# US 11,306,115 B2 · Aminoglycoside derivatives and uses thereof in treating genetic disorders

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- Number: US 11,306,115 B2
- Document ID: US11306115B2
- Status: Granted
- Kind: B2
- Application number: 15/756,665
- Filed: 2016-09-02
- Published: 2018-09-20
- Granted: 2022-04-19
- Earliest claimed: 2015-09-02
- Assignees: Eloxx Pharmaceuticals Ltd.
- Applicants: Eloxx Pharmaceuticals Ltd.
- Inventors: Timor Baasov
- Web page: https://patentgrep.com/patent/US11306115B2

## CPC

- C07H 15/224: with only one saccharide radical directly attached to the cyclohexyl radical, e.g. destomycin, fortimicin, neamine
- A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- A61P 7/12: Antidiuretics, e.g. drugs for diabetes insipidus (ADH A61P5/10)
- A61P 21/04: for myasthenia gravis
- C07H 15/23: with only two saccharide radicals in the molecule, e.g. ambutyrosin, butyrosin, xylostatin, ribostamycin
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Novel pseudo-disaccharide and pseudo-trisaccharide aminoglycosides, represented by Formulae I or Ia, as defined in the instant specification, designed to exhibit stop codon mutation readthrough activity, are provided. Also provided are pharmaceutical compositions containing the same, and uses thereof in the treatment of genetic diseases and disorders, such as diseases and disorders associated with stop codon mutations.

## Claims

### Claim 1

A compound represented by general formula I:
or a pharmaceutically acceptable salt thereof,
wherein:
the dashed lines indicates a stereo-configuration of position 6′ being an R configuration or an S configuration;
R1 is alkyl, cycloalkyl or aryl;
R2 is selected from a substituted or unsubstituted alkyl, OR′ and NR′R″, wherein each of R′ and R″ is independently selected from hydrogen, a substituted or unsubstituted alkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted alkaryl, and an acyl;
R4 is selected from an unsubstituted linear or branched alkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted alkaryl, a guanidinyl, and a guanyl; and
R3 is hydrogen or a monosaccharide moiety represented by Formula II:
wherein the curved line denotes a position of attachment; and
R5 and R6 are each independently selected from hydrogen, a substituted or unsubstituted alkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted alkaryl, and a substituted or unsubstituted heteroaryl, acyl, guanidinyl, and guanyl, or, alternatively, R5 and R6 form together a heterocyclic ring.

### Claim 2 (depends on 1)

The compound of claim 1, wherein R3 is said monosaccharide moiety, the compound being represented by Formula la:

### Claim 3 (depends on 1)

The compound of claim 1, wherein R1 is alkyl.

### Claim 4 (depends on 2)

The compound of claim 2, wherein R1 is alkyl.

### Claim 5 (depends on 1)

The compound of claim 1, wherein R2 is OR′.

### Claim 6 (depends on 2)

The compound of claim 2, wherein R2 is OR′.

### Claim 7 (depends on 5)

The compound of claim 5, wherein R′ is hydrogen.

### Claim 8 (depends on 6)

The compound of claim 6, wherein R′ is hydrogen.

### Claim 9 (depends on 1)

The compound of claim 1, wherein R4 is an unsubstituted linear or branched alkyl.

### Claim 10 (depends on 2)

The compound of claim 2, wherein R4 is an unsubstituted linear or branched alkyl.

### Claim 11 (depends on 1)

The compound of claim 1, wherein R4 is a substituted or unsubstituted alkaryl.

### Claim 12 (depends on 2)

The compound of claim 2, wherein R4 is a substituted or unsubstituted.

### Claim 13 (depends on 1)

The compound of claim 1, wherein R4 is an unsubstituted linear alkyl.

### Claim 14 (depends on 2)

The compound of claim 2, wherein R4 is an unsubstituted branched alkyl.

### Claim 15 (depends on 3)

The compound of claim 3, wherein R4 is an unsubstituted linear or branched alkyl or alkaryl.

### Claim 16 (depends on 5)

The compound of claim 5, wherein R4 is an unsubstituted linear or branched alkyl or alkaryl.

### Claim 17 (depends on 1)

The compound of claim 1, wherein R3 is hydrogen.

### Claim 18 (depends on 17)

The compound of claim 17, being selected from:

### Claim 19 (depends on 1)

The compound of claim 1, wherein R5 and R6 are each hydrogen.

### Claim 20 (depends on 19)

The compound of claim 19, being:

### Claim 21 (depends on 1)

A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.

### Claim 22 (depends on 1)

A method of treating a genetic disorder associated with a premature stop codon mutation in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of claim 1.

### Claim 23 (depends on 22)

The method of claim 22, wherein said genetic disorder is 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 disease, Becker muscular dystrophy (BMD), Congenital muscular dystrophy (CMD), Factor VII deficiency, Familial atrial fibrillation, HaileyHailey 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.