Pharmaceutical use of thiazole compound

Abstract

Provided is use of a thiazole compound represented by formula (I) or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating and / or preventing and / or alleviating nervous system diseases, heart diseases, and related diseases thereof, bone joint diseases, diseases in the digestive system, kidney injury or insufficiency, nephrotic syndrome, systemic lupus erythematosus, gout, acne, obesity, aging, and related diseases thereof, or thermoplegia. The compound of formula (I) is as follows: .

Description

Pharmaceutical uses of a thiazole compound

[0001] This application claims priority to an earlier application filed by the applicant with the China National Intellectual Property Administration on April 18, 2025, with patent application number 202510491753.5 entitled "Pharmaceutical Use of a Thiazole Compound"; the entire contents of the earlier application are incorporated herein by reference. Technical Field

[0002] This invention belongs to the pharmaceutical field, specifically relating to the pharmaceutical use of a thiazole compound. Background Technology

[0003] The inventors' prior research, such as CN 114099503A, discloses a class of thiazole compounds that can be used as CYP2E1 inhibitors to treat diseases such as glioma, liver cancer, sepsis, and rheumatoid arthritis. The inventors discovered that although elevated CYP2E1 levels represent a novel mechanism for the pathogenesis of certain diseases and a potential new target for prevention and treatment, its pathophysiological processes remain unclear. For example, CYP2E1 levels vary across different diseases, and even within the same disease, significant differences exist between individuals. Furthermore, the correlation between CYP2E1 levels and related diseases often presents contradictory research conclusions. In addition, the effectiveness of CYP2E1 inhibitors varies significantly across different diseases and between individuals with the same disease.

[0004] Through computer-aided drug design, virtual screening of small molecule library compounds, and the establishment and simulation of multiple models, as well as in-depth pharmacological research, the inventors discovered that these thiazole compounds may have excellent therapeutic effects and potential clinical application value for some indications through multiple complex mechanisms of action in vivo, and that they have high safety and good prospects for pharmaceutical development in related fields. Summary of the Invention

[0005] In order to improve the above-mentioned technical problems, in a first aspect, the present invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating and / or preventing and / or alleviating diseases of the nervous system, heart disease and related conditions, bone and joint diseases, diseases of the digestive system, kidney injury or insufficiency, nephrotic syndrome, systemic lupus erythematosus, gout, acne, obesity, aging and related diseases, or heatstroke.

[0006] According to an embodiment of the present invention,

[0007] The neurological disorders mentioned are selected from depression and pain;

[0008] The heart disease and related conditions mentioned are selected from heart disease, cardiomyopathy, myocardial injury, heart failure, ventricular hypertrophy (or hypertrophic cardiomyopathy), ventricular wall thickening, myocardial ischemia (or ischemic heart disease), myocardial infarction, myocardial fibrosis, and myocarditis.

[0009] The bone and joint diseases mentioned are selected from osteoarthritis or osteoarthropathy;

[0010] The digestive system diseases mentioned are selected from pancreatitis and colitis.

[0011] In some embodiments of the present invention, the drug can improve ventricular hypertrophy (e.g., left ventricular hypertrophy) and ventricular wall thickening caused by cardiac lesions. In some embodiments of the present invention, the drug can alleviate myocardial ischemia-reperfusion injury or myocardial infarction-reperfusion injury. In some embodiments, the cardiac disease and related conditions are selected from acute myocardial infarction. In some embodiments of the present invention, the drug has a cardioprotective effect. In some embodiments of the present invention, the myocarditis is selected from autoimmune myocarditis.

[0012] In some embodiments of the present invention, the depression includes pain-related / compound depression; in some embodiments of the present invention, the depression includes depression caused by chronic pain; in some embodiments of the present invention, the depression includes post-myocardial infarction depression and post-cerebral infarction depression. In some embodiments of the present invention, the drug can be used in the acute phase of depression.

[0013] In some embodiments of the invention, the pain is selected from pain caused by depression; in some embodiments, the pain is selected from depression-inflammatory pain comorbidity. In some embodiments of the invention, the pain is selected from acute pain, chronic pain, and neuropathic pain. In some embodiments of the invention, the drug can alleviate pain caused by osteoarthritis.

[0014] In some embodiments of the present invention, the drug can relieve osteoarthritis pain and / or cartilage damage.

[0015] In some embodiments of the present invention, the drug can further lower uric acid; in some embodiments of the present invention, the drug can be used to treat hyperuricemia; the hyperuricemia includes gout or gout complications caused by hyperuricemia; in some embodiments of the present invention, the gout includes acute gout or chronic gout; the gout complications include gouty arthritis, gout attacks, gouty nephropathy, and uric acid kidney stones. The gout is selected from acute gouty arthritis. In some embodiments of the present invention, the drug can be used to simultaneously lower uric acid and relieve arthritis, such as relieving swelling of arthritis. In some embodiments of the present invention, the drug is used to treat and / or relieve gouty joint pain.

[0016] In some embodiments of the present invention, the osteoarthritis or osteoarthropathy is selected from knee osteoarthritis or knee osteoarthropathy.

[0017] In some embodiments of the present invention, the pancreatitis is selected from acute pancreatitis, such as severe acute pancreatitis (SAP). SAP is a clinical syndrome characterized by pancreatic inflammation and accompanied by multiple organ dysfunction.

[0018] In some embodiments of the invention, the drug can alleviate nephrotoxicity, for example, it can alleviate nephrotoxicity caused by cisplatin treatment; in some embodiments of the invention, the kidney injury is selected from chronic kidney injury or acute kidney injury. In some embodiments of the invention, the kidney injury is selected from cisplatin-induced kidney injury.

[0019] In some embodiments of the present invention, the colitis is selected from acute colitis or chronic colitis; in some embodiments of the present invention, the colitis is ulcerative colitis (UC).

[0020] In some embodiments of the present invention, the aging and related diseases include age-related cognitive decline, muscle weakness, etc.

[0021] According to an embodiment of the present invention, the compound represented by formula (I) is selected from the following structures:

[0022] R1 is selected from hydrogen, halogen, C1-C 10 Alkyl, C 3-6 Epoxyalkyl and

[0023] R2 is selected from hydrogen, substituted C1-C 10 Any one of the following: alkyl group I, substituent shown in formula O-1, substituent shown in formula O-2, and substituent shown in formula O-3;

[0024] Among them, R 21 R 22 R 23 R 24 They may be the same or different, and are independently selected from hydrogen, C1-C. 10 Alkoxy, halogen, C1-C3 alkyl, C6-C 10 aryl;

[0025] R 25 Selected from hydroxyl, C1-C 10 Alkoxy;

[0026] R 26 Selected from H, C1-C 10Alkyl, halogenated C1-C 10 alkyl;

[0027] R3 is selected from hydrogen, C1-C 10 Alkyl, substituted C1-C 10 Alkyl groups.

[0028] Preferably, R1 is selected from hydrogen, C1-C4 alkyl, C 3-6 Epoxyalkyl.

[0029] Preferably, R1 is selected from

[0030] Preferably, R3 is selected from hydrogen, halogen, C1-C4 alkyl, halogenated C1-C4 alkyl, substituted C1-C4 alkyl II; more preferably, R3 is selected from hydrogen, methyl, ethyl, propyl.

[0031] Preferably, R 26 Selected from H, C1-C4 alkyl, and halogenated C1-C4 alkyl; more preferably, R 26 Selected from methyl, ethyl, propyl, and butyl. Optionally, the substituted C1-C 10 The substituent in the alkyl I is selected from at least one of the substituted amino I, the substituent shown in formula M-1, and the substituent shown in formula M-2;

[0032] Optionally, the substituents in the substituted amino I are selected from C6-C6. 10 At least one of aryl and substituted C1-C3 alkyl III.

[0033] Preferably, the substituents in the substituted C1-C3 alkyl III are selected from C6-C6. 10 Aryl groups.

[0034] Optionally, the substituted C1-C 10 The substituent in the alkyl II is selected from at least one of the substituted amino II, the substituent shown in formula M-3, and the substituent shown in formula M-4;

[0035] Optionally, the substituent in the substituted amino II is selected from substituted C1-C3 alkyl IV;

[0036] The substituents in the substituted C1-C3 alkyl IV are selected from at least one of pyridyl and halogen.

[0037] According to an embodiment of the present invention, the compound of formula (I) is further selected from the structure of formula (II):

[0038] Among them, R1, R26 R3 is defined as above.

[0039] According to an embodiment of the present invention, the compound of formula (I) is further selected from the following structures:

[0040] R1 and R3 are as defined above.

[0041] According to an embodiment of the present invention, formula (I) is selected from the following structures:

[0042] Preferably, the compound of formula (I) is selected from the following structures:

[0043] According to an embodiment of the present invention, the pharmaceutically acceptable salt is selected from the acid salt obtained by reacting the compound of formula (I) with an acid; the acid is selected from at least one of inorganic acids and organic acids.

[0044] Optionally, the inorganic acid is selected from at least one of hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, and phosphoric acid;

[0045] The organic acid is selected from at least one of acetic acid, oxalic acid, succinic acid, tartaric acid, succinic acid, malic acid, lactic acid, methanesulfonic acid, p-toluenesulfonic acid, citric acid, resinic acid, maleic acid, fumaric acid, salicylic acid, acetylsalicylic acid, and citric acid.

[0046] According to an embodiment of the present invention, the compound of formula (I) is selected from the following structure (i.e., 4-methyl-5-acetylthiazole, abbreviated as Q11):

[0047] According to an embodiment of the present invention, the pharmaceutically acceptable salt of the compound of formula (I) is selected from the hydrochloride or sulfate of Q11.

[0048] In some embodiments, the hydrochloride salt of Q11 has crystal form A, and the X-ray powder diffraction of crystal form A includes three or more 2θ values ​​selected from the group consisting of: 8.4±0.2°, 13.1±0.2°, 14.8±0.2°, 16.6±0.2°, 24.1±0.2°, 27.2±0.2°, 30.5±0.2°, 31.8±0.2°, 33.5±0.2°, 35.4±0.2°, and 35.7±0.2°. In some embodiments, the DSC-TGA plot shows a distinct endothermic peak between 70°C and 220°C, and thermal decomposition between 80°C and 170°C.

[0049] In some embodiments, the sulfate of Q11 has crystal form B, and the X-ray powder diffraction of crystal form B includes five or more 2θ values ​​selected from the group consisting of: 10.1±0.2°, 15.1±0.2°, 16.0±0.2°, 16.7±0.2°, 19.2±0.2°, 19.9±0.2°, 23.4±0.2°, 24.0±0.2°, 25.8±0.2°, 26.5±0.2°, 28.9±0.2°, 30.3±0.2°, and 32.2±0.2°. In some embodiments, the DSC-TGA plot shows at least one endothermic peak between 30°C and 85°C, 90°C and 160°C, and 215°C and 330°C, and thermal decomposition at 150°C and 350°C.

[0050] Secondly, the medicament of the present invention is a composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient.

[0051] Thirdly, the present invention provides a method for treating and / or preventing and / or alleviating conditions of the nervous system, heart disease and related conditions, bone and joint diseases, digestive system diseases, kidney injury or insufficiency, nephrotic syndrome, systemic lupus erythematosus, gout, acne, obesity, aging and related conditions, or heatstroke, said method comprising administering a therapeutically effective amount of the compound of formula (I) or a pharmaceutically acceptable salt thereof, or said composition.

[0052] The disease or condition is as defined in the first aspect.

[0053] Terminology Definition

[0054] Term "C" 1-10"alkyl" refers to a straight-chain or branched saturated monovalent hydrocarbon group having 1 to 10 carbon atoms, for example, a straight-chain or branched alkyl group having 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms. The alkyl group may optionally be substituted by one or more substituents described in this invention. In some embodiments, the alkyl group contains 1-6 carbon atoms (i.e., C1-C6 alkyl); in other embodiments, the alkyl group contains 1-6 carbon atoms; and in still other embodiments, the alkyl group contains 1-4 carbon atoms (i.e., C1-C4 alkyl). Examples of the alkyl group include, but are not limited to, methyl, ethyl, propyl, butyl, pentyl, etc. Hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neopentyl, 1,1-dimethylpropyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 2-ethylbutyl, 1-ethylbutyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 2,3-dimethylbutyl, 1,3-dimethylbutyl, or 1,2-dimethylbutyl, or their isomers. This definition applies whether the term "alkyl" is used alone or as part of other groups such as haloalkyl, alkoxy, etc.

[0055] The term "aryl" should be understood as referring to a monocyclic, bicyclic, or tricyclic hydrocarbon ring that is monovalent or partially aromatic, preferably "C". 6-10 "Aromatic". The term "C" 6-10 "Aryl" should be understood to preferably represent a monovalent aromatic or partially aromatic monocyclic or bicyclic hydrocarbon ring having 6, 7, 8, 9, or 10 carbon atoms, particularly a ring with 6 carbon atoms ("C6 aryl"), such as phenyl; or biphenyl, or a ring with 9 carbon atoms ("C9 aryl"), such as indenyl or indenyl, or a ring with 10 carbon atoms ("C9 aryl"). 10 Aryl), such as tetrahydronaphthyl, dihydronaphthyl or naphthyl.

[0056] Those skilled in the art will understand that, in this document, the term "drug" refers to a drug defined based on the compound represented by Formula (I) or a pharmaceutically acceptable salt thereof. A "drug" may be solely composed of the compound represented by Formula (I) or a pharmaceutically acceptable salt thereof, i.e., equivalent to "the compound represented by Formula (I) or a pharmaceutically acceptable salt thereof"; a "drug" may also be a composition comprising the compound represented by Formula (I) or a pharmaceutically acceptable salt thereof, i.e., the "drug" may include other (second or more) active ingredients and / or other excipients in addition to the compound represented by Formula (I) or a pharmaceutically acceptable salt thereof. Therefore, in this document, "the compound represented by Formula (I) or a pharmaceutically acceptable salt thereof" corresponds to the treatment and / or prevention and / or relief of diseases and symptoms, equivalent to the definition of a "drug" corresponding to the treatment and / or prevention and / or relief of diseases and symptoms. Attached Figure Description

[0057] Figure 1: Schematic illustration of the antidepressant effect of Q11. (A) Forced swimming test (FST) assesses the effect of Q11 on immobility time in LPS-induced inflammatory depression model mice. (B) Three-box social test assesses the effect of Q11 on the contact time between LPS-induced depression model mice and unfamiliar mice. (C) FST test assesses the effect of Q11 on immobility time in chronic unpredictable mild stress (CUMS) depression model mice. (D) Tail suspension test (TST) assesses the effect of Q11 on immobility time in CUMS depression model mice. (E) Three-box social test assesses the effect of Q11 on the contact time between CUMS depression model mice and unfamiliar mice.

[0058] Figure 2: Schematic illustration of Q11 regulating microglia polarization, protecting neurons, and inhibiting microglia phagocytosis. (A) Immunofluorescence staining method to detect the effect of Q11 on microglia (CD68) in the hippocampus of CUMS model mice. + / IBA-1 + Effects of Q11 on activation. (BC) Immunofluorescence staining was used to detect the effects of Q11 on M1 pro-inflammatory microglia (iNOS) cells in the hippocampus of CUMS model mice. + / IBA-1 + ) and M2 type anti-inflammatory microglia (CD206) + / IBA-1 + (D) Effects of polarization. (E) H&E staining to assess the effect of Q11 on neuronal damage in CUMS model mice. (JC / NeuN double-labeled immunofluorescence assay for the effect of Q11 on surviving neurons (FJC). - / NeuN + ) and degenerative neurons (FJC) + / NeuN +The effect of Q11 on the number of newly generated neurons in the hippocampal dentate gyrus. (F) DCX staining analysis. (G) IBA-1 / FJC - / NeuN + Three-standard confocal imaging analysis of the effect of Q11 on microglia phagocytosis.

[0059] Figure 3: Schematic of the analgesic effect of Q11. (A) Writhing test to assess the effect of Q11 on the number of writhing movements in a mouse model of pain induced by 0.6% glacial acetic acid. (B) Effect of Q11 on the total duration of pain response (pedipal licking / pedipal biting) in a formalin-induced bipolar pain model mouse.

[0060] Figure 4: Schematic illustration of the protective effect of Q11 on mice with myocardial infarction. (AB) TTC staining analysis of the effect of Q11 on the infarct area of ​​myocardial infarction in AMI model mice. (C) Effect of Q11 on cardiac index (heart weight / body weight) in AMI mice. (D) Effect of Q11 on the level of lactate dehydrogenase (LDH), a marker of cardiomyocyte damage, in the serum of AMI mice. (E) Echocardiographic assessment of the effects of Q11 on the long-axis B-mode membrane, M-mode membrane, and electrocardiogram of the left ventricle in AMI model mice on days 1 and 7. (F) Echocardiographic assessment of the effects of Q11 on cardiac function in AMI mice on days 1 and 7.

[0061] Figure 5: Schematic illustration of the protective effect of Q11 on myocardial infarction-reperfusion mice. (AB) TTC staining analysis of the effect of Q11 on the infarct area of ​​myocardial infarction in MIRI model mice. (CD) Effect of Q11 on the levels of lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB) in the serum of MIRI model mice. Echocardiography was used to assess the effect of Q11 on cardiac function in MIRI model mice, including (E) left ventricular ejection fraction (LVEF), (F) left ventricular fractional shortening (LVFS), (G) left ventricular end-diastolic diameter (LVID; d), (H) left ventricular end-systolic diameter (LVID; s), (I) left ventricular diastolic posterior wall thickness (LVPW; d), (J) left ventricular systolic posterior wall thickness (LVPW; s), (K) left ventricular diastolic volume (LVVol; d), and (L) left ventricular systolic volume (LVVol; s). (M) Echocardiography to detect the effects of Q11 on the long axis of the left ventricle, B membrane, M membrane, and electrocardiogram in MIRI mice.

[0062] Figure 6: Schematic illustration of the protective effect of Q11 on myocardial fibrosis. (A) Echocardiography assessing the effect of Q11 on cardiac function in mice with myocardial fibrosis. (BC) Effects of Q11 on cardiac function indices, ejection fraction (EF), and fractional shortening (FS) in mice with myocardial fibrosis. (D) Effect of Q11 on cardiac index (heart weight / body weight) in mice with myocardial fibrosis. (EF) Effect of Q11 on serum PICP and PIIINP levels in mice with myocardial fibrosis. (G) H&E staining assessing the effect of Q11 on histopathological changes in cardiac tissue in mice with myocardial fibrosis. (HI) Masson's trichrome staining method detecting the effect of Q11 on cardiac collagen deposition in mice with myocardial fibrosis.

[0063] Figure 7: Schematic illustration of Q11's effects on reducing inflammation, alleviating endoplasmic reticulum stress, and inhibiting the cleavage and activation of SREBP1. (A) Western blot analysis of the effects of Q11 on the expression of type I collagen (Col I), type III collagen (Col III), and pro-inflammatory factors (IL-1β, IL-6, TNFα) in the heart tissue of myocardial fibrosis mice. (BF) Quantitative analysis of the expression of Col I, Col III, IL-6, TNFα, and IL-1β proteins (normalized using GAPDH as an internal control). (G) Western blot analysis of the effects of Q11 on the expression of endoplasmic reticulum stress (ERS) marker proteins (p-PERK, p-IRE1, p-eIF2α, and XBP1s). (HM) Quantitative analysis of the expression of PERK, p-PERK, eIF2α, p-eIF2α, p-IRE1, and XBP1s proteins (normalized using GAPDH as an internal control). (N) Western blot analysis of the effect of Q11 on the expression of SREBP1 and its active form nSREBP1 in cardiac tissue. (OP) Quantitative analysis of SREBP1 and nSREBP1 protein expression (normalized using GAPDH as an internal reference).

[0064] Figure 8: Schematic illustration of the protective effect of Q11 on mice with myocarditis. (A) Effect of Q11 on body weight in EAM model mice. (B) Effect of Q11 on cardiac index (heart weight / body weight) in EAM model mice. (CF) Effect of Q11 on cardiac function in EAM mice, including left ventricular ejection fraction (EF), fractional shortening (FS), left ventricular end-diastolic volume (LV Vol; d), and left ventricular end-systolic volume (LV Vol; s). (G) Echocardiographic analysis of the effect of Q11 on the long axis image and activity waveform of the heart in EAM mice. (HI) Effect of Q11 on the levels of myocardial damage markers lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB) in the serum of EAM mice. (J) H&E staining to assess the effect of Q11 on the pathological changes in cardiac tissue of EAM mice. (KL) Masson trichrome staining to detect the effect of Q11 on collagen deposition in the heart of EAM mice.

[0065] Figure 9: Illustration of Q11's effect on cardiomyocyte mitochondrial morphology and function. (A) Transmission electron microscopy (TEM) to detect changes in cardiomyocyte mitochondrial morphology. (BC) qRT-PCR to detect changes in mRNA expression of key genes (atp5a1, bcl-2) in the mitochondrial damage pathway. (DE) Sea Horse analyzer to detect extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) of cardiomyocytes, and to calculate glycolysis and mitochondrial ATP production rates. (FG) Flow cytometry to detect the effect of Q11 on changes in cardiomyocyte membrane potential. (HI) Fluorescent staining to detect the effect of Q11 on the opening degree of the mitochondrial permeability transition pore (MPTP) in cardiomyocytes.

[0066] Figure 10: Schematic illustration of the protective effect of Q11 on AGA rats. (A) Appearance of rat paws 12 hours after the peak swelling period following MSU crystal injection modeling. (B) Representative photographs of H&E-stained ankle joint sections from AGA rats. (CD) Quantitative analysis of H&E-stained ankle joint synovial hyperplasia and inflammatory cell infiltration levels in each group. (EF) Line graph showing the dynamic changes in paw volume / thickness swelling rate of AGA rats after Q11 treatment. (GH) The anti-AGA effect of Q11 is dose-dependent.

[0067] Figure 11: Schematic illustration of the protective effect of Q11 on HUA mice. (AC) Effects of Q11 on plasma biochemical parameters, uric acid (UA), creatinine (Cr), and blood urea nitrogen (BUN), in HUA mice on day 7. (DF) Effects of Q11 on plasma biochemical parameters, uric acid (UA), creatinine (Cr), and blood urea nitrogen (BUN), in HUA mice on day 14. (G) H&E staining to observe the effect of Q11 on pathological damage in HUA mice.

[0068] Figure 12: Schematic illustration of the protective effect of Q11 on osteoarthritis. (A) Effect of Q11 on mechanical pain threshold (PWT) in MIA-induced knee osteoarthritis rats. (B) Effect of Q11 on the number of knee pain vomiting. (C) Effect of Q11 on the Pelletier score of the knee joint. (D) Representative images of femoral cartilage in each group of rats.

[0069] Figure 13: Schematic illustration of the protective effect of Q11 against pancreatitis. (AB) Effects of Q11 on serum amylase and lipase activities in Cae-SAP mice. (C) Effects of Q11 on pancreatic tissue edema in Cae-SAP mice. (D) Effects of Q11 on histopathological changes in pancreatic tissue of Cae-SAP mice observed by H&E staining. (E) Histopathological scores of pancreatic tissue in each group of mice. (F) Inflammatory cell infiltration scores of pancreatic tissue in each group of mice. (GH) Effects of Q11 on serum amylase and lipase activities in Arg-SAP mice. (I) Effects of Q11 on pancreatic tissue edema in Arg-SAP mice. (J) Effects of Q11 on histopathological changes in pancreatic tissue of Arg-SAP mice observed by H&E staining. (K) Histopathological scores of pancreatic tissue in each group of mice. (L) Inflammatory cell infiltration scores of pancreatic tissue in each group of mice.

[0070] Figure 14: Schematic illustration of the protective effect of Q11 against acute colitis. (A) Effect of Q11 on relative body weight changes in DSS-induced acute ulcerative colitis model mice. (B) Relative body weight changes in each group of mice on day 7. (C) Changes in disease activity index (DAI) scores of each group of mice over time. (D) Differences in DAI scores among groups of mice on day 7. (EF) Differences in colon length among groups of mice on day 7. (G) H&E staining and pathological score of the terminal colon. (H) Masson staining and goblet cell count of the terminal colon. (IJ) qRT-PCR detection of the effects of Q11 on the mRNA levels of inflammatory factors and intestinal barrier factors in DSS-induced acute ulcerative colitis model mice.

[0071] Figure 15: Schematic illustration of the protective effect of Q11 against chronic colitis. (A) Effect of Q11 on relative body weight change in DSS-induced chronic ulcerative colitis model mice on day 37. (B) Differences in Disease Activity Index (DAI) scores among groups of mice on day 37. (CD) Differences in colon length among groups of mice on day 46. (E) H&E staining and pathological score of the terminal colon. (F) Masson staining and goblet cell count of the terminal colon.

[0072] Figure 16: Schematic illustration of the protective effect of Q11 on kidney injury. (AB) Effects of Q11 on serum creatinine and blood urea nitrogen levels in AKI mice. (CD) H&E staining to observe the effect of Q11 on the pathological damage of kidney tissue in AKI mice. (EF) qRT-PCR detection of the effect of Q11 on the mRNA levels of NGAL and KIM-1 in kidney tissue of AKI mice. (G) Effect of Q11 on the survival time of AKI mice.

[0073] Figure 17: This illustrates how Q11 reduces ROS levels, increases GSH and CAT activity, effectively alleviates oxidative stress, and improves mitochondrial function. (A) Transmission electron microscopy observation of the effect of Q11 on mitochondrial morphology in AKI mouse kidney tissue, quantitative analysis of mitochondrial aspect ratio (molecular long axis / molecular short axis) and mitochondrial area. (B) Effect of Q11 on mitochondrial membrane potential and ATP levels in mRTEC cells. (CD) Effect of Q11 on mitochondrial membrane potential in HK-2 cells. (E) Effect of Q11 on ROS, GSH, and CAT levels in mRTEC cells. (F) Effect of Q11 on ROS, GSH, and CAT levels in HK-2 cells.

[0074] Figure 18: Schematic illustration of the protective effect of Q11 on acne. (A) Representative images of oleic acid-induced acne mice in various treatment groups. (B) H&E staining observation of the effect of Q11 on the histopathology of acne mouse skin tissue.

[0075] Figure 19: Schematic illustration of the protective effect of Q11 against obesity. (A) Gross condition of mice in each group. (B) Line graph of weekly weight change in mice in each group (n=10). (C) Food intake of mice in each group (g, n=12). (DG) Body composition analysis of mice in each group (n=7). (HJ) Effect of Q11 on the adipose tissue quality of prWAT, eWAT, and iWAT in obese mice. (K) Observation of the pathological effect of Q11 on eWAT in obese mice by H&E staining. (L) Quantification of surface area of ​​eWAT adipocytes. (M) Observation of the pathological effect of Q11 on iWAT in obese mice by H&E staining. (N) Quantification of surface area of ​​iWAT adipocytes. The control group was fed a low-fat, low-sugar diet; the model group and the drug-treated group were fed a high-fat, high-sugar diet.

[0076] Figure 20: Illustration of how Q11 promotes energy expenditure in obese mice. (AB) Effect of Q11 on oxygen consumption in obese mice. (CD) Effect of Q11 on carbon dioxide production in obese mice. (EF) Effect of Q11 on respiratory exchange ratio (RER) in obese mice. (GH) Effect of Q11 on energy expenditure (EE) in obese mice. (IJ) Effect of Q11 on activity level in obese mice.

[0077] Figure 21: Illustration of Q11's effects on mitochondrial morphology and function. (AB) Transmission electron microscopy observation of the effects of Q11 on the mitochondrial morphology of eWAT and iWAT cells in obese mice. (C) Flow cytometry detection of the effects of Q11 on ROS levels in adipocytes. (D) JC-1 assay kit detection of the effects of Q11 on mitochondrial membrane potential in adipocytes. (E) Effects of Q11 on oxidative phosphorylation (OCR) and ATP levels in adipocytes.

[0078] Figure 22: Schematic illustration of the protective effect of Q11 on aging mice. (AH) D-galactose-induced aging model: (A) dynamic changes in body weight; (B) dynamic changes in limb grip strength; (C) rotundus test drop latency; (D) water maze navigation escape latency; (E) water maze spatial exploration latency to first reach the original platform position; (F) number of times the original platform was crossed; (G) percentage of distance traveled in the target quadrant; (H) percentage of time spent in the target quadrant. (IP) Natural aging model: (I) frailty index; (J) limb grip strength; (K) rotundus test drop latency; (L) percentage of distance traveled in the central region of the open field test; (M) percentage of times explored new objects in the new object recognition test; (N) percentage of time spent in the new arm in the Y maze test. (O) Kaplan-Meier survival curves of male-female combined mice; (P) Kaplan-Meier survival curves of female mice.

[0079] Figure 23: Illustration of how Q11 improves the immune microenvironment in aging mice. (AC) Flow cytometry analysis of the proportions of CD3+ T cells (A), CD4+ T cells (B), and CD8+ T cells (C) in the spleen of mice in each group. (D) Composition ratio of naive, memory, and effector T cell subsets in CD4+ T cells. (E) Composition ratio of naive, memory, and effector T cell subsets in CD8+ T cells.

[0080] Figure 24: Schematic illustration of the protective effect of Q11 on mice with systemic lupus erythematosus. (A) Serum anti-dsDNA antibody levels in each group of mice. (B) Urinary albumin / creatinine ratio (UACR) in each group of mice. (C) Representative H&E staining images of spleen tissue in each group of mice. (D) Histopathological scores of spleen tissue in each group of mice. (E) Representative H&E staining images of kidney tissue in each group of mice. (F) Histopathological scores of kidney tissue in each group of mice. (G) Representative movement trajectories of mice in each group during the open field test. (H) Percentage of movement distance in the central region for each group of mice during the open field test.

[0081] Figure 25: Illustration of how Q11 improves the immune microenvironment in mice with systemic lupus erythematosus. Flow cytometry was used to detect the proportion of CD3+ T cells in the spleen tissue of each group of mice (A), as well as the levels of pro-inflammatory factors IFN-γ (B) and IL-17a (C).

[0082] Figure 26: Schematic illustration of the protective effect of Q11 on nephrotic syndrome. (A) Effect of Q11 on 24-hour urinary protein in PHN rats. (BD) Effect of Q11 on serum creatinine, blood urea nitrogen, and albumin in PHN rats. (E) H&E staining and PAS staining to assess the effect of Q11 on the histopathology of kidney tissue in PHN rats. (F) Effect of Q11 on kidney index in ADR mice. (G) Effect of Q11 on 24-hour urinary protein in ADR mice. (HI) Effect of Q11 on serum blood urea nitrogen and albumin in ADR mice. (JK) Effect of Q11 on serum TG and TC levels in ADR mice. (L) Representative images of H&E staining in kidney tissue. (M) Tubulointerstitial scores of mice in each group. (N) Representative images of PAS staining in kidney tissue. (O) Glomerular injury rate (%) in mice in each group.

[0083] Figure 27: Illustration of Q11 reducing oxidative stress levels and improving mitochondrial function. (A) Effect of Q11 on oxidative stress levels in the kidneys of PHN rats. (BC) Transmission electron microscopy observation of ultrastructural changes such as podocytes in the kidneys of PHN rats (B) and ADR mice (C). (D) Effect of Q11 on oxidative stress levels in an ADR-induced podocyte injury model. (E) Effect of Q11 on mitochondrial function in an ADR-induced podocyte injury model. Figure 28: Illustration of the protective effect of Q11 on heatstroke mice. (A) Core body temperature of mice in each group at the end of heat exposure. (B) Dynamic changes in core body temperature of mice in each group within 6 hours after removal from the high-temperature environment. (C) Effect of Q11 on survival time of heatstroke mice. Beneficial effects:

[0084] (1) The compounds of the present invention can effectively treat and / or prevent and / or alleviate nervous system diseases, heart disease and related conditions, bone and joint diseases, digestive system diseases, kidney damage or insufficiency, gout, acne or obesity, and have high safety and good pharmaceutical prospects in related fields.

[0085] (2) The compounds of the present invention, in some clinical applications for certain indications, may have comparable or even better technical effects than commercially available drugs. For example, in a mouse model of acute gouty arthritis, they can significantly improve / alleviate swelling of the ankle joint and foot sole, and their effect is better than that of the positive drug colchicine. For example, in mice with myocardial fibrosis, Q11 has a better effect on reducing PICP than the positive drug ATV. Therefore, Q11 is better than ATV in reducing Col I synthesis. Detailed Implementation

[0086] The technical solution of the present invention will be further described in detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative and explanatory of the present invention, and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are covered within the scope of protection intended by the present invention.

[0087] Unless otherwise stated, the raw materials and reagents used in the following examples are commercially available products or can be prepared by known methods.

[0088] Preparation Example 1:

[0089] Formula (I) of this invention includes the following specific compounds, which can be synthesized with reference to the method disclosed in CN114099503A.

[0090] in, That is, "Q11" as used in the embodiments.

[0091] Biological Example 1: Protective effect of the compounds of the present invention against depression.

[0092] 1 Experimental Methods

[0093] A C57BL / 6 mouse model of inflammatory depression was established using LPS (0.5 mg / kg, ip). The Q11 intervention group was divided into low-dose and high-dose groups, which were administered Q11 compound at 30 mg / kg and 60 mg / kg via intraperitoneal injection at the time of model establishment, respectively. The positive control group was administered venlafaxine (VNX, 10 mg / kg) via intraperitoneal injection. The drugs were then administered once daily until the model was terminated on day 7.

[0094] A C57BL / 6 mouse model of depression was established using chronic unpredictable mild stress (CUMS). After successfully inducing depressive-like behavior through 28 days of chronic unpredictable mild stress (including 24 hours of fasting, 24 hours of water deprivation, 2 hours of restraint, 3 hours of moist bedding, 3 hours of 45° cage tilt, and overnight alternating light), mice were randomly assigned to the CUMS group, the CUMS + 30 mg / kg Q11 group, the CUMS + 60 mg / kg Q11 group, and the CUMS + venlafaxine (VNX, 10 mg / kg, positive control) group. Modeling continued for 14 days, with the mice receiving the same intraperitoneal injections once daily until the model ended on day 14.

[0095] A multidimensional evaluation of the antidepressant effect of Q11 based on behavioral and neuropathological factors: Depressive-like behaviors in model mice were quantitatively analyzed using the forced swimming test (FST), tail suspension test (TST), and three-box social test; brain tissue from CUMS mice was collected, and immunofluorescence colocalization technology was used to detect the polarization status of microglia (marker IBA-1) in the hippocampus, including the M1 pro-inflammatory phenotype (iNOS). + / IBA-1 + ) and M2 anti-inflammatory phenotype (CD206) + / IBA-1 + The dynamic proportion of neurons was assessed; neuronal structural integrity was evaluated using H&E staining, and FJC / NeuN dual-label immunofluorescence was used to distinguish surviving neurons (FJC). - / NeuN + ) and degenerative neurons (FJC) + / NeuN + The number of newly generated neurons in the hippocampal dentate gyrus was quantified using DCX staining; further, IBA-1 / FJC was utilized. - / NeuN + Tri-scale confocal imaging analyzes the phagocytic activity of microglia on healthy neurons (phagocytosis).

[0096] 2 Experimental Results

[0097] Compared with the model group, Q11 significantly shortened the immobility time in the forced swimming test (Figure 1A, C) and tail suspension test (Figure 1D) of LPS-induced depressed (Figure 1A-B) and CUMS-induced depressed (Figure 1C-E) mice, and increased the contact time with stranger mice in the three-box social test (Figure 1B, E), indicating that Q11 has an effect on LPS-induced inflammatory depression (Figure 1A-B, E). * P<0.05, ** P<0.01, *** P<0.001) and CUMS-induced chronic depression (Figure 1C-E, * P<0.05, ** P<0.01, *** (P<0.001) showed a significant improvement effect, with the improvement effect of the 60mg / kg Q11 group being comparable to that of the positive drug group.

[0098] Further mechanistic studies showed that Q11 significantly reduced the overactivation of microglia in the hippocampus of CUMS-depressed mice, decreased the number of M1 pro-inflammatory microglia, and increased the number of M2 anti-inflammatory microglia (Figure 2A-C). * P<0.05, ** P<0.01, ***P<0.001). These results suggest that Q11 can regulate the polarization state of microglia and promote their conversion to an anti-inflammatory phenotype. Furthermore, the Q11 treatment group significantly inhibited neuronal damage and degenerative changes in the hippocampus of CUMS depressed mice (Figures 2D-E). * P<0.05, ** P<0.01, *** P<0.001), and increased the number of newly generated neurons (Figure 2F, * P<0.05, ** P<0.01, *** P<0.001). By inhibiting the phagocytosis of neurons by microglia (Figure 2G, * P<0.05, ** P<0.01, *** P<0.001), further confirming the protective effect of Q11 on neurons.

[0099] The above results indicate that Q11 can regulate microglia polarization, improve neuronal damage and degenerative changes, promote neuronal generation, and inhibit microglia phagocytosis, thus having a protective effect against depression.

[0100] Biological Example 2: The protective effect of the compounds of the present invention against pain.

[0101] 1. Experimental Methods

[0102] Acetic acid pain model: Kunming mice were intraperitoneally injected with 0.6% acetic acid solution. The Q11 intervention group was divided into low, medium and high dose groups, which were administered Q11 compound 30mg / kg, 90mg / kg and 150mg / kg by gavage daily for 3 days before modeling. The positive drug group was administered celecoxib (5mg / kg) by gavage. The number of writhing movements in mice within 15 minutes after modeling was recorded to evaluate the analgesic effect of Q11.

[0103] Formalin-induced biphasic pain model: Before the experiment, Kunming mice were placed in observation cages made of transparent acrylic plates and allowed to acclimatize for at least 30 minutes. The model group received a subcutaneous injection of 10 μL of 5% formalin solution (prepared fresh from 0.9% saline) into the left paw. The Q11 intervention group was divided into low (11 mg / kg), medium (33 mg / kg), and high (100 mg / kg) dose groups, which were administered the corresponding doses of Q11 compound by gavage 20 minutes before modeling, with 6 mice in each group. The total duration of pain response (paw licking / biting) was recorded within 0–5 minutes (phase I acute pain) and 20–40 minutes (phase II inflammatory pain) after formalin injection. The effect of Q11 on biphasic pain was evaluated.

[0104] 2. Experimental Results

[0105] In a pain model induced by glacial acetic acid, compared with the model group, mice in the Q11 administration groups (90 mg / kg and 150 mg / kg) showed significantly increased pain thresholds, with analgesic effects comparable to the positive control drug celecoxib group. Furthermore, the number of writhing movements decreased with increasing Q11 dose (Figure 3A). *** P<0.001 (vs. model group) indicates that Q11 has a significant analgesic effect, and that its analgesic effect is dose-dependent.

[0106] During the phase II inflammatory pain phase of the formalin biphasic pain model, mice in the 11 mg / kg and 100 mg / kg Q11 administration groups showed significantly reduced total duration of paw licking and biting compared to the control group (Figure 3B). * The result (P < 0.05 vs. control group) indicates that Q11 can significantly alleviate chronic pain in mice. These results demonstrate that Q11 has a significant analgesic effect.

[0107] Biological Example 3: Protective effect of the compounds of the present invention against myocardial infarction

[0108] 1 Experimental Methods

[0109] Acute myocardial infarction (AMI) and myocardial infarction-reperfusion (MIRI) models were established in C57BL / 6 mice using a left anterior descending coronary artery (LAD) ligation method. Mice were fixed in a supine position under isoflurane anesthesia. A 1.2 cm skin incision was made in the left chest, and muscle tissue was dissected layer by layer to expose the 3rd-4th intercostal space. A small hole was made in the 4th intercostal space using mosquito forceps to open the pleura and pericardium, allowing the heart to be gently ejected. The LAD was ligated using 6-0 silk suture, and successful ligation was confirmed when the anterior wall of the left ventricle turned white. After ligation, the heart was repositioned into the pleural cavity, air was expelled, and the surgical incision was sutured layer by layer. For the MIRI model mice, after LAD ligation, ischemia was observed for 45 minutes, followed by reperfusion for 24 hours.

[0110] The experiment was divided into a sham-operated group, a model group, a positive control group receiving metoprolol (Met, 10 mg / kg), and low (20 mg / kg), medium (40 mg / kg), and high-dose (80 mg / kg) Q11 groups, with 6 mice in each group. In the AMI model, the mice were administered the drugs via tail vein immediately after ischemia, once daily for 7 consecutive days. In the MIRI model, the mice were administered the drugs via tail vein 45 minutes after ischemia. Cardiac function was assessed by echocardiography on days 1 and 7 of the AMI model and 24 hours after reperfusion in the MIRI model. At the end of the experimental period, blood was collected from the orbital sinus to collect serum and detect cardiac function-related indicators, lactate dehydrogenase (LDH), and creatine kinase-MB (CK-MB) levels. Heart tissue was collected and stained with 2% TTC to observe the infarct area.

[0111] 2 Experimental Results

[0112] In the AMI model, compared with the model group, low, medium, and high doses of Q11 significantly reduced the infarct area (Figures 4A-B). *** P<0.001 vs. control group; ### P<0.001 vs. model group), cardiac index (Figure 4C, *** P<0.001 vs. control group; ### P<0.001 vs. model group) and the cardiomyocyte injury marker LDH (Figure 4D, *** P<0.001 vs. control group; # P<0.05, ### P<0.001 (vs. model group). Among them, the myocardial infarction area in the low, medium and high dose groups of Q11 decreased by 56%, 52% and 45%, respectively (Figure 4A-B). Echocardiographic results showed (Figure 4E-F) that Q11 significantly improved cardiac function in AMI model mice, as evidenced by significant increases in indicators such as left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS).

[0113] In the MIRI model, compared with the model group, low, medium, and high doses of Q11 all reduced the myocardial infarction area to varying degrees (Figures 5A-B). *** P<0.001 vs. control group; ## P<0.01, ### P<0.001 vs. model group) and myocardial injury markers LDH and CK-MB (Figures 5C-D, ** P<0.01, *** P<0.001 vs. control group; # P<0.05, ## P<0.01, ### P<0.001 vs. model group), with myocardial infarction area reduced by 26%, 32%, and 45%, respectively. Echocardiographic results showed that Q11 significantly improved cardiac function in MIRI model mice, specifically manifested as significant enhancement of LVEF and LVFS, as well as effective improvement in left ventricular end-diastolic diameter (LVID; d), left ventricular end-systolic diameter (LVID; s), left ventricular diastolic posterior wall thickness (LVPW; d), left ventricular systolic posterior wall thickness (LVPW; s), left ventricular diastolic volume (LV Vol; d), left ventricular systolic volume (LV Vol; s), left ventricular diastolic interventricular septal thickness (IVS; d), and left ventricular systolic interventricular septal thickness (IVS; s) (Figure 5E-L). * P<0.05, ** P<0.01, *** P<0.001 vs. control group; # P<0.05,## P<0.01, ### P < 0.001 vs. model group; & P<0.05, && P<0.01, &&& P<0.001 (vs. infarction group). Furthermore, ultrasound in the Q11-treated group showed significant improvement in the long-axis B-mode and M-mode membranes of the left ventricle (Figure 5M). These results indicate that Q11 exhibits significant cardioprotective effects in both AMI and MIRI models, effectively reducing myocardial infarction area and myocardial injury markers, and improving cardiac function.

[0114] Biological Example 4: Protective effect of the compounds of the present invention on myocardial fibrosis

[0115] 1. Experimental Methods

[0116] A C57BL / 6J mouse model of myocardial fibrosis was established by continuous subcutaneous injection of isoproterenol (ISO, 10 mg / kg, once daily for 10 days) into the back. The Q11 intervention group was divided into low, medium, and high dose groups, receiving Q11 compound 15 mg / kg, 30 mg / kg, and 60 mg / kg by gavage 6 hours after ISO subcutaneous injection, respectively. The positive control group received atorvastatin (ATV) 40 mg / kg by gavage. The control and model groups received an equal volume of physiological saline. Ten mice were in each group. At the end of the model on day 11, cardiac function was assessed by echocardiography. Heart tissue was collected, and cardiac pathological changes and the degree of fibrosis were assessed by H&E staining and Masson staining. Serum was collected, and PICP and PIIINP levels were detected by ELISA. Western blot was used to detect the expression of collagen I, collagen III, inflammatory factors, endoplasmic reticulum stress-related proteins, SREBP1, and nSREBP1 in heart tissue.

[0117] 2. Experimental Results

[0118] Compared with the model group, Q11 significantly improved cardiac ejection fraction (EF%) and fractional shortening (FS%) in mice with myocardial fibrosis, reduced cardiac index, and improved ventricular wall hypertrophy (Figures 6A-D). ** P<0.01, *** P<0.001 vs. control group; # P<0.05, ###P < 0.001 vs. model group). ELISA results showed that the levels of type I procollagen carboxyl-terminal peptide (PICP) and type III collagen precursor amino-terminal peptide (PIIINP) in the serum of mice treated with Q11 were significantly reduced, indicating that Q11 can inhibit the synthesis of type I collagen (Col I) and type III collagen (Col III), and its inhibitory effect on Col I is superior to that of the positive control drug ATV (Figure 6E-F). ** P<0.01, *** P<0.001 vs. control group; ## P<0.01, ### P < 0.001 (vs. model group). Further histopathological analysis revealed that Q11 improved cardiomyocyte necrosis and connective tissue proliferation (Figure 6G) and significantly reduced collagen volume fraction (Figure 6H-I). *** P<0.001 vs. control group; # P<0.05, ## P<0.01 (vs. model group). These results indicate that Q11 can inhibit collagen synthesis, reduce inflammatory response, and significantly improve cardiac function in mice with myocardial fibrosis.

[0119] Mechanistic studies have shown that, compared with the control group, the expression of Col I, Col III, and pro-inflammatory factors (IL-1β, IL-6, and TNFα) in the cardiac tissue of myocardial fibrosis mice was significantly increased (Figures 7A-F). * P<0.05, *** P<0.001 vs. control group; # P<0.05, ### P < 0.001 (vs. model group). However, the high-dose Q11 group significantly reduced the expression levels of the above proteins, indicating that Q11 can inhibit myocardial fibrosis and inflammatory response. Western blot analysis showed that the expression levels of endoplasmic reticulum stress (ERS) marker proteins p-PERK, p-eIF2α, p-IRE1, and XBP1s were all significantly increased in the cardiac tissue of myocardial fibrosis mice (Figure 7 G-M). * P<0.05, ** P<0.01, *** P<0.001 vs. control group; # P<0.05, ## P<0.01, ### P < 0.001 (vs. model group) indicates a severe ERS response. The high-dose Q11 group significantly reduced the expression of ERS marker-related proteins, indicating that Q11 can effectively alleviate the cardiac ERS response. Furthermore, Q11 also significantly reduced the level of nSREBP1 in cardiac tissue (Figure 7 N-P). ##The p-value < 0.01 (vs. model group) indicates that Q11 can inhibit the cleavage and activation of SREBP1. These results suggest that Q11 can alleviate inflammatory responses, relieve endoplasmic reticulum stress, and inhibit the cleavage and activation of SREBP1.

[0120] Biological Example 5: Protective effect of the compounds of the present invention against myocarditis

[0121] 1. Experimental Methods

[0122] An autoimmune myocarditis mouse model was established using the autoimmune mouse myocarditis antigen peptide MyHC-α614–631 (Ac-RSLKLMATLFSTYASADR-OH). Mice were divided into a control group, a model group, and low-dose (10 mg / kg), medium-dose (30 mg / kg), and high-dose (90 mg / kg) Q11 groups, with 10 mice in each group. Mice in the model group and the treatment groups were initially immunized by subcutaneous injection of the mouse myocarditis antigen peptide (200 μL / mouse, containing 0.2 mg of antigen peptide) into the axillary and inguinal lymph nodes. A second immunization was administered 7 days later, with a total dose of 0.4 mg / mouse. The control group received the same dose of physiological saline. Starting 24 hours after the initial immunization, mice were administered the corresponding dose of Q11 via gavage once daily until day 21, at which point the model was terminated. Echocardiography was used to examine the left ventricular ejection fraction (EF%), fractional shortening (FS%), left ventricular end-diastolic volume (LV Vol; d), and left ventricular end-systolic volume (LV Vol; s) in each group of mice. Hearts were collected, and H&E staining was used to detect cardiac inflammatory infiltration. Masson staining was used to detect the degree of cardiac fibrosis. Transmission electron microscopy was used to examine mitochondrial morphology. ELISA was used to detect the levels of CK-MB and LDH in mouse serum.

[0123] An in vitro myocarditis model was established using CVB3-induced HL-1 cardiomyocytes. Changes in the mRNA levels of key genes (bcl-2, atp5a1) in mitochondrial damage-related pathways were detected by qRT-PCR. Extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) of cardiomyocytes were measured using Sea Horse assays to calculate glycolysis and mitochondrial ATP production rates. Changes in cardiomyocyte membrane potential were analyzed by flow cytometry. The opening status of the mitochondrial permeability transition pore (MPTP) in cardiomyocytes was detected by fluorescent staining.

[0124] 2. Experimental Results

[0125] Compared with the control group, the body weight of mice in the model group was significantly reduced (Figure 8A, *** P<0.001 vs. control group; ### P<0.001 (vs. model group), cardiac index increased significantly (Figure 8B). *** P<0.001 vs. control group; ##P<0.01, ### P<0.001 (vs. model group) suggests pathological changes such as compensatory myocardial hypertrophy, while the medium and high dose groups of Q11 can significantly improve the above symptoms. Echocardiographic results show that Q11 significantly increases EF% and FE%, and reduces LV Vol;s and LV Vol;d, effectively improving cardiac function and reducing ventricular wall hypertrophy (Figure 8C-G). ** P<0.01, *** P<0.001 vs. control group; # P<0.05, ## P<0.01, ### P < 0.001 vs. model group. Furthermore, Q11 significantly reduced serum LDH and CK-MB levels (Figure 8H-I). *** P<0.001 vs. control group; # P<0.05, ## P<0.01, ### P<0.001 (vs. model group), further confirming its protective effect against myocardial injury. H&E staining results (Figure 8J) showed that the model group exhibited extensive myocardial cell necrosis and dissolution, replaced by proliferating connective tissue, accompanied by significant inflammatory cell infiltration. Q11 significantly reduced inflammatory cell infiltration and myocardial fiber necrosis. Masson staining results showed that Q11 dose-dependently inhibited abnormal collagen deposition and significantly improved the progression of myocardial fibrosis in mice (Figure 8K-L). *** P<0.001 vs. control group; # P<0.05, ## P<0.01, ### P < 0.001 (vs. model group).

[0126] Transmission electron microscopy results showed severe damage to myocardial fibers in the model group mice, manifested as blurred Z-lines, swollen mitochondria, broken or absent cristae, and significant loss and vacuolation of matrix. After Q11 treatment, myocardial fiber damage was alleviated, Z-lines straightened and M-lines became clearer, and mitochondrial morphology and structure were significantly improved (Figure 9A). qRT-PCR results showed that the mRAN expression levels of mitochondrial damage-related genes bcl-2 and atp5a1 were significantly decreased in the model group, while the expression levels in the Q11 group were significantly increased compared to the model group (Figures 9B-C). *** P<0.001 vs. control group; # P<0.05, ## P < 0.01 (vs. model group) indicates that Q11 can regulate the expression of mitochondrial-related apoptosis and energy metabolism genes. Sea horse energy metabolism analysis showed that Q11 restored ATP production dominated by oxidative phosphorylation and inhibited glycolytic metabolic shift (Figure 9D-E).** P<0.01, *** P<0.001 vs. control group; # P<0.05, ## P<0.01, ### P < 0.001 vs. model group. Membrane potential detection showed that Q11 effectively alleviated mitochondrial membrane potential depolarization (Figure 9F-G). *** P<0.001 vs. control group; ### P < 0.001 vs. model group. MPTP opening assays further revealed that Q11 significantly reduced the abnormal opening of the mitochondrial permeability transition pore (Figure 9H-I). *** P<0.001 vs. control group; ## P<0.01, ### P<0.001 (vs. model group), maintaining the integrity of mitochondrial structure.

[0127] The above results indicate that Q11 can improve the morphology and function of cardiomyocyte mitochondria and has a significant preventive and therapeutic effect on myocarditis.

[0128] Biological Example 6: Protective effect of the compound of the present invention against gout

[0129] 1. Experimental Methods

[0130] An acute gouty arthritis (AGA) model was established in SD rats using MSU crystals. The specific procedure was as follows: 2g of sodium urate powder was added to 400mL of boiled ultrapure water (containing 12mL of 1mol / L NaOH), stirred until dissolved, allowed to cool naturally to room temperature, the pH was adjusted to 7.5, and the solution was incubated overnight at 4℃. After filtration, the crystals were autoclaved at 121℃ for 30min and dried in an oven at 60℃. Under a microscope, the crystals appeared as needle-like points. 1g of crystals was weighed and added to 10mL of physiological saline to prepare a 100mg / mL suspension. 5mg of MSU crystals were administered subcutaneously to the right hind paw and to the ankle joint of each rat. The Q11 intervention group was divided into low, medium, and high dose groups, which were administered Q11 compound at 22.5mg / kg, 45mg / kg, and 90mg / kg by gavage daily starting 3 days before modeling. The positive control group was administered colchicine at 0.3mg / kg by gavage. The volume and thickness of the right hind paw of rats were measured using a rat paw edema meter and vernier calipers before modeling and at 2, 5, 8, 10, 12, 14, and 24 hours after modeling. The paw edema rate for each rat was calculated based on the changes in right hind paw volume and thickness relative to pre-modeling values ​​at each time point, and the differences in paw edema rates among groups were analyzed. Paw relief rate (%) = [(T M -T0)-(T C -T0)] / (T M-T0)×100%. T0: Foot volume of each group before molding, T C : Full volume of the drug-treated group, T M Simultaneously, the foot volume of the model group was measured. Serum and ankle joints were collected from rats at the peak of swelling (12 hours after modeling), and livers were collected at 24 hours after sacrifice. H&E staining was used to observe joint pathological changes. The pathological scoring criteria were as follows: no lesions or very few lesions were scored as 0; mild lesions or few lesions were scored as 1; moderate lesions or moderate amount of lesions were scored as 2; severe lesions or many lesions were scored as 3; and extremely severe lesions or many lesions were scored as 4.

[0131] A mouse model of hyperuricemia (HUA) was established using hypoxanthine (HX) and potassium oxonate (PO). 1.5 g of hypoxanthine and 2.5 g of potassium oxonate were weighed and added to 50 mL of 0.5% CMC-Na, then sonicated until homogenized. 300 mg / kg of hypoxanthine (HX) and 500 mg / kg of potassium oxonate (PO) were administered by gavage once daily for 14 days. The Q11 intervention group was divided into low, medium, and high dose groups, which were administered Q11 compound at doses of 22.5 mg / kg, 45 mg / kg, and 90 mg / kg daily by gavage starting 3 days before model establishment. The positive control group was administered allopurinol at 5 mg / kg once daily by gavage until the model was established on day 14. Blood samples were collected from the orbital cavity of HUA mice on days 7 and 14 after modeling, and kidney and liver tissues were collected on day 14. Uric acid (UA), creatinine (Cr), and blood urea nitrogen (BUN) in mouse plasma were detected by microplate method; XOD level was detected by colorimetric method; and H&E staining was used to observe pathological changes in kidney tissue.

[0132] 2. Experimental Results

[0133] Images of the rat paws showed that the Q11 group significantly improved ankle and plantar swelling, with better results than the positive control drug colchicine (Figure 10A). H&E staining revealed extensive necrosis of the synovial connective tissue in the model group, with pyknosis, fragmentation, and cytoplasmic disintegration of cells, accompanied by extensive infiltration of granulocytes and monocytes; a small amount of sloughed necrotic tissue was observed in the joint cavity; pannus covered by connective tissue was visible on the surface of the articular cartilage. In the Q11 group, synovial connective tissue necrosis was reduced, synovial hyperplasia was weakened, granulocyte and monocyte infiltration was decreased, and the articular cartilage surface was smooth without obvious abnormalities (Figure 10B). The scores for synovial hyperplasia and inflammatory cell infiltration were significantly decreased in the Q11 group (Figures 10C-D). *** P<0.001 vs. control group; # P<0.05, ## P<0.01, ###P < 0.001 (vs. model group), indicating that Q11 significantly improved the pathological joint damage in AGA rats. The dynamic change line graph of foot volume / thickness swelling rate showed that the model group rats reached peak swelling 12 hours after modeling. Q11 significantly alleviated foot swelling-related indicators (foot thickness and volume) in AGA rats from the 5th hour after modeling, and the allergic effect persisted for 24 hours. The foot volume relief rates in the low, medium, and high dose groups of Q11 were 32.98%, 36.73%, and 57.14%, respectively, which were superior to the 30.61% in the positive control group (Figure 10E-F). Furthermore, the Q11 dose showed a dose-dependent relationship with foot volume (A) and thickness (B) in AGA rats (Figure 10G-H, 0.3). <r<0.7,P<0.05)。

[0134] Compared with the control group, the model group mice showed improvement on day 7 after modeling (Figures 11A-C). *** P<0.001 vs. control group; ### P<0.001 vs. model group) and day 14 (Figure 11D-F, *** P<0.001 vs. control group; ### (P<0.001 vs. model group) Uric acid levels were significantly elevated. Q11 significantly reduced plasma uric acid (UA) levels in HUA mice 14 days after modeling. Renal pathological observation (Figure 11G) showed extensive renal tubular atrophy and luminal narrowing in the model group, decreased eosinophilicity of the tubular epithelial cells, and punctate lymphocyte infiltration in the interstitium. In the low, medium, and high dose groups of Q11, renal tubular dilation was reduced, and no significant fibrosis or inflammatory cell infiltration was observed, indicating that Q11 significantly alleviated the pathological damage to the kidney tissue of HUA mice.

[0135] The results above indicate that Q11 can significantly improve the symptoms in AGA and HUA model mice, suggesting that it can be used for the prevention and treatment of gout.

[0136] Biological Example 7: Protective effect of the compounds of the present invention on osteoarthritis

[0137] Osteoarthritis (OA) is a chronic musculoskeletal disease characterized by degenerative changes in articular cartilage, with knee osteoarthritis (KOA) being the most common clinical subtype. Its typical pathological feature is progressive destruction of articular cartilage, accompanied by subchondral bone sclerosis, synovitis, and osteophyte formation. Early symptoms include focal softening and loss of elasticity of the cartilage, which gradually progresses to roughness, erosion, ulceration, and even complete loss of cartilage, ultimately leading to joint dysfunction. KOA is one of the leading causes of chronic pain and disability worldwide. Currently, commonly used clinical treatments include nonsteroidal anti-inflammatory drugs (NSAIDs) (such as diclofenac sodium) and chondroprotective agents (such as glucosamine sulfate). The former achieves analgesic and anti-inflammatory effects by inhibiting cyclooxygenase (COX) activity, but long-term use may cause gastrointestinal side effects (such as ulcers and bleeding) and cardiovascular risks. The latter slows disease progression by regulating bone metabolism, but its pain relief effect is limited, and its clinical efficacy is controversial. Therefore, exploring new targets and drugs for the treatment of osteoarthritis is of great significance.

[0138] 1. Experimental Methods

[0139] This study established a knee osteoarthritis model in SD rats using a single intra-articular injection of sodium iodoacetate (MIA). The experiment was divided into a control group, a model group, and low (22.5 mg / kg), medium (45 mg / kg), and high (90 mg / kg) dose groups of Q11. On day 0, the model group and Q11 group received a single injection of 2 mg MIA (dissolved in 50 μL of sterile saline), while the control group received an equal volume of sterile saline. Starting from day 0, the Q11 intervention group received the corresponding dose of Q11 via gavage daily according to the above groupings. During the experiment, the rats underwent paw mechanical pain threshold measurement and knee pain vocalization tests on days 0, 3, 7, and 21. The experiment ended after three weeks, and the knee joint was dissected and Pelletier scores for cartilage damage were performed.

[0140] 2. Experimental Results

[0141] Compared with the model group, Q11 significantly improved the plantar mechanical pain threshold in rats with knee osteoarthritis (Figure 12A). *** P<0.001 vs. control group; ### P<0.001 vs. model group), number of audible ... *** P<0.001 vs. control group; ### P<0.001 vs. model group) and Pelletier score of knee cartilage damage (Figure 12C, *** P<0.001 vs. control group; ###P < 0.001 (vs. model group), and the mechanical pain threshold of the foot and the number of knee pain phonations in all three Q11 dose groups returned to the control group level, suggesting that Q11 can significantly inhibit knee osteoarthritis pain. Furthermore, compared with the model group, the low-dose Q11 group significantly improved the femoral cartilage structure and enhanced cartilage surface integrity (Figure 12D), indicating that Q11 has a certain protective effect against cartilage damage. These results suggest that Q11 can be used for the prevention and treatment of osteoarthritis in clinical practice.

[0142] Biological Example 8: Protective effect of the compounds of the present invention against pancreatitis.

[0143] 1. Experimental Methods

[0144] A Cae-SAP model was established in C57BL / 6J mice using a combination of lipolytic acid (LPS) and spirulina extract. Mice were divided into six groups of ten mice each (half male, half female): a control group, a model group, and a Q11 group (30 mg / kg, 45 mg / kg, 60 mg / kg, and 90 mg / kg). Two hours before modeling, mice were administered the drugs via gavage according to these groupings. Both the model and drug-treated groups received intraperitoneal injections of the same dose of spirulina extract (50 μg / kg) once per hour for seven consecutive hours. Following the last spirulina extract injection, mice were injected intraperitoneally with LPS (10 mg / kg) solution. The control group received the same volume of physiological saline intraperitoneally. The modeling process ended 24 hours after initiation. Serum was collected via orbital blood sampling to detect serum amylase and lipase activities in each group. The wet-to-dry weight ratio of pancreatic tissue was recorded. Hematoxylin and eosin (H&E) staining was used to observe the pathological changes in the pancreatic tissue of Cae-SAP mice.

[0145] A C57BL / 6J mouse Arg-SAP model was established by intraperitoneal injection of L-arginine (3.3 g / kg). The mice were divided into five groups: control group, model group, and low (30 mg / kg), medium (60 mg / kg), and high (90 mg / kg) Q11 dose groups, with eight mice in each group. Both the model group and the drug-treated groups received intraperitoneal injections of 3.3 g / kg L-arginine solution, once every hour for a total of three times, to establish the Arg-SAP model. The Q11 intervention groups received the corresponding dose of Q11 via gavage 24 hours after model establishment, once daily. The control group received the same volume of physiological saline. The model was terminated 72 hours after establishment. Serum was collected to detect serum amylase and lipase activities; the wet-to-dry weight ratio of pancreatic tissue was recorded; and H&E staining was used to observe the histopathological changes in the pancreatic tissue of Arg-SAP mice.

[0146] 2. Experimental Results

[0147] Compared with the control group, the serum amylase activity, lipase activity, and wet-to-dry weight ratio of pancreatic tissue were significantly upregulated in the Cae-SAP model group mice, and Q11 could reduce the above indicators to varying degrees (Figure 13A-C). *** P<0.001 vs. control group;# P<0.05, ## P<0.01, ### P < 0.001 vs. model group. Furthermore, H&E staining results showed that, compared with the control group, the pancreatic tissue of the model group mice exhibited significant edema, disordered acinar cell arrangement, accompanied by extensive inflammatory cell infiltration and a small amount of acinar cell necrosis; while Q11 significantly improved the pathological damage of the mouse pancreatic tissue and reduced the inflammatory response (Figure 13D-F). * P<0.05, *** P<0.001 vs. control group; # P<0.05, ### P < 0.001 (vs. model group).

[0148] In the Arg-SAP model, compared with the control group, the serum amylase activity, lipase activity, and wet-to-dry ratio of pancreatic tissue were significantly increased in the model group mice. The Q11 treatment group significantly reversed the increase of the above indicators (Figure 13G-I). *** P<0.001 vs. control group; # P<0.05, ### P<0.001 vs. model group). H&E staining results showed that the pancreatic tissue of mice in the model group exhibited extensive edema, with a large number of acinar cell necrosis and inflammatory cell infiltration in the pancreatic parenchyma; while in the Q11 intervention group, pancreatic tissue edema was significantly reduced, acinar cell necrosis was significantly reduced, and the level of inflammatory infiltration was significantly decreased (Figure 13 J-L, * P<0.05, ** P<0.01 vs. control group; # P < 0.05 (vs. model group).

[0149] The above results indicate that Q11 can be used for the prevention and treatment of clinical pancreatitis.

[0150] Biological Example 9: Protective effect of the compounds of the present invention against colitis.

[0151] 1. Experimental Methods

[0152] An acute ulcerative colitis model was established in BALB / c mice by allowing them free access to 2.5% DSS solution for 7 consecutive days. The Q11 intervention group was divided into low-, medium-, and high-dose groups, which were administered Q11 compound at doses of 10 mg / kg, 30 mg / kg, and 90 mg / kg by gavage daily for 5 days before model establishment until the model was established on day 7. There were 8 animals in each group.

[0153] A chronic ulcerative colitis model was established using the 2% DSS intermittent induction method, with three cycles, each lasting 15 days. Starting from day 6, mice were administered Q11 compound daily by gavage at doses of 10 mg / kg, 30 mg / kg, and 90 mg / kg until the model was established. Eight animals were in each group. Daily changes in body weight, severity of diarrhea, and fecal hemorrhage were recorded. The Disease Activity Index (DAI) score was calculated by averaging the scores of three factors: percentage of body weight loss, fecal characteristics, and occult blood test results (benzidine method). The scoring criteria are as follows:

[0154] Table 1 Disease Activity Index in Mice

[0155] After a 24-hour fast following the last administration, serum and colonic tissue were collected. The distance between the rectum and cecum, i.e., the colonic length (cm), was measured with a ruler, and the cecum tissue was removed. Approximately 1 cm of the distal colon was harvested and weighed (mg). The remaining colonic tissue was longitudinally dissected, and after removing feces from the intestinal lumen, its weight (mg) was measured. The weights of the two portions were added together and recorded as the mouse's colonic weight (mg). H&E staining and Masson staining were used to assess pathological damage to the distal colon in each group.

[0156] 2. Experimental Results

[0157] Compared with the model group, Q11 significantly increased the body weight of mice with DSS-induced acute ulcerative colitis and decreased the DAI score, with the greatest difference observed on the last day of modeling (day 7) (Figures 14A-D). * P<0.05, ** P<0.01, *** P < 0.001 (vs. model group). Furthermore, the colon length in all experimental groups in Q11 was greater than that in the DSS model group (Figures 14E-F). ** P<0.01, *** P < 0.001 vs. model group. H&E staining (Fig. 14G) and Masson staining (Fig. 14H) revealed that Q11 significantly improved the pathological damage in the terminal colon of model mice (Fig. 14G-H). ** P<0.01, *** P < 0.001 vs. model group. Furthermore, qPR-PCR analysis revealed that Q11 significantly reduced the expression of inflammatory factors in the terminal colon tissue of model mice and increased the expression of intestinal barrier factors (Figure 14I-J). * P<0.05, ** P<0.01, *** P < 0.001 (vs. model group).

[0158] Consistent with the results in the acute model, Q11 significantly increased the body weight of mice in the DSS-induced chronic ulcerative colitis model and decreased the DAI score (Figure 15A-B). * P<0.05, ** P<0.01, *** P < 0.001 (vs. model group). Furthermore, the colon length in both the low- and medium-dose Q11 groups was greater than that in the DSS model group (Figures 15C-D). * P<0.05 vs. model group). H&E staining and Masson staining results showed that the Q11 intervention group could improve the pathological damage of DSS model mice to varying degrees (Figure 15E-F). * P<0.05, ** P<0.01 vs. control group; ## P<0.01, vs. model group).

[0159] The above results indicate that Q11 significantly inhibits DSS-induced acute and chronic ulcerative colitis mouse models and can be used for the prevention and treatment of clinical colitis.

[0160] Biological Example 10: Protective effect of the compounds of the present invention against kidney injury.

[0161] 1. Experimental Methods

[0162] The preventive and therapeutic effects of Q11 on acute kidney injury in mice: A BALB / c mouse AKI model was established by a single intraperitoneal injection of cisplatin (14 mg / kg). Mice were divided into a control group, a model group, a positive control group receiving amifostine (AMF, 200 mg / kg), and low (15 mg / kg), medium (30 mg / kg), and high (60 mg / kg) Q11 groups, with 10 mice in each group. Starting 5 days before model establishment, mice were administered the drugs daily by gavage according to the above groupings. Model establishment began 0.5 hours after the last administration, and continued daily until the model was established on day 3. Serum was collected via orbital blood sampling to detect renal function-related indicators such as creatinine and blood urea nitrogen. Kidney tissue was collected and H&E staining was used to observe renal pathological changes. Transmission electron microscopy was used to observe mitochondrial morphological changes in the kidney tissue of AKI mice.

[0163] Effect of Q11 on the survival of mice with cisplatin-induced acute kidney injury: The survival of mice was observed over 7 days after intraperitoneal injection of cisplatin (18 mg / kg). Mice were divided into a control group, a model group, and a Q11 intervention group, with 12 animals in each group. The Q11 intervention group received Q11 compound 60 mg / kg daily by gavage starting 5 days before model initiation. Model initiation began 0.5 hours after the last administration, and the treatment was repeated daily for 7 days. Mice survival was then observed.

[0164] An in vitro cell damage model was established by stimulating mRTEC and HK-2 cells with 10 μM cisplatin for 24 hours, while simultaneously administering 25 μM, 50 μM, and 100 μM of Q11 compound. Changes in mitochondrial membrane potential and ATP content were detected using JC-1 staining and colorimetric methods; ROS, GSH, and CAT levels in cells were detected using the DCFH-DA fluorescent probe method and microplate assay.

[0165] 2. Experimental Results

[0166] Compared with the model group, the levels of creatinine and blood urea nitrogen in mice in the medium and high dose groups of amifostine and Q11 were significantly reduced (Figure 16A-B). *** P<0.001 vs. control group; # P<0.05, ## P<0.01, ### P < 0.001 vs. model group). H&E staining results showed that the kidney tissue of mice in the model group exhibited pathological changes such as inflammatory infiltration, renal tubular necrosis, and vacuolar degeneration of epithelial cell structure, while the pathological damage to the kidney tissue of mice in the amifostine and Q11 groups was significantly reduced, and the renal tubular injury score was significantly lower (Figure 16C-D). *** P<0.001 vs. control group; # P<0.05, ### P < 0.001 vs. model group. Furthermore, Q11 significantly reduced the mRNA levels of NGAL and KIM-1 in the kidney tissue of AKI mice (Figure 16E-F). * P<0.05, *** P<0.001 vs. control group; # P<0.05, ### P < 0.001 vs. model group. In the survival experiment, Q11 significantly prolonged the survival time of cisplatin-induced AKI mice, increasing the mean survival time from 2.7 days to 3.7 days, a 35.5% increase (Figure 16G). *** P<0.001 vs. control group; ## P < 0.01 (vs. model group).

[0167] Further mechanistic studies showed that the mitochondrial structure of the model group mice was significantly damaged, with an ellipsoidal shape, obvious swelling, and blurred outline. Quantitative morphological analysis showed that the mitochondrial aspect ratio (mitochondrial long axis / mitochondrial short axis) and mitochondrial area were significantly reduced, indicating mitochondrial fragmentation. In contrast, the Q11 treatment group of AKI mice showed an increased number of mitochondria and improved morphology (Figure 17A). ** P<0.01, *** P<0.001 vs. control group; #P < 0.05 (vs. model group). In vitro experiments showed that Q11 significantly restored the cisplatin-induced decrease in mitochondrial membrane potential and intracellular ATP depletion in renal tubular epithelial cells (mRTEC, Fig. 17B) and HK-2 cells (Fig. 17C-D). * P<0.05, *** P<0.001 vs. control group; # P<0.05, ## P<0.01, ### P < 0.001 vs. model group. Furthermore, compared to the control group, cisplatin-induced mRTEC cells (Fig. 17E) and HK-2 cells (Fig. 17F) showed increased ROS levels and decreased levels of antioxidant stress markers GSH and CAT, which Q11 significantly improved (Fig. 17E-F). * P<0.05, ** P<0.01, *** P<0.001 vs. control group; # P<0.05, ## P<0.01, ### P < 0.001 (vs. model group).

[0168] The above results indicate that Q11 can reduce oxidative stress, improve mitochondrial dysfunction, and has a significant protective effect against kidney damage.

[0169] Biological Example 11: Protective effect of the compounds of the present invention against acne.

[0170] 1. Experimental Methods

[0171] Male Balb / c mice aged 7-9 weeks were selected to establish a BALB / c mouse acne model by applying oleic acid to their backs and injecting testosterone subcutaneously. The model group received 0.1 mL of oleic acid per mouse daily for 14 days, and was subcutaneously injected with 10 mg / kg testosterone on days 7, 9, 11, and 13 of model establishment. The control group received an equal amount of glycerol and was injected with an equal amount of solvent. Starting on day 15, the Q11 intervention group was administered Q11 compound daily by gavage at doses of 15 mg / kg, 30 mg / kg, and 60 mg / kg, while the control and model groups were administered an equal amount of solvent by gavage for 7 days. At the end of the experimental period, H&E staining was used to observe the histopathological changes in the skin tissue of each group of mice.

[0172] 2. Experimental Results

[0173] Compared with the model group, the Q11 group showed significantly improved skin condition, good lesion healing, and restored hair coverage (Figure 18A). H&E staining results showed that the Q11 group had decreased epidermal thickness, improved keratinization, and reduced inflammatory cell infiltration compared with the model group (Figure 18B).

[0174] Biological Example 12: Protective effect of the compounds of the present invention against obesity.

[0175] 1. Experimental Methods

[0176] An obesity model was established in male C57BL / 6J mice by feeding them a high-fat diet containing 60% fat. The control group was fed a low-fat, low-sugar control diet. The Q11 intervention group was divided into low, medium, and high-dose groups, receiving Q11 compound at 15 mg / kg, 30 mg / kg, and 60 mg / kg daily by gavage at the start of the model, respectively. The positive control group received liraglutide 200 μg / kg subcutaneously. The control and model groups received an equal volume of physiological saline. Ten mice were in each group. Weekly food intake and body weight changes were recorded until the end of the 12-week model. Adipose tissue was harvested and weighed. Body composition analysis was used to assess mouse body weight. H&E staining was used to observe morphological changes in white adipose tissue.

[0177] Energy expenditure in mice was analyzed using small animal energy metabolism cages. Transmission electron microscopy was used to observe mitochondrial morphological changes in eWAT and iWAT cells of HFD-induced obese mice. An in vitro model was established by inducing 3T3-L1 cells to mature into adipocytes. Flow cytometry was used to detect mitochondrial membrane potential and ROS levels in the 3T3-L1 adipocyte model. Oxygen consumption rate and ATP content in 3T3-L1 adipocytes were measured using a multi-functional microplate reader.

[0178] 2. Experimental Results

[0179] Compared with the control group, the body weight of mice in the model group began to increase significantly at week 2, and the body weight increased by approximately 60% at week 12 (P<0.001). The body weight of mice in the low-dose Q11 group began to decrease significantly at week 5, while the body weight of mice in the medium- and high-dose Q11 groups began to decrease significantly at week 2, with weight losses of 10.5% and 21.2% respectively at week 12 (Figure 19B). *** P<0.001 vs. control group; # P<0.05, ## P < 0.01 (vs. model group). Representative images at the end of the experimental period showed significant differences in body condition among the control group, model group, and different drug intervention groups (Figure 19A). Body composition analysis showed no significant difference in lean mass among the groups, but the model group had significantly higher fat mass than the control group. Q11 dose-dependently reduced fat mass in obese mice and corrected for the decrease in lean mass percentage or increase in fat mass percentage in the model group (Figures 19D-G). *** P<0.001 vs. control group; # P<0.05, ## P<0.01, ###P < 0.001 vs. model group. Furthermore, Q11 had no significant effect on food intake in mice (Figure 19C). # P < 0.05 (vs. model group), indicating that Q11 does not exert its weight-loss effect by suppressing appetite. Compared with the model group, Q11 dose-dependently reduced the adipose tissue weight of prWAT, eWAT, and iWAT in mice (Figure 19H-J). *** P<0.001 vs. control group; # P<0.05, ## P<0.01, ### P < 0.001 (vs. model group). H&E staining results showed that the adipocytes of the eWAT (Fig. 19K-L) mice in the model group were plump and large in size, with an average cross-sectional area of ​​4920 μm. 2 The Q11 low, medium, and high dose groups showed a dose-dependent reduction in the cross-sectional area of ​​adipocytes, significantly higher than the control group. The high-dose Q11 group exhibited the most significant effect, with an average cross-sectional area of ​​3082 μm. 2 Furthermore, the morphological changes of adipocytes in iWAT (Fig. 19M-N) are basically consistent with those in eWAT (Fig. 19K-N). *** P<0.001 vs. control group; # P<0.05, ## P<0.01, ### P < 0.001 vs. model group; H&E staining scale was 80 μm.

[0180] The results of small animal energy metabolism monitoring in cages showed that, compared with the model group, the VO2 of mice in the Q11 group increased by 44.09% and 39.23% respectively during the light and dark cycles (Figures 20A-B). *** P<0.001 vs. control group; ### P<0.001 (vs. model group); VCO2 increased by 48.06% and 44.60% respectively (Figure 20C-D). *** P<0.001 vs. control group; ### P < 0.001 (vs. model group); the mean RER was higher than 0.8 of the model group (Figure 20E-F). *** P<0.001 vs. control group; # P<0.05 (vs. model group); EE increased by 44.80% and 40.21% respectively (Figure 20G-H). *** P<0.001 vs. control group; ### P < 0.001 vs. model group. Furthermore, Q11 significantly increased the activity level of obese mice during the photoperiod (Figure 20I-J). # P < 0.05 (vs. model group), suggesting that Q11 may promote energy consumption.

[0181] In eWAT, the mitochondria in the model group mice were ellipsoidal, swollen, and had broken and disappeared cristae; while in the Q11 group, mitochondrial swelling was significantly reduced, and the cristae structure was clearer. In iWAT, similarly, the mitochondrial morphology in the model group was severely damaged, showing abnormal swelling, broken and blurred cristae structure, while the mitochondrial morphology in the Q11 group was improved, showing a relaxed appearance, reduced swelling, and clearer cristae structure (Figures 21A-B). In vitro 3T3-L1 adipocyte model results showed that, compared with the control group, the ROS level in the model group was significantly increased, while Q11 concentration-dependently reduced ROS levels (Figure 21C). *** P<0.001 vs. control group; # P<0.05, ## P<0.01, ### P < 0.001 vs. model group). Q11 also significantly reduced mitochondrial membrane potential (Figure 21D). *** P<0.001 vs. control group; ## P<0.01, ### P < 0.001 (vs. model group), while promoting oxygen consumption, oxidative phosphorylation and ATP production (Figure 21E). ** P<0.01 vs. control group; # P < 0.05 (vs. model group).

[0182] The above results indicate that Q11 can reduce adipose tissue, enhance energy metabolism, and improve mitochondrial function, thus having a significant preventive and therapeutic effect on obesity.

[0183] Biological Example 13: Protective Effect of the Compounds of the Invention on Aging

[0184] 1 Experimental Methods

[0185] Observation of Healthy Lifespan in D-Galactose-Induced Aging Mice: An aging model of C57BL / 6 mice was induced by continuous intraperitoneal injection of D-galactose (D-gal) for 8 weeks. Mice were randomly divided into five groups (n=10 per group): a control group, a model group, and low, medium, and high dose Q11 groups. Simultaneously with model initiation, mice were administered Q11 compound at doses of 15 mg / kg, 30 mg / kg, and 60 mg / kg via gavage. The control and model groups received an equal volume of the solvent once daily for 8 weeks. At the end of the experimental period, the rotarod fatigue test was used to assess the mice's motor coordination ability; the Morris water maze test was used to assess the mice's spatial learning and memory abilities.

[0186] Observation of Healthy Lifespan in Naturally Aging Mice: 55-week-old C57BL / 6 mice were used as a natural aging mouse model. Mice were randomly divided into three groups of 36 mice each: a model group (i.e., aged control group) and low-dose (10 mg / kg) and high-dose (60 mg / kg) Q11 groups. At 55 weeks of age, mice were administered the drug via gavage according to the above groupings (once daily, 6 days a week), while the model group received an equal volume of the drug. At weeks 10 and 20 (i.e., 65 and 75 weeks of age), the frailty index was dynamically scored for each group according to the assessment system established by Whitehead et al. Subsequently, the motor function of the mice was assessed through limb grip strength tests and rotarod fatigue tests; their cognitive function was comprehensively assessed using open field tests, novel object recognition tests, and Y-maze tests; spleen tissue was collected, and the differentiation and changes of T cell subsets were detected by flow cytometry.

[0187] Lifespan observation in naturally aging mice: 55-week-old C57BL / 6 mice were randomly divided into a model group and a Q11 group, with 60 mice in each group (half male and half female). The mice were administered Q11 by gavage once daily, 6 days a week, at a dose of 60 mg / kg. The model group received an equal volume of the solvent. Mice were observed multiple times daily, and the time of death was recorded. Kaplan–Meier survival curves were plotted, and the Log-rank test was used to assess the effect of Q11 on mouse lifespan.

[0188] 2 Experimental Results

[0189] In a D-galactose-induced aging mouse model, compared with the control group, the model group mice showed significantly reduced body weight, limb grip strength, and rotarod drop latency, indicating impaired muscle strength and motor coordination. Medium and high doses of Q11 significantly improved these changes, increasing mouse body weight and limb grip strength, prolonging rotarod drop latency, and restoring muscle strength and motor coordination (Figures 22A-C). * P<0.05, ** P<0.01, *** P<0.001 vs. control group; # P<0.05, ## P<0.01, ### P < 0.001 vs. model group). Morris water maze test results showed that during the navigation phase, the high-dose Q11 group significantly shortened the escape latency for mice searching for hidden platforms (Figure 22D). *** P<0.001 vs. control group; # P < 0.05 (vs. model group); During the spatial exploration period, Q11 significantly shortened the latency of mice to first reach the original platform location, and increased the number of times they crossed the original platform location, as well as the running distance and dwell time in the target quadrant (Figure 22E-H). *P<0.05 vs. control group; # P<0.05, ## P < 0.01 (vs. model group). The above results indicate that Q11 significantly improved the spatial learning and memory abilities of D-galactose-induced aging mice.

[0190] In a naturally aging mouse model, after 10 weeks of continuous administration (65 weeks of age), the frailty index in the low- and high-dose Q11 groups decreased by 26.17% and 45.03%, respectively, compared to the model group (Figure 22I). *** P<0.001 vs. control group; ### P < 0.001 (vs. model group), indicating that Q11 can effectively improve the frailty state of aging mice. Regarding motor function, Q11 significantly improved the grip strength of aging mice (Fig. 22J) and prolonged the drop latency in the rotundus test (Fig. 22K), effectively reversing age-related motor dysfunction (Fig. 22J-K). *** P<0.001 vs. control group; # P<0.05, ### P < 0.001 vs. model group. In terms of neurobehavioral aspects, Q11 significantly increased the percentage of distance traveled in the central region during the open field test, the percentage of times mice explored new objects during the new object recognition test, and the percentage of time spent on the new arm during the Y-maze test (Figure 22 L-N). * P<0.05, ** P<0.01, *** P<0.001 vs. control group; ## P<0.01, ### P < 0.001 (vs. model group) indicates that Q11 can improve anxiety, exploratory behavior, and cognitive function in aging mice. Notably, these improvements were significant as early as week 10 of administration and remained stable until week 20 (75 weeks of age). Furthermore, Q11 significantly prolonged the lifespan of naturally aging mice. By week 92, the mortality rate in the Q11 treatment group decreased from 55.00% in the model group to 36.67%, an improvement of 33.33% (Figure 220). * P<0.05 (vs. model group). The improvement was particularly significant in female mice, with the mortality rate decreasing from 63.33% to 40.00%, an improvement rate of 36.84%, and median lifespan increasing by 12.34% (Figure 22P). * P < 0.05 (vs. model group).

[0191] Mechanistic studies have shown that CD3 in the spleen of model group mice + The proportion of T cells decreased significantly, and CD8... +The significantly increased proportion of T cells suggests that the mice exhibit typical immunosenescence characteristics; while Q11 intervention significantly upregulated CD3. + T cell ratio and downregulation of CD8 + T cell proportion (Figure 23A-C) *** P < 0.001 vs. control group; ## P < 0.01, ### P < 0.001 vs. model group. Further T cell subset analysis showed that the proportion of naive T cells in CD4+ T cells and CD8+ T cells in the model group was significantly decreased, while the proportion of memory / effective T cells was significantly increased; Q11 could significantly reverse the imbalance of CD4+ T cell subsets and downregulate the abnormally increased proportion of memory CD8+ T cells (Figure 23D-E). ** P < 0.01, *** P < 0.001 vs. control group; # P < 0.05 (vs. model group).

[0192] The above results indicate that Q11 can regulate T cell differentiation, remodel the immune microenvironment, and has a significant protective effect against aging.

[0193] Biological Example 14: Protective effect of the compounds of the present invention against systemic lupus erythematosus

[0194] 1 Experimental Methods

[0195] This study established a systemic lupus erythematosus (SLE) model in BALB / c mice using topical application of imiquimod (IMQ, a Toll-like receptor 7 agonist). Eight-week-old female mice were selected, and 25 mg of 5% IMQ cream was applied evenly to the skin of the right ear three times a week for four consecutive weeks. The control group (n=10) received the same amount of petroleum jelly in the same manner. At the end of the fourth week, blood was collected from the orbital cavity, and serum was separated. The level of anti-dsDNA antibodies was detected by ELISA to confirm the establishment of the model. Based on the anti-dsDNA level, the model mice were randomly divided into five groups (n=14): a model group, a positive control group (prednisolone acetate, PA, 7 mg / kg), and low, medium, and high dose Q11 groups (10, 30, and 60 mg / kg, respectively). From the fifth week onwards, the mice were administered the same dose of the drug via gavage daily for eight consecutive weeks, while the control and model groups were administered the same dose of the drug via gavage. After the experiment, blood was collected from the orbital cavity to separate serum and detect the level of anti-ds-DNA antibody; random urine was collected from mice using the tail lift reflex method to detect the urinary albumin-to-creatinine ratio (UACR); spleen and kidney tissues were collected, and H&E staining was used to assess histopathological changes; and changes in T cell subsets in spleen tissue were detected by flow cytometry.

[0196] 2 Experimental Results

[0197] Compared with the model group, Q11 significantly reduced serum anti-dsDNA antibody levels and urinary albumin-to-creatinine ratio (UACR) in SLE mice (Figure 24A-B). ** P < 0.01, *** P < 0.001 vs. control group; # P < 0.05 ## P < 0.01, ### P < 0.001 (vs. model group), suggesting that Q11 can significantly reduce autoantibody-mediated immune responses and improve kidney damage. H&E staining showed that the spleen of the model group mice exhibited typical SLE-related pathological changes such as white pulp dilation, increased extramedullary hematopoiesis, cell necrosis, and mild hemorrhage, while Q11 could restore the red and white pulp structure of the spleen to varying degrees (Fig. 24C) and reduce histopathological scores (Fig. 24D). *** P < 0.001 vs. control group; ### P < 0.001 (vs. model group). Renal pathological observation showed that the model group mice exhibited significant lesions in their kidneys, including glomerular mesangial cell proliferation, renal tubular epithelial cell degeneration and necrosis, renal tubular lumen dilation, interstitial inflammatory cell infiltration, and fibrous tissue proliferation. Q11 treatment improved these renal structural abnormalities to varying degrees and reduced the severity of pathological damage. (Figure 24E-F) ** P < 0.01 vs. control group; # P < 0.05 vs. model group. Open field test results showed that Q11 significantly increased the percentage of movement distance in the central region of SLE mice and alleviated anxiety-like behaviors associated with SLE (Figure 24G-H). *** P < 0.001 vs. control group; # P < 0.05 (vs. model group). Mechanistic studies showed that CD3 in model group mice... + The proportion of T cells decreased significantly, while the levels of IFN-γ and IL-17a increased significantly, suggesting overactivation of Th1 / Th17 pro-inflammatory subsets and dysregulation of immune tolerance; Q11 significantly upregulated CD3 in spleen tissue. + The proportion of T cells was reduced, and the levels of IFN-γ and IL-17a were decreased (Figure 25A-C). ** P < 0.01, *** P < 0.001 vs. control group; # P < 0.05 ## P < 0.01, ### P < 0.001 (vs. model group).

[0198] The above results indicate that Q11 can regulate the Th1 / Th17 cell balance, remodel the spleen's immune microenvironment, and has a significant protective effect against SLE.

[0199] Biological Example 15: Protective effect of the compounds of the present invention against nephrotic syndrome

[0200] 1 Experimental Methods

[0201] Protective effect of Q11 on passive hemangioglobulin rat model (PHN): The PHN rat model was established by tail vein injection of 0.5 mL / 100 g anti-Fax1A serum. The experiment was divided into control group, model group, positive control group, Q11 treatment group, and low, medium and high dose Q11 prevention groups (control group, n=8; other groups, n=10). One week after modeling, the positive control group was given 7 mg / kg of Prednisone acetate by gavage; the Q11 treatment group was given 60 mg / kg of Q11 by gavage one week after modeling; the Q11 prevention groups were given 10 mg / kg, 30 mg / kg and 60 mg / kg of Q11 at the same time during modeling; the control group and model group were given the same volume of solvent.

[0202] Protective effect of Q11 on an adriamycin-induced nephropathy (ADR) mouse model: An ADR mouse model was established by tail vein injection of 12.5 mg / kg adriamycin solution (2 mg / mL). The experiment was divided into a control group, a model group, a positive control group, a Q11 treatment group, and low, medium, and high dose Q11 prevention groups (control group, n=8; other groups, n=12). One week after modeling, the positive control group was administered 6 mg / kg of Prednisone acetate by gavage; one week after modeling, the Q11 treatment group was administered 60 mg / kg of Q11 by gavage; the Q11 prevention groups were administered 10 mg / kg, 30 mg / kg, and 60 mg / kg of Q11 simultaneously at modeling; the control group and the model group were given the same volume of solvent.

[0203] Sample collection and testing: During the experiment, 24-hour urine was collected weekly and the urine volume was recorded. After 5 weeks, the experimental cycle ended, and serum and kidney tissue were collected. Kidney function was detected using urine protein and creatinine kits. H&E staining and PAS staining were used to evaluate the pathological changes in kidney tissue. Metabolic changes were detected using triglyceride (TG) and total cholesterol (TC) kits. Oxidative stress levels in kidney tissue were detected using MDA, SOD, and GSH kits. Transmission electron microscopy was used to observe the morphological changes of mitochondria in the kidney tissue of AKI mice.

[0204] An in vitro podocyte injury model was established by inducing MPC-5 cells with 0.5 μg / mL doxorubicin, while simultaneously administering 25 μM, 50 μM, and 100 μM of Q11 compound. Oxidative stress levels in each treatment group were detected using MDA, SOD, and GSH kits; ROS levels in cells were detected using the DCFH-DA fluorescent probe method and microplate assay; and changes in mitochondrial membrane potential and ATP content were detected using JC-1 staining and colorimetric methods.

[0205] 2 Experimental Results

[0206] Compared with the model group, Q11 significantly reduced 24-hour urinary protein levels and serum creatinine levels in PHN model rats, and increased serum albumin levels. The improvement effect in the 60 mg / kg dose group was comparable to that in the positive control group (Figures 26A-D). *** P < 0.001 vs. control group; # P < 0.05 ### P < 0.001 (vs. model group). H&E staining showed that the glomerular morphology of rats in the Q11 group tended to be normal, and the dilation of renal tubules and epithelial cell necrosis were significantly reduced. The degree of inflammatory cell infiltration and fibrous tissue proliferation in the interstitial area was also significantly reduced. PAS staining further confirmed that Q11 could significantly reduce the deposition of positive substances in the mesangial area and basement membrane, making the deeply stained areas lighter and smaller (Figure 26E), suggesting that Q11 can significantly improve renal function damage in PHN rats.

[0207] In the ADR mouse model, the high-dose Q11 group effectively restored the kidney index of the model mice (Figure 26F). *** P < 0.001 vs. control group; # P < 0.05 vs. model group. Simultaneously, Q11 significantly reduced 24-hour urinary protein levels and downregulated serum TG and TC levels in ADR mice (Figure 26 G-K). *** P < 0.001 vs. control group; # P < 0.05 ## P < 0.01, ### P < 0.001 (vs. model group), suggesting that Q11 can alleviate lipid metabolism disorders caused by massive urinary protein loss. H&E and PAS staining results consistently showed that glomerular and tubular damage was significantly reduced in the Q11 group, and the tubulointerstitial injury score was significantly decreased (Figure 26 L-O). *** P < 0.001 vs. control group; # P < 0.05 ## P < 0.01 (vs. model group), suggesting that Q11 has a significant preventive and therapeutic effect on doxorubicin-induced kidney injury.

[0208] Furthermore, 60 mg / kg Q11 significantly reduced MDA levels in the kidney tissue of PHN rats and increased SOD activity and GSH content (Figure 27A). *** P < 0.001 vs. control group; ## P < 0.01, ###P < 0.001 vs. model group. Transmission electron microscopy results showed that the ultrastructure of the glomerular filtration barrier was significantly damaged in both PHN rat and ADR mouse models, manifested as extensive foot process fusion, loss of finger-like structures, and sheet-like cytoplasm of podocytes spread flat on the basement membrane surface; the basement membrane was locally thickened and the electron density was uneven. Simultaneously, mitochondria in podocytes were significantly swollen, the matrix was transparent, and the cristae were broken or disappeared, indicating severe energy metabolism disorders and cellular stress. The Q11 group effectively alleviated podocyte damage and protected the integrity of mitochondrial ultrastructure (Figure 27B-C). Cell experiments further confirmed that Q11 significantly reduced the oxidative stress level in the podocyte injury model and improved mitochondrial function, mainly by reducing MDA levels, increasing SOD activity and GSH content (Figure 27D), inhibiting ROS generation, restoring mitochondrial membrane potential, and enhancing ATP production (Figure 27D-E). ** P < 0.01, *** P < 0.001 vs. control group; # P < 0.05 ## P < 0.01, ### P < 0.001 (vs. model group).

[0209] The above results indicate that Q11 can reduce oxidative stress, improve mitochondrial function, and has a significant protective effect on mice with nephrotic syndrome.

[0210] Biological Example 16: Protective effect of the compounds of the present invention against heatstroke

[0211] 1 Experimental Methods

[0212] A heatstroke model was established in C57BL / 6J mice using an artificial climate chamber to simulate a high-temperature and constant-humidity environment. Eight-week-old male mice were randomly divided into a control group, a model group, and a Q11 intervention group, with six mice in each group. One hour before modeling, the Q11 group was administered 60 mg / kg of Q11 by gavage, while the control and model groups were administered an equal volume of the solvent by gavage. Subsequently, the mice were placed in an artificial climate chamber with a pre-set environment (temperature: 39.0 ± 0.5℃, relative humidity: 65 ± 5%) for continuous heat exposure for 80 min. Core body temperature changes were dynamically monitored for 2 hours after removal from the high-temperature environment, and survival was recorded for 6 hours after heat exposure.

[0213] 2 Experimental Results

[0214] Compared with the model group, Q11 significantly reduced the core body temperature of mice at the end of heat exposure, demonstrating a good thermoregulatory effect (Figure 28A). ***P < 0.001 (vs. model group). The core body temperature dynamics curve showed that 2 hours after removal from the high-temperature environment, the core body temperature of the Q11 group mice significantly decreased and stabilized, while the body temperature of the model group mice continued to decline and showed signs of hypothermia, suggesting that Q11 can accelerate body temperature recovery after heat stress (Figure 28B). ** P<0.01, *** P < 0.001 vs. model group. Furthermore, survival curve analysis showed that the survival rate of the Q11 group was significantly higher than that of the model group within 6 hours after heat stress, indicating that Q11 can reduce the risk of heat stress-related death and improve the survival rate of mice (Figure 28C). ** P < 0.01 (vs. model group).

[0215] The above results indicate that Q11 can significantly improve the symptoms of heatstroke in mice, suggesting that it can be used for the prevention and treatment of heatstroke.

[0216] The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiments. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. Use of the compound of formula (I) or a pharmaceutically acceptable salt thereof in the preparation of remedies for and / or prevention and / or relief of neurological, cardiac and related conditions, musculoskeletal disorders, digestive disorders, renal impairment or insufficiency, nephrotic syndrome, systemic lupus erythematosus, gout, acne, obesity, aging and related conditions, or heatstroke, wherein the compound of formula I is selected from the following structures: in, R1 is selected from hydrogen, halogens, and C1-C. 10 Alkyl, C 3-6 Epoxyalkyl and R2 is selected from hydrogen, substituted C1-C 10 Any one of the following: alkyl group I, substituent shown in formula O-1, substituent shown in formula O-2, and substituent shown in formula O-3; Among them, R 21 R 22 R 23 R 24 They may be the same or different, and are independently selected from hydrogen, C1-C. 10 Alkoxy, halogen, C1-C3 alkyl, C6-C 10 aryl; R 25 Selected from hydroxyl, C1-C 10 Alkoxy; R 26 Selected from H, C1-C 10 Alkyl, halogenated C1-C 10 alkyl; R3 is selected from hydrogen, C1-C 10 Alkyl, substituted C1-C 10 Alkyl groups.

2. The use according to claim 1, characterized in that, Preferably, R1 is selected from hydrogen, C1-C4 alkyl, C 3-6 Epoxyalkyl and Preferably, R3 is selected from hydrogen, halogen, C1-C4 alkyl, halogenated C1-C4 alkyl, substituted C1-C4 alkyl II; more preferably, R3 is selected from hydrogen, methyl, ethyl, propyl; Preferably, R 26 Selected from H, C1-C4 alkyl, and halogenated C1-C4 alkyl; more preferably, R 26 Selected from methyl, ethyl, propyl, butyl; optionally, the substituted C1-C 10 The substituent in the alkyl I is selected from at least one of the substituted amino I, the substituent shown in formula M-1, and the substituent shown in formula M-2; Optionally, the substituents in the substituted amino I are selected from C6-C6. 10 At least one of aryl and substituted C1-C3 alkyl III; Preferably, the substituents in the substituted C1-C3 alkyl III are selected from C6-C6. 10 aryl; Optionally, the substituted C1-C 10 The substituent in the alkyl II is selected from at least one of the substituted amino II, the substituent shown in formula M-3, and the substituent shown in formula M-4; Optionally, the substituent in the substituted amino II is selected from substituted C1-C3 alkyl IV; The substituents in the substituted C1-C3 alkyl IV are selected from at least one of pyridyl and halogen.

3. The use according to claim 1 or 2, characterized in that, The compound of formula (I) is further selected from the structure of formula (II): Among them, R1, R 26 R3 is as defined in claim 1; Preferably, the compound of formula (I) is further selected from the following structures: Wherein, R1 and R3 are as defined in claim 1.

4. The use according to any one of claims 1-3, characterized in that, The compound of formula (I) is selected from the following structures:

5. The use according to any one of claims 1-4, characterized in that, The pharmaceutically acceptable salt is selected from the acid salt obtained by reacting the compound of formula (I) with an acid; the acid is selected from at least one of inorganic acids and organic acids; Optionally, the inorganic acid is selected from at least one of hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, and phosphoric acid; The organic acid is selected from at least one of acetic acid, oxalic acid, succinic acid, tartaric acid, succinic acid, malic acid, lactic acid, methanesulfonic acid, p-toluenesulfonic acid, citric acid, resinic acid, maleic acid, fumaric acid, salicylic acid, acetylsalicylic acid, and citric acid.

6. The use according to any one of claims 1-5, characterized in that, The compound of formula (I) is selected from the following structures: Preferably, the pharmaceutically acceptable salt of the compound of formula (I) is selected from the hydrochloride or sulfate of Q11; Preferably, the hydrochloride salt of Q11 has crystal form A, and the X-ray powder diffraction of crystal form A includes three or more 2θ values ​​selected from the group consisting of: 8.4±0.2°, 13.1±0.2°, 14.8±0.2°, 16.6±0.2°, 24.1±0.2°, 27.2±0.2°, 30.5±0.2°, 31.8±0.2°, 33.5±0.2°, 35.4±0.2°, and 35.7±0.2°; preferably, the DSC-TGA plot shows a distinct endothermic peak between 70°C and 220°C, and thermal decomposition between 80°C and 170°C; Preferably, the sulfate of Q11 has crystal form B, and the X-ray powder diffraction of crystal form B includes five or more 2θ values ​​selected from the group consisting of: 10.1±0.2°, 15.1±0.2°, 16.0±0.2°, 16.7±0.2°, 19.2±0.2°, 19.9±0.2°, 23.4±0.2°, 24.0±0.2°, 25.8±0.2°, 26.5±0.2°, 28.9±0.2°, 30.3±0.2°, and 32.2±0.2°; preferably, the DSC-TGA plot shows at least one endothermic peak between 30°C and 85°C, 90°C and 160°C, and 215°C and 330°C, and thermal decomposition at 150°C and 350°C.

7. The use according to any one of claims 1-6, characterized in that, The neurological disorders mentioned are selected from depression and pain; The heart disease and related conditions mentioned are selected from heart disease, cardiomyopathy, myocardial injury, heart failure, ventricular hypertrophy (or hypertrophic cardiomyopathy), ventricular wall thickening, myocardial ischemia (or ischemic heart disease), myocardial infarction, myocardial fibrosis, and myocarditis. The bone and joint diseases mentioned are selected from osteoarthritis or osteoarthropathy; The digestive system diseases mentioned are selected from pancreatitis and colitis.

8. The use according to any one of claims 1-7, characterized in that, The drug can improve ventricular hypertrophy (e.g., left ventricular hypertrophy) and ventricular wall thickening caused by heart disease; And / or, the drug can alleviate myocardial ischemia-reperfusion injury or myocardial infarction-reperfusion injury; And / or, the heart disease and related conditions are selected from acute myocardial infarction; And / or, the drug has a cardioprotective effect, preferably, the myocarditis is selected from autoimmune myocarditis; And / or, the depression includes pain-related / comorbid depression; And / or, the depression includes depression caused by chronic pain; And / or, the depression includes post-myocardial infarction depression and post-cerebral infarction depression; And / or, the drug may be used during the acute phase of depression; And / or, the pain is selected from pain caused by depression; And / or, the pain is selected from depression-inflammatory pain comorbidity; And / or, the pain is selected from acute pain, chronic pain, and neuropathic pain; preferably, the drug can relieve pain caused by osteoarthritis; preferably, the drug can relieve joint pain and / or cartilage damage.

9. The use according to any one of claims 1-7, characterized in that, The medication can lower uric acid; And / or, the drug may be used to treat hyperuricemia; preferably, the hyperuricemia includes gout or gout complications caused by hyperuricemia; And / or, the gout includes acute gout or chronic gout; preferably, the gout complications include gouty arthritis, gout attack, gouty nephropathy, uric acid kidney stones; the gout is selected from acute gouty arthritis; And / or, the medication may be used to simultaneously lower uric acid and relieve arthritis, such as relieving swelling caused by arthritis; And / or, the osteoarthritis or osteoarthropathy is selected from knee osteoarthritis or knee osteoarthropathy; And / or, the pancreatitis is selected from acute pancreatitis, such as severe acute pancreatitis (SAP); And / or, the drug can reduce nephrotoxicity; And / or, the kidney injury is selected from chronic kidney injury or acute kidney injury; And / or, the colitis is selected from acute colitis or chronic colitis; preferably, the colitis is ulcerative colitis (UC); The aging and related diseases include age-related cognitive decline and muscle weakness.

10. The use according to any one of claims 1-8, characterized in that, The drug is a composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient.

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