1-[2-(2,4-Dimethylphenylsulfanyl)-Phenyl]Piperazine As A Compound With Combined Serotonin Reuptake, 5-HT3 And 5-HT1a Activity For The Treatment Of Cognitive Impairment

• US 20140248356A1
• Filed: 04/01/2014
• Published: 09/04/2014
• Est. Priority Date: 06/16/2006
• Status: Active Grant

• Current Assignee: H. Lundbeck A/S (Lundbeck Foundation)
• Original Assignee: H. Lundbeck A/S (Lundbeck Foundation)
• Inventors: Bang-Andersen, Benny, Mork, Arne, Moore, Nicholas, Stensbol, Tine Bryan
• Granted Patent: US 9,125,908 B2
• Time in Patent Office: Days
• US Class Current: 424/489
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/16 Central respiratory analeptics
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 19/10 for osteoporosis
• 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 25/16 Anti-Parkinson drugs
• 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 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/10 : Antioedematous agents; Diuretics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 295/096 : with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• CPC Class Codes: Y02P 20/55 : Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
• CPC Class Codes: Y10T 428/2982 : Particulate matter [e.g., sphere, flake, etc.]

Abstract

1-[2-(2,4-dimethylphenylsulphanyl)phenyl]piperazine exhibits potent activity on SERT, 5-HT₃ and 5-HT_1A and may as such be useful for the treatment of cognitive impairment, especially in depressed patients.

Claims

1-14. -14. (canceled)

15. A method of curative treating a disease selected from the group consisting of Alzheimer'"'"'s disease, cognitive impairment, and attention deficit hyperactivity disorder (ADHD), the method comprising administering a therapeutically effective amount of Compound I to patient in need thereof, wherein Compound I is 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine or a pharmaceutically acceptable salt thereof and is crystalline.

44. The method of claim 15, wherein Compound I is a hydrobromide salt of 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine.

45. The method of claim 44, wherein the hydrobromide salt is characterized by XRPD reflections at 6.89, 9.73, 13.78 and 14.64+/−

0.10°

2θ

.

46. The method of claim 45, wherein the hydrobromide salt is characterized by an XRPD as shown in FIG. 3.

47. The method of claim 45, wherein Compound I has a particle size distribution corresponding to:

D98%;

650-680 μ

m;

D50%;

230-250 μ

m; and

D5%;

40-60 μ

m;

D98%;

370-390 μ

m;

d50%;

100-120 μ

m; and

D5%;

5-15 μ

m;

D98%;

100-125 μ

m;

D50%;

15-25 μ

m; and

D5%;

1-3 μ

m;

or

D98%;

50-70 μ

m;

D50%;

3-7 μ

m; and

D5%;

0.5-2 μ

m.

48. The method of claim 15, wherein the disease is Alzheimer'"'"'s disease.

49. The method of claim 15, wherein the disease is cognitive impairment.

50. The method of claim 15, wherein the disease is ADHD.

16-43. -43. (canceled)