Aminoglycosides and uses thereof in treating genetic disorders

Patent metadata

Field	Value
Publication number	US-11865128-B2
Application number	US-202117226050-A
Country	US
Kind code	B2
Filing date	Apr 8, 2021
Priority date	Nov 18, 2010
Publication date	Jan 9, 2024
Grant date	Jan 9, 2024

Abstract

A new class of pseudo-trisaccharide aminoglycosides having an alkyl group at the 5″ position, exhibiting efficient stop codon mutation readthrough activity, low cytotoxicity and high selectivity towards eukaryotic translation systems are provided. Also provided are pharmaceutical compositions containing the same, and uses thereof in the treatment of genetic disorders, as well as processes of preparing these aminoglycosides. The disclosed aminoglycosides can be represented by the general formula I:or a pharmaceutically acceptable salt thereof, wherein R1 is selected from the group consisting of alkyl, cycloalkyl and aryl; and all other variables and features are as described in the specification.

First claim

What is claimed is:

1. A method for treating a genetic disorder associated with a premature stop codon mutation and/or a protein truncation phenotype, the method comprising administering to a subject in need thereof a therapeutically effective amount of the compound:

or a pharmaceutically acceptable salt thereof; and
the genetic disorder being selected from the group consisting of cystic fibrosis (CF), Duchenne muscular dystrophy (DMD), ataxia-telangiectasia, Hurler syndrome, hemophilia A, hemophilia B, Usher syndrome, Tay-Sachs Becker muscular dystrophy (BMD), Congenital muscular dystrophy (CMD), Factor VII deficiency, Familial atrial fibrillation, Hailey-Hailey disease, McArdle disease, Mucopolysaccharidosis, Nephropathic cystinosis, Polycystic kidney disease, Rett syndrome, Spinal muscular atrophy (SMA), X-linked nephrogenic diabetes insipidus (XNDI) and X-linked retinitis pigmentosa.

2. The method of claim 1 , further comprising administering to the subject an additional agent useful in treating the genetic disorder.

3. A pharmaceutical composition being packaged in a packaging material and identified in print, in or on said packaging material, for use in the treatment of a genetic disorder associated with a premature stop codon mutation and/or a protein truncation phenotype, the composition comprising the compound:

or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier; and
the genetic disorder being selected from the group consisting of cystic fibrosis (CF), Duchenne muscular dystrophy (DMD), ataxia-telangiectasia, Hurler syndrome, hemophilia A, hemophilia B, Usher syndrome, Tay-Sachs Becker muscular dystrophy (BMD), Congenital muscular dystrophy (CMD), Factor VII deficiency, Familial atrial fibrillation, Hailey-Hailey disease, McArdle disease, Mucopolysaccharidosis, Nephropathic cystinosis, Polycystic kidney disease, Rett syndrome, Spinal muscular atrophy (SMA), X-linked nephrogenic diabetes insipidus (XNDI) and X-linked retinitis pigmentosa.

Assignees

• Technion Res & Dev Foundation

Inventors

• Baasov Timor
• Atia-Glikin Dana
• Kandasamy Jeyakumar
• Belakhov Valery

Classifications

• A61K31/7036 Primary

  having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins · CPC title

• A61K45/06

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

• B65D79/00

  Kinds or details of packages, not otherwise provided for · CPC title

• C07H1/00 Primary

  Processes for the preparation of sugar derivatives · CPC title

• C07H5/06

  Aminosugars · CPC title