Organic compounds

Patent metadata

Field	Value
Publication number	US-11560382-B2
Application number	US-202017124224-A
Country	US
Kind code	B2
Filing date	Dec 16, 2020
Priority date	Apr 4, 2014
Publication date	Jan 24, 2023
Grant date	Jan 24, 2023

Abstract

This invention relates to particular substituted heterocycle fused gamma-carbolines, their prodrugs, in free, solid, pharmaceutically acceptable salt and/or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use in the treatment of diseases involving 5-HT2A receptor, serotonin transporter (SERT) and/or pathways involving dopamine D1/D2 receptor signaling systems, and/or the treatment of residual symptoms.

First claim

The invention claimed is:

1. A method for the treatment of a central nervous system disorder selected from anxiety, depression, psychosis, schizophrenia, post-traumatic stress disorder, impulse control disorders and intermittent explosive disorder, comprising administering to a patient in need thereof a therapeutically effective amount of compound of formula I:

wherein:
R 1 is CH 3 ;
R 2 and R 3 are each independently H or D;
R 4 and R 5 are each H;
provided that R 2 and R 3 are not both H,

and wherein D is deuterium;
in free or salt form;
wherein the compound of formula I is administered in the form of a sustained or delayed release pharmaceutical composition comprising the compound of formula I dispersed or dissolved in a polymeric matrix, and wherein the pharmaceutical composition is formulated for administration by injection.

2. The method according to claim 1 , wherein R 2 and R 3 are both D.

3. The method according to claim 1 , wherein R 2 is D and R 3 is H.

4. The method according to claim 1 , wherein said compound is in salt form.

5. The method according to claim 4 , wherein the salt is a toluenesulfonic acid addition salt.

6. The method according to claim 1 , wherein said disorder is selected from a group consisting of anxiety, depression, psychosis, and schizophrenia.

7. The method according to claim 6 , wherein said disorder is schizophrenia.

8. The method according to claim 6 , wherein said disorder is anxiety.

9. The method according to claim 1 , wherein the polymeric matrix comprises a polylactide, a polyglycolide, and/or a poly(d,l-lactide-co-glycolide) (PLGA).

10. The method according to claim 9 , wherein the polymeric matrix comprises PLGA 50:50, PLGA 75:25, PLGA 85:15, PLGA 90:10, or a combination thereof.

11. The method according to claim 9 , wherein the polymeric matrix comprises PLGA copolymer having a 75:25 to 50:50 molar ratio of lactide to glycolide.

12. The method according to claim 9 , wherein the polymeric matrix comprises PLGA copolymer having a weight-average molecular weight of 5,000 to 500,000 daltons, or a weight average molecular weight of about 150,000 daltons.

13. The method according to claim 1 , wherein the composition is formulated for intramuscular or subcutaneous injection.

14. The method according to claim 1 , wherein the composition releases the compound of formula I upon degradation of the polymeric matrix over a period of 30 to 180 days.

15. The method according to claim 1 , wherein the composition releases the compound of formula I upon degradation of the polymeric matrix over a period of 14 to 30 days.

16. The method according to claim 1 , wherein the composition comprises the polymeric matrix in the form of microparticles.

17. The method according to claim 1 , wherein the composition does not comprise the polymeric matrix in the form of microparticles.

18. The method according to claim 1 , wherein the composition comprises the polymeric matrix admixed with a water-miscible diluent or carrier.

19. The method according to claim 1 , wherein R 2 is D and R 3 is D, and wherein the compound of formula I is in the form of a toluenesulfonic acid addition salt, and wherein the polymeric matrix comprises a polylactide, a polyglycolide, and/or a poly(d,l-lactide-co-glycolide) (PLGA), and wherein the composition is formulated for intramuscular or subcutaneous injection.

20. The method according to claim 19 , wherein the polymeric matrix comprises PLGA copolymer having a 75:25 to 50:50 molar ratio of lactide to glycolide.

21. The method according to claim 20 , wherein the composition comprises the polymeric matrix admixed with a water-miscible diluent or carrier.

22. The method according to claim 1 , wherein R 2 is D and R 3 is D, and wherein the compound of formula I is free base form, and wherein the polymeric matrix comprises a polylactide, a polyglycolide, and/or a poly(d,l-lactide-co-glycolide) (PLGA), and wherein the composition is formulated for intramuscular or subcutaneous injection.

23. The method according to claim 22 , wherein the polymeric matrix comprises PLGA copolymer having a 75:25 to 50:50 molar ratio of lactide to glycolide.

24. The method according to claim 23 , wherein the composition comprises the polymeric matrix admixed with a water-miscible diluent or carrier.

25. The method according to claim 1 , wherein said disorder is bipolar depression.

Assignees

• Intra Cellular Therapies Inc

Inventors

• Mates Sharon
• Li Peng
• Wennogle Lawrence P
• Davis Robert

Classifications

• A61P25/22

  Anxiolytics · CPC title

• A61P25/18

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title

• C07D471/14

  Ortho-condensed systems · CPC title

• A61P25/24

  Antidepressants · CPC title

• C07D471/16 Primary

  Peri-condensed systems · CPC title