compound, R 2 is methyl in positions 2 and 3.
8. The method of claim 1 wherein the compound is in the form of a composition further comprising one or more pharmaceutically acceptable solvents, carriers or adjuvants.
9. The method of claim 1 wherein the compound is 9-Chloro-2,3-dimethyl-6-(N,N-dimethylaminoethylamino-2-oxoethyl)-6H-indolo-[2,3-b]quinoxaline or a pharmaceutically acceptable salt thereof.
10. The method of claim 2 wherein, in said compound, X is CO and Y is OH or NH 2 and R 1 is a halogen atom.
11. The method of claim 2 wherein, in said compound, X is CO and Y is NH—CH 2 —CH 2 —R 3 wherein R 3 is NH 2 or N(CH 3 ) 2 wherein R 1 is a chloro or fluoro atom.
12. The method of claim 2 wherein, in said compound, X is CO and Y is NH—CH 2 —CH 2 —R 3 wherein R 3 is NH 2 or N(CH 3 ) 2 .
13. The method of claim 2 wherein, in said compound, R 2 is methyl in positions 2 and 3.
14. The method of claim 2 wherein the compound is in the form of a composition further comprising one or more pharmaceutically acceptable solvents, carriers or adjuvants.
15. The method of claim 2 wherein the compound is selected from the group consisting of 2,3-Dimethylindolo[2,3-b]quinoxaline-6-yl-acetamide; 9-Chloro-2,3-dimethyl-indolo[2,3-b]quinoxaline-6-yl-acetamide; 2,3-Dimethyl-9-fluoro-indolo[2,3-b]quinoxaline-6-yl-acetamide; 2,3-Dimethyl-6-(N,N-dimethylaminoethylamino-2-oxoethyl)-6H-indolo[2,3-b]q-uinoxaline; 9-Chloro-2,3-dimethyl-6-(N,N-dimethylaminoethylamino-2-oxoethyl)-6H-indol-o[2,3-b]quinoxaline; 9-Chloro-2,3-dimethyl-6-(aminoethylamino-2-oxoethyl)-6H-indolo[2,3-b]quinoxaline; 2,3-Dimethyl-6-(aminoethylamino-2-oxoethyl)-9-fluoro-6H-indolo[2,3-b]quinoxaline; 2,3-Dimethyl-6-(N,N-dimethylaminoethylamino-2-oxoethyl)-9-fluoro-6H-indolo[2,3-b]quinoxaline; 2,3-Dimethyl-9-chloro-indolo[2,3-b]quinoxaline-6-yl acetic acid; and 2,3-dimethyl-9-fluoro-indolo[2,3-b]quinoxaline-6-yl-acetic acid, or a pharmaceutically acceptable salt thereof.
16. The method of claim 2 wherein the compound is 9-Chloro-2,3-dimethyl-6-(N,N-dimethylaminoethylamino-2-oxoethyl)-6H-indol-o-[2,3-b]quinoxaline or a pharmaceutically acceptable salt thereof.
17. The method of claim 3 wherein, in said compound, X is CO and Y is OH or NH 2 and R 1 is a halogen atom.
18. The method of claim 3 wherein, in said compound, X is CO and Y is NH—CH 2 —CH 2 —R 3 wherein R 3 is NH 2 or N(CH 3 ) 2 wherein R 1 is a chloro or fluoro atom.
19. The method of claim 3 wherein, in said compound, X is CO and Y is NH—CH 2 —CH 2 —R 3 wherein R 3 is NH 2 or N(CH 3 ) 2 .
20. The method of claim 3 wherein, in said compound, R 2 is methyl in positions 2 and 3.
21. The method of claim 3 wherein the compound is selected from the group consisting of 2,3-Dimethylindolo[2,3-b]quinoxaline-6-yl-acetamide; 9-Chloro-2,3-dimethyl-indolo[2,3-b]quinoxaline-6-yl-acetamide; 2,3-Dimethyl-9-fluoro-indolo[2,3-b]quinoxaline-6-yl-acetamide; 2,3-Dimethyl-6-(N,N-dimethylaminoethylamino-2-oxoethyl)-6H-indolo[2,3-b]q-uinoxaline; 9-Chloro-2,3-dimethyl-6-(N,N-dimethylaminoethylamino-2-oxoethyl)-6H-indol-o[2,3-b]quinoxaline; 9-Chloro-2,3-dimethyl-6-(aminoethylamino-2-oxoethyl)-6H-indolo[2,3b]quinoxaline; 2,3-Dimethyl-6-(aminoethylamino-2-oxoethyl)-9-fluoro-6H-indolo[2,3-b]quinoxaline; 2,3-Dimethyl-6-(N,N-dimethylaminoethylamino-2-oxoethyl)-9-fluoro-6H-indolo[2,3-b]quinoxaline; 2,3-Dimethyl-9-chloro-indolo[2,3-b]quinoxaline-6-yl acetic acid; and 2,3-dimethyl-9-fluoro-indolo[2,3-b]quinoxaline-6-yl-acetic acid, or a pharmaceutically acceptable salt thereof.
22. The method of claim 3 wherein the compound is 9-Chloro-2,3-dimethyl-6-(N,N-dimethylaminoethylamino-2-oxoethyl)-6H-indol-o[2,3-b]quinoxaline or a pharmaceutically acceptable salt thereof.
23. The method of claim 3 wherein the compound is in the form of a composition further comprising one or more pharmaceutically acceptable solvents, carriers or adjuvants.
24. The method of claim 1 wherein the compound is selected from the group consisting of 2,3-Dimethylindolo[2,3-b]quinoxaline-6-yl-acetamide; 9-Chloro-2,3-dimethyl-indolo[2,3-b]quinoxaline-6-yl-acetamide; 2,3-Dimethyl-9-fluoro-indolo[2,3-b]quinoxaline-6-yl-acetamide; 2,3-Dimethyl-6-(N,N-dimethylaminoethylamino-2-oxoethyl)-6H-indolo[2,3-b]q-uinoxaline; 9-Chloro-2,3-dimethyl-6-(N,N-dimethylaminoethylamino-2-oxoethyl)-6H-indol-o[2,3-b]quinoxaline; 9-Chloro-2,3-dimethyl-6-(aminoethylamino-2-oxoethyl)-6H-indolo[2,3-b]quinoxaline; 2,3-Dimethyl-6-(aminoethylamino-2-oxoethyl)-9-fluoro-6H-indolo[2,3-b]quinoxaline; 2,3-Dimethyl-6-(N,N-dimethylaminoethylamino-2-oxoethyl)-9-fluoro-6H-indolo[2,3-b]quinoxaline; 2,3-Dimethyl-9-chloro-indolo[2,3-b]quinoxaline-6-yl acetic acid; and 2,3-dimethyl-9-fluoro-indolo[2,3-b]quinoxaline-6-yl-acetic acid, or a pharmaceutically acceptable salt thereof.