Methods for treating antipsychotic-induced weight gain

1. A method of suppressing food intake comprising administering to the patient in need of treatment an effective amount of a compound of Formula I or pharmaceutically acceptable salt thereof,

wherein, A is chosen from —C(═O)NH 2 and —C(═S)NH 2 ;

R 1 and R 2 are both hydrogen or taken together R 1 and R 2 are ═O;

R 3 is chosen from hydrogen, alkyl, alkenyl, aryl, heterocyclyl and hydroxyalkyl;

R 4 is chosen from hydrogen, hydroxy, amino, alkoxy, C 1 -C 20 alkyl and C 1 -C 20 alkyl substituted with hydroxy or carbonyl;

R 5 is selected from hydrogen, hydroxyl, alkoxy and alkyl;

R 6 is chosen from hydrogen, hydroxy, alkoxy and —NR 10 R 11 ;

or together, R 5 and R 6 form a carbonyl or a vinyl substituent;

R 10 and R 11 are chosen independently from hydrogen and alkyl and aliphatic; and,

represents a single or double bond.

2. The method according to claim 1 , wherein said compound of Formula I is selected from a compound of Formula II or a pharmaceutically acceptable salt thereof,

wherein, R 3 , R 4 , R 5 , and R 6 are as defined above.

3. The method according to claim 2 , wherein

R 4 is selected from hydrogen and hydroxyl;

R 5 is selected from hydrogen, and hydroxyl; and

R 6 is hydrogen;

or together, R 5 and R 6 form a carbonyl or a vinyl substituent.

4. The method of claim 2 , wherein R 4 is hydroxyl; and together, R 5 and R 6 form a carbonyl substituent.

5. The method of claim 3 , wherein R 4 is hydroxyl; and together, R 5 and R 6 form a carbonyl substituent.

6. The method according to claim 1 , wherein the increased appetite is induced by administration of an atypical antipsychotic.

7. The method according to claim 6 , wherein the atypical antipsychotic is selected from olanzapine, clozapine, risperidone, quetiapine, aripiprazole, ziprasidone, and pharmaceutically acceptable salts thereof.

8. The method of claim 1 , wherein said compound of Formula I is administered in a daily dose of about 3 mg/day to about 30 mg/day.

9. The method according to claim 1 , wherein

R 4 is selected from hydrogen and hydroxyl;

R 5 is selected from hydrogen, and hydroxyl; and

R 6 is hydrogen;

or together, R 5 and R 6 form a carbonyl or a vinyl substituent.

10. The method of claim 9 , wherein R 4 is hydroxyl; and together, R 5 and R 6 form a carbonyl substituent.

11. The method of claim 1 , wherein R 4 is hydroxyl; and together, R 5 and R 6 form a carbonyl substituent.

12. The method according to claim 1 , wherein R 3 is selected from, hydrogen, cyclopropyl, cyclobutyl, vinyl, furan and tetrahydrofuran.

13. The method according to claim 1 , wherein said compound of Formula I is selected from:

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

or a pharmaceutically acceptable salt thereof.

14. The method according to claim 13 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

15. A method of suppressing food intake comprising administering to the patient in need of treatment an effective amount of a composition comprising an atypical antipsychotic and a compound of Formula I or pharmaceutically acceptable salt thereof,

wherein, A is chosen from —C(═O)NH 2 and —C(═S)NH 2 ;

R 1 and R 2 are both hydrogen or taken together R 1 and R 2 are ═O;

R 3 is chosen from hydrogen, alkyl, alkenyl, aryl, heterocyclyl and hydroxyalkyl;

R 4 is chosen from hydrogen, hydroxy, amino, alkoxy, C 1 -C 20 alkyl and C 1 -C 20 alkyl substituted with hydroxy or carbonyl;

R 5 is selected from hydrogen, hydroxyl, alkoxy and alkyl;

R 6 is chosen from hydrogen, hydroxy, alkoxy and —NR 10 R 11 ;

or together, R 5 and R 6 form a carbonyl or a vinyl substituent;

R 10 and R 11 are chosen independently from hydrogen and alkyl and aliphatic; and,

represents a single or double bond.

16. The method according to claim 15 , wherein said compound of Formula I is selected from a compound of Formula II or a pharmaceutically acceptable salt thereof,

wherein, R 3 , R 4 , R 5 , and R 6 are as defined above.

17. The method according to claim 16 , wherein

R 4 is selected from hydrogen and hydroxyl;

R 5 is selected from hydrogen, and hydroxyl; and

R 6 is hydrogen;

or together, R 5 and R 6 form a carbonyl or a vinyl substituent.

18. The method of claim 16 , wherein R 4 is hydroxyl; and together, R 5 and R 6 form a carbonyl substituent.

19. The method of claim 17 , wherein R 4 is hydroxyl; and together, R 5 and R 6 form a carbonyl substituent.

20. The method according to claim 15 , wherein the atypical antipsychotic is selected from olanzapine, clozapine, risperidone, quetiapine, aripiprazole, ziprasidone, and pharmaceutically acceptable salts thereof.

21. The method according to claim 15 , wherein the increased appetite is induced by administration of an atypical antipsychotic.

22. The method according to claim 15 , wherein said compound of Formula I is administered in a daily dose of about 3 mg/day to about 30 mg/day.

23. The method according to claim 15 , wherein said composition is in the form of a tablet.

24. The method according to claim 15 , wherein

R 4 is selected from hydrogen and hydroxyl;

R 5 is selected from hydrogen, and hydroxyl; and

R 6 is hydrogen;

or together, R 5 and R 6 form a carbonyl or a vinyl substituent.

25. The method of claim 24 , wherein R 4 is hydroxyl; and together, R 5 and R 6 form a carbonyl substituent.

26. The method of claim 15 , wherein R 4 is hydroxyl; and together, R 5 and R 6 form a carbonyl substituent.

27. The method according to claim 15 , wherein R 3 is selected from, hydrogen, cyclopropyl, cyclobutyl, vinyl, furan and tetrahydrofuran.

28. The method according to claim 15 , wherein said compound of Formula I is selected from:

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

or a pharmaceutically acceptable salt thereof.

29. The method according to claim 28 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.