JP-2026514525-A - Novel compounds containing an N-methylpiperazineethanolcarbamate structure and their applications

Abstract

This invention relates to a novel compound containing an N-methylpiperazine ethanol carbamate structure and its uses. [Selection Diagram] Figure 2

Inventors

• イ、ユン－ジン
• キム、ジヒ
• ナム、ジェ ギョン
• リュ、ヒョン チュ

Assignees

• コリア インスティテュート オブ ラジオロジカル アンド メディカル サイエンシズ

Dates

Publication Date

20260511

Application Date

20240426

Priority Date

20230428

Claims (9)

1. Compounds represented by the following chemical formula (1), or pharmaceutically acceptable salts or solvates thereof: In the above chemical formula (1), Ar is a trifluoromethyl (CF3) or halogen-substituted aryl or heteroaryl group. R is represented by the following chemical formula (2) or (3).
2. The Ar in the aforementioned chemical formula (1) is represented by chemical formula (6) or (7). The compound according to claim 1.
3. The aforementioned compound is represented by chemical formula (4) or (5). The compound according to claim 1.
4. A composition comprising a compound represented by the following chemical formula (1), or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier: In the above chemical formula (1), Ar is a trifluoromethyl (CF3) or halogen-substituted aryl or heteroaryl group. R is represented by the following chemical formula (2) or (3).
5. A pharmaceutical composition for the prevention or treatment of pulmonary fibrosis comprising a compound represented by the following chemical formula (1), or a pharmaceutically acceptable salt or solvate thereof: In the above chemical formula (1), Ar is a trifluoromethyl (CF3) or halogen-substituted aryl or heteroaryl group. R is represented by the following chemical formula (2) or (3).
6. The pulmonary fibrosis described above is selected from pulmonary fibrosis caused by radiation exposure and idiopathic pulmonary fibrosis. The pharmaceutical composition for the prevention or treatment of pulmonary fibrosis according to claim 5.
7. The aforementioned pharmaceutical composition is administered in combination with a pharmaceutical composition containing nintedanib as an active ingredient. The pharmaceutical composition for the prevention or treatment of pulmonary fibrosis according to claim 5.
8. A method for preventing or treating pulmonary fibrosis, comprising the step of administering a pharmaceutical composition according to any one of claims 5 to 7 to an individual.
9. Food compositions for the prevention or improvement of pulmonary fibrosis, comprising a compound represented by the following chemical formula (1), or a food-grade salt or solvate thereof: In the above chemical formula (1), Ar is a trifluoromethyl (CF3) or halogen-substituted aryl or heteroaryl group. R is represented by the following chemical formula (2) or (3).

Description

This invention relates to a novel compound containing an N-methylpiperazine ethanol carbamate structure and its applications. Pulmonary fibrosis refers to a condition in which fibrous connective tissue proliferates in the lungs, destroying normal lung structure and causing hardening and deterioration of the lung tissue. In particular, idiopathic pulmonary fibrosis is a disease in which chronic inflammatory cells invade the alveolar walls, causing various changes and hardening of the lungs, leading to serious structural changes in lung tissue and progressive deterioration of lung function. To date, there is no effective treatment. Furthermore, while radiotherapy is frequently used for NSCLC tumor patients who cannot undergo surgical resection, it often causes radiation-induced pulmonary fibrosis (RIPF). To date, Ofev, a compound containing nintedanib as its active ingredient manufactured by Boehringer Ingelheim, is known to have some effect in slowing the decline of lung function. However, there is a growing need to develop a more effective drug. This figure shows the MS analysis results of the synthesized DCTP.This figure shows the results of the H-NMR analysis of the synthesized DCTP.This figure shows the results of the H-NMR analysis of the synthesized DCTP.This figure shows the results of the H-NMR analysis of the synthesized DCTP.This figure shows the effect of administering nintedanib and/or DCTP to mice that had been given bleomycin to induce idiopathic pulmonary fibrosis, and then confirming the inhibitory effect on idiopathic pulmonary fibrosis by micro-CT imaging.This graph shows the degree of inflammation and fibrosis confirmed by H&E and Masson's Trichrome staining in mice that were administered bleomycin to induce idiopathic pulmonary fibrosis, and then nintedanib and/or DCTP.This figure shows the effect of administering nintedanib and/or DCTP to mice in which pulmonary fibrosis was induced by radiation, and then confirming the suppression of radiation-induced pulmonary fibrosis by micro-CT imaging.This graph shows the degree of inflammation and fibrosis observed in mice in which pulmonary fibrosis was induced by radiation, followed by administration of nintedanib and/or DCTP, and then confirmed by H&E and Masson's Trichrome staining.This figure shows the MS analysis results of the synthesized PXDP.This figure shows the H-NMR analysis results of the synthesized PXDP.This figure shows the effect of administering nintedanib and/or PXDP to mice that had been given bleomycin to induce idiopathic pulmonary fibrosis, and then confirming the inhibitory effect on idiopathic pulmonary fibrosis by micro-CT imaging.This graph shows the degree of inflammation and fibrosis confirmed by H&E and Masson's Trichrome staining after administering nintedanib and/or PXDP to mice that had been given bleomycin to induce idiopathic pulmonary fibrosis.This figure shows the results of administering nintedanib and/or PXDP to mice that had been given bleomycin to induce idiopathic pulmonary fibrosis, and then checking the survival rate of the mice.This figure shows the effect of administering nintedanib and/or PXDP to mice in which pulmonary fibrosis was induced by radiation, and then confirming the suppression of radiation-induced pulmonary fibrosis by micro-CT imaging.This graph shows the degree of inflammation and fibrosis observed in mice in which pulmonary fibrosis was induced by radiation, followed by administration of nintedanib and/or PXDP, and then confirmed by H&E and Masson's Trichrome staining. These will be explained in detail below. Note that each description and embodiment disclosed in this invention applies to other descriptions and embodiments. That is, any combination of the various elements disclosed in this invention is included. Furthermore, this invention is not limited to the following specific descriptions. Furthermore, a person with ordinary skill in the art would be able to recognize and confirm many equivalents of the specific embodiments of the present invention described herein using only ordinary experiments. Moreover, these equivalents are also intended to be included in the present invention. Furthermore, numerous papers and patent documents are referenced throughout this specification, and their citations are indicated. The disclosures of the cited papers and patent documents are incorporated in their entirety as references within this specification, thereby more clearly explaining the level of the art to which the present invention pertains and the content of the present invention. One aspect of the present invention provides a compound comprising an N-methylpiperazine ethanol carbamate structure represented by chemical formula (1), or a pharmaceutically acceptable salt or solvate thereof. In chemical formula (1), Ar is trifluoromethyl (CF3) or a halogen-substituted aryl or heteroaryl group, and R is represented by chemical formula (2) or (3). For example, the halogen may be Cl or F. For e