SARMs and method of use thereof

Patent metadata

Field	Value
Publication number	US-9844528-B2
Application number	US-201615190732-A
Country	US
Kind code	B2
Filing date	Jun 23, 2016
Priority date	Aug 24, 2006
Publication date	Dec 19, 2017
Grant date	Dec 19, 2017

Abstract

This invention is directed to substituted acylanilide compounds and uses thereof in treating muscular dystrophies such as Duchenne muscular dystrophy and Becker muscular dystrophy and in improving or preserving lung function and cardiac function in a subject suffering from Duchenne muscular dystrophy.

First claim

What is claimed is:

1. A method of treating, reducing the severity, reducing the incidence, delaying the onset, or reducing the pathogenesis of Duchenne muscular dystrophy in a subject in need thereof, comprising the step of administering to said subject a combination comprising a selective androgen receptor modulator (SARM) compound and a therapeutic agent selected from the group consisting of an exon-skipping anti-sense oligonucleotide, exon skipping anti-sense molecule, utrophin up-regulator, up-regulator of other proteins that co-localize with dystrophin, myostatin inhibitor, stem cell based gene therapy, virus vectored gene therapy, non-sense codon skipping molecule, respiratory supportive care, cardiac supportive care, anti-inflammatory agent, anti-fibrotic agent, anti-oxidant, anabolic agent, nitric oxide donor, nitric oxide precursor, nitric oxide modulator, agent that improves mitochondrial function, and/or agent that promotes calcium homeostasis;
wherein said SARM compound is represented by the structure of formula S-XXIII:

or its optical isomer, pharmaceutically acceptable salt, or any combination thereof.

2. The method of claim 1 , wherein said combination is a combination of the SARM compound and an exon-skipping molecule.

3. The method of claim 1 , wherein said combination is a combination of the SARM compound and an utrophin up-regulator.

4. The method of claim 1 , wherein said combination is a combination of the SARM compound and a myostatin inhibitor.

5. A method of increasing the physical function of a subject suffering from Duchenne muscular dystrophy, comprising the step of administering to said subject a combination comprising a selective androgen receptor modulator (SARM) compound and a therapeutic agent selected from the group consisting of an exon-skipping anti-sense oligonucleotide, exon skipping anti-sense molecule, utrophin up-regulator, up-regulator of other proteins that co-localize with dystrophin, myostatin inhibitor, stem cell based gene therapy, virus vectored gene therapy, non-sense codon skipping molecule, respiratory supportive care, cardiac supportive care, anti-inflammatory agent, anti-fibrotic agent, anti-oxidant, anabolic agent, nitric oxide donor, nitric oxide precursor, nitric oxide modulator, agent that improves mitochondrial function, and/or agent that promotes calcium homeostasis,
wherein said SARM compound is represented by the structure of formula S-XXIII:

or its optical isomer, pharmaceutically acceptable salt, or any combination thereof.

6. A method of increasing the quality of life of a subject suffering from Duchenne muscular dystrophy, comprising the step of administering to said subject a combination comprising a selective androgen receptor modulator (SARM) compound and a therapeutic agent selected from the group consisting of an exon-skipping anti-sense oligonucleotide, exon skipping anti-sense molecule, utrophin up-regulator, up-regulator of other proteins that co-localize with dystrophin, myostatin inhibitor, stem cell based gene therapy, virus vectored gene therapy, non-sense codon skipping molecule, respiratory supportive care, cardiac supportive care, anti-inflammatory agent, anti-fibrotic agent, anti-oxidant, anabolic agent, nitric oxide donor, nitric oxide precursor, nitric oxide modulator, agent that improves mitochondrial function, and/or agent that promotes calcium homeostasis, wherein said SARM compound is represented by the structure of formula S-XXIII:

or its optical isomer, pharmaceutically acceptable salt, or any combination thereof.

7. A method of increasing the survival of a subject suffering from Duchenne muscular dystrophy, comprising the step of administering to said subject a combination comprising a selective andrgen receptor modulator (SARM) compound and a therapeutic agent selected from the group consisting of an exon-skipping anti-sense oligonucleotide, exon skipping anti-sense molecule, utrophin up-regulator, up-regulator of other proteins that co-localize with dystrophin, myostatin inhibitor, stem cell based gene therapy, virus vectored gene therapy, non-sense codon skipping molecule, respiratory supportive care, cardiac supportive care, anti-inflammatory agent, anti-fibrotic agent, anti-oxidant, anabolic agent, nitric oxide donor, nitric oxide precursor, nitric oxide modulator, agent that improves mitochondrial function, and/or agent that promotes calcium homeostasis, wherein said SARM compound is represented by the structure of formula S-XXIII:

or its optical isomer, pharmaceutically acceptable salt, or any combination thereof.

8. A method of treating, reducing the severity, reducing the incidence, delaying the onset, or reducing the pathogenesis of cardiomyopathy in a subject suffering from Duchenne muscular dystrophy, comprising the step of administering to said subject a combination comprising a selective androgen receptor modulator (SARM) compound and a therapeutic agent selected from the group consisting of an exon-skipping anti-sense oligonucleotide, exon skipping anti-sense molecule, utrophin up-regulator, up-regulator of other proteins that co-localize with dystrophin, myostatin inhibitor, stem cell based gene therapy, virus vectored gene therapy, non-sense codon skipping molecule, respiratory supportive care, cardiac supportive care, anti-inflammatory agent, anti-fibrotic agent, anti-oxidant, anabolic agent, nitric oxide donor, nitric oxide precursor, nitric oxide modulator, agent that improves mitochondrial function, and/or agent that promotes calcium homeostasis, wherein said SARM compound is represented by the structure of formula S-XXIII:

or its optical isomer, pharmaceutically acceptable salt, or any combination thereof.

9. A method of treating, reducing the severity, reducing the incidence, delaying the onset, or reducing the pathogenesis of respiratory failure in a subject suffering from Duchenne muscular dystrophy, comprising the step of administering to said subject a combination comprising a selective androgen receptor modulator (SARM) compound and a therapeutic agent selected from the group consisting of an exon-skipping anti-sense oligonucleotide, exon skipping anti-sense molecule, utrophin up-regulator, up-regulator of other proteins that co-localize with dystrophin, myostatin inhibitor, stem cell based gene therapy, virus vectored gene therapy, non-sense codon skipping molecule, respiratory supportive care, cardiac supportive care, anti-inflammatory agent, anti-fibrotic agent, anti-oxidant, anabolic agent, nitric oxide donor, nitric oxide precursor, nitric oxide modulator, agent that improves mitochondrial function, and/or agent that promotes calcium homeostasis, wherein said SARM compound is represented by the structure of formula S-XXIII:

or its optical isomer, pharmaceutically acceptable salt, or any combination thereof.

10. A method of treating, reducing the severity, reducing the incidence, delaying the onset, or reducing the pathogenesis of Becker muscular dystrophy in a subject in need thereof, comprising the step of administering to said subject a combination compris

Assignees

• Univ Tennessee Res Found

Inventors

• Dalton James T
• Ponnusamy Thamarai
• Narayanan Ramesh

Classifications

• A61K45/06

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

• A61K31/277 Primary

  having a ring, e.g. verapamil · CPC title