Use of Sphingosine-1-phosphate (S1P) Receptor Agonists for the Treatment of Brain Degenerative Diseases

• US 20110124739A1
• Filed: 09/17/2010
• Published: 05/26/2011
• Est. Priority Date: 12/19/2003
• Status: Active Grant

• Current Assignee: Novartis Ag
• Original Assignee: Novartis Ag
• Inventors: Kaneider, Nicole, Wiedermann, Christian J., Brinkmann, Volker
• Granted Patent: US 8,519,006 B2
• Time in Patent Office: Days
• US Class Current: 514/653
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/133 having hydroxy groups, e.g. sphingosine
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/4245 Oxadiazoles
• CPC Class Codes: A61K 31/4725 containing further heterocyclic rings
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/498 Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
• CPC Class Codes: A61K 31/502 ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
• CPC Class Codes: A61K 31/5025 ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• CPC Class Codes: A61K 31/661 Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61K 31/7024 Esters of saccharides
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Disclosed is the use of sphingosine-1-phosphate (S1P) receptor agonists, preferably 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol, in the treatment of progressive dementia or brain degenerative diseases

Claims

1-3. -3. (canceled)

4. A pharmaceutical composition for use in treating progressive dementia or brain degeneration, β

-amyloid-related inflammatory diseases or disorders or for reducing or inhibiting loss of cognitive abilities comprising a sphingosine-1-phosphate (S1P) receptor agonist or a pharmaceutically acceptable salt thereof together with one or more pharmaceutically acceptable diluents or carriers therefore.

9. A composition according to claim 4, wherein the S1P receptor agonist is compound of formula I

10. A composition according to claim 9, wherein the S1P receptor agonist is 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol in free form or in a pharmaceutically acceptable salt form.

5. A pharmaceutical combination comprising a) a first agent which is a S1P receptor agonist or a pharmaceutically acceptable salt thereof and b) a co-agent useful in the alleviation or treatment of brain degenerative diseases or progressive dementia.

6. A combination according to claim 5, wherein co-agent b) is selected from an AMPA receptor agonist, a noortropic or anti-inflammatory agent or a painkiller.

11. A combination according to claim 5, wherein the S1P receptor agonist is compound of formula I

13. A combination according to claim 11, wherein the S1P receptor agonist is 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol in free form or in a pharmaceutically acceptable salt form.

7. A method for treating progressive dementia or brain degeneration or β

-amyloid-related inflammatory diseases or disorders or for reducing or inhibiting loss of cognitive abilities in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a sphingosine-1-phosphate (S1P) receptor agonist or a pharmaceutically acceptable salt thereof.

8. A method according to claim 7 comprising co-administration, e.g. concomitantly or in sequence, of b) a co-agent useful in the alleviation or treatment of brain degenerative diseases or progressive dementia.

12. A method according to claim 7, wherein the S1P receptor agonist is compound of formula I

14. A method according to claim 12, wherein the S1P receptor agonist is 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol in free form or in a pharmaceutically acceptable salt form.