The use of sgc activators and sgc stimulators for the treatment of cognitive impairment

Patent metadata

Field	Value
Publication number	US-2021052528-A1
Application number	US-201917051060-A
Country	US
Kind code	A1
Filing date	Apr 12, 2019
Priority date	Apr 30, 2018
Publication date	Feb 25, 2021
Grant date	—

Abstract

The present invention relates to sGC activators and sGC stimulators for use in the treatment of cognitive impairment in a mammal in need of such treatment, in particular for use in the treatment of vascular dementia.

First claim

1 - 14 . (canceled)

15 . A method of treating cognitive impairment in a mammal in need of such treatment, comprising administering to the mammal a therapeutically effective amount of a sGC activator or a pharmaceutically acceptable salt thereof, wherein the sGC activator is administered orally at a daily dose of 0.2 to 25 mg.

16 . The method of claim 15 , wherein the sGC activator is 3-(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)-3-cyclopropylpropanoic acid of formula (1)

or a pharmaceutically acceptable salt thereof.

17 . The method of claim 15 , wherein the orally administered daily dose is 1 to 10 mg.

18 . The method of claim 15 , wherein the orally administered daily dose does not significantly reduce blood pressure.

19 . The method of claim 15 , wherein cognitive impairment is selected from the group consisting of mild cognitive impairment, dementia, vascular dementia, Alzheimer dementia and cognitive impairment associated with cerebral infarctions, cerebral ischemia and ischemic stroke.

20 . The method of claim 19 , wherein cognitive impairment is vascular dementia.

21 . The method of claim 16 further comprising administering to the mammal at least one compound selected from the group consisting of organic nitrates and NO-donors, inhibitors of phosphodiesterases 1, 2, 3, 4 or 5, anti-inflammatory compounds, immunosuppressive compounds, acetylcholinesterase inhibitors, NMDA receptor antagonists, compounds suitable for lowering blood pressure, antithrombotic compounds, compounds suitable for altering fat metabolism and antidiabetic compounds.

22 . The method of claim 16 further comprising administering to the mammal at least one compound selected from the group consisting of donepezil, rivastigmine, galantamine and memantine.

23 . A method of treating cognitive impairment in a mammal in need of such treatment, comprising administering to the mammal a therapeutically effective amount of methyl{4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate of formula (5)

or a pharmaceutically acceptable salt thereof, wherein the compound of the formula (5) or a pharmaceutically acceptable salt thereof is administered orally at a daily dose of 1 to 6 mg.

24 . The method of claim 23 , wherein the compound of formula (5) or a pharmaceutically acceptable salt thereof is administered orally at a daily dose of 1 to 3 mg.

25 . The method of claim 23 , wherein the orally administered daily dose does not significantly reduce blood pressure.

26 . The method of claim 23 , wherein cognitive impairment is selected from the group consisting of mild cognitive impairment, dementia, vascular dementia, Alzheimer dementia and cognitive impairment associated with cerebral infarctions, cerebral ischemia and ischemic stroke.

27 . The method of claim 26 , wherein cognitive impairment is vascular dementia.

28 . The method of claim 23 further comprising administering to the mammal at least one compound selected from the group consisting of organic nitrates and NO-donors, inhibitors of phosphodiesterases 1, 2, 3, 4 or 5, anti-inflammatory compounds, immunosuppressive compounds, acetylcholinesterase inhibitors, NMDA receptor antagonists, compounds suitable for lowering blood pressure, antithrombotic compounds, compounds suitable for altering fat metabolism and antidiabetic compounds.

29 . The method of claim 23 further comprising administering to the mammal at least one compound selected from the group consisting of donepezil, rivastigmine, galantamine and memantine.

30 . A method of treating cognitive impairment in a mammal in need of such treatment, comprising administering to the mammal a therapeutically effective amount of ent-N-[(2S)-amino-2-methylbutyl]-8-[(2,6-difluorobenzyl)oxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxamide (enantiomer A) of formula (6)

or a pharmaceutically acceptable salt thereof, wherein the compound of formula (6) is administered orally at a daily dose of 0.2 to 6 mg.

31 . The method of claim 30 , wherein the compound of formula (6) or a pharmaceutically acceptable salt thereof is administered orally at a daily dose of 0.3 to 3 mg.

32 . The method of claim 30 , wherein the orally administered daily dose does not significantly reduce blood pressure.

33 . The method of claim 30 , wherein cognitive impairment is selected from the group consisting of mild cognitive impairment, dementia, vascular dementia, Alzheimer dementia and cognitive impairment associated with cerebral infarctions, cerebral ischemia and ischemic stroke.

34 . The method of claim 33 , wherein cognitive impairment is vascular dementia.

35 . The method of claim 30 further comprising administering to the mammal at least one compound selected from the group consisting of organic nitrates and NO-donors, inhibitors of phosphodiesterases 1, 2, 3, 4 or 5, anti-inflammatory compounds, immunosuppressive compounds, acetylcholinesterase inhibitors, NMDA receptor antagonists, compounds suitable for lowering blood pressure, antithrombotic compounds, compounds suitable for altering fat metabolism and antidiabetic compounds.

36 . The method of claim 30 further comprising administering to the mammal at least one compound selected from the group consisting of donepezil, rivastigmine, galantamine and memantine.

Assignees

• Bayer Ag

Inventors

• Sandner Peter
• Prickaerts Jos

Classifications

• A61K31/192 Primary

  having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid  {(cannabinoids A61K31/658)} · CPC title

• A61K31/13

  Amines {(A61K31/04 takes precedence)} · CPC title

• A61K31/506

  not condensed and containing further heterocyclic rings · CPC title

• A61K31/445

  Non condensed piperidines, e.g. piperocaine · CPC title

• A61K31/195

  having an amino group · CPC title