CN-122005572-A - Use of pyrimidine compounds for preparing medicines for preventing and/or treating osteoarthritis

CN122005572ACN 122005572 ACN122005572 ACN 122005572ACN-122005572-A

Abstract

The invention discloses an application of pyrimidine compounds in preparing medicines for preventing and/or treating osteoarthritis. The invention provides application of pyrimidine compounds in medicines for preventing and/or treating osteoarthritis for the first time. Experiments show that the compound can relieve pain in a joint region of a mouse, can obviously relieve cartilage injury of an osteoarthritis mouse and inhibit joint fibrosis process, and in addition, pyrimidine compounds can obviously inhibit osteophyte formation in the joint region, and in addition, the compound obviously inhibits the expression of inflammation related markers in the joint region and serum of an osteoarthritis model mouse. The experiment shows that the pyrimidine compound can play a role in improving osteoarthritis, and has very important significance for drug development, prevention and treatment of the diseases in future.

Inventors

ZHONG DANDAN
ZHANG ZIYI
LI JIE
YING CHANGJIANG
ZHANG XINXU
Xi Huiyu
SUN YING
SUN YUE

Assignees

徐州医科大学

Dates

Publication Date: 20260512
Application Date: 20260408

Claims (10)

1. Use of a pyrimidine compound or a pharmaceutically acceptable derivative thereof in the manufacture of a medicament for the prevention and/or treatment of osteoarthritis, the pyrimidine compound having a structure as shown in formula (I): ; Formula (I).
2. The method of claim 1, wherein the agent is capable of alleviating pain in the joint area of the mouse when the agent is administered to a mouse model of osteoarthritis.
3. The method according to claim 1, wherein the agent is capable of promoting stabilization of cartilage structure in mice when the agent acts on a mouse model of osteoarthritis; And/or, the agent is capable of inhibiting cartilage fibrosis in a mouse when the agent is applied to a mouse model of osteoarthritis.
4. The method of claim 1, wherein the agent reduces the formation of osteophytes in the joint region of the mouse when the agent acts on a mouse model of osteoarthritis.
5. The method according to claim 1, wherein the agent is capable of reducing serum inflammatory factor content in a mouse when the agent acts on a mouse model of osteoarthritis; And/or, the agent is capable of reducing the expression of an osteoarthritis-related inflammatory marker in a mouse when the agent acts on a mouse model of osteoarthritis, preferably the agent is capable of reducing the expression of an osteoarthritis-related inflammatory marker in a mouse by more than 30%, preferably the osteoarthritis-related inflammatory marker comprises matrix metalloproteinase 3, matrix metalloproteinase 13, interleukin-1 beta, or tumor necrosis factor-alpha.
6. The pharmaceutical composition for preventing and/or treating osteoarthritis is characterized by comprising a pyrimidine compound or a pharmaceutically acceptable derivative thereof, and a pharmaceutically acceptable carrier and/or excipient, wherein the pyrimidine compound has a structure shown as a formula (I): ; Formula (I); wherein the pharmaceutically acceptable derivatives include any one or more of pharmaceutically acceptable salts, polymorphs, co-crystals, radiolabeled forms.
7. The pharmaceutical composition of claim 6, wherein the pharmaceutical composition is capable of alleviating pain in the joint area of a mouse when the pharmaceutical composition is applied to a mouse model of osteoarthritis.
8. The pharmaceutical composition of claim 6, wherein the pharmaceutical composition is capable of at least promoting stabilization of cartilage structure in a mouse when acting on a mouse model of osteoarthritis; And/or, the pharmaceutical composition is capable of inhibiting cartilage fibrosis in a mouse when the pharmaceutical composition is applied to a mouse model of osteoarthritis; And/or, the pharmaceutical composition is capable of inhibiting osteophyte formation in a mouse joint region when the pharmaceutical composition acts on a mouse model of osteoarthritis.
9. The pharmaceutical composition of claim 6, wherein the pharmaceutical composition is capable of reducing serum inflammatory factor content in a mouse when acting on a mouse model of osteoarthritis; And/or, the pharmaceutical composition is capable of reducing the expression of an osteoarthritis-related inflammatory marker in a mouse when the pharmaceutical composition acts on a mouse model of osteoarthritis, preferably the pharmaceutical composition is capable of reducing the expression of an osteoarthritis-related inflammatory marker in a mouse by more than 30%, preferably the osteoarthritis-related inflammatory marker comprises matrix metalloproteinase 3, matrix metalloproteinase 13, interleukin-1 beta or tumor necrosis factor-alpha.
10. Use of a pharmaceutical composition according to any one of claims 6-9 for the manufacture of a medicament for the prevention and/or treatment of osteoarthritis.

Description

Use of pyrimidine compounds for preparing medicines for preventing and/or treating osteoarthritis Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to application of pyrimidine compounds in preparation of medicines for preventing and/or treating osteoarthritis. Background Osteoarthritis is a chronic, progressive total joint degenerative disease, mainly involving articular cartilage, synovium and subchondral bone, the pathological core of which is progressive degeneration and destruction of articular cartilage. Osteoarthritis has the characteristics of long course and slow progression, can be developed in early adulthood, is not uncommon even in people under 50 years old, affects the mobility and daily activities of patients for a long period of time, and can cause a decline in quality of life for decades. Therefore, early prevention or effective delay of disease progression has important clinical and social significance. Currently, first-line treatments for osteoarthritis mainly include pharmaceutical interventions, physical treatments, and surgical procedures. In the medicine treatment, although the nonsteroidal anti-inflammatory drug can relieve pain in a short period, the long-term use of the nonsteroidal anti-inflammatory drug is easy to cause gastrointestinal damage and hepatorenal toxicity, the cartilage protective agent has slow effect, and the curative effect of the intermediate and late patients is limited. Physical therapy such as hot compress, massage, acupuncture and moxibustion can only temporarily relieve symptoms, and is difficult to reverse pathological processes. Although the operation treatment such as joint replacement can obviously improve joint function, the operation treatment has the disadvantages of larger wound, high cost, accompanying with risks of infection, thrombus and the like, certain requirements on the general condition of patients and is not universally applicable. In summary, the understanding of the pathogenesis of osteoarthritis is still insufficient at the present stage, and the existing treatment methods have different limits, so that the development of safer, effective and convenient novel treatment strategies is needed to improve the current dilemma prevention and treatment. Disclosure of Invention The invention mainly aims to provide an application of pyrimidine compounds in preparing medicines for preventing and/or treating osteoarthritis so as to overcome the defects of the prior art. In order to achieve the purpose of the invention, the technical scheme adopted by the invention comprises the following steps: the embodiment of the invention provides application of a pyrimidine compound (SQ-030 compound) or a pharmaceutically acceptable derivative thereof in preparation of a medicament for preventing and/or treating osteoarthritis, wherein the pyrimidine compound has a structure shown as a formula (I): ; Formula (I). The embodiment of the invention also provides a pharmaceutical composition for preventing and/or treating osteoarthritis, which comprises a pyrimidine compound or a pharmaceutically acceptable derivative thereof, and a pharmaceutically acceptable carrier and/or excipient, wherein the pyrimidine compound has a structure shown as a formula (I): ; Formula (I); wherein the pharmaceutically acceptable derivatives include any one or more of pharmaceutically acceptable salts, polymorphs, co-crystals, radiolabeled forms. The embodiment of the invention also provides application of the medicinal composition in preparing a medicament for preventing and/or treating osteoarthritis. Compared with the prior art, the invention has the beneficial effects that the invention firstly provides the application of the SQ-030 compound or the pharmaceutically acceptable derivative thereof in the medicines for preventing and/or treating osteoarthritis. Experiments show that the SQ-030 compound can remarkably relieve pain in joint regions of mice, meanwhile, the SQ-030 compound remarkably increases the number of chondrocytes and resists fibrosis of bone joint tissues, in addition, the SQ-030 compound can remarkably inhibit osteophyte formation in the joint regions, and in addition, the SQ-030 compound remarkably inhibits expression of inflammation related markers in serum of mice with osteoarthritis models. The experiments show that the SQ-030 compound can play a role in improving osteoarthritis, and has very important significance for drug development, prevention and treatment of the diseases in the future. Drawings In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings that are required to be used in the embodiments or the description of the prior art will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments described in the present application, and other drawings may be