4-hydroxybutyric acid analogs

Patent metadata

Field	Value
Publication number	US-2016326086-A1
Application number	US-201615095545-A
Country	US
Kind code	A1
Filing date	Apr 11, 2016
Priority date	Feb 14, 2011
Publication date	Nov 10, 2016
Grant date	—

Abstract

This invention relates to novel derivatives of 4-hydroxybutyric acid and prodrugs thereof, and pharmaceutically acceptable salts of the foregoing. This invention also provides pharmaceutical compositions comprising a compound of this invention and the use of such compositions in methods of treating narcolepsy, fibromyalgia, other disorders or conditions that are beneficially treated by improving nocturnal sleep or by administering sodium oxybate.

First claim

1 . A compound of Formula IV-b:

or a pharmaceutically acceptable salt thereof.

2 . A pharmaceutical composition comprising an effective amount of a compound of Formula IV

wherein:
A is hydrogen, deuterium, —CH 2 —C(O)OR 2 or —CH(R 1 )—C(O)OR 2 ;
R 1 is a C 1-6 alkyl, C 2-10 alkoxyalkyl, or C 3-6 cycloalkyl group that is optionally substituted by an R 3 group;
R 3 is C 1-3 alkyl, C 1-3 alkoxy, phenyl, —O—(CH 2 CH 2 O) n —CH 3 , or -(heterocyclyl)-C 1-3 alkyl where the heterocyclyl moiety is a four to six-membered ring having an oxygen ring atom;
n is 1, 2, or 3;
R 2 is hydrogen, deuterium, —C 1-4 alkyl, —C 1-4 alkyl-phenyl, —C 3-6 cycloalkyl, —C 3-6 cycloalkyl-phenyl, —CH 2 —(C 3-6 cycloalkyl), —CH 2 —(C 3-6 cycloalkyl)-phenyl, phenyl, or biphenyl;
X is hydrogen, deuterium, —C(O)-indanyl, —C(O)-indenyl, —C(O)-tetrahydronaphthyl, —C(O)—C 1-6 alkyl, —C(O)—C 1-6 alkenyl, —C(O)—C 1-6 alkynyl, —C(O)—C 1-3 alkyl-(C 3-6 cycloalkyl), or —C(O)—C 3-6 cycloalkyl optionally substituted by C 1-6 alkyl, phenyl or naphthyl; and
each Y is independently selected from hydrogen and deuterium,

or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

3 . The composition of claim 2 , wherein the compound is a compound of the formula IV-a:

or a pharmaceutically acceptable salt thereof.

4 . The composition of claim 2 , wherein the compound is a compound of the formula IV-b:

or a pharmaceutically acceptable salt thereof.

5 . The composition of claim 2 , wherein the compound is a compound of the formula IV-c:

or a pharmaceutically acceptable salt thereof.

6 . The composition of claim 2 , wherein the compound is a compound of the formula IV-d:

or a pharmaceutically acceptable salt thereof.

7 . The composition of claim 2 , additionally comprising a second therapeutic agent selected from a dual serotonin-norepinephrine reuptake inhibitor and an alpha2-delta subunit calcium channel modulator.

8 . The composition of claim 7 , wherein the second therapeutic agent is selected from duloxetine, milnacipran, venlafaxine, pregabalin, gabapentin, and prodrugs thereof.

9 . A method of treating a disease or disorder selected from abnormal nocturnal sleep, narcolepsy, fibromyalgia, excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, sleep paralysis, fragmented sleep, alcohol withdrawal and dependence, Parkinson's disease, narcolepsy with cataplexy, obstructive sleep apnea syndrome, insomnia including insomnia associated to schizophrenia,
sleep initiation and maintenance disorders, chronic fatigue syndrome, essential tremor, hemiplegia in patients with alternating hemiplegia of childhood, sedative abuse, binge eating disorder, or other diseases or disorders beneficially treated by improving nocturnal sleep or by administering sodium oxybate, comprising the step of administering to a patient in need thereof an effective amount of a composition of claim 2 .

10 . The method of claim 9 , wherein the disease or disorder is selected from abnormal nocturnal sleep, narcolepsy, fibromyalgia, and other diseases or disorders beneficially treated by improving nocturnal sleep or by administering sodium oxybate.

11 .- 29 . (canceled)

Assignees

• Concert Pharmaceuticals Inc

Inventors

• Tung Roger D
• Morgan Adam J
• Silverman I Robert

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title

• A61P25/02

  for peripheral neuropathies · CPC title

• A61P25/20

  Hypnotics; Sedatives · CPC title

• A61P3/00

  Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) · CPC title