Compounds and methods

Patent metadata

Field	Value
Publication number	US-11958852-B2
Application number	US-202117405736-A
Country	US
Kind code	B2
Filing date	Aug 18, 2021
Priority date	Apr 14, 2012
Publication date	Apr 16, 2024
Grant date	Apr 16, 2024

Abstract

The present invention relates to use of particular substituted heterocycle fused gamma-carbolines as described herein, in free, pharmaceutically acceptable salt or prodrug form, and pharmaceutical composition comprising the same optionally in combination with one or more agents, for the prophylaxis or treatment of one or more disorders associated with dementia, particularly behavioral or mood disturbances (e.g., agitation/aggression), psychosis, depression and sleep disturbances among others in patients suffering from dementia.

First claim

What we claim is:

1. A method for the treatment of mild cognition impairment associated with dementia, comprising administering to a patient in need thereof, a therapeutically effective amount of a compound of Formula I:

wherein:
X is —N(CH 3 )—; and
Y is —C(═O);
in free, or pharmaceutically acceptable salt form.

2. The method according to claim 1 , wherein the dementia is Alzheimer's disease.

3. The method according to claim 1 , wherein the dementia is selected from senile dementia, Alzheimer's disease, Pick's disease, frontotemporal dementia, vascular dementia, Huntington's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis.

4. The method according to claim 1 , wherein the patient suffers from one or more co-morbid disorders selected from: (1) behavioral or mood disorders; (2) psychosis; (3) depression; and (4) sleep disorders.

5. The method according to claim 4 , wherein the patient suffers from co-morbid behavioral or mood disorders.

6. The method according to claim 1 , wherein the dosage of the Compound of Formula I in free, or pharmaceutically acceptable salt form, is about 10-100 mg.

7. The method according to claim 5 , wherein the co-morbid behavioral or mood disorders are selected from agitation/irritation, aggressive/assaultive behavior, anger, physical and emotional outbursts.

8. The method according to claim 1 , wherein the patient suffers from co-morbid sleep disorders.

9. The method according to claim 6 , wherein the dosage of the Compound of Formula I in free, or pharmaceutically acceptable salt form, is about 1-10 mg.

10. The method according to claim 1 , wherein the method further comprises administering one or more additional therapeutic agents selected from acetylcholinesterase inhibitors and N-methyl D-aspartate (NMDA) receptor antagonists.

11. The method according to claim 10 , wherein the therapeutic agent is an acetylcholinesterase inhibitor.

12. The method according to claim 11 , wherein the acetylcholinesterase inhibitor is selected from the group consisting of Tacrine, rivastigmine, donepezil and galantamine.

13. The method according to claim 10 , wherein the therapeutic agent is an NMDA receptor antagonist.

14. The method according to claim 13 , wherein the NMDA receptor antagonist is memantine.

15. The method according to claim 10 , wherein the therapeutic agents are donepezil and memantine.

16. The method according to claim 4 , wherein the behavior or mood disorders are selected from agitation/irritation, aggressive/assaultive behavior, anger, physical outbursts, and emotional outbursts.

Assignees

• Intra Cellular Therapies Inc

Inventors

• Mates Sharon
• Davis Robert
• Vanover Kimberly
• Wennogle Lawrence

Classifications

• C07D471/14 Primary

  Ortho-condensed systems · CPC title

• A61K31/445 Primary

  Non condensed piperidines, e.g. piperocaine · CPC title

• A61K31/4985 Primary

  Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems · CPC title

• A61K31/5383

  ortho- or peri-condensed with heterocyclic ring systems · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title