Indolone compounds useful to treat cognitive impairment

1. A method of treating a subject suffering from a memory impairment comprising administering to the subject an amount of a compound effective to enhance the subject's memory, wherein the compound has the structure:

wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR, 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 , and Y 4 present on adjacent carbon atoms can constitute a methylenedioxy group;

wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;

wherein A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl(C 1 -C 6 )alkyl;

wherein A′ is

wherein R 1 and R 2 are each independently —H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , or —CN;

wherein R 3 is —H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 6 aryl or heteroaryl;

wherein R 5 , is straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 —, OR 6 , or aryl;

wherein R 6 is straight chained or branched C 1 -C 7 alkyl or aryl; wherein B is aryl, or heteroaryl; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following: —H, —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;

wherein each n is independently an integer from 1 to 4 inclusive; wherein the compound is a pure Z imine isomer, a pure E imine isomer, or a mixture of Z and E imine isomers;

or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein the compound is enantiomerically and diastereomerically pure.

3. The method of claim 1 , wherein the compound is enantiomerically or diastereomerically pure.

4. The method of claim 1 , wherein the compound is a pure Z imine isomer.

5. The method of claim 1 , wherein the compound is a pure E imine isomer.

6. The method of claim 1 , wherein the compound is a mixture of Z and E imine isomers.

7. The method of claim 1 , wherein the compound has the structure:

wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, —CF 3 , —F, —Cl, —Br, —I, —OR 4 , —N(R 4 ) 2 , or —CON(R 5 ) 2 ;

wherein each R 4 independently H, straight chained or branched C 1 -C 7 alkyl, —CF 3 , or phenyl;

wherein A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl(C 1 -C 6 )alkyl; and

wherein A′ is

8. The method of claim 7 , wherein B is aryl.

9. The method of claim 8 , wherein B is phenyl and the phenyl is optionally substituted with one or more of the following: —H; —F, —Cl, —Br, —CF 3 , straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 4 , —COR 4 , —NCOR 4 , —CO 2 R 4 , or —CON(R 4 ) 2 .

10. The method of claim 9 , wherein A is aryl.

11. The method of claim 9 , wherein A is heteroaryl.

12. A method of treating a subject suffering from a memory impairment comprising administering to the subject an amount of a compound effective to enhance the subject's memory, wherein the compound has the structure:

wherein each R 24 is independently one or more of the following: H, F, Cl, Br, I, CF 3 or OCH 3 ;

wherein R 25 is methyl, ethyl, allyl, or phenyl and the phenyl is optionally substituted with F, Cl, Br, CF 3 , or OR 4 , and

wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl.