# US 2022/0033359 A1 · Edaravone prodrug compound and pharmaceutical use thereof in treatment or alleviation of neurodegenerative or motor neuron disease

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- Number: US 2022/0033359 A1
- Document ID: US20220033359A1
- Status: Published application
- Kind: A1
- Application number: 17/276,351
- Filed: 2019-09-09
- Published: 2022-02-03
- Earliest claimed: 2018-09-17
- Assignees: J2H Biotech Inc.; Theragen Etex Co., Ltd
- Applicants: J2H Biotech Inc.; Theragen Etex Co., Ltd
- Inventors: Jae-Sun KIM; Hyung-Chul RYU; Jee-Woong LIM; Eun-Bi KANG; Hyuk-Min KIM; Hyunjun YANG; Dukho CHANG; Dong-Gyu KIM; Byung Hwan RYOO; Yong-Ho OH
- Web page: https://patentgrep.com/patent/US20220033359A1

## CPC

- C07D 231/22: with aryl radicals attached to ring nitrogen atoms
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- C07D 231/20: One oxygen atom attached in position 3 or 5
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention provides a novel prodrug of an edaravone compound or a pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising same as an active ingredient, and a use thereof in treatment or alleviation of neurodegenerative and/or motor neuron disease.

## Claims

### Claim 1

A compound represented by the following Chemical formula 1 or a pharmaceutically acceptable salt thereof.
In Chemical Formula 1,
R1 and R2 are each independently hydrogen or (C1-C3)alkyl,
R3 is any one selected from the group consisting of (C1-C3)alkyl, (C3-C7)cycloalkyl, phenyl, —CH2NH2, —CH(CH3)NH2, —CH(CH2OH)NH2, —CH(CH(CH3)OH)NH2, —CH(CH2SH)NH2, —CH(CH(CH3)2)NH2, —CH(C(CH3)3)NH2, —CH(CH2CH(CH3)2)NH2, —CH(CH(CH3)CH2CH3)NH2, —CH(CH2CH2SCH3)NH2, pyrrolidin-2-yl, —CH(CH2Ph)NH2, —CH(CH2PhOH-p)NH2, —CH(1H-indole-3-yl-CH2)NH2, —CH(CH2CO2H)NH2, —CH(CH2CH2CO2H)NH2, —CH(CH2CONH2)NH2, —CH(CH2CH2CONH2)NH2, —CH(1H-imidazol-4-yl-CH2)NH2, —CH2CH2CH2CH2NH2, and —CH2CH2CH2NHC(NH)NH2.

### Claim 2 (depends on 1)

The compound or a pharmaceutically acceptable salt thereof according claim 1, wherein the compound is
3-methyl-1-phenyl-1H-pyrazol-5-yl 4-acetylpiperazine-1-carboxylate;
(S)-3-methyl-1-phenyl-1H-pyrazol-5-yl 4-acetyl-2-methylpiperazine-1-carboxylate;
(R)-3-methyl-1-phenyl-1H-pyrazol-5-yl 4-acetyl-2-methylpiperazine-1-carboxylate;
3-methyl-1-phenyl-1H-pyrazol-5-yl 4-(cyclohexanecarbonyl)piperazine-1-carboxylate;
3-methyl-1-phenyl-1H-pyrazol-5-yl 4-benzoylpiperazine-1-carboxylate;
3-methyl-1-phenyl-1H-pyrazol-5-yl 4-(2-aminoacetyl)piperazine-1-carboxylate;
(S)-3-methyl-1-phenyl-1H-pyrazol-5-yl 4-(2-aminopropanoyl)piperazine-1-carboxylate;
(S)-3-methyl-1-phenyl-1H-pyrazol-5-yl 4-(2-amino-3-hydroxypropanoyl)piperazine-1-carboxylate;
(R)-3-methyl-1-phenyl-1H-pyrazol-5-yl 4-(2-amino-3-mercaptopropanoyl)piperazine-1-carboxylate;
(S)-3-methyl-1-phenyl-1H-pyrazol-5-yl 4-(2-amino-3-methylbutanoyl)piperazine-1-carboxylate;
(R)-3-methyl-1-phenyl-1H-pyrazol-5-yl 4-((S)-2-amino-3-methylbutanoyl)-2-methylpiperazine-1-carboxylate;
(S)-3-methyl-1-phenyl-1H-pyrazol-5-yl 4-((S)-2-amino-3-methylbutanoyl)-2-methylpiperazine-1-carboxylate;
(R)-3-methyl-1-phenyl-1H-pyrazol-5-yl 4-((S)-2-amino-3-methylbutanoyl)-2-ethylpiperazine-1-carboxylate;
(S)-3-methyl-1-phenyl-1H-pyrazol-5-yl 4-((S)-2-amino-3-methylbutanoyl)-3-methylpiperazine-1-carboxylate;
(S)-3-methyl-1-phenyl-1H-pyrazol-5-yl 4-(2-amino-3,3-dimethylbutanoyl)piperazine-1-carboxylate;
(S)-3-methyl-1-phenyl-1H-pyrazol-5-yl 4-(2-amino-4-(methylthio)butanoyl)piperazine-1-carboxylate;
(S)-3-methyl-1-phenyl-1H-pyrazol-5-yl 4-(2-amino-3-phenylpropanoyl)piperazine-1-carboxylate;
(S)-3-methyl-1-phenyl-1H-pyrazol-5-yl 4-(2,4-diamino-4-oxobutanoyl)piperazine-1-carboxylate;
or
(S)-3-methyl-1-phenyl-1H-pyrazol-5-yl 4-(2,6-diaminohexanoyl)piperazine-1-carboxylate.

### Claim 3 (depends on 1)

A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

### Claim 4 (depends on 1)

A method for treating or alleviating a neurodegenerative disease or a motor neuron disease in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

### Claim 5 (depends on 4)

The method of claim 4, wherein the neurodegenerative or motor neuron disease is Alzheimer's disease, Parkinson's disease, Huntington's disease, Lou Gehrig's disease, multiple sclerosis, dystonia, spinal muscular atrophy, inflammatory neuropathy, or alcoholic dementia.

### Claim 6 (depends on 2)

A pharmaceutical composition comprising the compound of claim 2 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

### Claim 7 (depends on 2)

A method for treating or alleviating a neurodegenerative disease or a motor neuron disease in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising the compound of claim 2 or a pharmaceutically acceptable salt thereof as an active ingredient.

### Claim 8 (depends on 7)

The method of claim 7, wherein the neurodegenerative or motor neuron disease is Alzheimer's disease, Parkinson's disease, Huntington's disease, Lou Gehrig's disease, multiple sclerosis, dystonia, spinal muscular atrophy, inflammatory neuropathy, or alcoholic dementia.