Granted Patent B2

US 12,624,037 · App. 16/926,552 · Granted May 12, 2026

Inventors: Sharon Mates (New York, NY); Robert Davis (San Diego, CA); Kimberly Vanover (New York, NY)

Assignee: INTRA-CELLULAR THERAPIES, INC.

C07D471/14A61K31/445A61K31/4985A61K31/5383A61K45/06A61P25/28C07D471/16

Abstract

Claims (34)

1 . A method for the treatment of a disorder selected from agitation, aggressive behavior, and impulse control disorder, comprising administering to a patient in need thereof an effective amount of a compound of Formula I:

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

2 . The method according to claim 1 , wherein the compound of Formula I is selected from a group consisting of compounds of formula I wherein:

X is —O— and Y is —C(H)(OH)—,

X is —NH— and Y is —C(H)(OH)—,

X is —N(CH 3 )— and Y is —C(H)(OH)—,

X is —O— and Y is —C(O)—,

X is —O— and Y is —O—,

X is —N(CH 3 )— and Y is —C(O)—,

X is —N(CH 3 )— and Y is —O—,

X is —NH— and Y is —C(O)—, and

X is —NH— and Y is —O—.

3 . The method of claim 1 , wherein X is —N(CH 3 )— and Y is —C(O)—.

4 . The method of claim 1 , wherein the disorder is impulse control disorder.

5 . The method of claim 4 wherein the impulse control disorder is intermittent explosive disorder.

6 . The method of claim 1 , wherein the administration of the compound of Formula I is an adjunct to the administration of one or more additional antidepressants.

7 . The method of claim 6 , wherein the administration of one of more additional antidepressants is an adjunct to administration of the compound of Formula I.

8 . The method of claim 6 , wherein the antidepressant is selected from one or more of amitriptyline, amoxapine, bupropion, citalopram, clomipramine, desipramine, doxepin, duloxetine, escitalopram, fluoxetine, fluvoxamine, imipramine, isocarboxazid, maprotiline, mirtazapine, nefazodone, nortriptyline, paroxetine, phenelzine sulfate, protriptyline, sertraline, tranylcypromine, trazodone, trimipramine, and venlafaxine, in free or pharmaceutically acceptable salt form.

9 . The method of claim 6 , wherein the antidepressant is one or more antidepressants selected from selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants.

10 . The method of claim 9 , wherein the antidepressant is a SSRI.

11 . The method of claim 1 , wherein the compound of Formula I is administered orally as a composition comprising a pharmaceutically acceptable diluent or carrier as an oral unit dose form that is a tablet or capsule.

12 . The method of claim 1 , wherein the effective amount of the compound of Formula I is a daily dose of about 1 mg to about 100 mg.

13 . The method of claim 1 , wherein the effective amount of the compound of Formula I is a daily dose of about 10 mg to about 50 mg.

14 . The method of claim 1 , wherein the effective amount of the compound of Formula I is a daily dose of about 20 mg to about 40 mg.

15 . The method of claim 1 , wherein the effective amount of the compound of Formula I is a daily dose of about 1 mg to about 10 mg.

16 . The method of claim 1 , further comprising administering one or more additional therapeutic agents selected from compounds that modulate GABA activity, a 5-HT modulator, a melatonin agonist, an ion channel modulator, a serotonin-2 antagonist/reuptake inhibitor, an orexin receptor antagonist, an H3 agonist, a noradrenergic antagonist, a galanin agonist, a CRH antagonist, human growth hormone, a growth hormone agonist, estrogen, an estrogen agonist, a neurokinin-1 drug, and an antipsychotic agent, in free or pharmaceutically acceptable salt form.

17 . The method of claim 1 , further comprising administering one or more additional therapeutic agents selected from a group consisting of modafinil, armodafinil, doxepin, alprazolam, bromazepam, clobazam, clonazepam, clorazepate, diazepam, flunitrazepam, flurazepam, lorazepam, midazolam, nitrazepam, oxazepam, temazepam, triazolam, indiplon, zopiclone, eszopiclone, zaleplon, Zolpidem, gaboxadol, vigabatrin, tiagabine, estazolam, ketanserin, risperidone, eplivanserin, volinanserin, pruvanserin, repinotan, sarizotan, eptapirone, buspirone, melatonin, ramelteon agomelatine, lamotrigine, gabapentin, pregabalin, orexin, ritanserin, nefazodone, serzone, trazodone, Casopitant, amitriptyline, amoxapine, bupropion, citalopram, clomipramine, desipramine, doxepin, duloxetine, escitalopram, fluoxetine, fluvoxamine, imipramine, isocarboxazid, maprotiline, mirtazapine, nortriptyline, paroxetine, phenelzine sulfate, protriptyline, sertraline, tranylcypromine, trimipramine, venlafaxine, chlorpromazine, haloperidol, droperidol, fluphenazine, loxapine, mesoridazine molindone, perphenazine, pimozide, prochlorperazine, promazine, thioridazine, thiothixene, trifluoperazine, clozapine, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone, and paliperidone, in free or pharmaceutically acceptable salt form.

18 . The method of claim 1 , wherein the patient has not responded adequately to treatment with another antidepressant or combination of antidepressants.

19 . The method of claim 17 , wherein the patient has not responded to treatment with one or more antidepressants selected from selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants.

20 . The method of claim 19 , wherein the patient has not responded to treatment with a SSRI.

21 . The method of claim 19 , wherein the selective serotonin reuptake inhibitors are selected from the group consisting of citalopram, escitalopram oxalate, fluoxetine, fluvoxamine maleate, paroxetine, sertraline, and dapoxetine.

22 . The method of claim 19 , wherein the serotonin-norepinephrine reuptake inhibitors are selected from venlafaxine, desvenlafaxine, duloxetine, milnacipran, levomilnacipran, and sibutramine.

23 . The method of claim 20 , wherein the selective serotonin reuptake inhibitors are selected from the group consisting of citalopram, fluoxetine, paroxetine, and sertraline.

24 . The method of claim 3 , wherein the compound of Formula I is in the form of a toluenesulfonic acid salt.

Assignments (1)

Continuity (7)

References Cited (288)