Benzenesulfonanilide compounds suitable for treating disorders that respond to modulation of the serotonin 5-HT6 receptor
View Patent ↗The present invention relates to novel benzenesulfonanilide compounds of the formulae I and I′ and physiologically tolerated acid addition salts and the N-oxides thereof. The compounds possess valuable therapeutic properties and are particularly suitable, for treating diseases that respond to modulation of the serotonin 5-HT 6 receptor. wherein R 1 is hydrogen or methyl R 2 is hydrogen or methyl R 3 hydrogen, fluorine C 1 -C 2 alkoxy or fluorinated C 1 -C 2 alkoxy; R 4 is hydrogen, C 1 -C 4 alkyl or fluorinated C 1 -C 4 alkyl; R 5 is hydrogen, fluorine, C 1 -C 2 alkyl, fluorinated C 1 -C 2 alkyl, C 1 -C 2 alkoxy or fluorinated C 1 -C 2 alkoxy; and R 6 is hydrogen, fluorine or chlorine.
1. Benzenesulfonanilide compounds of formulae I and I′:
wherein
R 1 is hydrogen or methyl;
R 2 is hydrogen or methyl;
R 3 hydrogen, fluorine, C 1 -C 2 alkoxy or fluorinated C 1 -C 2 alkoxy;
R 4 is hydrogen or C 1 -C 4 alkyl or fluorinated C 1 -C 4 alkyl;
R 5 is hydrogen, fluorine, C 1 -C 2 alkyl, fluorinated C 1 -C 2 alkyl, C 1 -C 2 alkoxy or fluorinated C 1 -C 2 alkoxy; and
R 6 is hydrogen, fluorine or chlorine;
and physiologically tolerated acid addition salts and the N-oxides thereof.
2. The compounds as claimed in claim 1 , wherein R 1 is hydrogen.
3. The compounds as claimed in claim 1 , wherein R 2 is hydrogen.
4. The compounds as claimed in claims 1 or 2 , wherein R 2 is methyl.
5. The compounds as claimed in claim 4 , wherein the carbon atom that carries R 2 has S-configuration.
6. The compounds as claimed in claim 4 , wherein the carbon atom that carries R 2 has R-configuration.
7. The compounds as claimed in claim 1 , wherein R 3 is methoxy.
8. The compounds as claimed in claim 1 , wherein R 3 is hydrogen or fluorine.
9. The compounds as claimed in claim 1 , wherein R 4 is hydrogen or C 1 -C 2 alkyl.
10. The compounds as claimed in claim 9 , wherein R 4 is hydrogen.
11. The compounds as claimed in claim 1 , wherein R 5 is hydrogen.
12. The compounds as claimed in claim 1 , wherein R 5 is methoxy or difluoromethoxy.
13. The compounds as claimed in claim 1 , wherein R 6 is hydrogen.
14. The compounds as claimed in claim 1 , wherein R 5 and R 6 are hydrogen, R 3 is selected from the group consisting of C 1 -C 2 alkoxy and fluorinated C 1 -C 2 alkoxy and R 4 is selected from the group consisting of hydrogen or C 1 -C 2 alkyl.
15. The compounds as claimed in claim 1 , wherein one or more of the following provisos a), b), c) or d) are met:
a) R 5 is selected from the group consisting of fluorine, C 1 -C 2 alkyl fluorinated C 1 -C 2 alkyl, C 1 -C 2 alkoxy or fluorinated C 1 -C 2 alkoxy;
b) R 6 is fluorine or chlorine;
c) R 3 is hydrogen or fluorine; and/or
d) R 4 is C 3 -C 4 -alkyl or fluorinated C 1 -C 4 -alkyl;
16. The compounds as claimed in claim 15 , wherein R 6 is fluorine or chlorine, which is located in the 6-position of the benzene ring.
17. The compounds as claimed in claim 15 , wherein R 6 is fluorine or chlorine, which is located in the 5-position of the benzene ring.
18. The compounds as claimed in any of claims 15 , 16 or 17 , wherein R 3 is hydrogen.
19. The compounds as claimed in any of claims 15 , 16 or 17 , wherein R 5 is methoxy.
20. The compounds as claimed in claim 15 , wherein R 3 is hydrogen.
21. The compounds as claimed in claim 1 , wherein the OCHF 2 -radical in formula I is located on the benzene ring in the ortho-position with respect to the sulfonyl group.
22. The compounds as claimed in claim 1 , wherein the OCHF 2 -radical in formula I is located on the benzene ring in the meta-position with respect to the sulfonyl group.
23. The compounds as claimed in claim 1 , wherein the OCHF 2 -radical in formula I is located on the benzene ring in the para-position with respect to the sulfonyl group.
24. A pharmaceutical composition comprising at least one compound as claimed in claim 1 , optionally together with at least one physiologically acceptable carrier or auxiliary substance.
25. A method for treating a medical disorder selected from diseases of the central nervous system, addiction diseases or obesity, said method comprising administering an effective amount of at least one compound as claimed in any of claims 1 to 23 to a subject in need thereof.
26. The method as claimed in claim 25 , wherein the medical disorder is a disease of the central nervous system.
27. The method as claimed in claim 26 , for treating cognitive dysfunctions.
28. The method as claimed in claim 26 , for treating cognitive dysfunctions associated with Alzheimer's disease.
29. The method as claimed in claim 26 , for treating cognitive dysfunctions associated with schizophrenia.
30. The method as claimed in claim 25 , wherein the medical disorder is an addiction disease.
31. The method as claimed in claim 25 , wherein the medical disorder is obesity.