# US 10,245,260 B2 · Organic compounds

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- Number: US 10,245,260 B2
- Document ID: US10245260B2
- Status: Granted
- Kind: B2
- Application number: 15/660,615
- Filed: 2017-07-26
- Published: 2017-11-09
- Granted: 2019-04-02
- Earliest claimed: 2016-01-26
- Assignees: Intra-Cellular Therapies, Inc.
- Applicants: Intra-Cellular Therapies, Inc.
- Inventors: Wei Yao; Peng Li; Robert Davis; Sharon Mates; Kimberly Vanover; Gretchen Snyder
- Web page: https://patentgrep.com/patent/US10245260B2

## CPC

- A61K 31/4985: Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
- A61K 9/0019: {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)}
- A61K 9/16: Agglomerates; Granulates; Microbeadlets {; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction (A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51)}
- A61K 31/445: Non condensed piperidines, e.g. piperocaine
- A61K 45/00: Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 25/00: Drugs for disorders of the nervous system
- C07D 241/40: Benzopyrazines
- C07D 471/16: Peri-condensed systems
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## 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-HT2A receptor, the serotonin transporter (SERT), pathways involving the dopamine D1 and D2 receptor signaling system, and/or the μ-opioid receptor.

## Claims

### Claim 1

A method for the treatment of a central nervous system disorder, comprising administering to a patient in need thereof a compound of a Formula I:
wherein:
X is —NH—;
L is O;
Z is —O— or —C(O)—;
in free or salt form;
wherein the 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 disorders, cephalic pain, neuropathic pain, idiopathic pain, chronic pain, fibromyalgia, chronic fatigue, opiate dependency, cocaine dependency, amphetamine dependency, alcohol dependency, and combinations thereof.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the compound is:

### Claim 3 (depends on 1)

The method according to claim 1, wherein the compound is:

### Claim 4 (depends on 1)

The method according to claim 1, wherein the compound is in the form of a pharmaceutically acceptable salt.

### Claim 5 (depends on 1)

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

### Claim 6 (depends on 5)

The method of claim 5, wherein the pharmaceutically acceptable diluent or carrier comprises a polymeric matrix.

### Claim 7 (depends on 6)

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

### Claim 8 (depends on 1)

The method according to claim 1 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.

### Claim 9 (depends on 8)

The method according to claim 8, wherein the central nervous system disorder is obsessive-compulsive disorder (OCD) or obsessive-compulsive personality disorder (OCPD).

### Claim 10 (depends on 1)

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).

### Claim 11 (depends on 10)

The method according to claim 10, wherein the selective serotonin reuptake inhibitor (SSRI) is selected from the group consisting of citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline.

### Claim 12 (depends on 1)

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).

### Claim 13 (depends on 12)

The method according to claim 12, wherein the serotonin-norepinephrine reuptake inhibitor (SNRI) is selected from the group consisting of venlafaxine, sibutramine, duloxetine, atomoxetine, desvenlafaxine, milnacipran, and levomilnacipran.

### Claim 14 (depends on 1)

The method according to claim 1, wherein said patient is not responsive to or cannot tolerate the side effects from treatment with antipsychotic agents.

### Claim 15 (depends on 14)

The method according to claim 14, wherein the antipsychotic agent is selected from the group consisting of clomipramine, risperidone, quetiapine and olanzapine.