Use of non-steroidal mineralocorticoid receptor antagonists alone or in combination for the treatment of muscular or neuromuscular diseases

Patent metadata

Field	Value
Publication number	US-11439628-B2
Application number	US-201917051923-A
Country	US
Kind code	B2
Filing date	May 10, 2019
Priority date	May 11, 2018
Publication date	Sep 13, 2022
Grant date	Sep 13, 2022

Abstract

The present invention relates to non-steriodal mineralocorticoid receptor (MR) and the pharmacology of mineralocorticoid receptor antagonists (MR Antagonists, MRAs). In particular, the invention relates to the use of MRAs alone and in combination preferably in combination with sGC stimulators and/or sGC activators for preparation of medicaments for the prevention and/or treatment of muscular or neuromuscular diseases, especially for the treatment of Duchenne Muscular Dystrophy (DMD).

First claim

The invention claimed is:

1. A method for the treatment and/or prevention of Duchenne muscular dystrophy in a human or animal comprising administering a therapeutically effective amount of a non-steroidal mineralocorticoid receptor antagonist that is (4S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1, 6-naphthyridine-3-carboxamide according to formula (I)

or a pharmaceutically acceptable salt thereof to a human or animal in need thereof.

2. The method of claim 1 , further comprising administering to the human or animal an additional therapeutic agent that is an sGC stimulator.

3. The method of claim 2 , wherein the sGC stimulator is selected from the group consisting of
methyl 4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl(methyl)carbamate,
methyl {4,6-diamino-245-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]pyrimidin-5-yl}carbamate,
3-(4-amino-5-cyclopropylpyrimidin-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine and
1, 1,1,3,3,3-hexafluoro-2-[({5-fluoro-2-[(2-fluorobenzyl)-5-(1,2-oxazol-3-yl)-1H-pyrazol-3-yl]-4-pyrimidinyl}amino)methyl]-2-propanol
or a pharmaceutically acceptable salt thereof.

4. The method of claim 2 , wherein the sGC stimulator is 3-(4-amino-5-cyclopropylpyrimidin-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine or a pharmaceutically acceptable salt thereof.

5. The method of claim 1 , wherein the non-steroidal mineralocorticoid receptor antagonist is administered at a dose of 5 to 40 mg once daily to a child having a body weight of approximately 70 to 80 kg.

6. The method of claim 5 , wherein the non-steroidal mineralocorticoid receptor antagonist is administered at a dose of 10 to 20 mg once daily.

7. The method of claim 2 , wherein the non-steroidal mineralocorticoid receptor antagonist is administered at a dose of 5 to 40 mg once daily to a child having a body weight of approximately 70 to 80 kg.

8. The method of claim 7 , wherein the non-steroidal mineralocorticoid receptor antagonist is administered at a dose of 10 to 20 mg once daily.

Assignees

• Bayer Ag

Inventors

• Sandner Peter
• Kolkhof Peter
• Mathar Ilka
• Breitenstein Stefanie

Classifications

• A61P21/00

  Drugs for disorders of the muscular or neuromuscular system · CPC title

• A61K31/506

  not condensed and containing further heterocyclic rings · CPC title

• A61K31/4375 Primary

  the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine · CPC title

• A61P21/04

  for myasthenia gravis · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title