Indolone derivatives, processes for preparing them and their uses
View Patent ↗The present invention relates to indolone derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals.
1. A method of treating, ameliorating, or inhibiting the effects of movement disorders and/or motor fluctuations in a subject suffering from Parkinson's disease, the method comprising administering to the subject an effective amount of a compound of formula I,
wherein
X is CH 2 or CF 2 ;
R 1 is selected from hydrogen or C 1-4 alkyl optionally substituted by at least one hydroxy;
R 2 is selected from hydrogen or C 1-4 alkyl optionally substituted by at least one hydroxy;
R 3 is selected from hydrogen or unsubstituted C 1-4 alkyl;
R 3a is selected from hydrogen or unsubstituted C 1-4 alkyl;
R 4 is selected from hydrogen; halogen; C 1-4 alkyl optionally substituted by at least a group selected independently from halogen and a phenyl group; or C 1-4 alkoxy optionally substituted by at least a group selected independently from halogen, C 1-4 alkoxy and a phenyl group;
R 5 is selected from hydrogen; halogen; C 1-4 alkyl optionally substituted by at least a group selected independently from halogen and a phenyl group; or C 1-4 alkoxy optionally substituted by at least a group selected independently from halogen, C 1-4 alkoxy and a phenyl group;
R 6 is selected from hydrogen; halogen; C 1-4 alkyl optionally substituted by at least a group selected independently from halogen and a phenyl group; or C 1-4 alkoxy optionally substituted by at least a group selected independently from halogen, C 1-4 alkoxy and a phenyl group;
R 7 is selected from hydrogen; halogen; C 1-4 alkyl optionally substituted by at least a group selected independently from halogen and a phenyl group; or C 1-4 alkoxy optionally substituted by at least a group selected independently from halogen, C 1-4 alkoxy and a phenyl group;
with the proviso that if X is CH 2 , then R 7 is different from hydrogen;
or a pharmaceutically acceptable salt thereof or a stereoisomeric forms thereof.
2. The method according to claim 1 , wherein X is CH 2 and R 7 is halogen; C 1-4 alkyl optionally substituted by at least a group selected independently from halogen and a phenyl group; or C 1-4 alkoxy optionally substituted by at least a group selected independently from halogen, C 1-4 alkoxy and a phenyl group.
3. The method according to claim 1 , wherein X is CF 2 .
4. The method according to claim 1 , wherein
X is CH 2 or CF 2 ;
R 1 is selected from hydrogen or unsubstituted C 1-4 alkyl;
R 2 is selected from hydrogen or unsubstituted C 1-4 alkyl;
R 1 is selected from hydrogen or unsubstituted C 1-4 alkyl;
R 3a is selected from hydrogen or unsubstituted C 1-4 alkyl;
R 4 is selected from hydrogen; halogen; unsubstituted C 1-4 alkyl; or unsubstituted C 1-4 alkoxy;
R 5 is selected from hydrogen; halogen; unsubstituted C 1-4 alkyl; or unsubstituted C 1-4 alkoxy;
R 6 is selected from hydrogen; halogen; unsubstituted C 1-4 alkyl; or unsubstituted C 1-4 alkoxy;
R 7 is selected from hydrogen; halogen; unsubstituted C 1-4 alkyl; trifluoromethyl; or unsubstituted C 1-4 alkoxy.
5. The method according to claim 1 , wherein X is CH 2 or CF 2 ; R 1 , R 2 , R 3 , R 3a , R 4 and R 5 are hydrogen; and R 6 is hydrogen, methyl, bromine, chlorine or fluorine; and R 7 is hydrogen, chlorine, fluorine or trifluoromethyl.
6. The method according to claim 1 , wherein X is CH 2 ; R 1 , R 2 , R 3 , R 3a , R 4 and R 5 are hydrogen; R 6 is hydrogen, chlorine or bromine; and R 7 is chlorine or fluorine.
7. The method according to claim 1 , wherein X is CH 2 ; R 1 , R 2 , R 3 , R 3a , R 4 and R 5 are hydrogen; R 6 is hydrogen; and R 7 is fluorine.
8. The method according to claim 1 , wherein X is CF 2 ; R 1 , R 2 , R 3 , R 3a , R 4 and R 5 are hydrogen; R 6 is chlorine or fluorine; and R 7 is hydrogen.
9. A method of treating, ameliorating, or inhibiting the effects of movement disorders and/or motor fluctuations in a subject suffering from Parkinson's disease, the method comprising administering to the subject an effective amount of a compound selected from
2-(4-chloro-2-oxo-2,3-dihydro-1H-indol-1-yl)acetamide;
2-(5-bromo-4-chloro-2-oxo-2,3-dihydro-1H-indol-1-yl)acetamide;
2-(4-fluoro-2-oxo-2,3-dihydro-1H-indol-1-yl)acetamide;
2-(4,5-dichloro-2-oxo-2,3-dihydro-1H-indol-1-yl)acetamide;
2-(3,3-difluoro-2-oxo-2,3-dihydro-1H-indol-1-yl)acetamide;
2-(5-chloro-3,3-difluoro-2-oxo-2,3-dihydro-1H-indol-1-yl)acetamide;
2-(5-bromo-3,3-difluoro-2-oxo-2,3-dihydro-1H-indol-1-yl)acetamide;
2-(3,3-difluoro-5-methyl-2-oxo-2,3-dihydro-1H-indol-1-yl)acetamide;
2-(3,3,5-trifluoro-2-oxo-2,3-dihydro-1H-indol-1-yl)acetamide; and
2-[2-oxo-4-(trifluoromethyl)-2,3-dihydro-1H-indol-1-yl]acetamide;
or a pharmaceutically acceptable salt thereof or a stereoisomeric form thereof.
10. A method of treating, ameliorating, or inhibiting the effects of movement disorders and/or motor fluctuations in a subject suffering from Parkinson's disease, the method comprising administering to the subject an effective amount of a compound selected from
2-(4-chloro-2-oxo-2,3-dihydro-1H-indol-1-yl)acetamide;
2-(4-fluoro-2-oxo-2,3-dihydro-1H-indol-1-yl)acetamide;
2-(5-chloro-3,3-difluoro-2-oxo-2,3-dihydro-1H-indol-1-yl)acetamide; and
2-(5-bromo-3,3-difluoro-2-oxo-2,3-dihydro-1H-indol-1-yl)acetamide;
or a pharmaceutically acceptable salt thereof or a stereoisomeric form thereof.
11. A method of treating, ameliorating, or inhibiting the effects of movement disorders and/or motor fluctuations in a subject suffering from Parkinson's disease, the method comprising administering to the subject an effective amount of 2-(4-fluoro-2-oxo-2,3-dihydro-1H-indol-1-yl)acetamide or a pharmaceutically acceptable salt thereof or a stereoisomeric form thereof.