Benzenesulfonanilide compounds suitable for treating disorders that respond to modulation of the serotonin 5-HT
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 and is positioned vicinal to the radical R 1 ; R 3 hydrogen, C 1 -C 3 alkyl, halogen, C 1 -C 3 alkoxy, fluorinated C 1 -C 3 alkyl or fluorinated C 1 -C 3 alkoxy; R 4 is hydrogen, C 1 -C 4 alkyl, C 3 -C 4 cycloalkyl, C 3 -C 4 cycloalkylmethyl or fluorinated C 1 -C 4 alkyl; R 5 is hydrogen, fluorine, chlorine, C 1 -C 4 alkyl, fluorinated C 1 -C 4 alkyl, C 1 -C 4 alkoxy or fluorinated C 1 -C 4 alkoxy; and R 6 is hydrogen, fluorine or chlorine.
1. A benzenesulfonanilide compound of formulae I or I′
wherein
R 1 is hydrogen or methyl;
R 2 is hydrogen or methyl;
R 3 hydrogen, C 1 -C 3 alkyl, halogen, C 1 -C 3 alkoxy, fluorinated C 1 -C 3 alkyl or fluorinated C 1 -C 3 alkoxy;
R 4 is hydrogen, C 1 -C 4 alkyl, C 3 -C 4 cycloalkyl, C 3 -C 4 cycloalkylmethyl or fluorinated C 1 -C 4 alkyl;
R 5 is hydrogen, fluorine, chlorine, C 1 -C 4 alkyl, fluorinated C 1 -C 4 alkyl, C 1 -C 4 alkoxy or fluorinated C 1 -C 4 alkoxy; and
R 6 is hydrogen, fluorine or chlorine;
wherein R 2 is positioned vicinal to the radical R 1 ;
and physiologically tolerated acid addition salts and the N-oxides thereof.
2. The compound of claim 1 , wherein R 1 is hydrogen.
3. The compound of claim 1 , wherein R 1 is methyl.
4. The compound of claim 1 , wherein R 2 is hydrogen.
5. The compound of claim 1 , wherein R 2 is methyl.
6. The compound of claim 5 , wherein the carbon atom that carries R 2 has S-configuration.
7. The compound of claim 5 , wherein the carbon atom that carries R 2 has R-configuration.
8. The compound of claim 1 , wherein R 3 is hydrogen, halogen, C 1 -C 3 alkoxy, fluorinated C 1 -C 3 alkyl or fluorinated C 1 -C 3 alkoxy.
9. The compound of claim 1 , wherein R 3 is C 1 -C 3 alkyl.
10. The compound of claim 8 , wherein R 3 is methoxy.
11. The compound of claim 8 , wherein R 3 is hydrogen or fluorine.
12. The compound of claim 1 , wherein R 4 is hydrogen or C 1 -C 3 alkyl.
13. The compound of claim 1 , wherein R 5 is hydrogen.
14. The compound of claim 1 , wherein R 5 is methyl, methoxy or difluoromethoxy.
15. The compound of claim 1 , wherein R 6 is hydrogen.
16. The compound of claim 1 , wherein R 5 and R 6 are hydrogen, R 3 is selected from the group consisting of C 1 -C 3 alkoxy and fluorinated C 1 -C 2 alkoxy and R 4 is selected from the group consisting of hydrogen and C 1 -C 3 alkyl.
17. The compound of claim 1 , wherein R 5 and R 6 are hydrogen, R 3 is C 1 -C 3 alkyl and R 4 is selected from the group consisting of hydrogen and C 1 -C 3 alkyl.
18. The compound of 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.
19. The compound of 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.
20. The compound of 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.
21. The compound of claim 1 , selected from the group consisting of:
N-(3-[1,4]diazepan-1-yl-4-methoxy-phenyl)-3-difluoromethoxy-benzenesulfonamide;
3-difluoromethoxy-N-[4-methoxy-3-(4-methyl-[1,4]diazepan-1-yl)-phenyl]-benzenesulfonamide;
N-(3-[1,4]diazepan-1-yl-4-methoxy-phenyl)-2-difluoromethoxy-benzenesulfonamide;
2-difluoromethoxy-N-[4-methoxy-3-(4-methyl-[1,4]diazepan-1-yl)-phenyl]-benzenesulfonamide;
N-(3-[1,4]diazepan-1-yl-4-methyl-phenyl)-2-difluoromethoxy-benzenesulfonamide;
N-(3-[1,4]diazepan-1-yl-4-methyl-phenyl)-3-difluoromethoxy-N-methyl-benzenesulfonamide;
N-(3-[1,4]diazepan-1-yl-4-methyl-phenyl)-3-difluoromethoxy-benzenesulfonamide; and
2-difluoromethoxy-N-[4-methyl-3-(4-methyl-[1,4]diazepan-1-yl)-phenyl]-benzenesulfonamide;
and physiologically tolerated acid addition salts and the N-oxides thereof.
22. A method for treating obesity, said method comprising administering to a subject in need thereof an effective amount of a compound of formula I or I′
wherein
R 1 is hydrogen or methyl;
R 2 is hydrogen or methyl;
R 3 hydrogen, C 1 -C 3 alkyl, halogen, C 1 -C 3 alkoxy, fluorinated C 1 -C 3 alkyl or fluorinated C 1 -C 3 alkoxy;
R 4 is hydrogen, C 1 -C 4 alkyl, C 3 -C 4 cycloalkyl, C 3 -C 4 cycloalkylmethyl or fluorinated C 1 -C 4 alkyl;
R 5 is hydrogen, fluorine, chlorine, C 1 -C 4 alkyl, fluorinated C 1 -C 4 alkyl, C 1 -C 4 alkoxy or fluorinated C 1 -C 4 alkoxy; and
R 6 is hydrogen, fluorine or chlorine;
wherein R 2 is positioned vicinal to the radical R 1 ;
and physiologically tolerated acid addition salts and the N-oxides thereof.
23. A method for treating a cognitive dysfunction associated with Alzheimer's disease or schizophrenia, said method comprising administering to a subject in need thereof an effective amount of a compound of formula I or I′
wherein
R 1 is hydrogen or methyl;
R 2 is hydrogen or methyl;
R 3 hydrogen, C 1 -C 3 alkyl, halogen, C 1 -C 3 alkoxy, fluorinated C 1 -C 3 alkyl or fluorinated C 1 -C 3 alkoxy;
R 4 is hydrogen, C 1 -C 4 alkyl, C 3 -C 4 cycloalkyl, C 3 -C 4 cycloalkylmethyl or fluorinated C 1 -C 4 alkyl;
R 5 is hydrogen, fluorine, chlorine, C 1 -C 4 alkyl, fluorinated C 1 -C 4 alkyl, C 1 -C 4 alkoxy or fluorinated C 1 -C 4 alkoxy; and
R 6 is hydrogen, fluorine or chlorine;
wherein R 2 is positioned vicinal to the radical R 1 ;
and physiologically tolerated acid addition salts and the N-oxides thereof.