4-hydroxybutyric acid analogs

• US 9,309,182 B2
• Filed: 04/17/2014
• Issued: 04/12/2016
• Est. Priority Date: 02/14/2011
• Status: Active Grant

• Current Assignee: Sun Pharmaceutical Industries, Inc. (Sun Pharmaceutical Industries Limited)
• Original Assignee: Concert Pharmaceuticals Inc.
• Inventors: Tung, Roger D., Morgan, Adam J.
• Primary Examiner(s): DRAPER, LESLIE A ROYDS
• Application Number:
  US14/255,331
• Publication Number:
  US 20140343119A1
• Time in Patent Office: 726 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/22 of acyclic acids, e.g. pravastatin
• CPC Class Codes: A61K 31/225 Polycarboxylic acids
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 11/16 Central respiratory analeptics
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 25/32 Alcohol-abuse
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07B 2200/05 Isotopically modified compounds, e.g. labelled
• CPC Class Codes: C07B 59/001 Acyclic or carbocyclic compounds
• CPC Class Codes: C07C 59/01 : Saturated compounds having only one carboxyl group and containing hydroxy or O-metal groups
• CPC Class Codes: C07C 59/115 : containing halogen
• CPC Class Codes: C07C 59/125 : Saturated compounds having only one carboxyl group and containing ether groups, groups, groups, or groups
• CPC Class Codes: C07C 69/67 : of saturated acids
• CPC Class Codes: C07C 69/675 : of saturated hydroxy-carboxylic acids
• CPC Class Codes: C07C 69/708 : Ethers

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.

Claims

1. A pharmaceutical composition comprising an effective amount of a compound of Formula IV-a, wherein the compound of Formula IV-a is represented by the following structural formula:

2. The composition of claim 1, additionally comprising a second therapeutic agent selected from the group consisting of a dual serotonin-norepinephrine reuptake inhibitor and an alpha2-delta subunit calcium channel modulator.

3. The composition of claim 2, wherein the second therapeutic agent is selected from the group consisting of duloxetine, milnacipran, venlafaxine, pregabalin, gabapentin, and a prodrug thereof.

4. The composition of claim 1 wherein the composition is pyrogen-free.

5. The composition of claim 1 wherein the pharmaceutically acceptable salt is a sodium salt.

6. The composition of claim 5 where the compound has an isotopic abundance at each position indicated as “

D”

of at least 75%.

7. The composition of claim 6 where the compound has an isotopic abundance at each position indicated as “

D”

of at least 95%.

8. The composition of claim 5 where the compound has an isotopic abundance at each position indicated as “

D”

of at least 82.5%.

9. The composition of claim 5 where the compound has an isotopic abundance at each position indicated as “

D”

of at least 90%.

10. The composition of claim 5 where the compound has an isotopic abundance at each position indicated as “

D”

of at least 97%.

11. A method of treating a disease or disorder selected from the group consisting of excessive daytime sleepiness (EDS), narcolepsy with cataplexy, and obstructive sleep apnea syndrome, comprising the step of administering to a patient in need of such treatment an effective amount of the composition of claim 1.

12. The method of claim 11 comprising the additional step of administering to the patient in need thereof a second therapeutic agent selected from the group consisting of a dual serotonin-norepinephrine reuptake inhibitor and an alpha2-delta subunit calcium channel modulator.

13. The method of claim 12, wherein the second therapeutic agent is selected from the group consisting of duloxetine, milnacipran, venlafaxine, pregabalin, gabapentin, and a prodrug thereof.