CN-121971427-A - Application of compound in preparing medicine for preventing/treating diseases related to GSK-3 beta activity or expression quantity

Abstract

The invention belongs to the technical field of biological medicine, and particularly discloses application of a compound or pharmaceutically acceptable salt thereof in preparing a medicament for preventing/treating diseases related to GSK-3 beta activity or expression level, wherein the molecular structural formula of the compound is shown as formula I: The compound has good safety and affinity, and simultaneously has good GSK-3 beta inhibition activity, and can be used for treating or preventing neurodegenerative diseases, metabolic and cardiovascular diseases, tumors, immune diseases and other diseases.

Inventors

• LIU YAO
• ZHANG WENYUAN
• CHENG SHIQI
• LIU FANG
• PENG DAN

Assignees

• 中国人民解放军陆军特色医学中心

Dates

Publication Date

20260505

Application Date

20260401

Claims (6)

1. 1. The application of a compound or pharmaceutically acceptable salt thereof in preparing a medicament for preventing/treating diseases related to GSK-3 beta activity or expression level is characterized in that the molecular structural formula of the compound is shown as formula I: (I)。
2. 2. the use of claim 1, further comprising a pharmaceutically acceptable carrier.
3. 3. The use according to claim 2, wherein the disease comprises one of neurodegenerative diseases, metabolic and cardiovascular diseases, tumors and immune diseases.
4. 4. The use according to claim 3, wherein the neurodegenerative disease includes, but is not limited to, alzheimer's disease.
5. 5. The use according to claim 3, wherein the metabolic and cardiovascular diseases include, but are not limited to, diabetes.
6. 6. The use according to claim 3, wherein said tumor and immune diseases include, but are not limited to, ischemia/reperfusion injury.

Description

Application of compound in preparing medicine for preventing/treating diseases related to GSK-3 beta activity or expression quantity Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to application of a compound in preparation of a medicine for preventing/treating diseases related to GSK-3 beta activity or expression quantity. Background Glycogen synthase kinase-3 (Glycogensynthasekinase, GSK-3) is a highly conserved serine/threonine protein kinase, and plays an important role in cell division, differentiation, apoptosis and the like. Studies have shown that in brain tissue of Alzheimer's Disease (AD) patients, GSK-3 beta activity is abnormally increased, and GSK-3 beta with increased activity or increased expression level can trigger AD pathology through various pathways, such as overactive GSK-3 beta induces inflammation through NF- κB, damages axon transport, and promotes apoptosis. Therefore, the targeted inhibition of GSK-3 beta becomes a very attractive strategy in AD control, and the development of drug research taking GSK-3 beta inhibitor as the protection effect of the nervous system provides a new view for the effective control of AD. According to statistics of drug-transition Cyber data, only 9 GSK-3 beta inhibitors are currently approved and applied to the market, and 5 are in clinical stage III (fig. 1). Many ATP competitive GSK-3 beta inhibitors (e.g., CHIR 99021) have problems of poor selectivity, insufficient blood brain barrier penetration, drug-induced resistance, toxic side effects, and the like, and fail to enter the clinic. The substrate competitive GSK-3 beta inhibitor has the limitations of undefined mechanism and specificity of substrate binding site, and another important challenge of GSK-3 beta inhibitor is the ability to enter AD blood brain barrier and the defect of pharmacokinetics. Disclosure of Invention The present invention aims to solve at least one of the technical problems in the related art to some extent. Therefore, the main purpose of the invention is to provide an application of a compound in preparing a medicine for preventing/treating diseases related to GSK-3 beta activity or expression level, and the application provides a new solution for treating neurodegenerative diseases, metabolic and cardiovascular diseases, tumors and immune diseases, and has important clinical significance and market potential. The invention aims at realizing the following technical scheme: the application of a compound or pharmaceutically acceptable salt thereof in preparing a medicament for preventing/treating diseases related to GSK-3 beta activity or expression level is characterized in that the molecular structural formula of the compound is shown as formula I: (I) In certain embodiments, the disease comprises one of a neurodegenerative disease, a metabolic and cardiovascular disease, a tumor, and an immune disease. In certain embodiments, the neurodegenerative disease includes, but is not limited to, alzheimer's disease. In certain embodiments, the metabolic and cardiovascular disease includes, but is not limited to, diabetes. In certain embodiments, the tumor and immune disease include, but are not limited to, ischemia/reperfusion injury. The expression for a drug: preferably, the medicament further comprises a pharmaceutically acceptable carrier, such carriers including, but not limited to, diluents, buffers, suspensions, emulsions, granules, encapsulates, excipients, fillers, binders, sprays, transdermal absorbents, wetting agents, disintegrants, absorption enhancers, surfactants, colorants, flavoring agents, or adsorption carriers. The medicament of the invention can be prepared into various dosage forms according to requirements, including but not limited to tablets, solutions, granules, patches, pastes, capsules, aerosols or suppositories. The route of administration of the drug of the present invention is not limited as long as it can exert a desired therapeutic effect or prophylactic effect, including, but not limited to, oral administration, intravenous injection, intramuscular injection, subcutaneous injection, sublingual infusion, rectal infusion, nasal spray, oral spray, transdermal administration of the skin locally or systemically. The medicine of the invention can also be combined with other medicines for treating neurodegenerative diseases, metabolism and cardiovascular diseases, tumors and immune diseases, and the like, and the combination of a plurality of medicines can greatly improve the success rate of treatment. Compared with the prior art, the invention has at least the following advantages: The compound provided by the invention has good safety and affinity, and simultaneously has good GSK-3 beta inhibition activity, and can be used for treating or preventing GSK-3 beta mediated diseases. Drawings In order to more clearly illustrate the embodiments of the present invention, the drawings that are used