US-12616684-B2 - Pulmonary fibrosis medicine containing pyrazole derivative

Abstract

A pharmaceutical composition or an antiviral agent for the treatment of pulmonary fibrosis is disclosed. The composition or the antiviral agent contains a compound of Formula 1, which is a pyrazole derivative, or a pharmaceutically acceptable salt thereof.

Inventors

• Sung Hwan Moon
• Soo Jin Lee
• Hyunkyung Yu
• Yoo-Kyung GOH

Assignees

• APTABIO THERAPEUTICS INC.

Dates

Publication Date

20260505

Application Date

20210323

Priority Date

20200413

Claims (9)

1. 1 . A method of treating virus-induced pulmonary fibrosis in a mammal in need thereof, comprising administering an effective amount of a compound of following Formula 1 or a pharmaceutically acceptable salt thereof to the mammal: wherein R is a linear or branched alkyl group having 1 to 6 carbon atoms, and wherein the compound of Formula 1 is used together with an antiviral agent.
2. 2 . The method according to claim 1 , wherein the compound of Formula 1 is: 3-phenyl-4-methyl-1-(pyridin-2-yl)-1H-pyrazol-5-ol or a hydrochloride salt thereof; 3-phenyl-4-ethyl-1-(pyridin-2-yl)-1H-pyrazol-5-ol or a hydrochloride salt thereof, 3-phenyl-4-n-propyl-1-(pyridin-2-yl)-1H-pyrazol-5-ol or a hydrochloride salt thereof, 3-phenyl-4-isopropyl-1-(pyridin-2-yl)-1H-pyrazol-5-ol or a hydrochloride salt thereof, 3-phenyl-4-n-butyl-1-(pyridin-2-yl)-1H-pyrazol-5-ol or a hydrochloride salt thereof, 3-phenyl-4-tert-butyl-1-(pyridin-2-yl)-1H-pyrazol-5-ol or a hydrochloride salt thereof, 3-phenyl-4-n-pentyl-1-(pyridin-2-yl)-1H-pyrazol-5-ol or a hydrochloride salt thereof, or 3-phenyl-4-n-hexyl-1-(pyridin-2-yl)-1H-pyrazol-5-ol or a hydrochloride salt thereof.
3. 3 . The method according to claim 2 , wherein the compound of Formula 1 is 3-phenyl-4-n-propyl-1-(pyridin-2-yl)-1H-pyrazol-5-ol or a hydrochloride salt thereof.
4. 4 . The method according to claim 1 , wherein the pulmonary fibrosis is caused by pulmonary inflammatory fibrosis, chronic obstructive pulmonary disease (COPD) combined pulmonary fibrosis, idiopathic pulmonary fibrosis (IPF) or asthma.
5. 5 . The method according to claim 4 , wherein the pulmonary inflammatory fibrosis is caused by any one or combination of viral pneumonia, bacterial pneumonia, fungal pneumonia, mycoplasmal pneumonia, hypersensitivity pneumonitis, aspiration pneumonia, interstitial pulmonary disease, and pneumoconiosis.
6. 6 . The method according to claim 5 , wherein the viral pneumonia is caused by a virus selected from adenovirus, vaccinia virus, herpes simplex virus, parainfluenza virus, rhinovirus, varicella zoster virus, measles virus, respiratory syncytial virus, dengue virus, human immunodeficiency virus (HIV), influenza virus, coronavirus, severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV2), middle east respiratory syndrome coronavirus (MERS-CoV), or variant viruses of these viruses.
7. 7 . The method according to claim 4 , wherein the pulmonary fibrosis is caused by idiopathic pulmonary fibrosis.
8. 8 . The method according to claim 1 , wherein the method further comprises administering a pharmaceutically acceptable carrier or excipient to the mammal.
9. 9 . The method according to claim 1 , wherein the compound of Formula 1 is used further together with a second therapeutic agent, wherein the second therapeutic agent is an antibiotic, an antifungal agent, an anti-inflammatory agent, or any combination thereof.

Description

CROSS REFERENCE TO RELATED APPLICATIONS This application is a National Stage of International Application No. PCT/KR2021/003537 filed Mar. 23, 2021, claiming priority based on Korean Patent Application No. 10-2020-0044598 filed Apr. 13, 2020 and Korean Patent Application No. 10-2021-0036863 filed Mar. 22, 2021, the disclosure of which are herein incorporated by reference in their entirety. INCORPORATION BY REFERENCE OF SEQUENCE LISTING The content of the electronically submitted sequence listing, file name: Q277371_SEQ_LIST_ST25.txt; size: 1,628 bytes; and date of creation: Sep. 4, 2025, is incorporated herein by reference in its entirety. TECHNICAL FIELD The present invention relates to a pyrazole derivative useful for preventing or treating pulmonary fibrosis, a method for preparing the same, and a pharmaceutical composition thereof. BACKGROUND ART Pulmonary fibrosis (PF) is a type of chronic interstitial lung disease and characterized by infiltration of inflammatory cells such as lymphocytes and macrophages into the lung interstitium, proliferation of fibroblasts, and deposition of fibrous connective tissue into the lung interstitium. Pulmonary fibrosis is caused by various internal and external etiology of the lungs, is a result of chronic lung damage or disease progressing to the end, and seriously threatens human health. The etiology of pulmonary fibrosis includes factors such as immune dysfunction, viral or bacterial infection, drugs and chemicals, radiation, and air pollution (smog, cigarette smoke, dust, and the like). As mentioned above, there are patients who may diagnose the clear cause of pulmonary fibrosis, but there are also cases where the cause cannot be elucidated, wherein such cases are called idiopathic pulmonary fibrosis (IPF). Idiopathic pulmonary fibrosis is a type of interstitial pneumonia in which fibrosis of the lung parenchyma is progressively progressing, and is known to have a high risk of death due to respiratory failure within a few years after diagnosis and a very poor prognosis. The 5-year survival rate is about 20%, similar to that of lung cancer. In addition, the incidence and prevalence of pulmonary fibrosis are rapidly increasing with the aging population. Pulmonary fibrosis is a complex pathological and physiological process, wherein in the early stage, a large number of inflammatory cells infiltrate around the inflammatory site of the lung to cause the alveolar wall to become chronically thickened, and in the middle/end stage, normal lung tissue structure is destroyed due to overgrowth, alveolar deformation, hardening and scarring of the lung tissue caused by excessive deposition of extracellular matrix elements such as collagen by fibroblasts to result in loss of function. Fibroblasts play a role in the recruitment of immune cells to sites of inflammation and tissue damage. In addition, fibroblasts produce and respond to many inflammatory cytokines. Thus, fibroblasts may contribute to chronic inflammation, and conversely, inflammatory cytokines promote the conversion of fibroblasts to myofibroblasts, thereby promoting fibrosis. Therefore, injury or inflammation of the lung tissue may lead to pulmonary fibrosis. Lung transplantation is the only method to repair lung tissue with progressive fibrosis due to pulmonary fibrosis, and the 5-year survival rate after diagnosis is only 43%. Although many clinical studies are being conducted to develop a therapeutic agent for pulmonary fibrosis, there is still no therapeutic agent for lung fibrosis, and immunosuppressants, which are steroids or cytotoxic drugs, are mainly used as a first-line. Among steroids and cytotoxic drugs, steroids are used first, and a combination therapy of steroids and azathioprine or cyclophosphamide is currently being used. In addition, pirfenidone and nintedanib are the only approved drugs for the treatment of pulmonary fibrosis. It has been reported that pirfenidone has a mild therapeutic effect and is used at a very high dose of about 2.4 g/day, but there is little or no significant improvement in survival, and since it tends to decrease the quality of life of patients due to severe side effects such as gastrointestinal disorders (nausea, diarrhea, dyspepsia), skin disorders (photosensitive rash) and metabolic and nutritional disorders (anorexia, anepithymia) and weakens the liver function, continuous administration is difficult. It has been reported that nintedanib is used at a dose of 200 to 400 mg/day and reduces the incidence of acute exacerbations of mild to severe idiopathic pulmonary fibrosis, but continuous administration is difficult due to many side effects and gastrointestinal side effects. Therefore, there is an urgent need to develop new drugs that may treat the underlying cause rather than alleviate the progression of the symptoms of a disease. Although many studies are being conducted on the causes of pulmonary fibrosis, the pathogenesis is still unclear, making it difficult to devel