Granted Patent
B2
US 12,440,489 · App. 18/502,460 · Granted Oct 14, 2025
Organic compounds
Inventors:
Wei Yao (New Milford, NJ); Peng Li (New Milford, NJ); Robert Davis (San Diego, CA); Sharon Mates (New York, NY); Kimberly Vanover (New York, NY); Gretchen Snyder (New York, NY)
Assignee:
INTRA-CELLULAR THERAPIES, INC.
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Abstract
The 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 the 5-HT 2A receptor, the serotonin transporter (SERT), pathways involving the dopamine D 1 and D 2 receptor signaling system, and/or the μ-opioid receptor.
Claims (24)
1. A method for the treatment of a central nervous system disorder, comprising administering to a patient in need of such treatment, a compound of a Formula I:
wherein:
X is —NH—;
L is O; and
Z is —O—;
in toluenesulfonic acid addition salt form;
wherein the central nervous system disorder is selected from the group consisting of 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, pain disorder, chronic fatigue, opiate dependency, cocaine dependency, amphetamine dependency, alcohol dependency, substance addiction, substance-use disorder, substance-abuse disorder, and combinations thereof;
wherein said patient is not responsive to or cannot tolerate the side effects from treatment with selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or antipsychotic agents.
2. The method according to claim 1 , wherein the compound is administered to the patient in the form of a pharmaceutically acceptable composition comprising the compound, in admixture with a pharmaceutically acceptable diluent or carrier.
3. The method of claim 2 , wherein the pharmaceutically acceptable diluent or carrier comprises a polymeric matrix.
4. The method according to claim 3 , wherein the polymeric matrix is a biodegradable poly(d,l-lactide-co-glycolide) microsphere.
5. The method according to claim 1 , wherein the central nervous system disorder is selected from the group consisting of 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.
6. The method according to claim 5 , wherein the central nervous system disorder is obsessive-compulsive disorder (OCD) or obsessive-compulsive personality disorder (OCPD).
7. The method according to claim 1 , wherein said patient is not responsive to or cannot tolerate the side effects from treatment with selective serotonin reuptake inhibitors (SSRIs).
8. The method according to claim 7 , wherein the selective serotonin reuptake inhibitor (SSRI) is selected from the group consisting of citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline.
9. The method according to claim 1 , wherein said patient is not responsive to or cannot tolerate the side effects from treatment with serotonin-norepinephrine reuptake inhibitors (SNRIs).
10. The method according to claim 9 , wherein the serotonin-norepinephrine reuptake inhibitor (SNRI) is selected from the group consisting of venlafaxine, sibutramine, duloxetine, atomoxetine, desvenlafaxine, milnacipran, and levomilnacipran.
11. The method according to claim 1 , wherein said patient is not responsive to or cannot tolerate the side effects from treatment with antipsychotic agents.
12. The method according to claim 11 , wherein the antipsychotic agent is selected from the group consisting of clomipramine, risperidone, quetiapine and olanzapine.
13. The method according to claim 1 , wherein the pain disorder is selected from the group consisting of neuropathic pain, idiopathic pain, chronic pain, and fibromyalgia.
14. The method according to claim 1 , wherein the central nervous system disorder is a substance addiction, a substance-use disorder, or a substance-induced disorder.
15. The method according to claim 14 , wherein the central nervous system disorder is selected from the group consisting of intoxication, withdrawal, substance-induced psychosis, substance-induced bipolar disorder, substance-induced depressive disorder, substance-induced anxiety disorder, substance-induced obsessive-compulsive disorder, substance-induced sleep disorder, substance-induced sexual dysfunction, substance-induced delirium, and substance-induced neurocognitive disorder.
16. The method according to claim 1 , wherein the patient is not responsive to or cannot tolerate the side effects of non-narcotic analgesics and/or opiate and opioid drugs, or wherein the use of opiate drugs are contraindicated in said patient, due to prior substance abuse or a high potential for substance abuse.
17. The method according to claim 16 , wherein said drugs are selected from the group consisting of morphine, codeine, thebaine, oripavine, morphine dipropionate, morphine dinicotinate, dihydrocodeine, buprenorphine, etorphine, hydrocodone, hydromorphone, oxycodone, oxymorphone, fentanyl, alpha-methylfentanyl, alfentanyl, trefantinil, brifentanil, remifentanil, ocfentanil, sufentanil, carfentanyl, meperidine, prodine, promedol, propoxyphene, dextropropoxyphene, methadone, diphenoxylate, dezocine, pentazocine, phenazocine, butorphanol, nalbuphine, levorphanol, levomethorphan, tramadol, tapentadol, and anileridine, or any combinations thereof.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 13, 2023
From: YAO, WEI; LI, PENG; MATES, SHARON; VANOVER, KIMBERLY; SNYDER, GRETCHEN; DAVIS, ROBERT
To: INTRA-CELLULAR THERAPIES, INC.
Reel/Frame 065859/0539 →
Continuity (7)
Continuation In Part
PCTUS2017015178
· Jan 26, 2017
Provisional Application
62440130
· Dec 29, 2016
Provisional Application
62287264
· Jan 26, 2016
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