Organic compound

Patent metadata

Field	Value
Publication number	US-12195462-B2
Application number	US-201917415565-A
Country	US
Kind code	B2
Filing date	Dec 17, 2019
Priority date	Dec 17, 2018
Publication date	Jan 14, 2025
Grant date	Jan 14, 2025

Abstract

The invention relates to a particular substituted heterocycle fused gamma-carboline, in free, or pharmaceutically acceptable salt, and/or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use in the treatment of diseases involving the 5-HT 2A receptor, the serotonin transporter (SERT), and/or pathways involving the dopamine D 1 and D 2 receptor signaling system.

First claim

What is claimed:

1. The compound of Formula I, in free or pharmaceutically acceptable salt form,

wherein the compound is in isolated or purified form.

2. The compound according to claim 1 , wherein the compound is in pharmaceutically acceptable acid addition salt form with an acid selected from hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric, acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, and isethionic acid.

3. The compound according to claim 1 , wherein the compound is in toluenesulfonic acid addition salt form.

4. A pharmaceutical composition comprising the compound of Formula I:

in free or pharmaceutically acceptable salt form; in admixture with a pharmaceutically acceptable diluent or carrier.

5. The composition according to claim 4 , wherein the composition is formulated for sustained or delayed release, optionally as an injectable depot.

6. The composition according to claim 5 , wherein the composition further comprises a polymeric matrix.

7. The composition according to claim 6 , wherein the polymeric matrix is a biodegradable poly(d,l-lactide-co-glycolide) microsphere.

8. A method for the treatment of a central nervous system disorder, comprising administering to a patient in need thereof a composition according to claim 4 .

9. The method according to claim 8 , wherein the central nervous system disorder is a disorder involving serotonin 5-HT 2 A, dopamine D2 and/or D1 receptor system and/or the serotonin reuptake transporter (SERT) pathways.

10. The method according to claim 8 , wherein the central nervous system disorder is a disorder selected from the group consisting of obesity, anxiety, depression, psychosis, schizophrenia, sleep disorders, sexual disorders, migraine, cephalic pain, social phobias, agitation in dementia, agitation in autism, dementia, mood disorders, obsessive-compulsive disorder (OCD), obsessive-compulsive personality disorder (OCPD), general anxiety disorder, social anxiety disorder, panic disorder, agoraphobia, compulsive gambling disorder, compulsive eating disorder, body dysmorphic disorder, hypochondriasis, pathological grooming disorder, kleptomania, pyromania, attention deficit-hyperactivity disorder (ADHD), attention deficit disorder (ADD), impulse control disorder, and combination thereof.

11. The method according to claim 8 , wherein the central nervous system disorder is a disorder selected from the following: (1) psychosis; (2) depression in a patient suffering from psychosis; (3) mood disorders associated with psychosis; (4) sleep disorders associated with psychosis; and (5) substance use disorders and/or substance-induced disorders.

12. The method according to claim 8 , wherein the central nervous system disorder is selected from obsessive-compulsive disorder (OCD), obsessive-compulsive personality disorder (OCPD), general anxiety disorder, social anxiety disorder, panic disorder, agoraphobia, compulsive gambling disorder, compulsive eating disorder, body dysmorphic disorder, hypochondriasis, pathological grooming disorder, kleptomania, pyromania, attention deficit-hyperactivity disorder (ADHD), attention deficit disorder (ADD), and impulse control disorder.

13. The method according to claim 8 , wherein the central nervous system disorder is depression, anxiety or a combination thereof.

14. The method according to claim 13 , wherein the depression and/or anxiety is acute depression and/or acute anxiety.

15. The method according to claim 8 , wherein the central nervous system disorder is acute anxiety.

16. The method according to claim 15 , wherein the acute anxiety is a short-duration anxious episode associated with generalized anxiety disorder, panic disorder, specific phobias, or social anxiety disorder, or social avoidance.

17. The method according to claim 8 , wherein the central nervous system disorder is acute depression.

18. The method according to claim 17 , wherein the acute depression is an acute major depressive episode, acute short-duration depressive episode, or acute recurrent brief depressive episode.

19. The method according to claim 8 , wherein the central nervous system disorder is treatment resistant depression.

20. The method according to claim 19 , wherein the treatment resistant depression is depression which has not responded to treatment with an antidepressant agent selected from a selective serotonin reuptake inhibitor (SSRI), a serotonin reuptake inhibitor (SRI), a tricyclic antidepressant, a monoamine oxidase inhibitor, a norepinephrine reuptake inhibitor (NRI), a dopamine reuptake inhibitor (DRI), an SRI/NRI, an SRI/DRI, an NRI/DRI, an SRI/NRI/DRI (triple reuptake inhibitor), a serotonin receptor antagonist, or any combination thereof.

21. The method according to claim 8 , wherein said patient is not responsive to or cannot tolerate the side effects from, treatment with selective serotonin reuptake inhibitors (SSRIs).

22. The method according to claim 21 , wherein the selective serotonin reuptake inhibitor is selected from citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline.

23. The method according to claim 8 , wherein said patient is not responsive to or cannot tolerate the side effects from, treatment with serotonin-norepinephrine reuptake inhibitors (SNRIs).

24. The method according to claim 23 , wherein the serotonin-norepinephrine reuptake inhibitor is selected from venlafaxine, sibutramine, duloxetine, atomoxetine, desvenlafaxine, milnacipran, and levomilnacipran.

25. The method according to claim 8 , wherein said patient is not responsive to or cannot tolerate the side effects from, treatment with antipsychotic agents.

26. The method according to claim 25 , wherein the antipsychotic agent is selected from clomipramine, risperidone, quetiapine, and olanzapine.

27. The method according to claim 8 , wherein the central nervous system disorder is bipolar depression or major depressive disorder.

28. The method according to claim 27 , wherein the central nervous system disorder is an acute major depressive episode associated with major depressive disorder.

29. The method according to claim 8 , wherein the patient is diagnosed as having suicidal ideation and/or suicidal tendencies.

30. The method according to claim 8 , wherein the treatment provides an acute response within less than 1 week, or from 1 to 7 days, or from 1 to 5 days, or from 1 to 3 days, after initial dosing of the compound.

31. The method according to claim 8 , wherein the compound of Formula I is in pharmaceutically acceptable acid addition salt form with an acid selected from hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric, acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic,

Assignees

• Intra Cellular Therapies Inc

Inventors

• Li Peng
• Zhang Qiang
• Davis Robert

Classifications

• A61K9/1647

  Polyesters, e.g. poly(lactide-co-glycolide) · CPC title

• A61P25/22

  Anxiolytics · CPC title

• A61P25/24

  Antidepressants · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title