# US 11,992,469 B2 · Targeting mitochondrial dynamics by mitochondrial fusion promoter M1 as a treatment strategy for nervous system injury

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- Number: US 11,992,469 B2
- Document ID: US11992469B2
- Status: Granted
- Kind: B2
- Application number: 17/448,215
- Filed: 2021-09-21
- Published: 2022-03-24
- Granted: 2024-05-28
- Earliest claimed: 2020-09-22
- Assignees: City University of Hong Kong
- Applicants: City University of Hong Kong
- Inventors: Chi Him Eddie Ma; Ngan Pan Bennett Au
- Web page: https://patentgrep.com/patent/US11992469B2

## CPC

- A61K 31/15: Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) {; Imines (C—N=C)}
- A61P 25/02: for peripheral neuropathies
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Provided herein are methods of treating a nerve injury in a subject in need thereof and methods of treating an injured neuron using diaryl hydrazones.

## Claims

### Claim 1

A method of treating a nerve injury in a subject in need thereof, the method comprising administering a therapeutically effective amount of a compound to the subject, wherein the compound has Formula I:
or a conjugate salt thereof, wherein
m is a whole number selected from 1-4;
n is a whole number selected from 1-4;
R1 and R2 for each instance is independently selected from the group consisting of halide, nitrite, nitro, phosphate, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, —OR, —SR, and —NR2;
R3 is C1-C6 alkyl;
R4 is hydrogen or alkyl; and
R for each instance is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, and heteroaryl.

### Claim 2 (depends on 1)

The method of claim 1, wherein R4 is hydrogen.

### Claim 3 (depends on 1)

The method of claim 1, wherein R1 and R2 for each instance is independently halide, nitrite, nitro, phosphate, —OR, —SR, and —NR2, wherein R for each instance is independently hydrogen or alkyl.

### Claim 4 (depends on 1)

The method of claim 1, wherein R1 and R2 for each instance is independently halide or hydroxyl.

### Claim 5 (depends on 1)

The method of claim 1, wherein m is a whole number selected from 1-2; n is a whole number selected from 1-3; R1 and R2 for each instance is independently halide, nitrite, nitro, phosphate, —OR, —SR, and —NR2, wherein R for each instance is independently hydrogen or alkyl; R3 is C1-C6 alkyl; and R4 is hydrogen.

### Claim 6 (depends on 5)

The method of claim 5, wherein the compound has the Formula II:
or a conjugate salt thereof, wherein each of R5, R6, R7, R8, and R9 is independently halide, nitrile, nitro, phosphate, methyl, —OR, —SR, or —NR2, wherein R for each instance is independently hydrogen or alkyl; and R3 is C1-C6 alkyl.

### Claim 7 (depends on 6)

The method of claim 6, wherein each of R5, R6, R7, R8, and R9 is independently halide, methyl, or OR, wherein R for each instance is independently hydrogen or C1-C6 alkyl.

### Claim 8 (depends on 6)

The method of claim 6, wherein R3 is methyl.

### Claim 9 (depends on 1)

The method of claim 1, wherein the compound is:
or a conjugate salt thereof.

### Claim 10 (depends on 1)

The method of claim 1, wherein the nerve injury comprises at least one of a central nervous system injury or a peripheral nervous system injury.

### Claim 11 (depends on 1)

The method of claim 1, wherein the compound promotes the regrowth of injured axons.

### Claim 12 (depends on 1)

The method or claim 1, wherein the compound is administered intravitreally, intraperitoneally, suprachoroidally, subconjunctivally, retrobulbarly, intracamerally, or subretinally.

### Claim 13 (depends on 1)

The method of claim 1, wherein the compound is co-administered with a therapeutically effective amount of a phosphatase and tensin homolog (Pten) inhibitor.

### Claim 14 (depends on 1)

The method of claim 1, wherein the compound is:
or a conjugate salt thereof.

### Claim 15

A method of treating an injured neuron, the method comprising contacting the injured neuron with a compound, wherein the compound has Formula I:
or a conjugate salt thereof, wherein
m is a whole number selected from 1-4;
n is a whole number selected from 1-4;
R1 and R2 for each instance is independently selected from the group consisting of halide, nitrile, nitro, phosphate, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, —OR, —SR, and —NR2;
R3 is C1-C6 alkyl;
R4 is hydrogen or allyl; and
R for each instance is independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, and heteroaryl, wherein the step of contacting the injured neuron occurs in vitro or ex vivo.

### Claim 16 (depends on 15)

The method of claim 15, wherein m is a whole number selected from 1-2; n is a whole number selected from 1-3; R1 and R2 for each instance is independently halide, nitrile, nitro, phosphate, —OR, —SR, and —NR2, wherein R for each instance is independently hydrogen or alkyl; R3 is C1-C6 alkyl; and R4 is hydrogen.

### Claim 17 (depends on 16)

The method of claim 16, wherein the compound has the Formula II:
or a conjugate salt thereof, wherein each of R5, R6, R7, R8, and R9 is independently halide, nitrile, nitro, phosphate, methyl, —OR, —SR, or —NR2, wherein R for each instance is independently hydrogen or alkyl; and R3 is C1-C6 alkyl.

### Claim 18 (depends on 17)

The method of claim 17, each of R5, R6, R7, R8, and R9 is independently halide, methyl, and OR, wherein R for each instance is independently hydrogen or C1-C6 alkyl.

### Claim 19 (depends on 17)

The method of claim 17, wherein the injured neuron is an injured retinal ganglion cell or an injured dorsal root ganglion neuron.