3-imino-2-indolones for the treatment of depression and/or anxiety
This invention is directed to indolone derivatives which are selective antagonists for the GalR3 receptor. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention also provides a pharmaceutical composition made by combining a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention further provides a process for making a pharmaceutical composition comprising combining a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention also provides a method of treating a subject suffering from depression and/or anxiety which comprises administering to the subject an amount of a compound of the invention effective to treat the subject's depression and/or anxiety. This invention also provides a method of treating depression and/or anxiety in a subject which comprises administering to the subject a composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a GalR3 receptor antagonist.
1. A compound having the structure:
wherein each of Y 1 , Y 2 and Y 3 is independently —H, straight chained or branched C 1 –C 7 alkyl, monofluoroalkyl or polyfluoroalkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 3 , —OCOR 3 , —NCOR 3 , —N(R 3 ) 2 , —CON(R 3 ) 2 , —COOR 3 , aryl, heteroaryl or any two of Y 1 , Y 2 and Y 3 moieties present on adjacent carbon atoms can constitute a methylenedioxy group;
wherein R 1 is straight chained or branched C 1 –C 7 alkyl, —F, —Cl, —Br, —I, —N 3 , —CN, —OR 3 , —CON(R 3 ) 2 , —COOR 3 , C 3 –C 7 cycloalkyl or C 5 –C 7 cycloalkenyl, aryl or heteroaryl;
wherein each R 2 is independently —H, straight chained or branched C 1 –C 7 alkyl, monofluoroalkyl or polyfluoroalkyl, —F, —Cl, —Br, —I, —N 3 , —CN, —OR 3 , —CON(R 3 ) 2 , —COOR 3 , aryl, heteroaryl, C 3 –C 7 cycloalkyl or cycloalkenyl or any two R 2 moieties present on adjacent carbon atoms can constitute a methylenedioxy group or a difluoromethylenedioxy group or any two R 2 moieties present on adjacent carbon atoms along with the adjacent carbon atom can constitute an aryl or a heteroaryl ring;
wherein each R 3 is independently —H, straight chained or branched C 1 –C 7 alkyl, monofluoroalkyl or polyfluoroalkyl, C 3 –C 7 cycloalkyl or C 5 –C 7 cycloalkenyl, aryl or heteroaryl; and
wherein R 4 is —H, —F, —Cl or methyl;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein each Y 1 , Y 2 , and Y 3 is —H, —F, —CN, —C 1 –C 4 alkyl or polyfluoroalkyl;
wherein each R 2 is independently —H, —F, —Cl, —Br, —I, —CN, straight chained or branched C 1 –C 4 alkyl or any two R 2 moieties present on adjacent carbon atoms can constitute a difluoromethylenedioxy group; and
wherein each R 4 is H.
3. The compound of claim 2 , wherein the compound is selected from the group consisting of:
4. The compound of claim 1 , wherein the compound is enantiomerically pure.
5. The compound of claim 1 , wherein the compound is diastereomerically pure.
6. The compound of claim 4 , wherein the compound is enantiomerically and diastereomerically pure.
7. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 and a pharmaceutically acceptable carrier.
8. A process of making a pharmaceutical composition comprising admixing a therapeutically effective amount of the compound of claim 1 and a pharmaceutically acceptable carrier.
9. A method of treating a subject suffering from depression, which comprises administering to the subject a dose of the compound of claim 1 effective to treat the subject's depression.
10. A method of treating a subject suffering from anxiety, which comprises administering to the subject a dose of the compound of claim 1 effective to treat the subject's anxiety.
11. The compound of claim 5 , wherein the compound is enantiomerically and diastereomerically pure.