1-(4-(2-((1-(3,4-DIFLUOROPHENYL)-1H-PYRAZOL-3-YL)METHOXY)ETHYL)PIPERAZIN-1-YL)ETHANONE SALTS

• US 20180251430A1
• Filed: 09/01/2016
• Published: 09/06/2018
• Est. Priority Date: 09/02/2015
• Status: Active Grant

• Current Assignee: Esteve Pharmaceuticals S.A. (Corporation Quimico Farmaceutica Esteve SA)
• Original Assignee: Laboratories Del Dr Esteve SA (Corporation Quimico Farmaceutica Esteve SA)
• Inventors: Torrens-Jover, Antoni, Almansa Rosales, Carmen
• Granted Patent: US 10,640,468 B2
• Time in Patent Office: Days
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 25/32 Alcohol-abuse
• CPC Class Codes: A61P 25/34 Tobacco-abuse
• CPC Class Codes: A61P 25/36 Opioid-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 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/06 : Antiarrhythmics
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07B 2200/13 : Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07D 231/12 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 403/12 : linked by a chain containing hetero atoms as chain links

Abstract

The present invention relates to 1-(4-(2-((1-(3,4-difluorophenyl)-1 H-pyrazol-3-yl)methoxy)ethyl)piperazin-1-yl)ethanone salts, specifically to the hydrochloride and to the maleate, to pharmaceutical compositions comprising them, and to their use in therapy and/or prophylaxis of sigma receptor associated diseases.

Claims

1-12. -12. (canceled)

13. A crystalline salt of 1-(4-(2-((1-(3,4-difluorophenyl)-1H-pyrazol-3-yl)methoxy)ethyl)piperazin-1-yl)ethanone.

14. The crystalline salt according to claim 13 wherein the salt is selected from the group consisting of inorganic acids, sulphonic acids and organic acids.

15. The crystalline salt according to claim 13 wherein said salt is selected from hydrochloride, maleate, fumarate, malonate, succinate, oxalate and/or hydrobromide.

16. The crystalline salt according to claim 13 wherein the salt is the hydrochloride salt of 1-(4-(2-((1-(3,4-difluorophenyl)-1H-pyrazol-3-yl)methoxy)ethyl)piperazin-1-yl)ethanone.

17. The crystalline salt according to claim 13 wherein the salt is the maleate salt of 1-(4-(2-((1-(3,4-difluorophenyl)-1H-pyrazol-3-yl)methoxy)ethyl)piperazin-1-yl)ethanone.

18. A pharmaceutical composition comprising at least a crystalline salt according to claim 13.

19. A method for the manufacture of a medicament comprising combining the crystalline salt as defined in claim 13 with a pharmaceutically acceptable excipient.

20. A method for the treatment and/or prophylaxis of a sigma receptor mediated disease, comprising administering to a patient in need of such a treatment or prophylaxis a therapeutically effective amount of a crystalline salt as defined in claim 13.

21. The method according to claim 20 wherein the disease is selected from the group consisting of diarrhoea;

lipoprotein disorders;

migraine;

obesity;

arthritis;

hypertension;

arrhythmia;

ulcer;

learning, memory and attention deficits;

cognition disorders;

neurodegenerative diseases;

demyelinating diseases;

addiction to drugs and chemical substances;

tardive dyskinesia;

epilepsy;

stroke;

stress;

cancer;

psychotic conditions;

inflammation;

or autoimmune diseases.

22. The method according to claim 21, wherein the addiction to drugs and chemical substances is selected from addiction to cocaine, amphetamine, ethanol or nicotine;

wherein the stroke is ischemic stroke; and

wherein the psychotic conditions are selected from depression, anxiety or schizophrenia.

23. The method according to claim 20 wherein the disease is pain.

24. The method according to claim 23 wherein the pain is neuropathic pain, inflammatory pain or other pain conditions involving allodynia and/or hyperalgesia.

25. The method according to claim 23 wherein the salt administered to the patient is the hydrochloride salt of 1-(4-(2-((1-(3,4-difluorophenyl)-1H-pyrazol-3-yl)methoxy)ethyl)piperazin1-yl)ethanone.

26. The method according to claim 24 wherein the salt administered to the patient is the hydrochloride salt of 1-(4-(2-((1-(3,4-difluorophenyl)-1H-pyrazol-3-yl)methoxy)ethyl)piperazin-1-yl)ethanone.

27. The method according to claim 23 wherein the salt administered to the patient is the maleate salt of 1-(4-(2-((1-(3,4-difluorophenyl)-1H-pyrazol-3-yl)methoxy)ethyl)piperazin-1-yl)ethanone.

28. The method according to claim 24 wherein the salt administered to the patient is the maleate salt of 1-(4-(2-((1-(3,4-difluorophenyl)-1H-pyrazol-3-yl)methoxy)ethyl)piperazin-1-yl)ethanone.