Methods for treating antipsychotic-induced weight gain

Patent metadata

Field	Value
Publication number	US-9943514-B2
Application number	US-201615342263-A
Country	US
Kind code	B2
Filing date	Nov 3, 2016
Priority date	Aug 23, 2010
Publication date	Apr 17, 2018
Grant date	Apr 17, 2018

Abstract

The present invention relates to the discovery of a novel opioid modulator effective in reducing pharmacologically induced weight gain associated with atypical antipsychotic use. The present invention provides methods of reducing antipsychotic induced weight gain, methods for suppressing food intake and reducing ghrelin levels induced by atypical antipsychotic medications in a patient.

First claim

What is claimed is:

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

Assignees

• Alkermes Pharma Ireland Ltd

Inventors

• Deaver Daniel
• Todtenkopf Mark

Classifications

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• A61K31/439

  the ring forming part of a bridged ring system, e.g. quinuclidine (8-azabicyclo [3.2.1] octanes A61K31/46) · CPC title

• C07D405/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D221/28

  Morphinans · CPC title

• A61K31/551

  having two nitrogen atoms, e.g. dilazep · CPC title