# US 12,594,282 B2 · Use of small molecule compounds in the treatment of diseases mediated by lung epithelial cell injury and/or vascular endothelial cell injury

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- Number: US 12,594,282 B2
- Document ID: US12594282B2
- Status: Granted
- Kind: B2
- Application number: 17/802,870
- Filed: 2021-02-26
- Published: 2023-03-23
- Granted: 2026-04-07
- Earliest claimed: 2020-02-28
- Assignees: Guangzhou Cellprotek Pharmaceutical Co., Ltd.
- Applicants: Guangzhou Cellprotek Pharmaceutical Co., Ltd.
- Inventors: Bingzheng Lu; Yupin Chen; Yana Wang; Jiayu Huang; Chunhui Huang; Jiesi Chen
- Web page: https://patentgrep.com/patent/US12594282B2

## CPC

- A61K 31/568: substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/10: Antioedematous agents; Diuretics
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/12: Antihypertensives
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 13/00: Drugs for disorders of the urinary system
- A61P 13/12: of the kidneys
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/24: Antidepressants
- 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
- A61P 31/14: for RNA viruses
- 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

Disclosed is use of 5α-androst-3β,5,6β-triol or an analogue, a deuterated compound or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment of a pulmonary disease in a patient. These compounds can significantly inhibit the up-regulation of PFKFB3 expression, significantly inhibit the accumulation of lactate, significantly reduce vascular endothelial cell injury, significantly reduce alveolar epithelial cell injury, significantly inhibit alveolar septum thickening, significantly reduce alveolar damage, and thus can be used to treat diseases mediated by lung epithelial cell injury and/or vascular endothelial cell injury, such as in the lung.

## Claims

### Claim 1

A method for treating a disease mediated by lung epithelial cell injury in a subject, the method comprising administering to the subject an effective amount of a compound of formula I:
or a deuterated compound or a pharmaceutically acceptable salt thereof,
wherein R1 is selected from H, —CN, fluoro, chloro, C1-10 alkyl, fluoro or chloro substituted C1-10 alkyl, C1-10 alkoxy, fluoro or chloro substituted C1-10 alkoxy, and C3-10 cycloalkyl,
wherein the disease mediated by lung epithelial cell injury is selected from one or more of acute lung injury, acute respiratory distress syndrome, pulmonary fibrosis, chronic lung disease in premature infants, chronic obstructive pulmonary disease, and pneumocystis disease.

### Claim 2 (depends on 1)

The method of claim 1, wherein R1 is H, —CHCH2CH3, —CH(CH3)2, —CH(CH2)3CH3, or —CH(CH3)(CH2)3CH(CH3)2.

### Claim 3 (depends on 1)

The method of claim 1, wherein R1 is H.

### Claim 4 (depends on 1)

The method of claim 1, wherein the acute lung injury or acute respiratory distress syndrome is caused by hyperoxia, viral infection, bacterial infection, trauma, shock, ischemia-reperfusion, acute pancreatitis, inhalation injury, diffuse alveolar damage, or poisoning.

### Claim 5 (depends on 4)

The method of claim 4, wherein the virus is a coronavirus, influenza virus, respiratory syncytial virus, adenovirus, parainfluenza virus, measles virus, cytomegalovirus, or a combination thereof.

### Claim 6 (depends on 5)

The method of claim 5, wherein the virus is a coronavirus.

### Claim 7 (depends on 6)

The method of claim 6, wherein the coronavirus is SARS-CoV-2.

### Claim 8 (depends on 1)

The method of claim 1, wherein the acute lung injury is a lung injury caused by a surgery.

### Claim 9 (depends on 8)

The method of claim 8, wherein the surgery is pneumonectomy, lung tumor resection, or lung transplantation.

### Claim 10 (depends on 9)

The method of claim 9, wherein the pneumonectomy is sublobectomy, lobectomy, or total pneumonectomy.

### Claim 11 (depends on 1)

The method of claim 1, wherein the disease mediated by lung epithelial cell injury is manifested as overexpression of PFKFB3 protein.