Use of naphthalene ring-based low molecular weight compounds

Abstract

This application discloses the use of naphthalene ring-based low-molecular-weight compounds. This application is the first to discover that compounds represented by general formula I have excellent therapeutic effects against various intractable diseases, including reproductive system diseases, autoimmune diseases, skin diseases, eye diseases, muscle or bone degenerative diseases, neurological diseases, anemia, adrenal diseases, chronic gastritis, myocarditis, periodontitis, hypothyroidism, alopecia, liver damage, tinnitus, and chronic obstructive pulmonary disease. Therefore, this has extremely great application value in the prevention and treatment of the aforementioned diseases.

Description

Cross-reference of related applications

[0001] This patent application claims priority to a Chinese patent application filed on March 20, 2023, with application number 2023102998399 and title of invention "Use of Low Molecular Weight Compound Having a Naphthylamine Structure," which is incorporated herein by reference in its entirety.

[0002] This patent application claims priority to a Chinese patent application filed on 30 June 2023, application number 2023108029717, with the title of the invention "Naphthalene Ring Low Molecular Weight Compounds," which is incorporated herein by reference in its entirety.

[0003] This patent application claims priority to a Chinese patent application filed on November 20, 2023, with application number 2023115501191 and title of invention "Naphthalene Ring Low Molecular Weight Compounds," which is incorporated herein by reference in its entirety. [Technical Field]

[0004] This invention relates to the field of biopharmaceuticals, and more particularly to the use of naphthalene ring-based low-molecular-weight compounds. [Background technology]

[0005] Premature ovarian failure (POF) is a leading cause of female infertility, affecting at least 1-5% of women under 40, yet there is no established effective treatment. Women with POF experience infertility, various menopausal symptoms, and serious complications such as psychological stress, osteoporosis, autoimmune diseases, and ischemic heart disease, which can even lead to an increased risk of death. Clinical treatment for women with POF includes hormone replacement therapy combined with psychological support. However, this treatment has significant side effects and limitations in achieving a cure.

[0006] Systemic lupus erythematosus (SLU) is a typical autoimmune disease characterized by a loss of immune tolerance. Lupus nephritis is a major cause of incidence and mortality in SLU. Most cases of lupus nephritis eventually progress to end-stage renal failure. Currently, there is no specific treatment for lupus nephritis, and clinically, steroid pulse therapy and immunosuppressive therapy are the main treatments, but these two therapies have many serious side effects and can worsen kidney damage.

[0007] Sarcopenia is a syndrome characterized by age-related decline in skeletal muscle mass, muscle strength, and muscle function. Sarcopenia is an early clinical symptom of frailty, and research into it is still in its early stages. Resistance exercise is the primary treatment for sarcopenia. Sarcopenia has a high incidence in middle-aged and older adults, is a major cause of stroke and falls, significantly reduces the quality of life (QOL) of older adults, and increases disease morbidity and mortality. With conventional technology, there is neither a cure nor a treatment for the symptoms.

[0008] The causes of liver damage are diverse, with common examples including alcoholic fatty liver disease and drug-induced liver injury. Alcoholic fatty liver disease is a type of alcoholic liver disease caused by long-term heavy drinking. Alcoholic liver disease is the most common chronic liver disease in the world. Alcoholic liver disease progresses from alcoholic fatty liver to alcoholic steatohepatitis, and chronic alcoholic steatohepatitis leads to fibrosis and cirrhosis. Drug-induced liver injury is an adverse reaction to drugs or other foreign substances, where exposure to toxic doses of certain compounds can have harmful effects on the liver of some susceptible individuals. These risk factors alter liver metabolism, leading to cellular stress, cell death, activation of adaptive immune responses, and decreased adaptive capacity, ultimately progressing to significant liver damage. The progression of liver damage to liver fibrosis and cirrhosis is usually chronic and difficult to reverse. Current treatments for liver damage include antiviral therapy and surgery, but antiviral therapy has the disadvantage of a slow onset of action, and surgery presents challenges due to its high invasiveness.

[0009] In recent years, oligospermia has become a common symptom and a major indicator of male infertility. This can be caused by congenital reproductive organ dysfunction, such as congenital testicular dysplasia, acquired systemic diseases like chronic radiation damage, or unhealthy lifestyle habits and environments such as smoking and drinking. Some infertile men are sensitive to nicotine and alcohol in tobacco and alcohol, and the spermatogenic cells of the testes are particularly susceptible to the effects of these toxic substances, leading to decreased sperm motility, viability, and sperm count. Statistics show that the incidence of infertility in married couples is approximately 15%, with male factors accounting for about 50% of these cases. Currently, infertility due to oligospermia can be treated with gonadotropin-releasing hormone, gonadotropins, or androgens, but hormone therapy is not curative and can carry serious side effects.

[0010] Rheumatoid arthritis (RA) is a common chronic, systemic, progressive autoimmune disease whose specific etiology remains unclear. Clinically, the main symptoms are joint swelling, pain, and stiffness, while pathophysiological findings are characterized by synovial cell proliferation and persistent synovial inflammation. If not treated effectively at the appropriate time, damage to joint structures and loss of function can occur, ultimately leading to joint deformity and disability. The long duration of rheumatoid arthritis and its poor prognosis have a significant impact on the lives of patients and their families. Current treatments cannot adequately and effectively cure this disease.

[0011] Cataracts are a disease characterized by clouding of the lens of the eye. They are caused by damage to the lens capsule due to factors such as aging, genetics, metabolic disorders, trauma, radiation, poisoning, and localized malnutrition. This damage increases the permeability of the lens capsule, leading to loss of its barrier function, or inhibits lens metabolism, causing denaturation of lens proteins and resulting in clouding. Cataracts are classified into congenital and acquired types. Currently, treatment for cataracts is mainly surgical, requiring either intraocular lens implantation or surgical extraction depending on the individual's symptoms, and is costly and carries significant risks.

[0012] Cushing's syndrome (CS), also known as hypercortisolism, is caused by chronic hyperglucocorticoidemia and presents with a typical clinical phenotype and multi-organ complications. Glucocorticoids, secreted by the adrenal glands and regulated by the hypothalamic-pituitary system, play a role in regulating a variety of physiological processes, including cellular processes such as proliferation, cardiovascular tone, immune response, growth, reproduction, behavior, and energy metabolism. Cushing's syndrome leads to many related disorders and significantly impacts the patient's quality of life. Conventional techniques often treat Cushing's syndrome with a combination of surgery and medication, but surgery carries the risk of postoperative Nelson syndrome, and while medication can alleviate some clinical symptoms, it cannot restore the patient's function to normal.

[0013] Hashimoto's thyroiditis (HT) is a chronic lymphocytic thyroiditis caused by a defect in the autoimmune system. Currently, this disease is mainly treated with thyroid hormone replacement therapy, immunotherapy, and surgery. While these treatments can alleviate the patient's symptoms to some extent, they do not regulate the abnormal immune system and have the drawback of being prone to relapse.

[0014] Chronic obstructive pulmonary disease (COPD) is a chronic respiratory destructive disease with high morbidity and mortality rates, and most patients are middle-aged or older. Incompletely reversible airflow limitation is a common symptom in patients with COPD and usually presents as a respiratory illness. Although COPD is a respiratory disease, there is currently no established effective method to completely halt the decline in lung function.

[0015] Tinnitus is a common functional disorder, with an increasing prevalence with age, ranging from 10% to 15%, and significantly impacting the quality of life of patients. Traditionally, tinnitus has been considered a hearing impairment, but it manifests as a symptom when physiological limits are exceeded. While tinnitus can be caused by various factors, the most common trigger is hearing loss. Patients with tinnitus suffer long-term distress, and currently, only symptomatic treatments are available; there is no established cure.

[0016] Psoriasis develops due to the interaction of multiple factors, including immune, genetic, and environmental factors, and is primarily mediated by T lymphocytes, involving multiple immune cells. Psoriasis can affect muscles, joints, nails, and even the eyes, and may occur in conjunction with cardiovascular disease, cerebrovascular disease, metabolic syndrome, tumors, and other autoimmune diseases. The histopathological features of psoriasis are generally characterized by hyperkeratosis with parakeratosis and marked cortical thickening. Immunotherapy is being used as a new treatment for psoriasis, replacing antibiotics, but there are currently no effective medications.

[0017] Age-related macular degeneration (AMD) is a structural change in the macula associated with aging. While the etiology remains unclear, it may be linked to genetic factors, chronic light exposure, nutritional deficiencies, poisoning, immune disorders, and systemic diseases such as cardiovascular and respiratory illnesses. Multiple factors may also contribute to its development. Currently, vision correction is the most common treatment, but its effectiveness is very limited, and many patients are unable to prevent a decline in central vision.

[0018] Retinal pigmentosa (RP) is a progressive, hereditary retinal degeneration. Its main clinical symptoms are night blindness and progressive visual field constriction, which typically begin in childhood. The global prevalence is approximately 1 in 3,000 to 1 in 7,000. Its pathological mechanism is thought to be progressive photoreceptor apoptosis due to primary genetic defects or secondary degeneration of retinal pigment epithelial cells. Currently, there is no established effective treatment for RP. Research suggests that RP is a chronic inflammatory disease, with inflammatory factors and immunomodulatory processes playing a crucial role in disease progression. Over the past several decades, researchers have proposed various strategies for treating RP, including neurotrophic factors, herbal medicine, visual prostheses, and gene therapy. However, none of these strategies have been satisfactory, and a clearly effective treatment remains elusive.

[0019] Multiple sclerosis (MS) is an autoimmune demyelinating disease with a complex etiology that affects the central nervous system. It is characterized by multiple lesions, relapsing, and a high rate of disability, severely impacting patients' daily lives. The pathogenesis is still not fully understood, but it is thought to be caused by various factors, including immune factors, environmental factors, and genetic factors. Currently, it is believed that the etiology involves an abnormal immune attack that disrupts the blood-brain barrier, allowing multiple inflammatory factors and immune cells to invade the central nervous system. These cells act on microglia and immune cells in the central nervous system, triggering an inflammatory response that leads to demyelination, neuronal cell death, and axonal damage. Current treatment for multiple sclerosis mainly focuses on anti-inflammatory therapy, but these therapies are only effective during relapses and remissions. Therefore, developing treatments for multiple sclerosis is an urgent task.

[0020] Hypothyroidism, also known as hypothyroidism, is a condition characterized by insufficient or deficient production of thyroid hormones by the tissues. It is more common in women than men and its prevalence increases with age. In modern medicine, hypothyroidism is caused by various factors, but the majority of cases are thought to be caused by autoimmune thyroiditis, radioactive iodine therapy to the thyroid gland, or thyroid surgery. In modern medicine, thyroid hormone replacement therapy is often used to treat hypothyroidism. However, long-term use of thyroid hormones may directly stimulate the action of osteoclasts on bone resorption, potentially increasing the risk of osteoporosis, coronary artery disease, and heart failure. Therefore, finding safer and more effective treatments for the prevention and treatment of hypothyroidism is an urgent task.

[0021] Chronic atrophic gastritis (CAG) is a common clinical condition whose incidence and prevalence increase with age. It is characterized by a decrease in proper glands due to recurrent damage to the gastric mucosal epithelium, sometimes accompanied by intestinal metaplasia or pseudopyloric metaplasia, and its symptoms are generally nonspecific. Those who do experience symptoms may have nonspecific indigestion symptoms such as upper abdominal bloating and pain, and may also be accompanied by nausea, loss of appetite, acid reflux, stomach heaviness, and a bitter taste in the mouth. Recurrence is common. Currently, there is no established effective treatment that can alleviate all clinical symptoms.

[0022] Myocarditis is a disease characterized by localized or diffuse acute, subacute, or chronic inflammatory lesions of the heart muscle, primarily affecting children and young adults. If left untreated, it can lead to dilated cardiomyopathy and chronic heart failure. Myocarditis is classified into three types: idiopathic, autoimmune, and infectious. Clinical treatment for myocarditis primarily focuses on intervention in the early stages of acute inflammation. As the disease progresses to the chronic phase, conservative treatment and reduction of cardiac strain become the main treatment options, and no specific treatment has been established.

[0023] Alopecia is hair loss on the scalp caused by autoimmune deficiency. Seborrheic alopecia, alopecia areata, and male pattern baldness are the three most common types of alopecia. Due to stress and changes in diet, seborrheic alopecia is currently the most common type of alopecia. Minoxidil and finasteride are currently approved as treatments for seborrheic alopecia. However, both drugs can cause serious side effects, such as sexual dysfunction with finasteride use and atopic dermatitis, myocardial infarction, and loss of appetite with topical minoxidil. Therefore, finding a safe and biologically active treatment for alopecia is an urgent task.

[0024] Primary aldosteronism (PA) is a group of heterogeneous diseases characterized by excessive aldosterone secretion from the adrenal cortex, leading to clinical symptoms such as increased blood volume, sodium retention and potassium excretion, metabolic alkalosis, hypertension, and hypokalemia. Currently, there is no effective treatment.

[0025] Erectile dysfunction (EDD) refers to a condition in which a man is unable to achieve or maintain an erection sufficient for satisfactory sexual intercourse (for at least six months). The main characteristic of EDD is the inability to achieve or maintain an erection, often accompanied by symptoms such as decreased libido and premature ejaculation. It is one of the most common disorders in men. Epidemiological data shows that approximately 52% of men aged 40-70 worldwide suffer from EDD to varying degrees. However, treatment for EDD primarily involves hormone injections, which can have serious side effects.

[0026] Periodontitis is a chronic inflammatory disease that damages the health of the tissues supporting the teeth. Severe periodontitis can not only lead to tooth loss but also increase the risk of systemic diseases such as atherosclerosis, rheumatoid arthritis, aspiration pneumonia, and cancer. Currently, the most effective treatment for periodontitis is the mechanical removal of local irritants. However, certain bud structures, such as root bifurcations, limit instrument penetration and hinder the effective removal of accumulated plaque. The development of effective periodontitis treatments is now an urgent issue.

[0027] Stroke is a serious cerebrovascular disease and a leading cause of long-term disability and premature death. Most stroke cases (approximately 80%) are ischemic strokes caused by vascular occlusion due to arterial thrombosis. Currently, the most effective treatment for ischemic stroke is rapid restoration of blood flow, but ischemia-reperfusion injury associated with revascularization can further worsen brain damage and neuromotor dysfunction, making the recovery of neurological function an urgent and critical issue.

[0028] Epilepsy is one of the most common clinical neurological disorders. It is a chronic brain disorder caused by abnormal electrical activity in the brain and is clinically characterized by recurrent epileptic seizures. In addition to the risks of epileptic seizures themselves, cognitive impairment is one of the most common complications in patients with recurrent epileptic seizures. Patients with epilepsy may experience difficulties with learning and memory, and a significant decline in problem-solving and concept formation abilities. Furthermore, while currently used antiepileptic drugs are effective in suppressing seizures in many epileptic patients, they may also impair cognitive function and behavior by increasing the expression of inhibitory neurotransmitters or suppressing neuronal excitability. Therefore, finding drugs that improve cognitive function in epileptic patients, and even drugs that reduce epileptic seizures while improving cognitive function, is a highly beneficial and urgent task.

[0029] Melasma is an acquired skin pigmentation disorder that typically manifests as symmetrical light brown to dark brown facial discoloration patches. In traditional Chinese medicine, this condition is classified as "facial discoloration." This disease is more common in women of childbearing age, is difficult to treat, disfigures the face, and has a serious impact on the patient's mental health. However, there is currently no established effective treatment.

[0030] Vitiligo is a common pigment disorder seen in dermatology, characterized by localized white or milky white patches or plaques of varying sizes and shapes. These patches are smooth, well-defined, and painless. While vitiligo can occur anywhere, it most commonly appears on the face, neck, back, trunk, and genitals, and can also cause hair to turn white. Vitiligo can have serious physical and mental health consequences. Currently, vitiligo is primarily treated with hormone therapy, which carries significant side effects.

[0031] Beta-thalassemia, also known as Mediterranean anemia or globin synthesis disorder anemia, is a hemolytic anemia caused by a gene mutation and is a widely occurring single-gene genetic disorder worldwide. This disease is a hemolytic genetic disorder caused by a decrease or absence of β-globin chain synthesis, resulting in an imbalance between α-chains and non-α-chains in the hemoglobin tetramer. Microcytic hypochromic anemia with elevated HbF and HbA2 levels is a typical clinical finding. Currently, beta-thalassemia is most prevalent and one of the most serious genetic disorders in the provinces south of the Yangtze River in China, but there is still no established effective treatment.

[0032] Lumbar disc herniation is the most common spinal surgical disease, a widespread and prevalent condition in clinical practice, placing a heavy burden on society and families. Lumbar disc herniation is a syndrome characterized by disc degeneration, annulus fibrosus rupture, nucleus pulposus protrusion, and irritation or compression of the nerve roots and cauda equina. It is a common and prevalent disease affecting human health and is a frequent cause of lower back and leg pain. In China, the incidence of disc degeneration is increasing year by year due to the aging population and changing lifestyles. Current clinical treatments mainly consist of non-surgical therapies (steroidal anti-inflammatory drugs, physical therapy, pain management, etc.) and surgical therapies, but neither can fundamentally prevent the onset and progression of lumbar disc herniation. Developing therapeutic drugs that focus on the disease mechanism and restoring disc function is urgently needed.

[0033] Polycystic ovary syndrome (PCOS) is a heterogeneous disorder affecting multiple bodily systems, primarily impacting the reproductive function of women of childbearing age and being one of the most important causes of ovulatory infertility. Pathological symptoms of PCOS include hormonal imbalances, impaired follicular development and ovulation, abnormally elevated serum androgen levels, insulin resistance, and obesity. This disorder not only affects women's reproductive function but also significantly increases the risk of long-term complications such as type 2 diabetes, cardiovascular disease, and endometrial cancer. Currently, the incidence of polycystic ovary syndrome is high, but existing treatments have serious side effects such as severe menstrual irregularities, weight gain, infertility, and hirsutism, making the development of effective treatments with fewer side effects an urgent task.

[0034] As described above, there are no existing drugs that can effectively treat the above-mentioned diseases using conventional technology, and the search for drugs that can safely and effectively treat these diseases is an urgent task in this field. [Overview of the project]

[0035] The object of the present invention is to provide the use of naphthalene ring-based low molecular weight compounds.

[0036] In a first aspect of the present invention, the use of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or prodrug thereof in the preparation of a medicament for (i) preventing and / or treating the following diseases, and / or (ii) preventing and / or treating the following diseases, wherein the diseases include genital diseases, autoimmune diseases, dermatitis, retinitis, ocular degenerative diseases, musculoskeletal or ossicular degenerative diseases, neurological diseases, anemia, adrenal diseases, chronic gastritis, myocarditis, periodontitis, hypothyroidism, alopecia, liver disorders, tinnitus, and chronic obstructive pulmonary disease. TIFF2026509562000002.tif61170 Here, Z is TIFF2026509562000003.tif21170 or a sulfur atom, R 1 is hydrogen, C 1~6Alkyl, TIFF2026509562000004.tif18170, where R 11 and R 12 are each independently C 1~6 alkyl or C 1~6 cycloalkyl, n is 1 - 4, R 2 is hydrogen, C 1~6 alkyl, 3 - 6 member cycloalkyl, 3 - 6 member epoxyalkyl, phenyl, C 2-1 alkyl substituted with at least one hydrogen by R 1~6 phenyl substituted with at least one hydrogen by R 2-1 , where R 2-1 is hydroxyl, halogen, amino or C 1~6 alkoxy, R 3 is TIFF2026509562000005.tif19170 Here, R 3-1 is hydrogen, hydroxyl, C 1~6 alkyl, C 1~6 alkoxy, C 3~6 cycloalkyl, 3 - 6 member epoxyalkyl, amino, C 1~6 amine group, -CH2C(O)R 3-2 , -CH2C(O)OR 3-2 , -CH2C(O)N(R 3-2 R 3-2a ), and R 3-2 and R 3-2a are each independently hydrogen, C 1~6 alkyl or 3 - 6 member cycloalkyl, [ [[ID=]58]m is 1 - 6, and Ar is phenyl, naphthyl, 5 - or [6 - member monocyclic heteroaryl, 8 - 10 member fused bicyclic heteroaryl, phenyl substituted with at least one hydrogen atom by R 3-3 naphthyl substituted with at least one hydrogen atom by R 3-3 5 - or 6 - member monocyclic heteroaryl substituted with at least one hydrogen atom by R 3-3 8 - 10 member fused bicyclic heteroaryl substituted with at least one hydrogen atom by R 3-3It is an 8-10 member condensed bicyclic heteroaryl substituted with the R 3-3 Hydrogen, halogen, C 1~6 Alkyl, 3-6 membered cycloalkyl, hydroxyl, C 1~6 Alkoxy, 3-6 member epoxyalkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, -N(R 3-3a R 3-3b ) or phenyl, R 3-3a and R 3-3b Each is independently hydrogen and C 1~6 Alkyl or 3-6 membered cycloalkyl, R 4 teeth TIFF2026509562000006.tif25170 Here, R 4-1 R is phenyl, naphthyl, with at least one hydrogen atom 4-11 Phenyl substituted with R, 5-membered or 6-membered monocyclic heteroaryl, at least one hydrogen atom is R 4-11 5-membered or 6-membered monocyclic heteroaryls substituted with R, 8-10 membered fused bicyclic heteroaryls, at least one hydrogen atom is R 4-11 It is an 8-10 member condensed bicyclic heteroaryl substituted with R, 4-11 Hydrogen, halogen, nitro, nitrile, hydroxyl, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, -N(R 4-1a R 4-1b ), phenyl, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -C(O)OR 4-12 , -C(O)R 4-12 ,-C(O)N(R 4-1a R 4-1b ), -S(O)2R 4-12 ,-S(O)R 4-12 ,-OC(O)R 4-12 -OC(O)OR 4-12 or TIFF2026509562000007.tif16170, R 4-12, R 4-1a and R 4-1b are each independently hydrogen, C 1~6 alkyl, C 3~6 cycloalkyl, C 2~6 alkenyl, C 2~6 alkynyl, C in which at least one hydrogen is substituted by halogen 1~6 alkyl, C in which at least one hydrogen is substituted by halogen 2~6 alkenyl, C in which at least one hydrogen is substituted by halogen 3~6 cycloalkyl, C in which at least one hydrogen is substituted by halogen 2~6 alkynyl, and R 4-1a and R 4-1b are bonded to each other to form a ring, R 4-2 is C 1~6 alkyl, C 3~6 cycloalkyl, C alkyl in which at least one hydrogen is substituted by hydroxyl 1~6 alkyl, C 3~6 epoxyalkyl, or R 2 is C 1~6 alkyl and R 4-2 is C 1~6 alkyl, when R 4-2 and R 2 are bonded to form a 4- to 8-membered ring, R 4-3 is C 1~6 alkyl or C 1~6 alkoxy, R 5 is in the range of 0 to 5, and R 5 is, in each occurrence, independently hydrogen, halogen, nitro, nitrile, -N + (R 5-1 )3, C 1~6 haloalkyl, -C(O)OR 5-1 , -C(O)R 5-1 , -C(O)N(R<00​​​​​​​​​​​​​​), -N=C(R 5-1 R 5-1a ), hydroxyl, C 1~6 Alkyl, phenyl, at least one hydrogen is R 5-1 Phenyl substituted with C 1~6 Alkoxy, -N(R 5-1 R 5-1a ), -N(R 5-1 )C(O)R 5-1a , -N(R 5-1 )C(O)OR 5-1a , -N(R 5-1 )C(O)N(R 5-1a R 5-1b ), -OC(O)R 5-1 , -OC(O)OR 5-1 ,-OC(O)N(R 5-1 R 5-1a ) or -SR 5-1 And here, R 5-1 , R 5-1a and R 5-1b Each is independently hydrogen and C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkynyl, a C atom in which at least one hydrogen atom is substituted with a halogen. 1~6 Alkyl, C in which at least one hydrogen is substituted with a halogen. 2~6 Alkenyl or C where at least one hydrogen atom is substituted with a halogen 2~6 It is alkinyl.

[0037] In some preferred modes, Z is TIFF2026509562000008.tif21170 or a sulfur atom, R 1 is hydrogen, C 1~4 Alkyl, The file is TIFF2026509562000009.tif18170, where R 11 and R 12 Each is independently C 1~4 Alkyl or C 1~4 It is a cycloalkyl group, and n is 1 or 2. R 2 is hydrogen, C 1~4Alkyl, 3-6 member cycloalkyl, 3-6 member epoxyalkyl, phenyl, at least one hydrogen R 2-1 C replaced by 1~4 Alkyl, at least one hydrogen is R 2-1 It is a phenyl substituted with, where R 2-1 is hydroxyl, halogen, amino or C 1~4 It is an alkoxy, R 3 teeth TIFF2026509562000010.tif19170 Here, R 3-1 is hydrogen, hydroxyl, C 1~4 Alkyl, C 1~4 Alkoxy, -N(R 3-2 R 3-2a ) and R 3-2 and R 3-2a Each is independently hydrogen or C 1~4 It is alkyl, R 3-3a and R 3-3b Each is independently hydrogen or C 1~4 It is alkyl, m is 1 to 4. Ar is phenyl, a 5-membered or 6-membered monocyclic heteroaryl, with at least one hydrogen atom being R 3-3 A 5-membered or 6-membered monocyclic heteroaryl substituted with the R 3-3 is hydrogen, halogen, C 1~4 Alkyl, hydroxyl, C 1~4 Alkoxy, C 1~4 Haloalkyl or -N(R) 3-3a R 3-3b ) and R 4 teeth TIFF2026509562000011.tif25170 Here, R 4-1 Phenyl, with at least one hydrogen atom R 4-11 Phenyl substituted with R, 5-membered or 6-membered monocyclic heteroaryl, at least one hydrogen atom is R 4-11 A 5-membered or 6-membered monocyclic heteroaryl substituted with the R 4-11 Hydrogen, halogen, nitro, C 1~4 Alkyl, C3~6 Cycloalkyl, C 1~4 Alkoxy, -N(R 4-1a R 4-1b ), phenyl, C 1~4 Haloalkyl, C 1~4 Haloalkoxy or TIFF2026509562000012.tif16170, R 4-1a and R 4-1b Each is independently hydrogen and C 1~4 Alkyl or C 3~6 It is cycloalkyl and R 4-1a and R 4-1b They bond to each other to form a ring, R 4-2 is C 1~4 Alkyl, C 3~5 Cycloalkyl, C in which at least one hydrogen is substituted with a hydroxyl group. 1~4 Alkyl, C 3~5 It is epoxyalkyl, or R 2 C 1~4 Alkyl and R 4-2 C 1~4 If it is alkyl, R 4-2 and R 2 They combine to form a 4-8 membered ring. R 4-3 is C 1~4 Alkyl or C 1~4 It is an alkoxy, R 5 In each appearance, hydrogen, halogen, nitro, nitrile, and -N appear independently. + (R 5-1 )3, C 1~4 Haloalkyl, -C(O)OR 5-1 , -C(O)R 5-1 ,-C(O)N(R 5-1 R 5-1a ), -S(O)2R 5-1 ,-S(O)R 5-1 -N=C(R 5-1 R 5-1a ), hydroxyl, C 1~4 Alkyl, phenyl, at least one hydrogen is R 5-1 Phenyl substituted with C 1~4 Alkoxy, -N(R 5-1R 5-1a ), -N(R 5-1 )C(O)R 5-1a or -OC(O)R 5-1 And here, R 5-1 , R 5-1a and R 5-1b Each is independently hydrogen and C 1~4 Alkyl, C in which at least one hydrogen is substituted with a halogen. 1~4 It is alkyl.

[0038] In some preferred modes, Z is TIFF2026509562000013.tif21170 or a sulfur atom, In some preferred modes, R 1 is hydrogen, The file is TIFF2026509562000014.tif18170, where R 11 and R 12 Each of these is independently methyl, ethyl, n-propyl, or isopropyl, where n is 1.

[0039] In some preferred modes, R 2 These are hydrogen, methyl, ethyl, n-propyl, isopropyl, ethyl with one hydrogen replaced by a hydroxyl, n-propyl with one hydrogen replaced by a hydroxyl, phenyl, The filename is TIFF2026509562000015.tif32170.

[0040] In some preferred modes, R 3 teeth TIFF2026509562000016.tif19170 Here, R 3-1 is hydrogen, hydroxyl, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, sec-butoxy, or isobutoxy. m is 1, Ar is a phenyl, 5-membered or 6-membered nitrogen-containing monocyclic heteroaryl.

[0041] In some preferred modes, R 4 teeth TIFF2026509562000017.tif25170 Here, R 4-1 Phenyl, with at least one hydrogen atom R 4-11 Phenyl substituted with R, 5-membered or 6-membered monocyclic heteroaryl, at least one hydrogen atom is R 4-11 5-membered or 6-membered monocyclic heteroaryls substituted with R, 8-10 membered fused bicyclic heteroaryls, at least one hydrogen atom is R 4-11 It is an 8-10 member condensed bicyclic heteroaryl substituted with, and the R 4-11 Halogen, nitro, methyl, ethyl, n-propyl, isopropyl, TIFF2026509562000018.tif35170 Fluoromethyl, fluoroethyl, fluoro-n-propyl, fluoroisopropyl, chloromethyl, chloroethyl, chloro-n-propyl, chloroisopropyl, bromomethyl, bromoethyl, bromo-n-propyl, bromoisopropyl, iodomethyl, iodoethyl, iodo-n-propyl, iodoisopropyl, fluoromethoxy, fluoroethoxy, fluoro-n-propoxy, fluoroisopropoxy, chloromethoxy, chloroethoxy, chloro-n-propoxy, chloroisopropoxy, bromomethoxy, bromoethoxy, bromo-n-propoxy, bromoisopropoxy, iodooxymethyl, iodoethoxy, iodo-n-propoxy, iodoisopropoxy or TIFF2026509562000019.tif14170R 4-2 These include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, ethyl with one hydrogen substituted with hydroxyl, n-propyl with one hydrogen substituted with hydroxyl, and n-butyl with one hydrogen substituted with hydroxyl. TIFF2026509562000020.tif14170 or phenyl, or R 2 is methyl, ethyl, or n-propyl, and R 4-2 If R is methyl or ethyl, 4-2 and R 2They bond to form a 4-8 membered ring, R 4-3 These are methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, or isopropoxy.

[0042] In some preferred modes, R 5 In each appearance, hydrogen, halogen, nitro, nitrile, and -N appear independently. + (R 5-1 )3, fluoromethyl, fluoroethyl, fluoro-n-propyl, fluoroisopropyl, chloromethyl, chloroethyl, chloro-n-propyl, chloroisopropyl, bromomethyl, bromoethyl, bromo-n-propyl, bromoisopropyl, -C(O)OR 5-1 , -C(O)R 5-1 ,-C(O)N(R 5-1 R 5-1a ), -S(O)2R 5-1 ,-S(O)R 5-1 -N=C(R 5-1 R 5-1a ), hydroxyl, methyl, ethyl, n-propyl, isopropyl, phenyl, at least one hydrogen R 5-1 Phenyl, methoxy, ethoxy, n-propoxy, isopropoxy, -N(R) substituted 5-1 R 5-1a ), -N(R 5-1 )C(O)R 5-1a -OC(O)R 5-1 And here, R 5-1 , R 5-1a and R 5-1b Each of these is independently hydrogen, methyl, ethyl, n-propyl, isopropyl, fluoromethyl, fluoroethyl, fluoro-n-propyl, fluoroisopropyl, chloromethyl, chloroethyl, chloro-n-propyl, chloroisopropyl, bromomethyl, bromoethyl, bromo-n-propyl, or bromoisopropyl.

[0043] In some preferred modes, R 1 is hydrogen, The filename is TIFF2026509562000021.tif16170.

[0044] In some preferred modes, R 2 is hydrogen, methyl, TIFF2026509562000022.tif14170 or phenyl.

[0045] In some preferred modes, R 3 teeth The filename is TIFF2026509562000023.tif16170.

[0046] In some preferred modes, R 4 teeth TIFF2026509562000024.tif25170 Here, R 4-1 Phenyl, with at least one hydrogen atom R 4-11 Phenyl substituted with R, a 5-membered monocyclic heteroaryl, at least one hydrogen is R 4-11 A 5-membered monocyclic heteroaryl, a 9-membered condensed bicyclic heteroaryl, or naphthyl substituted with, where R 4-11 bromine, fluorine, chlorine, methyl, nitro, phenyl, trifluoromethyl, TIFF2026509562000025.tif14170 Methoxy, cyclopropyl, trifluoromethoxy, nitro or TIFF2026509562000026.tif13170R 4-2 is methyl, ethyl, TIFF2026509562000027.tif14170 or phenyl, or R 2 is methyl, ethyl, or n-propyl, and R 4-2 If R is methyl or ethyl, 4-2 and R 2 They combine to form a 4-6 membered ring. R 4-3 These are methoxy, ethoxy, n-propoxy, or isopropoxy.

[0047] In some preferred modes, R 5In each occurrence, these are independently halogen, nitro, nitrile, carboxyl, -NHC(O)CH3, methoxy, or hydroxyl.

[0048] In several preferred embodiments, the compound is selected from one of the following compounds. TIFF2026509562000028.tif233170TIFF2026509562000029.tif255170TIFF2026509562000030.tif244170TIFF2026509562000031.t if244170TIFF2026509562000032.tif233170TIFF2026509562000033.tif249170TIFF2026509562000034.tif238170TIFF20265095620 00035.tif233170TIFF2026509562000036.tif244170TIFF2026509562000037.tif238170TIFF2026509562000038.tif244170TIFF202 6509562000039.tif238170TIFF2026509562000040.tif255170TIFF2026509562000041.tif255167TIFF2026509562000042.tif194170

[0049] In some preferred modes, Z is not a sulfur atom.

[0050] In some preferred embodiments, in the compound represented by the general formula I, Z is, TIFF2026509562000043.tif18170R 1 is hydrogen, and R 2 is hydrogen, and R 3 is hydrogen TIFF2026509562000044.tif20170R 4 teeth, TIFF2026509562000045.tif20170 Here R 3-1 is hydroxyl, and R4-1 Phenyl, with at least one hydrogen atom R 4-11 A phenyl substituted with R 4-11 These are halogen-substituted methyl, halogen-substituted ethyl, ethyl, methyl, ethyl, or halogen.

[0051] In some preferred embodiments, in the compound represented by the general formula I, Z is, TIFF2026509562000046.tif18170R 1 is hydrogen, and R 2 is hydrogen, and R 3 is hydrogen TIFF2026509562000047.tif20170R 4 teeth TIFF2026509562000048.tif20170 Here, R 3-1 is hydroxyl, and R 4-1 These are phenyl, phenyl in which at least one hydrogen atom is substituted with trifluoromethyl, and phenyl in which at least one hydrogen atom is substituted with a halogen.

[0052] In some preferred embodiments, the compound represented by general formula I is The filename is TIFF2026509562000049.tif40170.

[0053] In some particularly preferred embodiments, the compound represented by general formula I is The filename is TIFF2026509562000050.tif38170.

[0054] In some preferred embodiments, the liver injury is acute alcoholic liver injury, chronic alcoholic liver injury, drug-induced liver injury, non-alcoholic fatty liver, or liver injury due to cholecystitis.

[0055] In some preferred embodiments, the reproductive system disorders include premature ovarian failure, ovarian dysfunction, polycystic ovary syndrome, oligospermia, and erectile dysfunction.

[0056] In some preferred embodiments, the autoimmune disease includes systemic lupus erythematosus nephritis, rheumatoid arthritis, multiple sclerosis, and Hashimoto's disease.

[0057] In some preferred embodiments, the dermatitis includes psoriasis, melasma, vitiligo, and chronic eczema.

[0058] In some preferred embodiments, the retinitis includes retinitis pigmentosa.

[0059] In some preferred embodiments, the eye disease includes cataract and age-related macular degeneration.

[0060] In some preferred embodiments, the degenerative disease of muscle or bone includes sarcopenia and lumbar intervertebral disc herniation.

[0061] In some preferred embodiments, the neurological disease includes epilepsy and stroke.

[0062] In some preferred embodiments, the anemia includes β-thalassemia.

[0063] In some preferred embodiments, the adrenal disease includes primary aldosteronism and Cushing's syndrome.

[0064] In some preferred embodiments, the chronic gastritis includes chronic atrophic gastritis.

[0065] In some preferred embodiments, the liver disorder is acute alcoholic liver injury, chronic alcoholic liver injury, drug-induced liver injury, non-alcoholic fatty liver or liver injury caused by cholecystitis.

[0066] In some preferred embodiments, (a1) Preparation of a medicament for preventing and / or treating premature ovarian insufficiency, and / or (a2) Prevention and / or treatment of premature ovarian insufficiency, and / or (b1) Preparation of medicines for the prevention and / or treatment of ovarian insufficiency, and / or (b2) Prevention and / or treatment of ovarian insufficiency, and / or (c1) Preparation of medicines for the prevention and / or treatment of systemic lupus erythematosus nephritis, and / or (c2) Prevention and / or treatment of systemic lupus erythematosus nephritis, and / or (d1) Preparation of medicines for the prevention and / or treatment of sarcopenia, and / or (d2) Prevention and / or treatment of sarcopenia, and / or (e1) Preparation of medicines for the prevention and / or treatment of liver damage, and / or (e2) Prevention and / or treatment of liver damage, and / or (f1) Preparation of medicines for the prevention and / or treatment of oligospermia, and / or (f2) Prevention and / or treatment of oligospermia, and / or (g1) Preparation of medicines for the prevention and / or treatment of rheumatoid arthritis, and / or (g2) Prevention and / or treatment of rheumatoid arthritis, and / or (h1) Preparation of medicines for the prevention and / or treatment of cataracts, and / or (h2) Prevention and / or treatment of cataracts, and / or (i1) Preparation of medicines for the prevention and / or treatment of Cushing's syndrome, and / or (i2) Prevention and / or treatment of Cushing's syndrome, and / or (j1) Preparation of medicines for the prevention and / or treatment of Hashimoto's disease, and / or (j2) Prevention and / or treatment of Hashimoto's disease, and / or (k1) Preparation of pharmaceuticals for the prevention and / or treatment of chronic obstructive pulmonary disease, and / or (k2) Prevention and / or treatment of chronic obstructive pulmonary disease, and / or (l1) Preparation of a medicament for preventing and / or treating tinnitus, and / or (l2) Prevention and / or treatment of tinnitus, and / or (m1) Preparation of a medicament for preventing and / or treating psoriasis, and / or (m2) Prevention and / or treatment of psoriasis, and / or (n1) Preparation of a medicament for preventing and / or treating chronic eczema, and / or (n2) Prevention and / or treatment of chronic eczema, and / or (o1) Preparation of a medicament for preventing and / or treating age-related macular degeneration, and / or (o2) Prevention and / or treatment of age-related macular degeneration, and / or (p1) Preparation of a medicament for preventing and / or treating retinitis pigmentosa, and / or (p2) Prevention and / or treatment of retinitis pigmentosa, (q1) Preparation of a medicament for preventing and / or treating multiple sclerosis, and / or (q2) Prevention and / or treatment of multiple sclerosis, (r1) Preparation of a medicament for preventing and / or treating hypothyroidism, and / or (r2) Prevention and / or treatment of hypothyroidism, (s1) Preparation of a medicament for preventing and / or treating chronic atrophic gastritis, and / or (s2) Prevention and / or treatment of chronic atrophic gastritis, (t1) Preparation of a medicament for preventing and / or treating myocarditis, and / or (t2) Prevention and / or treatment of myocarditis, (u1) Preparation of a medicament for preventing and / or treating alopecia, and / or (u2) Prevention and / or treatment of alopecia, (v1) Preparation of a medicament for preventing and / or treating primary aldosteronism, and / or (v2) Prevention and / or treatment of primary aldosteronism, (w1) Preparation of medicines for the prevention and / or treatment of erectile dysfunction, and / or (w2) Prevention and / or treatment of erectile dysfunction, (x1) Preparation of medicines for the prevention and / or treatment of periodontitis, and / or (x2) Prevention and / or treatment of periodontitis, (y1) Preparation of medicines for the prevention and / or treatment of stroke, and / or (y2) Prevention and / or treatment of stroke, (z1) Preparation of medicines for the prevention and / or treatment of epilepsy, and / or (z2) Prevention and / or treatment of epilepsy, (Aa1) Preparation of medicines for the prevention and / or treatment of melasma, and / or (Aa2) Prevention and / or treatment of melasma, and / or (Ab1) Preparation of medicines for the prevention and / or treatment of vitiligo, and / or (Ab2) Prevention and / or treatment of vitiligo, and / or Preparation of medicines for the prevention and / or treatment of (Ac1)β-thalassemia, and / or (Ac2) β-thalassemia prevention and / or treatment, and / or (Ad1) Preparation of medicines for the prevention and / or treatment of lumbar disc herniation, and / or (Ad2) Prevention and / or treatment of lumbar disc herniation, and / or (Ae1) Preparation of medicines for the prevention and / or treatment of polycystic ovary syndrome, and / or (Ae2) Provides the use of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug for use in the prevention and / or treatment of polycystic ovary syndrome.

[0067] A second aspect of the present invention provides a method for preventing and / or treating premature ovarian failure, comprising administering to a subject requiring the administration of an effective amount of a compound represented by general formula (I) described in the present invention or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0068] A third aspect of the present invention provides a method for preventing and / or treating ovarian dysfunction, comprising administering to a subject requiring the administration of an effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof as described in the present invention.

[0069] A fourth aspect of the present invention provides a method for preventing and / or treating systemic lupus erythematosus nephritis, comprising administering to a subject as needed an effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof as described in the present invention.

[0070] A fifth aspect of the present invention provides a method for preventing and / or treating sarcopenia, comprising administering to a subject requiring the administration of an effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof as described in the present invention.

[0071] A sixth aspect of the present invention provides a method for preventing and / or treating liver damage, comprising administering to a subject requiring the administration of an effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof as described in the present invention.

[0072] A seventh aspect of the present invention provides a method for preventing and / or treating oligospermia, comprising administering to a subject as needed an effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof as described in the present invention.

[0073] An eighth aspect of the present invention provides a method for preventing and / or treating rheumatoid arthritis, comprising administering to a subject as needed an effective amount of a compound represented by general formula (I) described in the present invention or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0074] A ninth aspect of the present invention provides a method for preventing and / or treating cataracts, comprising administering to a subject as needed an effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof as described in the present invention.

[0075] A tenth aspect of the present invention provides a method for preventing and / or treating Cushing's syndrome, comprising administering to a subject requiring the administration of an effective amount of a compound represented by general formula (I) described in the present invention or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0076] An eleventh aspect of the present invention provides a method for preventing and / or treating Hashimoto's disease, comprising administering to a subject as needed an effective amount of a compound represented by general formula (I) described in the present invention or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0077] A twelfth aspect of the present invention provides a method for preventing and / or treating chronic obstructive pulmonary disease, comprising administering to a subject requiring an effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof as described in the present invention.

[0078] A thirteenth aspect of the present invention provides a method for preventing and / or treating tinnitus, comprising administering to a subject as needed an effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof as described in the present invention.

[0079] A fourteenth aspect of the present invention provides a method for preventing and / or treating psoriasis, comprising administering to a subject as needed an effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof as described in the present invention.

[0080] A fifteenth aspect of the present invention provides a method for preventing and / or treating chronic eczema, comprising administering to a subject as needed an effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof as described in the present invention.

[0081] A sixteenth aspect of the present invention provides a method for preventing and / or treating age-related macular degeneration, comprising administering to a subject requiring the administration of an effective amount of a compound represented by general formula (I) described in the present invention or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0082] A seventeenth aspect of the present invention provides a method for preventing and / or treating multiple sclerosis, comprising administering to a subject requiring the administration of an effective amount of a compound represented by general formula (I) described in the present invention or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0083] An eighteenth aspect of the present invention provides a method for preventing and / or treating hypothyroidism, comprising administering to a subject requiring the administration of an effective amount of a compound represented by general formula (I) described in the present invention or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0084] A 19th aspect of the present invention provides a method for preventing and / or treating chronic atrophic gastritis, comprising administering to a subject requiring the administration of an effective amount of a compound represented by general formula (I) described in the present invention or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0085] A 20th aspect of the present invention provides a method for preventing and / or treating myocarditis, comprising administering to a subject as needed an effective amount of a compound represented by general formula (I) described in the present invention or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0086] A 21st aspect of the present invention provides a method for preventing and / or treating alopecia, comprising administering to a subject as needed an effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof as described in the present invention.

[0087] A 22nd aspect of the present invention provides a method for preventing and / or treating primary aldosteronism, comprising administering to a subject requiring the administration of an effective amount of a compound represented by general formula (I) described in the present invention or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0088] A 23rd aspect of the present invention provides a method for preventing and / or treating erectile dysfunction, comprising administering to a subject requiring the administration of an effective amount of a compound represented by general formula (I) described in the present invention or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0089] A 24th aspect of the present invention provides a method for preventing and / or treating periodontitis, comprising administering to a subject as needed an effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof as described in the present invention.

[0090] A 25th aspect of the present invention provides a method for preventing and / or treating stroke, comprising administering to a subject as needed an effective amount of a compound represented by general formula (I) described in the present invention or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0091] A 26th aspect of the present invention provides a method for preventing and / or treating epilepsy, comprising administering to a subject requiring the administration of an effective amount of a compound represented by general formula (I) described in the present invention or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0092] A 27th aspect of the present invention provides a method for preventing and / or treating melasma, comprising administering to a subject as needed an effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof as described in the present invention.

[0093] A 28th aspect of the present invention provides a method for preventing and / or treating vitiligo, comprising administering to a subject requiring the administration of an effective amount of a compound represented by general formula (I) described in the present invention or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0094] A 29th aspect of the present invention provides a method for preventing and / or treating β-thalassemia, comprising administering to a subject as needed an effective amount of a compound represented by general formula (I) described in the present invention or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0095] A 30th aspect of the present invention provides a method for preventing and / or treating lumbar disc herniation, comprising administering to a subject as needed an effective amount of a compound represented by general formula (I) described in the present invention or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0096] A 31st aspect of the present invention provides a method for preventing and / or treating polycystic ovary syndrome, comprising administering to a subject requiring the administration of an effective amount of a compound represented by general formula (I) described in the present invention or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0097] A 32nd aspect of the present invention provides a method for preventing and / or treating retinitis pigmentosa, comprising administering to a subject as needed an effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof as described in the present invention.

[0098] Compared to the prior art, the present invention has at least the following advantages.

[0099] (1) When the compounds represented by general formula (I) provided by the present invention are used in the treatment of premature ovarian failure, they can increase ovarian weight and ovarian index, raise E2, FSH and BDNF levels in the patient's serum, and improve ovarian function. Of the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0100] (2) When the compounds represented by general formula (I) provided by the present invention are used to treat ovarian dysfunction, they can increase ovarian weight and ovarian organ index, raise E2 and FSH levels in the patient's serum, and improve ovarian function. Of the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0101] (3) When the compounds represented by general formula (I) provided by the present invention are used in the treatment of systemic lupus erythematosus nephritis, they can reduce proteinuria, lower creatinine and urea nitrogen concentrations, lower inflammatory cytokine concentrations in renal tissue, lower systemic lupus erythematosus-specific antibody concentrations, and improve renal function. Among the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0102] (4) When the compounds represented by general formula (I) provided by the present invention are used to treat sarcopenia, they can improve the patient's muscle strength level, increase the weight of the calf muscle, and alleviate the symptoms of muscular atrophy. Of the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0103] (5) When the compounds represented by general formula (I) provided by the present invention are used to treat liver damage (e.g., acute alcoholic liver injury, chronic alcoholic liver injury, drug-induced liver injury, non-alcoholic fatty liver disease, liver damage due to cholecystitis), they can lower the levels of liver function indicators such as AST, ALT, TG, and TC, and improve liver function. Among the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0104] (6) When the compounds represented by general formula (I) provided by the present invention are used to treat oligospermia, they can increase sex hormone levels in the body, increase the testicular organ index, increase the sperm count in the semen, and improve low sperm count. Of the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0105] (7) When the compounds represented by general formula (I) provided by the present invention are used in the treatment of rheumatoid arthritis, they can reduce joint swelling, decrease the thickness of the hind plantar, and improve the symptoms of rheumatoid arthritis. Among the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0106] (8) When the compounds represented by general formula (I) provided by the present invention are used in the treatment of cataracts, they can improve lens opacity and alleviate the symptoms of cataracts, and among the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0107] (9) When the compounds represented by general formula (I) provided by the present invention are used in the treatment of Cushing's syndrome, they can lower plasma insulin levels and alleviate the symptoms of Cushing's syndrome, and among the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0108] (10) When the compounds represented by general formula (I) provided by the present invention are used in the treatment of Hashimoto's disease, they can lower the TPO-Ab level, which is a diagnostic marker for Hashimoto's disease, and improve the symptoms of Hashimoto's disease. Among the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0109] (11) When the compounds represented by general formula (I) provided by the present invention are used in the treatment of chronic obstructive pulmonary disease, they can reduce the level of the inflammatory factor TNFα in the body, suppress the increase in inflammatory indicators due to chronic obstructive pulmonary disease, and alleviate the symptoms of chronic obstructive pulmonary disease. Among the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0110] (12) When the compounds represented by general formula (I) provided by the present invention are used to treat tinnitus, the range of response in patients' tinnitus can be reduced, and among the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows a significantly superior therapeutic effect compared to the other compounds and exhibits dose-dependent properties.

[0111] (13) When the compounds represented by general formula (I) provided by the present invention are used in the treatment of psoriasis, they can alleviate symptoms of parakeratosis and epidermal thickening, and among the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds and exhibits dose-dependent effects.

[0112] (14) When the compounds represented by general formula (I) provided by the present invention are used in the treatment of chronic eczema, they can increase the water content of the stratum corneum, reduce water loss, and alleviate eczema symptoms. Among the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds and exhibits dose-dependent effects.

[0113] (15) When the compounds represented by general formula (I) provided by the present invention are used in the treatment of age-related macular degeneration, they can improve retinal photosensitivity and restore normal retinal structure, and among the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0114] (16) When the compounds represented by general formula (I) provided by the present invention are used in the treatment of retinitis pigmentosa, they can increase the thickness of the retinal photoreceptor layer, increase the density of retinal microglia, and improve the symptoms of retinitis pigmentosa. Among the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0115] (17) When the compounds represented by general formula (I) provided by the present invention are used in the treatment of multiple sclerosis, they can improve the spatial learning ability and memory ability of patients, and among the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows a significantly superior therapeutic effect compared to the other compounds.

[0116] (18) When the compounds represented by general formula (I) provided by the present invention are used in the treatment of hypothyroidism, they can improve T3, T4FT3, FT4 and FSH levels, and among the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0117] (19) When the compounds represented by general formula (I) provided by the present invention are used in the treatment of chronic atrophic gastritis, they can reduce inflammatory factor levels and improve pepsin levels, and among the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0118] (20) When the compounds represented by general formula (I) provided by the present invention are used in the treatment of myocarditis, they can lower LVIDd and LVIDs levels, EF and FS, and CK-MB levels, and improve cardiac function. Of the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0119] (21) When the compounds represented by general formula (I) provided by the present invention are used in the treatment of alopecia, they can improve positive cell infiltration in the area of ​​alopecia areata and reduce inflammation, and among the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows a significantly superior therapeutic effect compared to the other compounds.

[0120] (22) When the compounds represented by general formula (I) provided by the present invention are used in the treatment of primary aldosteronism, they can improve sodium retention and potassium excretion symptoms, lower sodium ion levels while improving potassium ion levels, and among the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0121] (23) When the compounds represented by general formula (I) provided by the present invention are used to treat erectile dysfunction, they can improve symptoms of erectile dysfunction or decreased erectile function, improve erectile function, and increase sex hormone levels. Among the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0122] (24) When the compound represented by general formula (I) provided by the present invention is used in the treatment of periodontitis, it can improve the condition of the alveolar bone and the symptoms of periodontal tissue resorption, and compound I-1 (TJ01-013) shows a significantly superior therapeutic effect compared to other compounds.

[0123] (25) When the compounds represented by general formula (I) provided by the present invention are used in the treatment of stroke, they can reduce the apoptosis rate of hippocampal neurons and improve cognitive function, and among the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0124] (26) When the compounds represented by general formula (I) provided by the present invention are used in the treatment of epilepsy, they can improve the patient's cognitive impairment, seizure frequency and onset symptoms, and reduce inflammatory factor levels. Of the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0125] (27) When the compounds represented by general formula (I) provided by the present invention are used to treat melasma, they can reduce the area of ​​melanin-positive cells and the surface density of melanin in the patient's skin tissue, and reduce the number of scaly patches on the face. Of the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0126] (28) When the compounds represented by general formula (I) provided by the present invention are used to treat vitiligo, they can reduce the number of melanin hair follicles in the patient and the serum concentrations of TYR and MDA, and among the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0127] (29) When the compounds represented by general formula (I) provided by the present invention are used in the treatment of β-thalassemia, they can restore the patient's red blood cell count and hemoglobin count and improve anemia symptoms, and among the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0128] (30) When the compounds represented by general formula (I) provided by the present invention are used in the treatment of lumbar disc herniation, they can reduce PLA2 activity and inflammatory factor levels in the patient's nucleus pulposus tissue and improve intervertebral disc function. Of the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0129] (31) When the compounds represented by general formula (I) provided by the present invention are used to treat polycystic ovary syndrome, they can lower serum levels of testosterone T, luteinizing hormone LH, and follicle-stimulating hormone FSH, increase ovarian weight, and improve ovulation disorders. Of the compounds summarized by general formula (I), compound I-1 (TJ01-013) shows significantly superior therapeutic effects compared to the other compounds.

[0130] It should be understood that each of the above technical features of the present invention and each of the technical features specifically described below (for example, in the examples) can be combined with each other within the scope of the present invention to constitute novel or preferred technical solutions. Due to space limitations, each will not be explained in detail here. [Brief explanation of the drawing]

[0131] One or more embodiments are illustrated with reference to the attached drawings, but these drawings are not intended to limit the embodiments.

[0132] [Figure 1] Figure 1 is a quantitative analysis of body weight, ovarian weight, and ovarian organ index in mice after administration of the compound TJ0113 in a chemotherapy-induced premature birth ovarian failure model according to one embodiment of the present invention.

[0133] [Figure 2] Figure 2 shows the quantitative analysis of serum FSH in mice in a chemotherapy-induced premature ovarian failure model according to one embodiment of the present invention, after administration of the compound TJ0113.

[0134] [Figure 3] Figure 3 shows the quantitative analysis of serum E2 levels in mice after administration of the compound TJ0113 in a chemotherapy-induced premature ovarian failure model according to one embodiment of the present invention.

[0135] [Figure 4] Figure 4 shows the quantitative analysis of BDNF in ovarian tissue after administration of the compound TJ0113 to mice in a chemotherapy-induced premature ovarian failure model according to one embodiment of the present invention.

[0136] [Figure 5] Figure 5 is a quantitative analysis of body weight, ovarian weight, and ovarian organ index after administering the compound TJ0113 to mice in a spontaneous aging model of ovarian dysfunction according to one embodiment of the present invention.

[0137] [Figure 6] Figure 6 is a quantitative analysis of FSH levels in mice after administration of compound TJ0113 in a spontaneous aging model of ovarian dysfunction according to one embodiment of the present invention.

[0138] [Figure 7] Figure 7 is a quantitative analysis of E2 levels in mice after administration of compound TJ0113 in a spontaneous aging model of ovarian dysfunction according to one embodiment of the present invention.

[0139] [Figure 8] Figure 8 shows the quantitative analysis of random urine uPCR after administration of compound TJ0113 to mice in a lupus nephritis model according to one embodiment of the present invention.

[0140] [Figure 9] Figure 9 shows the quantitative analysis of serum creatinine and urea nitrogen in mice after administration of compound TJ0113 in a lupus nephritis model according to one embodiment of the present invention.

[0141] [Figure 10] Figure 10 is a quantitative analysis of serum ANA after administration of compound TJ0113 to mice in a lupus nephritis model according to one embodiment of the present invention.

[0142] [Figure 11] Figure 11 shows the quantitative analysis of serum dsDNA after administration of compound TJ0113 to mice in a lupus nephritis model according to one embodiment of the present invention.

[0143] [Figure 12] Figure 12 shows the quantitative analysis of TNFα and IL-6 in kidney tissue after administration of compound TJ0113 to mice in a lupus nephritis model according to one embodiment of the present invention.

[0144] [Figure 13] Figure 13 is a quantitative analysis of swimming time in mice after administration of compound TJ0113 in a sarcopenia model according to one embodiment of the present invention.

[0145] [Figure 14] Figure 14 is a quantitative analysis of the hindlimb traction force in mice after administration of the compound TJ0113 in a sarcopenia model according to one embodiment of the present invention. [Figure 15] Figure 15 shows the quantitative analysis of serum AST and ALT after administration of compound TJ0113 to patients with acute alcoholic liver injury according to one embodiment of the present invention.

[0146] [Figure 16] Figure 16 is a quantitative analysis of TG and TC in liver tissue after administration of compound TJ0113 to patients with acute alcoholic liver injury according to one embodiment of the present invention.

[0147] [Figure 17] Figure 17 shows the quantitative analysis of serum AST and ALT after administration of compound TJ0113 to a patient with chronic alcoholic liver disease according to one embodiment of the present invention.

[0148] [Figure 18] Figure 18 shows the HE staining of liver tissue after administration of compound TJ0113 to a patient with chronic alcoholic liver disease according to one embodiment of the present invention.

[0149] [Figure 19] Figure 19 shows an oil-red stained image of liver tissue after administration of compound TJ0113 to a patient with chronic alcoholic liver disease according to one embodiment of the present invention.

[0150] [Figure 20] Figure 20 shows the quantitative analysis of serum AST and ALT after administration of compound TJ0113 to a patient with drug-induced liver injury according to one embodiment of the present invention.

[0151] [Figure 21] Figure 21 is a quantitative analysis of serum ALP after administration of compound TJ0113 to a patient with drug-induced liver injury according to one embodiment of the present invention.

[0152] [Figure 22] Figure 22 shows the quantitative analysis of serum FSH, LH, and T levels after administration of compound TJ0113 to an oligospermia model according to one embodiment of the present invention.

[0153] [Figure 23] Figure 23 is a quantitative analysis of testicular wet weight and testicular organ index after administration of compound TJ0113 to an oligospermia model according to one embodiment of the present invention.

[0154] [Figure 24]Figure 24 is a quantitative analysis of sperm density after administration of compound TJ0113 to an oligospermia model according to one embodiment of the present invention.

[0155] [Figure 25] Figure 25 is a quantitative analysis of the AI ​​score after administering the compound TJ0113 to a rheumatoid arthritis model according to one embodiment of the present invention.

[0156] [Figure 26] Figure 26 is a quantitative analysis of ankle joint swelling after administration of compound TJ0113 to a rheumatoid arthritis model according to one embodiment of the present invention.

[0157] [Figure 27] Figure 27 is a quantitative analysis of the lateral thickness of the foot after administration of compound TJ0113 to a rheumatoid arthritis model according to one embodiment of the present invention.

[0158] [Figure 28] Figure 28 is a quantitative analysis of thymic and splenic organ coefficients after administration of compound TJ0113 to a rheumatoid arthritis model according to one embodiment of the present invention.

[0159] [Figure 29] Figure 29 is a quantitative analysis of fundus scores after administration of compound TJ0113 to a cataract model according to one embodiment of the present invention.

[0160] [Figure 30] Figure 30 is a quantitative analysis of fundus scores after administration of compound TJ0113 to Cushing's syndrome according to one embodiment of the present invention.

[0161] [Figure 31] Figure 31 is a quantitative analysis of serum THS and FT3 after administration of compound TJ0113 to a patient with Hashimoto's disease according to one embodiment of the present invention.

[0162] [Figure 32] Figure 32 is a quantitative analysis of serum TGAb and TPOAb after administration of compound TJ0113 to a patient with Hashimoto's disease according to one embodiment of the present invention.

[0163] [Figure 33] Figure 33 shows the quantitative analysis of serum TNFα and CXCL1 after administration of compound TJ0113 to patients with chronic obstructive pulmonary disease according to one embodiment of the present invention.

[0164] [Figure 34] Figure 34 is a quantitative analysis of tinnitus indices after administration of compound TJ0113 to tinnitus according to one embodiment of the present invention.

[0165] [Figure 35] Figure 35 is a quantitative analysis of skin thickness after administration of compound TJ0113 to psoriasis according to one embodiment of the present invention.

[0166] [Figure 36] Figure 36 is a quantitative analysis of transepidermal water loss after administration of compound TJ0113 to chronic eczema according to one embodiment of the present invention.

[0167] [Figure 37] Figure 37 is a quantitative analysis of the water content of the stratum corneum after administration of compound TJ0113 to chronic eczema according to one embodiment of the present invention.

[0168] [Figure 38] Figure 38 is an analysis of the fatty degeneration score after administration of compound TJ0113 to non-alcoholic fatty liver according to one embodiment of the present invention.

[0169] [Figure 39] Figure 39 is an analysis of inflammation level scores after administration of compound TJ0113 to non-alcoholic fatty liver disease according to one embodiment of the present invention.

[0170] [Figure 40] Figure 40 is an analysis of the fibrosis level score after administration of compound TJ0113 to non-alcoholic fatty liver according to one embodiment of the present invention.

[0171] [Figure 41] Figure 41 is an analytical diagram of liver biochemical indicators ALT, AST, and TBIL levels after administration of compound TJ0113 to a patient with cholecystitis according to one embodiment of the present invention.

[0172] [Figure 42] Figure 42 is a quantitative analysis of the photoreceptor cell layer thickness after administration of compound TJ01-013 to mice in a retinitis pigmentosa model according to one embodiment of the present invention.

[0173] [Figure 43] Figure 43 is a quantitative analysis of retinal microglia density in mice in a retinitis pigmentosa model according to one embodiment of the present invention, after administration of compound TJ01-013.

[0174] [Figure 44] Figure 44 is a quantitative analysis of the number of times mice entered an elevated cruciate maze after being administered the compound TJ01-013 to mice in a multiple sclerosis model according to one embodiment of the present invention.

[0175] [Figure 45] Figure 45 is a quantitative analysis of the distance traveled by mice on an elevated platform after administration of compound TJ01-013 to mice in a multiple sclerosis model according to one embodiment of the present invention.

[0176] [Figure 46] Figure 46 is a quantitative analysis of the time it took for mice in a multiple sclerosis model according to one embodiment of the present invention to enter an elevated cruciform maze after being administered the compound TJ01-013.

[0177] [Figure 47]Figure 47 is a quantitative analysis of the number of times mice crossed the platform after being administered compound TJ01-013 to mice in a multiple sclerosis model according to one embodiment of the present invention.

[0178] [Figure 48] Figure 48 shows the quantitative analysis of serum T3 and T4 levels in mice in a hypothyroidism model according to one embodiment of the present invention, after administration of compound TJ01-013.

[0179] [Figure 49] Figure 49 shows the quantitative analysis of serum FT3 and FT4 levels in mice in a hypothyroidism model according to one embodiment of the present invention, after administration of compound TJ01-013.

[0180] [Figure 50] Figure 50 is a quantitative analysis of serum FSH levels in mice in a hypothyroidism model according to one embodiment of the present invention, after administration of the compound TJ01-013.

[0181] [Figure 51] Figure 51 is a quantitative analysis of serum IgG in mice in a hypothyroidism model according to one embodiment of the present invention, after administration of the compound TJ01-013.

[0182] [Figure 52] Figure 52 shows the quantitative analysis of serum IL-6, IL-1β, and TNF-α in mice in a chronic atrophic gastritis model according to one embodiment of the present invention, after administration of compound TJ01-013.

[0183] [Figure 53] Figure 53 shows the quantitative analysis of serum PGI, PGII, and GAS in mice in a chronic atrophic gastritis model according to one embodiment of the present invention, after administration of compound TJ01-013.

[0184] [Figure 54]Figure 54 is a quantitative analysis of LVIDd and LVIDs in mice in a myocarditis model according to one embodiment of the present invention after administration of compound TJ01-013.

[0185] [Figure 55] Figure 55 is a quantitative analysis of EF and FS in mice in a myocarditis model according to one embodiment of the present invention, after administration of compound TJ01-013.

[0186] [Figure 56] Figure 56 is a quantitative analysis of serum CK-MB levels in mice in a myocarditis model according to one embodiment of the present invention, after administration of compound TJ01-013.

[0187] [Figure 57] Figure 57 is a quantitative analysis of the number of CD4+ and CD8+ T cells around hair follicles in mice in an alopecia model according to one embodiment of the present invention, after administration of compound TJ01-013.

[0188] [Figure 58] Figure 58 shows the quantitative analysis of inflammatory factors TNF-α and IFN-γ in the skin tissue of mice in an alopecia model according to one embodiment of the present invention after administration of compound TJ01-013.

[0189] [Figure 59] Figure 59 shows the quantitative analysis of serum Na+ and K+ in mice in a hyperaldosteronism model according to one embodiment of the present invention after administration of compound TJ01-013.

[0190] [Figure 60] Figure 60 shows the quantitative analysis of serum PAC and PRA in mice in a hyperaldosteronism model according to one embodiment of the present invention after administration of compound TJ01-013.

[0191] [Figure 61]Figure 61 is a quantitative analysis of the number of erections in mice in an erectile dysfunction model according to one embodiment of the present invention, after administration of compound TJ01-013.

[0192] [Figure 62] Figure 62 is a quantitative analysis of kidney and testicular weights in mice in an erectile dysfunction model according to one embodiment of the present invention, after administration of compound TJ01-013.

[0193] [Figure 63] Figure 63 is a quantitative analysis of the left spermatic vein diameter in mice in an erectile dysfunction model according to one embodiment of the present invention, after administration of compound TJ01-013.

[0194] [Figure 64] Figure 64 shows the quantitative analysis of serum FSH, LH, and T levels in mice in an erectile dysfunction model according to one embodiment of the present invention, after administration of compound TJ01-013.

[0195] [Figure 65] Figure 65 is a quantitative analysis of CEJ-ABC in mice in a periodontitis model according to one embodiment of the present invention, after administration of compound TJ01-013.

[0196] [Figure 66] Figure 66 is a quantitative analysis of the escape latency after administration of compound TJ01-013 to a stroke model according to one embodiment of the present invention.

[0197] [Figure 67] Figure 67 is a quantitative analysis of the number of platform cross-sections after administration of compound TJ01-013 to a stroke model according to one embodiment of the present invention.

[0198] [Figure 68]Figure 68 is a quantitative analysis of the neuronal apoptosis rate after administration of compound TJ01-013 to a stroke model according to one embodiment of the present invention.

[0199] [Figure 69] Figure 69 is a quantitative analysis of seizure levels after administration of compound TJ01-013 to an epilepsy model according to one embodiment of the present invention.

[0200] [Figure 70] Figure 70 is a quantitative analysis of the post-stimulation latency in a jumping experiment after administration of compound TJ01-013 to an epilepsy model according to one embodiment of the present invention.

[0201] [Figure 71] Figure 71 is a quantitative analysis of the post-stimulation latency in a dark avoidance experiment after administration of compound TJ01-013 to an epilepsy model according to one embodiment of the present invention.

[0202] [Figure 72] Figure 72 shows the quantitative analysis of serum inflammatory factors after administration of compound TJ01-013 to an epilepsy model according to one embodiment of the present invention.

[0203] [Figure 73] Figure 73 is a quantitative analysis of the number of melanin-positive cells and melanin number density after administration of compound TJ01-013 to a melasma model according to one embodiment of the present invention.

[0204] [Figure 74] Figure 74 is a quantitative analysis of the melanin-positive target area and melanin surface density after administration of compound TJ01-013 to a melasma model according to one embodiment of the present invention.

[0205] [Figure 75] Figure 75 is a quantitative analysis of the vitiligo score after administration of compound TJ01-013 to a vitiligo model according to one embodiment of the present invention.

[0206] [Figure 76] Figure 76 is a quantitative analysis of the proportion of melanin-containing hair follicles after administration of compound TJ01-013 to a vitiligo model according to one embodiment of the present invention.

[0207] [Figure 77] Figure 77 is a quantitative analysis of serum TYR and MDA levels after administration of compound TJ01-013 to a vitiligo model according to one embodiment of the present invention.

[0208] [Figure 78] Figure 78 is a quantitative analysis of hemoglobin Hb after administration of compound TJ01-013 to a thalassemia model according to one embodiment of the present invention.

[0209] [Figure 79] Figure 79 is a quantitative analysis of the red blood cell count (RBC) after administration of compound TJ01-013 to a thalassemia model according to one embodiment of the present invention.

[0210] [Figure 80] Figure 80 shows the quantitative analysis of phospholiase A2 activity in nucleus pulposus tissue after administration of compound TJ01-013 to a lumbar disc herniation model according to one embodiment of the present invention.

[0211] [Figure 81] Figure 81 is a quantitative analysis of the levels of the inflammatory factor TNF-α sum IL-6 in the nucleus pulposus tissue after administration of compound TJ01-013 to a lumbar disc herniation model according to one embodiment of the present invention.

[0212] [Figure 82] Figure 82 is a quantitative analysis of ovarian weight after administration of compound TJ01-013 to a polycystic ovary syndrome model according to one embodiment of the present invention.

[0213] [Figure 83]Figure 83 is a quantitative analysis of serum E2 levels after administration of compound TJ01-013 to a polycystic ovary syndrome model according to one embodiment of the present invention.

[0214] [Figure 84] Figure 84 is a quantitative analysis of serum LH, T, and FSH levels after administration of compound TJ01-013 to a polycystic ovary syndrome model according to one embodiment of the present invention. [Modes for carrying out the invention]

[0215] The inventors have conducted an extensive application search for a conventionally developed compound represented by general formula (I) (the compound represented by general formula I can be prepared by the method described in Chinese Patent Application 202111108417.6, the full text of which is incorporated into the text) and have discovered that it shows excellent efficacy in treating many diseases. These diseases include reproductive system diseases, autoimmune diseases, dermatitis, retinitis, ocular degenerative diseases, muscle or bone degenerative diseases, neurological diseases, anemia, adrenal diseases, chronic gastritis, myocarditis, periodontitis, hypothyroidism, alopecia, liver damage, tinnitus, and chronic obstructive pulmonary disease, and more specifically, premature ovarian failure, ovarian dysfunction, systemic lupus erythematosus nephritis, sarcopenia, liver damage, oligospermia, rheumatoid arthritis, cataracts, Cushing's syndrome, Hashimoto's disease, chronic obstructive pulmonary disease, tinnitus, psoriasis, chronic eczema, age-related macular degeneration, and retinitis pigmentosa. Compounds represented by general formula (I) and / or pharmaceutically acceptable salts, stereoisomers, solvates, or prodrugs thereof have been found to dose-dependently alleviate some indicators of the aforementioned diseases, including multiple sclerosis, hypothyroidism, chronic atrophic gastritis, myocarditis, alopecia, primary aldosteronism, erectile dysfunction, periodontitis, stroke, epilepsy, melasma, vitiligo, β-thalassemia, lumbar disc herniation, and polycystic ovary syndrome, and have been found to have extremely great application value in the prevention and treatment of the aforementioned diseases.

[0216] Application of compounds The present invention relates to the use of a compound represented by general formula (I) in the treatment of at least one disease selected from the following, and / or in the preparation of a medicament for the treatment of at least one of the following diseases, wherein these diseases are: reproductive system diseases (e.g., premature ovarian failure, ovarian dysfunction, polycystic ovary syndrome, oligospermia, erectile dysfunction), autoimmune diseases (e.g., systemic lupus erythematosus nephritis, rheumatoid arthritis, multiple sclerosis, Hashimoto's disease, or alopecia), skin diseases (e.g., psoriasis, melasma, vitiligo, chronic eczema, etc.), eye diseases (e.g., cataracts, age-related macular degeneration, retinal This includes inflammation (e.g., retinitis pigmentosa), degenerative diseases of muscle or bone (e.g., sarcopenia, lumbar disc herniation), neurological disorders (e.g., epilepsy, stroke, etc.), anemia (e.g., beta-thalassemia), adrenal disorders (e.g., primary aldosteronism, Cushing's syndrome, etc.), chronic gastritis (e.g., chronic atrophic gastritis), myocarditis, periodontitis, hypothyroidism, alopecia, liver disorders (e.g., acute alcoholic liver injury, chronic alcoholic liver injury, drug-induced liver injury, liver injury due to non-alcoholic fatty liver or cholecystitis, etc.), tinnitus, and chronic obstructive pulmonary disease.

[0217] The present invention relates to (a1) preparation of a pharmaceutical for the prevention and / or treatment of premature ovarian failure, and / or (a2) preparation of a pharmaceutical for the prevention and / or treatment of premature ovarian failure, and / or (b1) preparation of a pharmaceutical for the prevention and / or treatment of ovarian dysfunction, and / or (b2) preparation of a pharmaceutical for the prevention and / or treatment of ovarian dysfunction, and / or (c1) preparation of a pharmaceutical for the prevention and / or treatment of systemic lupus erythematosus nephritis, and / or (c2) preparation of a pharmaceutical for the prevention and / or treatment of systemic lupus erythematosus nephritis, and / or (d1) preparation of a pharmaceutical for the prevention and / or treatment of sarcopenia. Preparation of medicines for the treatment of (d2) sarcopenia and / or treatment of (e1) liver damage and / or treatment of (e2) liver damage and / or treatment of (f1) oligospermia and / or treatment of (f2) oligospermia and / or treatment of (g1) rheumatoid arthritis and / or treatment of (g2) rheumatoid arthritis and / or treatment of ( h1) Preparation of a medicine for the prevention and / or treatment of cataracts, and / or (h2) the prevention and / or treatment of cataracts, and / or (i1) the preparation of a medicine for the prevention and / or treatment of Cushing's syndrome, and / or (i2) the prevention and / or treatment of Cushing's syndrome, and / or (j1) the preparation of a medicine for the prevention and / or treatment of Hashimoto's disease, and / or (j2) the prevention and / or treatment of Hashimoto's disease, and / or (k1) the preparation of a medicine for the prevention and / or treatment of chronic obstructive pulmonary disease, and / or (k2) chronic obstructive pulmonary disease Preparation of a medicament for the prevention and / or treatment of obstructive pulmonary disease, and / or (l1) for the prevention and / or treatment of tinnitus, and / or (l2) for the prevention and / or treatment of tinnitus, and / or (m1) for the prevention and / or treatment of psoriasis, and / or (m2) for the prevention and / or treatment of psoriasis, and / or (n1) for the prevention and / or treatment of chronic eczema, and / or (n2) for the prevention and / or treatment of chronic eczema, and / or (o1) for the prevention and / or treatment of age-related macular degeneration.and / or (o2) preparation of a medicine for the prevention and / or treatment of age-related macular degeneration, (p1) preparation of a medicine for the prevention and / or treatment of retinitis pigmentosa, and / or (p2) preparation of a medicine for the prevention and / or treatment of (q1) multiple sclerosis, and / or (q2) preparation of a medicine for the prevention and / or treatment of (r1) hypothyroidism, and / or (r2) preparation of a medicine for the prevention and / or treatment of hypothyroidism, and / or (s1) preparation of a medicine for the prevention and / or treatment of chronic atrophic gastritis Preparation of pharmaceuticals for (s2) prevention and / or treatment of chronic atrophic gastritis, (t1) prevention and / or treatment of myocarditis, and / or (t2) prevention and / or treatment of myocarditis, (u1) prevention and / or treatment of alopecia, and / or (u2) prevention and / or treatment of alopecia, (v1) prevention and / or treatment of primary aldosteronism, and / or (v2) prevention and / or treatment of primary aldosteronism, (w1) prevention and / or treatment of erectile dysfunction (Aa1) Preparation of pharmaceuticals for the treatment and / or (w2) prevention and / or treatment of erectile dysfunction, (x1) preparation of pharmaceuticals for the prevention and / or treatment of periodontitis, and / or (x2) prevention and / or treatment of periodontitis, (y1) preparation of pharmaceuticals for the prevention and / or treatment of stroke, and / or (y2) prevention and / or treatment of stroke, (z1) preparation of pharmaceuticals for the prevention and / or treatment of epilepsy, and / or (z2) prevention and / or treatment of epilepsy, (Aa1) preparation of pharmaceuticals for the prevention and / or treatment of melasma. Preparation of a medicine for the prevention and / or treatment of (Aa2) melasma, and / or (Ab1) vitiligo, and / or (Ab2) vitiligo, and / or (Ac1) β-thalassemia, and / or (Ac2) β-thalassemia, and / or (Ad1) lumbar disc herniation, and / or (Ad2) lumbar disc herniation,and / or (Ae1) preparation of pharmaceuticals for the prevention and / or treatment of polycystic ovary syndrome, and / or (Ae2) use of compounds represented by general formula (I) for the prevention and / or treatment of polycystic ovary syndrome.

[0218] In this invention, the compounds represented by general formula (I) are as follows: TIFF2026509562000051.tif61170 Here, Z is TIFF2026509562000052.tif21170 or a sulfur atom.

[0219] R 1 is hydrogen, C 1~6 Alkyl, The file is TIFF2026509562000053.tif18170, where R 11 and R 12 Each is independently C 1~6 Alkyl or C 1~6 It is a cycloalkyl group, and n is 1 to 4. R 2 is hydrogen, C 1~6 Alkyl, 3-6 member cycloalkyl, 3-6 member epoxyalkyl, phenyl, at least one hydrogen R 2-1 C replaced by 1~6 Alkyl, at least one hydrogen is R 2-1 It is a phenyl substituted with, where R 2-1 is hydroxyl, halogen, amino or C 1~6 It is an alkoxy, R 3 teeth TIFF2026509562000054.tif19170 Here, R 3-1 is hydrogen, hydroxyl, C 1~6 Alkyl, C 1~6 Alkoxy, C 3~6 Cycloalkyl, 3-6 member epoxyalkyl, amino, C 1~6 Amine group, -CH2C(O)R 3-2 -CH2C(O)OR 3-2 -CH2C(O)N(R 3-2 R 3-2a) and R 3-2 and R 3-2a Each is independently hydrogen and C 1~6 Alkyl or 3-6 membered cycloalkyl, m is 1 to 6, and Ar is a phenyl, naphthyl, 5- or 6-membered monocyclic heteroaryl, 8- to 10-membered condensed bicyclic heteroaryl, with at least one hydrogen atom being R 3-3 Phenyl substituted with R, at least one hydrogen atom is R 3-3 Naphthyl substituted with R, at least one hydrogen atom is R 3-3 A 5-membered or 6-membered monocyclic heteroaryl substituted with R, at least one hydrogen atom is R 3-3 It is an 8-10 member condensed bicyclic heteroaryl substituted with the R 3-3 Hydrogen, halogen, C 1~6 Alkyl, 3-6 membered cycloalkyl, hydroxyl, C 1~6 Alkoxy, 3-6 member epoxyalkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, -N(R 3-3a R 3-3b ) or phenyl, R 3-3a and R 3-3b Each is independently hydrogen and C 1~6 Alkyl or 3-6 membered cycloalkyl, R 4 teeth TIFF2026509562000055.tif25170 Here, R 4-1 R is phenyl, naphthyl, with at least one hydrogen atom 4-11 Phenyl substituted with R, 5-membered or 6-membered monocyclic heteroaryl, at least one hydrogen atom is R 4-11 5-membered or 6-membered monocyclic heteroaryls substituted with R, 8-10 membered fused bicyclic heteroaryls, at least one hydrogen atom is R 4-11 It is an 8-10 member condensed bicyclic heteroaryl substituted with R, 4-11 Hydrogen, halogen, nitro, nitrile, hydroxyl, C 1~6 Alkyl, C 3~6 Cycloalkyl, C1~6 Alkoxy, -N(R 4-1a R 4-1b ), phenyl, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -C(O)OR 4-12 , -C(O)R 4-12 ,-C(O)N(R 4-1a R 4-1b ), -S(O)2R 4-12 ,-S(O)R 4-12 -OC(O)R 4-12 , -OC(O)OR 4-12 or The filename is TIFF2026509562000056.tif16170, and R 4-12 , R 4-1a and R 4-1b Each is independently hydrogen and C 1~6 Alkyl, C 3~6 Cycloalkyl, C 2~6 Alkenil, C 2~6 Alkynyl, a C atom in which at least one hydrogen atom is substituted with a halogen. 1~6 Alkyl, C in which at least one hydrogen is substituted with a halogen. 2~6 Alkenyls, C12C 3~6 Cycloalkyl, C in which at least one hydrogen is substituted with a halogen. 2~6 It is an alkynyl and also R 4-1a and R 4-1b They bond to each other to form a ring, R 4-2 is C 1~6 Alkyl, C 3~6 Cycloalkyl, C in which at least one hydrogen is substituted with a hydroxyl group. 1~6 Alkyl, C 3~6 It is epoxyalkyl, or R 2 C 1~6 Alkyl and R 4-2 C 1~6 If it is alkyl, R 4-2 and R 2 They bond to form a 4-8 membered ring, R 4-3 is C 1~6 Alkyl or C 1~6 It is an alkoxy, R 5 The number is 0 to 5, R 5 In each appearance, hydrogen, halogen, nitro, nitrile, and -N appear independently. + (R 5-1 )3, C 1~6 Haloalkyl, -C(O)OR 5-1 , -C(O)R 5-1 ,-C(O)N(R 5-1 R 5-1a ), -S(O)2R 5-1 ,-S(O)R 5-1 -S(O)2N(R 5-1 R 5-1a ), -S(O)N(R 5-1 R 5-1a ), -N=C(R 5-1 R 5-1a ), hydroxyl, C 1~6 Alkyl, phenyl, at least one hydrogen is R 5-1 Phenyl substituted with C 1~6 Alkoxy, -N(R 5-1 R 5-1a ), -N(R 5-1 )C(O)R 5-1a , -N(R 5-1 )C(O)OR 5-1a , -N(R 5-1 )C(O)N(R 5-1a R 5-1b ), -OC(O)R 5-1 , -OC(O)OR 5-1 ,-OC(O)N(R 5-1 R 5-1a ) or -SR 5-1 And here, R 5-1 , R 5-1a and R 5-1b Each is independently hydrogen and C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkynyl, a C atom in which at least one hydrogen atom is substituted with a halogen. 1~6 Alkyl, C in which at least one hydrogen is substituted with a halogen. 2~6 C is an alkenyl or a C in which at least one hydrogen atom is substituted with a halogen. 2~6 It is alkinyl.

[0220] In some preferred modes, Z is TIFF2026509562000057.tif21170 or a sulfur atom, R 1 is hydrogen, C 1~4 Alkyl, The file is TIFF2026509562000058.tif18170, where R 11 and R 12 Each is independently C 1~4 Alkyl or C 1~4 It is a cycloalkyl group, and n is 1 or 2. R 2 is hydrogen, C 1~4 Alkyl, 3-6 member cycloalkyl, 3-6 member epoxyalkyl, phenyl, at least one hydrogen R 2-1 C replaced by 1~4 Alkyl, at least one hydrogen is R 2-1 It is a phenyl substituted with, where R 2-1 is hydroxyl, halogen, amino or C 1~4 It is an alkoxy, R 3 teeth TIFF2026509562000059.tif19170 Here, R 3-1 is hydrogen, hydroxyl, C 1~4 Alkyl, C 1~4 Alkoxy, -N(R 3-2 R 3-2a ) and R 3-2 and R 3-2a Each is independently hydrogen or C 1~4 It is alkyl, R 3-3a and R 3-3b Each is independently hydrogen or C 1~4 It is alkyl, m is 1 to 4. Ar is phenyl, a 5-membered or 6-membered monocyclic heteroaryl, with at least one hydrogen atom being R 3-3 A 5-membered or 6-membered monocyclic heteroaryl substituted with the R 3-3 is hydrogen, halogen, C 1~4 Alkyl, hydroxyl, C 1~4 Alkoxy, C1~4 Haloalkyl or -N(R) 3-3a R 3-3b ) and R 4 teeth TIFF2026509562000060.tif25170 Here, R 4-1 Phenyl, with at least one hydrogen atom R 4-11 Phenyl substituted with R, 5-membered or 6-membered monocyclic heteroaryl, at least one hydrogen atom is R 4-11 A 5-membered or 6-membered monocyclic heteroaryl substituted with the R 4-11 Hydrogen, halogen, nitro, C 1~4 Alkyl, C 3~6 Cycloalkyl, C 1~4 Alkoxy, -N(R 4-1a R 4-1b ), phenyl, C 1~4 Haloalkyl, C 1~4 Haloalkoxy or TIFF2026509562000061.tif16170, R 4-1a and R 4-1b Each is independently hydrogen and C 1~4 Alkyl or C 3~6 It is cycloalkyl and R 4-1a and R 4-1b They bond to each other to form a ring, R 4-2 is C 1~4 Alkyl, C 3~5 Cycloalkyl, C in which at least one hydrogen is substituted with a hydroxyl group. 1~4 Alkyl, C 3~5 It is epoxyalkyl, or R 2 C 1~4 Alkyl and R 4-2 C 1~4 If it is alkyl, R 4-2 and R 2 They combine to form a 4-8 membered ring. R 4-3 is C 1~4 Alkyl or C 1~4 It is an alkoxy, R 5In each appearance, hydrogen, halogen, nitro, nitrile, and -N appear independently. + (R 5-1 )3, C 1~4 Haloalkyl, -C(O)OR 5-1 , -C(O)R 5-1 ,-C(O)N(R 5-1 R 5-1a ), -S(O)2R 5-1 ,-S(O)R 5-1 -N=C(R 5-1 R 5-1a ), hydroxyl, C 1~4 Alkyl, phenyl, at least one hydrogen is R 5-1 Phenyl substituted with C 1~4 Alkoxy, -N(R 5-1 R 5-1a ), -N(R 5-1 )C(O)R 5-1a or -OC(O)R 5-1 And here, R 5-1 , R 5-1a and R 5-1b Each is independently hydrogen and C 1~4 Alkyl, C in which at least one hydrogen is substituted with a halogen. 1~4 It is alkyl.

[0221] In some preferred modes, Z is TIFF2026509562000062.tif21170 or a sulfur atom, In some preferred modes, R 1 is hydrogen, The file is TIFF2026509562000063.tif18170, where R 11 and R 12 Each of these is independently methyl, ethyl, n-propyl, or isopropyl, where n is 1.

[0222] In some preferred modes, R 2 These are hydrogen, methyl, ethyl, n-propyl, isopropyl, ethyl with one hydrogen replaced by a hydroxyl, n-propyl with one hydrogen replaced by a hydroxyl, phenyl, The filename is TIFF2026509562000064.tif32170.

[0223] In some preferred modes, R 3 teeth TIFF2026509562000065.tif19170 Here, R 3-1 is hydrogen, hydroxyl, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, sec-butoxy, or isobutoxy. m is 1, Ar is a phenyl, 5-membered or 6-membered nitrogen-containing monocyclic heteroaryl.

[0224] In some preferred modes, R 4 teeth TIFF2026509562000066.tif25170 Here, R 4-1 Phenyl, with at least one hydrogen atom R 4-11 Phenyl substituted with R, 5-membered or 6-membered monocyclic heteroaryl, at least one hydrogen atom is R 4-11 5-membered or 6-membered monocyclic heteroaryls substituted with R, 8-10 membered fused bicyclic heteroaryls, at least one hydrogen atom is R 4-11 It is an 8-10 member condensed bicyclic heteroaryl substituted with, and the R 4-11 Halogen, nitro, methyl, ethyl, n-propyl, isopropyl, TIFF2026509562000067.tif35170 Fluoromethyl, fluoroethyl, fluoro-n-propyl, fluoroisopropyl, chloromethyl, chloroethyl, chloro-n-propyl, chloroisopropyl, bromomethyl, bromoethyl, bromo-n-propyl, bromoisopropyl, iodomethyl, iodoethyl, iodo-n-propyl, iodoisopropyl, fluoromethoxy, fluoroethoxy, fluoro-n-propoxy, fluoroisopropoxy, chloromethoxy, chloroethoxy, chloro-n-propoxy, chloroisopropoxy, bromomethoxy, bromoethoxy, bromo-n-propoxy, bromoisopropoxy, iodooxymethyl, iodoethoxy, iodo-n-propoxy, iodoisopropoxy or TIFF2026509562000068.tif14170R 4-2 These include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, ethyl with one hydrogen substituted with hydroxyl, n-propyl with one hydrogen substituted with hydroxyl, and n-butyl with one hydrogen substituted with hydroxyl. TIFF2026509562000069.tif14170 or phenyl, or R 2 is methyl, ethyl, or n-propyl, and R 4-2 If R is methyl or ethyl, 4-2 and R 2 They bond to form a 4-8 membered ring, R 4-3 These are methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, or isopropoxy.

[0225] In some preferred modes, R 5 In each appearance, hydrogen, halogen, nitro, nitrile, and -N appear independently. + (R 5-1)3, fluoromethyl, fluoroethyl, fluoro-n-propyl, fluoroisopropyl, chloromethyl, chloroethyl, chloro-n-propyl, chloroisopropyl, bromomethyl, bromoethyl, bromo-n-propyl, bromoisopropyl, -C(O)OR 5-1 , -C(O)R 5-1 ,-C(O)N(R 5-1 R 5-1a ), -S(O)2R 5-1 ,-S(O)R 5-1 -N=C(R 5-1 R 5-1a ), hydroxyl, methyl, ethyl, n-propyl, isopropyl, phenyl, at least one hydrogen R 5-1 Phenyl, methoxy, ethoxy, n-propoxy, isopropoxy, -N(R) substituted 5-1 R 5-1a ), -N(R 5-1 )C(O)R 5-1a -OC(O)R 5-1 And here, R 5-1 , R 5-1a and R 5-1b Each of these is independently hydrogen, methyl, ethyl, n-propyl, isopropyl, fluoromethyl, fluoroethyl, fluoro-n-propyl, fluoroisopropyl, chloromethyl, chloroethyl, chloro-n-propyl, chloroisopropyl, bromomethyl, bromoethyl, bromo-n-propyl, or bromoisopropyl.

[0226] In some preferred modes, R 1 is hydrogen, The filename is TIFF2026509562000070.tif16170.

[0227] In some preferred modes, R 2 is hydrogen, methyl, TIFF2026509562000071.tif16170 or phenyl.

[0228] In some preferred modes, R 3 teeth The filename is TIFF2026509562000072.tif16170.

[0229] In some preferred modes, R 4 teeth TIFF2026509562000073.tif25170 Here, R 4-1 Phenyl, with at least one hydrogen atom R 4-11 Phenyl substituted with R, a 5-membered monocyclic heteroaryl, at least one hydrogen is R 4-11 A 5-membered monocyclic heteroaryl, a 9-membered condensed bicyclic heteroaryl, or naphthyl substituted with, where R 4-11 bromine, fluorine, chlorine, methyl, nitro, phenyl, trifluoromethyl, TIFF2026509562000074.tif14170 Methoxy, cyclopropyl, trifluoromethoxy, nitro or TIFF2026509562000075.tif13170R 4-2 is methyl, ethyl, TIFF2026509562000076.tif16170 or phenyl, or R 2 is methyl, ethyl, or n-propyl, and R 4-2 If R is methyl or ethyl, 4-2 and R 2 They combine to form a 4-6 membered ring. R 4-3 These are methoxy, ethoxy, n-propoxy, or isopropoxy.

[0230] In some preferred modes, R 5 In each occurrence, these are independently halogen, nitro, nitrile, carboxyl, -NHC(O)H, methoxy, or hydroxyl.

[0231] In some preferred modes, C 1~6 Alkyl is C 1~4 Alkyl, and the C 1~4The alkyl group is preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, or tert-butyl, for example, methyl or ethyl.

[0232] In several preferred embodiments, the 3-6 membered cycloalkyl is preferably C 3~5 It is a cycloalkyl, and the C 3~5 Cycloalkyls are preferably TIFF2026509562000077.tif14170

[0233] In some preferred embodiments, the 3-6 member epoxyalkyl is preferably The filename is TIFF2026509562000078.tif16170.

[0234] In some preferred modes, C 1~6 Alkyl-substituted phenyl is preferably C 1~4 The phenyl is alkyl-substituted, and more preferably phenyl substituted with methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, or tert-butyl.

[0235] In some preferred modes, C 1~6 The alkoxy is preferably C 1~4 The alkoxy is, more preferably, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, sec-butoxy, or isobutoxy.

[0236] In some preferred modes, -N(R 3-2 R 3-2a ), -N(R 3-3a R 3-3b ), -N(R 4-1a R 4-1b ), -N(R 5-1 R 5-1a ) is preferable The filename is TIFF2026509562000079.tif42170.

[0237] In some preferred embodiments, the 5-membered or 6-membered monocyclic heteroaryl is preferably TIFF2026509562000080.tif21170, where Y1, Y2, Y3, Y4, Y5, Y6, Y7, Y8, Y9 are each independently selected from C, N, O, or S, and Y1, Y2, Y3, Y4 are all not C, and Y5, Y6, Y7, Y8, Y9 are all not C, and the 5-membered or 6-membered monocyclic heteroaryl is more preferably pyrrolyl, furyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl, pyranyl, thiopyranil, pyridadinyl, pyrimidinyl, pyrazinyl, piperazinyl, triazolyl, tetrazolyl, and the 5-membered or 6-membered monocyclic heteroaryl is more preferably TIFF2026509562000081.tif128170, and more preferably, the 5-membered or 6-membered monocyclic heteroaryl is a 5-membered or 6-membered nitrogen-containing monocyclic heteroaryl, for example: TIFF2026509562000082.tif40170, and most preferably, the 5-membered or 6-membered monocyclic heteroaryl is a 5-membered nitrogen-containing monocyclic heteroaryl, for example: The filename is TIFF2026509562000083.tif18170.

[0238] In several preferred embodiments, the 8-10 membered condensed bicyclic heteroaryl is TIFF2026509562000084.tif63170, where Y 11 , Y 12 , Y 13 , Y 14 , Y 15 , Y 16 , Y 17 , Y 18 and Y 19 Each is independently selected from C, N, O, or S, and Y 11 , Y 12 , Y 13 , Y 14 , Y 15 , Y 16 , Y17 , Y 18 and Y 19 All are Y, not C. 21 , Y 22 , Y 23 , Y 24 , Y 25 and Y 26 Each is independently selected from C, N, O, or S, and Y 21 , Y 22 , Y 23 , Y 24 , Y 25 and Y 26 All are Y, not C. 31 , Y 32 , Y 33 , Y 34 , Y 35 , Y 36 and Y 37 Each is independently selected from C, N, O, or S, and Y 31 , Y 32 , Y 33 , Y 34 , Y 35 , Y 36 and Y 37 Not all are carbon, and the 8-10 membered condensed bicyclic heteroaryl is more preferably indolyl, benzindolyl, benzothienyl, carbazolyl, quinolyl, pteridinyl, and prinyl, and the 8-10 membered condensed bicyclic heteroaryl is most preferably The filename is TIFF2026509562000085.tif23170.

[0239] In some preferred embodiments, the halogen is preferably fluorine, chlorine, bromine, or iodine.

[0240] In some preferred modes, C 1~6 Haloalkyl is preferably C 1~3The material is a haloalkyl, more preferably fluoromethyl, fluoroethyl, fluoro-n-propyl, fluoroisopropyl, chloromethyl, chloroethyl, chloro-n-propyl, chloroisopropyl, bromomethyl, bromoethyl, bromo-n-propyl, bromoisopropyl, iodomethyl, iodoethyl, iodo-n-propyl, iodoisopropyl, and most preferably trifluoromethyl.

[0241] In some preferred modes, C 1~6 Haloalkoxy is preferably C 1~3 The haloalkoxy is more preferably fluoromethoxy, fluoroethoxy, fluoro-n-propoxy, fluoroisopropoxy, chloromethoxy, chloroethoxy, chloro-n-propoxy, chloroisopropoxy, bromomethoxy, bromoethoxy, bromo-n-propoxy, bromoisopropoxy, iodooxymethyl, iodoethoxy, iodo-n-propoxy, iodoisopropoxy, and most preferably trifluoromethoxy.

[0242] In some preferred modes, C 2~6 Alkenyl is preferably C 2~4 It is an alkenyl, and in the field, -CH=CH2, -CH=CH-CH3, -CH2-CH=CH2, -CH=CH-CH2-CH3, and -CH=CH-CH=CH2.

[0243] In some preferred modes, C 2~6 Alkinyl is preferably C 2~6 It is an alkynyl, and more preferably -C≡CH, -CH2-C≡CH, -CH2-CH2-C≡CH, or -CH2-C≡C-CH3.

[0244] Based on the beneficial effects of improving the metabolic stability of the compound and reducing its toxicity, in a preferred embodiment, Z is not a sulfur atom.

[0245] In a preferred embodiment of the present invention, in a compound represented by general formula (I), Z is TIFF2026509562000086.tif18170, R 1 is hydrogen, R 2 is hydrogen, and R 3 is hydrogen The filename is TIFF2026509562000087.tif20170, and R 4 teeth, The filename is TIFF2026509562000088.tif20170, where R 3-1 R is hydrogen, hydroxyl, 4-1 Phenyl, with at least one hydrogen atom R 4-11 A phenyl substituted with R 4-11 These are halogen-substituted methyl, halogen-substituted ethyl, methyl, ethyl, or halogen.

[0246] In some preferred embodiments, in the compound represented by the general formula I, Z is, TIFF2026509562000089.tif18170, R 1 is hydrogen, and R 2 is hydrogen, and R 3 is hydrogen The filename is TIFF2026509562000090.tif20170, and R 4 teeth The filename is TIFF2026509562000091.tif20170, where R 3-1 is hydroxyl, and R 4-1 These are phenyl, phenyl in which at least one hydrogen atom is substituted with trifluoromethyl, and phenyl in which at least one hydrogen atom is substituted with a halogen.

[0247] In a particularly preferred embodiment of the present invention, compound I-1 (also known as TJ01-013 or TJ0113) has the structure shown in the following formula. Through extensive experimental studies, the inventors have found that compound I-1 exhibits superior therapeutic effects compared to other compounds summarized by general formula (I) in its application to the prevention and / or treatment of at least one disease selected from premature ovarian failure, ovarian dysfunction, systemic lupus erythematosus nephritis, sarcopenia, liver damage, oligospermia, rheumatoid arthritis, cataracts, Cushing's syndrome, Hashimoto's thyroiditis, chronic obstructive pulmonary disease, tinnitus, psoriasis, chronic eczema, and age-related macular degeneration, and that it shows a dose-dependent effect in improving indicators of these diseases.

[0248] TIFF2026509562000092.tif41170

[0249] It should be understood that derivatives of the compound represented by general formula (I) of the present invention have similar uses to the compound represented by general formula (I) and can be used for the prevention and / or treatment of at least one disease selected from premature ovarian failure, ovarian dysfunction, systemic lupus erythematosus nephritis, sarcopenia, liver damage, oligospermia, rheumatoid arthritis, cataracts, Cushing's syndrome, Hashimoto's disease, chronic obstructive pulmonary disease, tinnitus, psoriasis, chronic eczema, and age-related macular degeneration. In this specification, the term “derivative of a compound” refers to a pharmaceutically usable salt, stereoisomer, solvate, or prodrug of a compound, which may be modified for factors such as improved formulation convenience or solubility, but without altering the parental ring structure or basic function of the compound.

[0250] In the present invention, the compound represented by general formula I can be prepared by the method described in Chinese Patent Application No. 202111108417.6, the details of which are incorporated herein by reference.

[0251] In this specification, “pharmaceutically usable salt” and “pharmaceutically acceptable salt” may be used interchangeably, and in specific cases, a pharmaceutically acceptable salt is obtained by reacting a compound described herein with an acid or a base. The term “pharmaceutically acceptable salt” may also refer to a pharmaceutically acceptable addition salt formed by reacting a compound having an acidic group with a base, or by other previously specified methods. A pharmaceutically acceptable salt is not particularly limited as long as it is usable for pharmaceutical purposes. Examples of salts formed by the compounds described herein with bases include salts with inorganic bases such as sodium, potassium, magnesium, calcium, and aluminum; salts with organic bases such as methylamine, ethylamine, and ethanolamine; salts with dicyclohexylamine, N-methyl-D-glucamine, or tris(hydroxymethyl)methylamine; salts with basic amino acids such as lysine and ornithine; and ammonium salts. The aforementioned salts may be acid addition salts, and specifically include salts with inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, and phosphoric acid; organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, methanesulfonic acid, and ethanesulfonic acid; and acidic amino acids such as aspartic acid and glutamic acid.

[0252] It should be understood that the compounds represented by general formula (I) of the present invention or their derivatives can be mixed with pharmaceutically acceptable excipients to form pharmaceutical compositions. These pharmaceutical compositions have similar uses to the compounds represented by general formula (I) and may be applied to the prevention and / or treatment of at least one disease selected from premature ovarian failure, ovarian dysfunction, systemic lupus erythematosus nephritis, sarcopenia, liver damage, oligospermia, rheumatoid arthritis, cataracts, Cushing's syndrome, Hashimoto's disease, chronic obstructive pulmonary disease, tinnitus, psoriasis, chronic eczema, and age-related macular degeneration.

[0253] In this specification, the terms “excipient” or “pharmaceutically acceptable excipient” refer to pharmaceutically acceptable materials, compositions, or media, such as liquid or solid fillers, diluents, carriers, solvents, or encapsulating materials. In certain embodiments, each component is “pharmaceutically acceptable” in the sense that it is compatible with other components of a pharmaceutical formulation and is suitable for use in contact with human and animal tissues or organs without causing excessive toxicity, irritation, allergic reactions, immunogenicity, or other problems or complications commensurate with a reasonable benefit / risk ratio. Unless otherwise specified, pharmaceutical compositions according to the present invention are prepared by methods known in themselves, e.g., conventional mixing, granulation, coating, dissolution, or freeze-drying processes. When preparing compositions for oral dosage forms, commonly used pharmaceutical media such as water, glycol, oil, and ethanol; carriers such as starch, sugar, or microcrystalline cellulose; diluents, granulators, lubricants, binders, disintegrants, etc. are used. Tablets and capsules are the most advantageous oral unit dosage forms because they are easy to administer, and it is obvious that solid pharmaceutical carriers are used.

[0254] Treatment method The present invention also relates to a method for preventing and / or treating premature ovarian failure, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0255] In this invention, the term "premature ovarian failure (POF)" refers to menopausal symptoms occurring before the age of 40 due to ovarian failure. Its characteristics include primary or secondary menopause accompanied by elevated blood gonadotropin levels and decreased estrogen levels, as well as varying degrees of hypoestrogen symptoms. Preferably, premature ovarian failure is chemotherapy-induced premature ovarian failure.

[0256] As a method for treating premature ovarian failure, the method of administration of the compound represented by general formula (I) of the present invention is not particularly limited, and is preferably suitable for oral or enteral administration such as rectal administration, or parenteral administration such as intramuscular, intravenous, nasal, or transdermal administration. In a preferred embodiment, the compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof is administered orally to the subject.

[0257] The dosage of the compound represented by the general formula (I) of the present invention administered as a treatment for premature ovarian failure is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dose. The term "therapeutically effective dose" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In the present invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0258] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 30 mg / kg. In a preferred embodiment, when the subject is a human, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 30 mg / kg.

[0259] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for premature ovarian failure, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least three consecutive days (preferably at least five days, more preferably at least seven days, more preferably at least ten days, more preferably at least twelve days, more preferably at least fourteen days).

[0260] In a preferred embodiment, as a treatment method for premature ovarian failure, a therapeutically effective dose of I-14-1 is administered to the subject.

[0261] In a preferred embodiment, as a treatment method for premature ovarian failure, a therapeutically effective dose of I-1 is administered to the subject (TJ01-013). Compared with other compounds of the present invention, administration of compound I-1 to the test subject significantly increases ovarian weight, ovarian index, and BDNF levels in ovarian tissue, and significantly improves ovarian function.

[0262] The present invention also relates to a method for preventing and / or treating ovarian dysfunction, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0263] In this invention, the term "ovarian dysfunction" refers to a decline in ovarian function in women under 40 years of age, typically exhibiting symptoms of menstrual irregularities and anovulation. Preferably, the ovarian dysfunction is due to natural aging.

[0264] As a method for treating ovarian dysfunction, the method of administration of the compound represented by general formula (I) of the present invention is not particularly limited, and is preferably suitable for oral or enteral administration such as rectal administration, or parenteral administration such as intramuscular, intravenous, nasal, or transdermal administration. In a preferred embodiment, the compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof is administered orally to a subject.

[0265] The dosage of the compound represented by the general formula (I) of this invention administered as a treatment for ovarian dysfunction is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dose. The term "therapeutically effective dose" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In this invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0266] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 30 mg / kg. In a preferred embodiment, when the subject is a human, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 30 mg / kg.

[0267] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for ovarian dysfunction, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least three consecutive days (preferably at least five days, more preferably at least seven days, more preferably at least ten days, more preferably at least twenty days, more preferably at least thirty days).

[0268] In a preferred embodiment, as a method for treating ovarian dysfunction, a therapeutically effective dose of I-14-1 is administered to the subject.

[0269] In a preferred embodiment, as a treatment method for ovarian dysfunction, a therapeutically effective dose of I-1 is administered to the subject (TJ01-013). Compared with other compounds of the present invention, administration of compound I-1 to the test subject significantly increases ovarian weight, ovarian index, and the patient's serum E2 and FSH levels, and significantly improves ovarian function.

[0270] The present invention also relates to a method for preventing and / or treating systemic lupus erythematosus nephritis, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0271] In this invention, the terms "systemic lupus erythematosus nephritis" and "lupus nephritis" can be used interchangeably and refer to a disease in which systemic lupus erythematosus (SLE) is complicated by different types of pathological immune disorders in both kidneys, accompanied by clear clinical symptoms of renal impairment.

[0272] As a method for treating systemic lupus erythematosus nephritis, the method of administration of the compound represented by general formula (I) of the present invention is not particularly limited, and is preferably suitable for oral or enteral administration such as rectal administration, or parenteral administration such as intramuscular, intravenous, nasal, or transdermal administration. In a preferred embodiment, the compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof is administered orally to a subject.

[0273] The dosage of the compound represented by general formula (I) of the present invention administered as a treatment for systemic lupus erythematosus nephritis is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dose. The term "therapeutically effective dose" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In the present invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0274] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 30 mg / kg. When the subject is a human, in a preferred embodiment, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 10 mg / kg or 30 mg / kg.

[0275] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for systemic lupus erythematosus nephritis, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least three consecutive days (preferably at least one day, more preferably at least seven days, more preferably at least 14 days, more preferably at least 21 days, more preferably at least 28 days, more preferably at least 35 days, more preferably at least 42 days, more preferably at least 49 days, more preferably at least 56 days, more preferably at least 63 days, more preferably at least 70 days).

[0276] In a preferred embodiment, as a treatment method for systemic lupus erythematosus nephritis, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared with other compounds of the present invention, when compound I-1 is administered to the subject, the occurrence of proteinuria is significantly reduced, creatinine and urea nitrogen levels are significantly lowered, inflammatory factor levels in renal tissue are significantly lowered, levels of specific antibodies against systemic lupus erythematosus are significantly lowered, and renal function is significantly alleviated.

[0277] The present invention also relates to a method for preventing and / or treating sarcopenia, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0278] In this invention, the term "sarcopenia" refers to a syndrome characterized by age-related decrease in skeletal muscle mass, muscle strength, and muscle function. Sarcopenia is an early clinical symptom of frailty syndrome.

[0279] As a method for treating sarcopenia, the method of administration of the compound represented by general formula (I) of the present invention is not particularly limited, and is preferably suitable for oral or enteral administration such as rectal administration, or parenteral administration such as intramuscular, intravenous, nasal, or transdermal administration. In a preferred embodiment, the compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof is administered orally to a subject.

[0280] The dosage of the compound represented by the general formula (I) of this invention administered as a treatment for sarcopenia is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dosage. The term "therapeutically effective dosage" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In this invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0281] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 30 mg / kg. When the subject is a human, in a preferred embodiment, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 10 mg / kg or 30 mg / kg.

[0282] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for sarcopenia, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least three consecutive days (preferably at least five days, more preferably at least seven days, more preferably at least ten days, more preferably at least twenty days, more preferably at least thirty days).

[0283] In a preferred embodiment, as a method for treating sarcopenia, a therapeutically effective amount of compound I-14-1 is administered to the subject.

[0284] In a preferred embodiment, as a treatment method for sarcopenia, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared with other compounds of the present invention, when compound I-1 is administered to the subject, it can significantly improve muscle strength, significantly increase calf muscle weight, and significantly alleviate the symptoms of muscular atrophy.

[0285] The present invention also relates to a method for preventing and / or treating liver damage, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0286] In the present invention, the term "liver injury" refers to a condition in which there is a certain degree of functional decline or damage to the liver due to external stimuli, internal inflammation, or genetic factors. Preferably, the liver injury is selected from at least one of acute alcoholic liver injury, chronic alcoholic liver injury, drug-induced liver injury, non-alcoholic fatty liver disease, and liver injury due to cholecystitis.

[0287] As a method for treating liver damage, the administration method of the compound represented by general formula (I) of the present invention is not particularly limited, and is preferably suitable for oral or enteral administration such as rectal administration, or parenteral administration such as intramuscular, intravenous, nasal, or transdermal administration. In a preferred embodiment, the compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug is administered orally to a subject.

[0288] The dosage of the compound represented by the general formula (I) of the present invention administered as a treatment for liver damage is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dosage. The term "therapeutically effective dosage" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In the present invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0289] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg, for example 10 mg / kg, of the compound represented by the general formula (I) of the present invention. In a preferred embodiment, when the subject is a human, the subject is administered 1 to 200 mg / kg, for example 10 mg / kg, of the compound represented by the general formula (I) of the present invention.

[0290] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for liver damage, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least three consecutive days (preferably at least five days, more preferably at least seven days).

[0291] In a preferred embodiment, as a treatment method for liver damage, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared with other compounds of the present invention, when compound I-1 is administered to the test subject, it can significantly reduce the levels of liver function indicators such as AST, ALT, TG, and TC, and significantly improve liver function.

[0292] The present invention also relates to a method for preventing and / or treating oligospermia, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0293] In this invention, the term "oligospermia" refers to a condition in which the number of sperm in the semen is less than the number of sperm in a normal, healthy, and fertile man.

[0294] As a method for treating oligospermia, the method of administration of the compound represented by general formula (I) of the present invention is not particularly limited, and is preferably suitable for oral or enteral administration such as rectal administration, or parenteral administration such as intramuscular, intravenous, nasal, or transdermal administration. In a preferred embodiment, the compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug is administered orally to a subject.

[0295] The dosage of the compound represented by the general formula (I) of the present invention administered as a treatment for oligospermia is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dose. The term "therapeutically effective dose" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In the present invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0296] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 30 mg / kg. When the subject is a human, in a preferred embodiment, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 10 mg / kg or 30 mg / kg.

[0297] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for oligospermia, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least three consecutive days (preferably at least five days, more preferably at least seven days, more preferably at least ten days, more preferably at least twenty days, more preferably at least thirty days).

[0298] In a preferred embodiment, as a treatment method for oligospermia, a therapeutically effective dose of I-14-1 is administered to the subject.

[0299] In a preferred embodiment, as a treatment method for oligospermia, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared with other compounds of the present invention, when compound I-1 is administered to the test subject, it significantly increases the levels of sex hormones in the body, the testicular organ index, and the sperm count in the semen, and can greatly improve the symptoms of oligospermia.

[0300] The present invention also relates to a method for preventing and / or treating rheumatoid arthritis, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0301] In this invention, the term "rheumatoid arthritis (RA)" refers to a chronic systemic autoimmune disease. This disease primarily affects the joints throughout the body, manifesting as multiple, symmetrical, diffuse proliferative synovitis, causing destruction of articular cartilage and joint capsules, ultimately leading to joint ankylosis and deformity.

[0302] As a method of treating rheumatoid arthritis, the method of administration of the compound represented by general formula (I) of the present invention is not particularly limited, and is preferably suitable for oral or enteral administration such as rectal administration, or parenteral administration such as intramuscular, intravenous, nasal, or transdermal administration. In a preferred embodiment, the compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof is administered orally to a subject.

[0303] The dosage of the compound represented by the general formula (I) of the present invention administered as a treatment for rheumatoid arthritis is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dose. The term "therapeutically effective dose" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In the present invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0304] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 30 mg / kg. In a preferred embodiment, when the subject is a human, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 30 mg / kg.

[0305] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for rheumatoid arthritis, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least three consecutive days (preferably at least five days, more preferably at least seven days, more preferably at least ten days, and more preferably at least fourteen days).

[0306] In a preferred embodiment, as a treatment method for rheumatoid arthritis, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared with other compounds of the present invention and dexamethasone, administration of compound I-1 to the subject can reduce joint swelling, decrease the thickness of the hind plantar wall, and improve the symptoms of rheumatoid arthritis.

[0307] The present invention also relates to a method for preventing and / or treating cataracts, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0308] In this invention, the term "cataract" refers to a disease caused by damage to the lens capsule due to aging, genetics, metabolic disorders, trauma, radiation, poisoning, localized malnutrition, etc., resulting in increased permeability of the lens capsule, loss of barrier function, or inhibition of lens metabolism, denaturation of lens proteins, and clouding.

[0309] As a method for treating cataracts, the method of administration of the compound represented by general formula (I) of the present invention is not particularly limited, and is preferably suitable for oral or enteral administration such as rectal administration, or parenteral administration such as intramuscular, intravenous, nasal, or transdermal administration. In a preferred embodiment, the compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug is administered orally to a subject.

[0310] The dosage of the compound represented by the general formula (I) of the present invention administered as a treatment for cataracts is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dosage. The term "therapeutically effective dosage" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In the present invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0311] In a preferred embodiment, when the subject is a mouse, the subject is administered 0.1 to 200 mg / kg, for example 1 mg / kg, of the compound represented by the general formula (I) of the present invention. In a preferred embodiment, when the subject is a human, the subject is administered 0.1 to 200 mg / kg, for example 1 mg / kg, of the compound represented by the general formula (I) of the present invention.

[0312] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for cataracts, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least three consecutive days (preferably at least five days, more preferably at least seven days, and more preferably at least ten days).

[0313] In a preferred embodiment of the treatment method for cataracts, a therapeutically effective dose of I-14-1 is administered to the subject.

[0314] In a preferred embodiment, as a treatment method for cataracts, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared with other compounds of the present invention, when compound I-1 is administered to the test subject, lens opacity is significantly improved and cataract symptoms are significantly improved.

[0315] The present invention also relates to a method for preventing and / or treating Cushing's syndrome, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0316] In this invention, the term "Cushing's syndrome" refers to a series of symptoms caused by excessive secretion of glucocorticoids (mainly cortisol) from the adrenal cortex due to various causes. In the elderly, it is usually caused by long-term use of glucocorticoids. Cortisol hypertension due to adrenocortical carcinoma and ectopic ACTH syndrome is more common in the elderly than in younger individuals.

[0317] As a method for treating Cushing's syndrome, the method of administration of the compound represented by general formula (I) of the present invention is not particularly limited, and is preferably suitable for oral or enteral administration such as rectal administration, or parenteral administration such as intramuscular, intravenous, nasal, or transdermal administration. In a preferred embodiment, the compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug is administered orally to the subject.

[0318] The dosage of the compound represented by the general formula (I) of this invention administered as a treatment for Cushing's syndrome is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dosage. The term "therapeutically effective dosage" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In this invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0319] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg, for example 15 mg / kg, of the compound represented by the general formula (I) of the present invention. In a preferred embodiment, when the subject is a human, the subject is administered 1 to 200 mg / kg, for example 15 mg / kg, of the compound represented by the general formula (I) of the present invention.

[0320] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for Cushing's syndrome, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least three consecutive days (preferably at least five days, more preferably at least seven days, more preferably at least ten days, and more preferably at least fourteen days).

[0321] In a preferred embodiment, as a treatment method for Cushing's syndrome, a therapeutically effective dose of I-14-1 is administered to the subject.

[0322] In a preferred embodiment, as a treatment method for Cushing's syndrome, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared with other compounds of the present invention, when compound I-1 is administered to the test subject, plasma insulin levels are significantly reduced and the symptoms of Cushing's syndrome are significantly improved.

[0323] The present invention also relates to a method for preventing and / or treating Hashimoto's disease, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0324] In this invention, the term "Hashimoto's thyroiditis" refers to an abnormality in the body's immune function that produces autoantibodies against antigenic components (such as thyroglobulin, mitochondria, and peroxidase) of thyroid follicular epithelial cells, causing damage and dysfunction of thyroid tissue cells.

[0325] As a method of treating Hashimoto's disease, the method of administration of the compound represented by general formula (I) of the present invention is not particularly limited, and is preferably suitable for oral or enteral administration such as rectal administration, or parenteral administration such as intramuscular, intravenous, nasal, or transdermal administration. In a preferred embodiment, the compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug is administered orally to the subject.

[0326] The dosage of the compound represented by the general formula (I) of the present invention administered as a treatment for Hashimoto's disease is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dosage. The term "therapeutically effective dosage" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In the present invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0327] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 15 mg / kg. When the subject is a human, in a preferred embodiment, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 15 mg / kg or 30 mg / kg.

[0328] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment method for Hashimoto's disease, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least three consecutive days (preferably at least five days, more preferably at least seven days, more preferably at least ten days, and more preferably at least fourteen days).

[0329] In a preferred embodiment, as a treatment method for Hashimoto's disease, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared with other compounds of the present invention, when compound I-1 is administered to the test subject, the level of the Hashimoto's disease diagnostic marker TPO-Ab is significantly reduced, and the symptoms of Hashimoto's disease can be significantly improved.

[0330] The present invention also relates to a method for preventing and / or treating chronic obstructive pulmonary disease, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0331] In this invention, the term "chronic obstructive pulmonary disease (COPD)" is a general term for chronic airway obstruction diseases, mainly referring to chronic bronchitis and emphysema with irreversible airway obstruction, and is inherited through multiple genes. The onset is gradual, the disease is long-lasting, and the main symptoms include chronic cough, sputum, shortness of breath, respiratory distress, wheezing, and chest tightness.

[0332] As a method for treating chronic obstructive pulmonary disease, the method of administration of the compound represented by general formula (I) of the present invention is not particularly limited, and is preferably suitable for oral or enteral administration such as rectal administration, or parenteral administration such as intramuscular, intravenous, nasal, or transdermal administration. In a preferred embodiment, the compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof is administered orally to a subject.

[0333] The dosage of the compound represented by the general formula (I) of the present invention administered as a treatment for chronic obstructive pulmonary disease is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dose. The term "therapeutically effective dose" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In the present invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0334] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 7.5 mg / kg, 15 mg / kg, or 30 mg / kg. In a preferred embodiment, when the subject is a human, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 7.5 mg / kg, 15 mg / kg, or 30 mg / kg.

[0335] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for chronic obstructive pulmonary disease, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least three consecutive days (preferably at least five days, more preferably at least seven days, more preferably at least fourteen days, and more preferably at least 21 days).

[0336] In a preferred embodiment, as a treatment method for chronic obstructive pulmonary disease, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared with other compounds of the present invention, when compound I-1 is administered to the subject, it significantly reduces the levels of the inflammatory factor TNFα in the body and the increase in inflammatory indicators due to chronic obstructive pulmonary disease, and significantly alleviates the symptoms of chronic obstructive pulmonary disease.

[0337] The present invention also relates to a method for preventing and / or treating tinnitus, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0338] In this invention, the term "tinnitus" refers to a condition in which a subjective sound is heard in the absence of auditory stimulation. This is caused by pathological stimulation of auditory receptors and their conduction pathways or lesions of the auditory center.

[0339] As a method for treating tinnitus, the method of administration of the compound represented by general formula (I) of the present invention is not particularly limited, and is preferably suitable for oral or enteral administration such as rectal administration, or parenteral administration such as intramuscular, intravenous, nasal, or transdermal administration. In a preferred embodiment, the compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof is administered orally to the subject.

[0340] The dosage of the compound represented by the general formula (I) of this invention administered as a treatment for tinnitus is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dose. The term "therapeutically effective dose" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In this invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0341] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 7.5 mg / kg, 15 mg / kg, or 30 mg / kg. In a preferred embodiment, when the subject is a human, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 7.5 mg / kg, 15 mg / kg, or 30 mg / kg.

[0342] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for tinnitus, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least two consecutive days (preferably at least three days, more preferably at least four days).

[0343] In a preferred embodiment, as a treatment method for tinnitus, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared with other compounds of the present invention, when compound I-1 is administered to the test subject, the range of the patient's tinnitus response can be significantly reduced.

[0344] The present invention also relates to a method for preventing and / or treating psoriasis, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0345] In this invention, the term "psoriasis" refers to a disease caused by multiple genetic defects. It can be triggered by various factors, such as trauma, infection, and medication. Typical skin lesions are well-defined erythematous patches covered with silvery-white scales. When the scales are scraped, a glossy membrane is revealed, and when the membrane is broken, petechial hemorrhages occur. Psoriasis often occurs on the extensor surfaces of the limbs and the lumbar region, and in severe cases, it can affect the entire body and joints. Preferably, the psoriasis is imiquimod cream-induced psoriasis.

[0346] As a method for treating psoriasis, the method of administration of the compound represented by general formula (I) of the present invention is not particularly limited, and is preferably suitable for oral or enteral administration such as rectal administration, or parenteral administration such as intramuscular, intravenous, nasal, or transdermal administration. In a preferred embodiment, the compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof is administered orally to a subject.

[0347] The dosage of the compound represented by the general formula (I) of the present invention administered as a treatment for psoriasis is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dosage. The term "therapeutically effective dosage" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In the present invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0348] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 7.5 mg / kg, 15 mg / kg, or 30 mg / kg. In a preferred embodiment, when the subject is a human, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 7.5 mg / kg, 15 mg / kg, or 30 mg / kg.

[0349] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for psoriasis, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least three consecutive days (preferably at least five days, more preferably at least seven days, and more preferably at least ten days).

[0350] In a preferred embodiment, as a treatment method for psoriasis, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared with other compounds of the present invention, when compound I-1 is administered to the test subject, it can alleviate the symptoms of parakeratosis and epidermal thickening in the patient. The present invention also relates to a method for preventing and / or treating chronic eczema, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0351] In this invention, the terms "chronic eczema" and "eczema" can be used interchangeably, referring to inflammation of the superficial dermis and epidermis, often caused by various internal and external factors, and accompanied by exudative secretion. The etiology is complex and is generally thought to be related to allergic reactions. Clinically, it is a type of chronic disease characterized by symmetrically distributed pleomorphic lesions, severe itching, erythema, and moist, clustered papules, and is prone to recurrence.

[0352] As a method for treating chronic eczema, the method of administration of the compound represented by general formula (I) of the present invention is not particularly limited, and is preferably suitable for oral or enteral administration such as rectal administration, or parenteral administration such as intramuscular, intravenous, nasal, or transdermal administration. In a preferred embodiment, the compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof is administered orally to a subject.

[0353] The dosage of the compound represented by the general formula (I) of the present invention administered as a treatment for chronic eczema is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dosage. The term "therapeutically effective dosage" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In the present invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0354] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 7.5 mg / kg, 15 mg / kg, or 30 mg / kg. In a preferred embodiment, when the subject is a human, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 7.5 mg / kg, 15 mg / kg, or 30 mg / kg.

[0355] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a method for treating chronic eczema, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least three consecutive days (preferably at least five days, more preferably at least seven days, more preferably at least ten days, more preferably at least twelve days, more preferably at least fourteen days).

[0356] In a preferred embodiment, as a treatment method for chronic eczema, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared with other compounds of the present invention, when compound I-1 is administered to the test subject, it can increase the water content of the stratum corneum, reduce water loss, and alleviate eczema symptoms.

[0357] The present invention also relates to a method for preventing and / or treating age-related macular degeneration, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0358] In this invention, the term "age-related macular degeneration (ARMD)" refers to age-related structural changes in the macula. The main symptom is a decrease in the ability of retinal pigment epithelial cells to phagocytose and digest the outer membrane of photoreceptor cells. As a result, incompletely digested membrane residues accumulate in the cytoplasm of basal cells. These residues are then expelled from the cells and deposited in Bruch's membrane, forming drusen (more prominent in the macula), leading to macular degeneration. Early symptoms often include decreased visual acuity, while later symptoms include decreased central visual acuity (scotoma in the center of the visual field), blurred vision, and, in severe cases, blindness.

[0359] As a method for treating age-related macular degeneration, the method of administration of the compound represented by general formula (I) of the present invention is not particularly limited, and is preferably suitable for oral or enteral administration such as rectal administration, or parenteral administration such as intramuscular, intravenous, nasal, or transdermal administration. In a preferred embodiment, the compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof is administered orally to a subject.

[0360] The dosage of the compound represented by the general formula (I) of this invention administered as a treatment for age-related macular degeneration is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dose. The term "therapeutically effective dose" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In this invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0361] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 7.5 mg / kg, 15 mg / kg, or 30 mg / kg. In a preferred embodiment, when the subject is a human, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 7.5 mg / kg, 15 mg / kg, or 30 mg / kg.

[0362] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for age-related macular degeneration, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least three consecutive days (preferably at least five days, more preferably at least seven days, more preferably at least ten days, more preferably at least twelve days, more preferably at least fourteen days).

[0363] In a preferred embodiment, as a treatment method for age-related macular degeneration, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared with other compounds of the present invention, when compound I-1 is administered to the test subject, it significantly improves retinal photosensitivity and can restore normal retinal structure.

[0364] The present invention also relates to a method for preventing and / or treating retinitis pigmentosa, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0365] In this invention, the term "Retinal Pigmentosa (RP)" refers to a progressive hereditary retinal degeneration, the main clinical symptoms of which are night blindness and progressive visual field constriction that develop in childhood, with a global prevalence of approximately 1 / 3000 to 1 / 7000. Its pathological mechanism is thought to be progressive photoreceptor apoptosis due to primary genetic defects or secondary degeneration of retinal pigment epithelial cells. Currently, there is no established effective treatment for RP. Research suggests that RP is a chronic inflammatory disease, and that inflammatory factors and immunomodulatory processes play a significant role in disease progression. Over the past several decades, researchers have proposed various strategies for treating RP, including neurotrophic factors, herbal medicine, visual prostheses, and gene therapy, but none of these strategies have been satisfactory, and a clearly effective treatment has yet to be established.

[0366] The dosage of the compound represented by the general formula (I) of this invention administered as a treatment for retinitis pigmentosa is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dosage. The term "therapeutically effective dosage" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In this invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0367] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 30 mg / kg. When the subject is a human, in a preferred embodiment, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 1 mg / kg, 2.5 mg / kg, or 5 mg / kg.

[0368] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for retinitis pigmentosa, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least one week (preferably at least three weeks, more preferably at least eight weeks) consecutively.

[0369] In a preferred embodiment of the treatment method for retinitis pigmentosa, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared with other compounds of the present invention, when compound I-1 is administered to the test subject, it can significantly reduce the density of microglia in the posterior retina and significantly increase the thickness of the photosensitive cell layer.

[0370] The present invention also relates to a method for preventing and / or treating multiple sclerosis, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0371] The dosage of the compound represented by the general formula (I) of the present invention administered as a treatment for multiple sclerosis is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dosage. The term "therapeutically effective dosage" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In the present invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0372] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 30 mg / kg. When the subject is a human, in a preferred embodiment, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 1 mg / kg, 2.5 mg / kg, or 5 mg / kg.

[0373] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment method for multiple sclerosis, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least 7 consecutive days (preferably at least 14 days, more preferably at least 21 days, more preferably at least 35 days, more preferably at least 49 days, and more preferably at least 84 days).

[0374] In a preferred embodiment, as a treatment method for multiple sclerosis, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared to other compounds of the present invention, when compound I-1 is administered to the subject, the number of open arms in the elevated cross maze experiment is reduced, the walking distance and time within the open arms are shortened, the number of platform crossings in the water maze experiment is increased, and spatial learning and memory abilities are improved.

[0375] The present invention also relates to a method for preventing and / or treating hypothyroidism, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0376] The dosage of the compound represented by the general formula (I) of the present invention administered as a treatment for hypothyroidism is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dosage. The term "therapeutically effective dosage" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In the present invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0377] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 30 mg / kg. When the subject is a human, in a preferred embodiment, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 1 mg / kg, 2.5 mg / kg, or 5 mg / kg.

[0378] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for hypothyroidism, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least 7 consecutive days (preferably at least 14 days, more preferably at least 21 days, and more preferably at least 28 days).

[0379] In a preferred embodiment, as a treatment method for hypothyroidism, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared to other compounds of the present invention, when compound I-1 is administered to the test subject, it can significantly increase T3 and T4 levels, serum FT3 and FT4 levels, and decrease FSH levels.

[0380] The present invention also relates to a method for preventing and / or treating chronic atrophic gastritis, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0381] The dosage of the compound represented by the general formula (I) of the present invention administered as a treatment for chronic atrophic gastritis is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dose. The term "therapeutically effective dose" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In the present invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0382] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 7.5 mg / kg, 15 mg / kg, or 30 mg / kg. When the subject is a human, in a preferred embodiment, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 1 mg / kg, 2.5 mg / kg, or 5 mg / kg.

[0383] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for chronic atrophic gastritis, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least 7 consecutive days (preferably at least 21 days, more preferably at least 35 days, more preferably at least 42 days, more preferably at least 49 days, and more preferably at least 56 days).

[0384] In a preferred embodiment, as a treatment method for chronic atrophic gastritis, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared with other compounds of the present invention, when compound I-1 is administered to the test subject, serum IL-1β, IL-6, and TNF-α levels are significantly reduced, and serum PGI, PGII, and GAS levels are significantly increased.

[0385] The present invention also relates to a method for preventing and / or treating myocarditis, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0386] The dosage of the compound represented by the general formula (I) of the present invention administered as a treatment for myocarditis is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dose. The term "therapeutically effective dose" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In the present invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0387] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 7.5 mg / kg, 15 mg / kg, or 30 mg / kg. When the subject is a human, in a preferred embodiment, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 1 mg / kg, 2.5 mg / kg, or 5 mg / kg.

[0388] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for myocarditis, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least 7 consecutive days (preferably at least 14 days, more preferably at least 21 days, and more preferably at least 28 days).

[0389] In a preferred embodiment, as a treatment method for myocarditis, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared to other compounds of the present invention, when compound I-1 is administered to the test subject, it can lower LVIDd and LVIDs levels, increase EF and FS levels, and lower CK-MB levels.

[0390] The present invention also relates to a method for preventing and / or treating alopecia, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0391] In this invention, the term "alopecia" refers to hair loss on the scalp caused by autoimmune deficiency, and includes seborrheic alopecia, alopecia areata, and male pattern baldness.

[0392] The dosage of the compound represented by the general formula (I) of the present invention administered as a treatment for alopecia is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dosage. The term "therapeutically effective dosage" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In the present invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0393] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 7.5 mg / kg, 15 mg / kg, or 30 mg / kg. When the subject is a human, in a preferred embodiment, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 1 mg / kg, 2.5 mg / kg, or 5 mg / kg.

[0394] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for alopecia, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least 7 consecutive days (preferably at least 14 days, more preferably at least 21 days, and more preferably at least 28 days).

[0395] In a preferred embodiment, as a treatment method for alopecia, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared to other compounds of the present invention, when compound I-1 is administered to the subject, it can significantly reduce the IFN-γ and TNF-α content in skin tissue and reduce the total number and percentage of diseased hair follicles.

[0396] The present invention also relates to a method for preventing and / or treating primary aldosteronism, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0397] In this invention, the term "primary aldosteronism (PA)" refers to a group of heterogeneous diseases characterized by excessive aldosterone secretion from the adrenal cortex, which causes clinical symptoms such as increased blood volume, sodium retention and potassium excretion, metabolic alkalosis, hypertension, and hypokalemia.

[0398] The dosage of the compound represented by the general formula (I) of this invention administered as a treatment for primary aldosteronism is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dosage. The term "therapeutically effective dosage" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In this invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0399] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 7.5 mg / kg, 15 mg / kg, or 30 mg / kg. When the subject is a human, in a preferred embodiment, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 1 mg / kg, 2.5 mg / kg, or 5 mg / kg.

[0400] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for primary aldosteronism, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least 7 consecutive days (preferably at least 14 days, more preferably at least 21 days, and more preferably at least 28 days).

[0401] In a preferred embodiment, as a treatment method for primary aldosteronism, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared with other compounds of the present invention, when compound I-1 is administered to the subject, it can improve sodium retention and potassium excretion in the subject and lower PAC levels.

[0402] The present invention also relates to a method for preventing and / or treating erectile dysfunction, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0403] The dosage of the compound represented by the general formula (I) of the present invention administered as a treatment for erectile dysfunction is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dosage. The term "therapeutically effective dosage" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In the present invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0404] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 7.5 mg / kg, 15 mg / kg, or 30 mg / kg. When the subject is a human, in a preferred embodiment, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 1 mg / kg, 2.5 mg / kg, or 5 mg / kg.

[0405] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for erectile dysfunction, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least 7 consecutive days (preferably at least 21 days, more preferably at least 35 days, more preferably at least 49 days, more preferably at least 63 days, and more preferably at least 84 days).

[0406] In a preferred embodiment, as a treatment method for erectile dysfunction, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared to other compounds of the present invention, when compound I-1 is administered to the subject, it can significantly lower luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, increase the sex hormone testosterone (T) levels, and improve the frequency and duration of erections in the patient.

[0407] The present invention also relates to a method for preventing and / or treating periodontitis, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0408] The dosage of the compound represented by the general formula (I) of the present invention administered as a treatment for periodontitis is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dosage. The term "therapeutically effective dosage" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In the present invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0409] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 7.5 mg / kg, 15 mg / kg, or 30 mg / kg. When the subject is a human, in a preferred embodiment, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 1 mg / kg, 2.5 mg / kg, or 5 mg / kg.

[0410] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for periodontitis, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least 7 consecutive days (preferably at least 21 days, more preferably at least 35 days, more preferably at least 49 days, and more preferably at least 56 days).

[0411] In a preferred embodiment, as a treatment method for periodontitis, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared with other compounds of the present invention, when compound I-1 is administered to the test subject, it can significantly improve the periodontal condition and alveolar bone growth state, and improve the symptoms of periodontitis.

[0412] The present invention also relates to a method for preventing and / or treating stroke, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0413] The dosage of the compound represented by the general formula (I) of this invention administered as a treatment for stroke is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dosage. The term "therapeutically effective dosage" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In this invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0414] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 7.5 mg / kg, 15 mg / kg, or 30 mg / kg. When the subject is a human, in a preferred embodiment, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 1 mg / kg, 2.5 mg / kg, or 5 mg / kg.

[0415] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for stroke, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least 7 consecutive days (preferably at least 21 days, more preferably at least 35 days, more preferably at least 49 days, and more preferably at least 56 days).

[0416] In a preferred embodiment, as a treatment method for stroke, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared to other compounds of the present invention, when compound I-1 is administered to the subject, it can shorten the avoidance latency in a water maze experiment, increase the number of rat form crossings, improve memory and cognitive abilities, and reduce the apoptosis rate of hippocampal neurons.

[0417] The present invention also relates to a method for preventing and / or treating epilepsy, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0418] The dosage of the compound represented by the general formula (I) of the present invention administered as a treatment for epilepsy is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dosage. The term "therapeutically effective dosage" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In the present invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0419] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 7.5 mg / kg, 15 mg / kg, or 30 mg / kg. When the subject is a human, in a preferred embodiment, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 1 mg / kg, 2.5 mg / kg, or 5 mg / kg.

[0420] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for epilepsy, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least three consecutive days (preferably at least five days, more preferably at least seven days, more preferably at least ten days, more preferably at least twelve days, and more preferably at least 21 days).

[0421] In a preferred embodiment, as a treatment method for epilepsy, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared to other compounds of the present invention, when compound I-1 is administered to the subject, it can increase the post-stimulation latency in the jumping board experiment and the latency in the dark avoidance experiment, improve cognitive function, and lower serum inflammatory factor levels.

[0422] The present invention also relates to a method for preventing and / or treating melasma, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0423] The dosage of the compound represented by the general formula (I) of this invention administered as a treatment for melasma is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dosage. The term "therapeutically effective dosage" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In this invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0424] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 7.5 mg / kg, 15 mg / kg, or 30 mg / kg. When the subject is a human, in a preferred embodiment, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 1 mg / kg, 2.5 mg / kg, or 5 mg / kg.

[0425] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for melasma, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least 7 consecutive days (preferably at least 14 days, more preferably at least 28 days, more preferably at least 42 days, and more preferably at least 56 days).

[0426] In a preferred embodiment, as a treatment method for melasma, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared with other compounds of the present invention, when compound I-1 is administered to the test subject, it can significantly reduce the pathological skin area and distribution, and reduce the number and density of spots.

[0427] The present invention also relates to a method for preventing and / or treating vitiligo, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0428] The dosage of the compound represented by the general formula (I) of this invention administered as a treatment for vitiligo is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dose. The term "therapeutically effective dose" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In this invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0429] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 7.5 mg / kg, 15 mg / kg, or 30 mg / kg. When the subject is a human, in a preferred embodiment, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 1 mg / kg, 2.5 mg / kg, or 5 mg / kg.

[0430] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for vitiligo, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least 7 consecutive days (preferably at least 14 days, more preferably at least 28 days, more preferably at least 42 days, and more preferably at least 56 days).

[0431] In a preferred embodiment, as a treatment method for vitiligo, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared with other compounds of the present invention, when compound I-1 is administered to the test subject, tyrosinase activity can be increased and the MDA content can be reduced.

[0432] The present invention also relates to a method for preventing and / or treating β-thalassemia, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0433] The dosage of the compound represented by the general formula (I) of this invention administered as a treatment for β-thalassemia is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dose. The term "therapeutically effective dose" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In this invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0434] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 7.5 mg / kg, 15 mg / kg, or 30 mg / kg. When the subject is a human, in a preferred embodiment, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 1 mg / kg, 2.5 mg / kg, or 5 mg / kg.

[0435] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment method for β-thalassemia, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least 7 consecutive days (preferably at least 14 days, more preferably at least 28 days, more preferably at least 42 days, and more preferably at least 56 days).

[0436] In a preferred embodiment, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject as a treatment method for β-thalassemia. Compared to other compounds of the present invention, when compound I-1 is administered to the test subject, it can significantly increase hemoglobin (Hb) and red blood cell count levels, and Hb and RBC levels, thereby improving anemia symptoms.

[0437] The present invention also relates to a method for preventing and / or treating lumbar disc herniation, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0438] The dosage of the compound represented by the general formula (I) of this invention administered as a treatment for lumbar disc herniation is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dose. The term "therapeutically effective dose" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In this invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0439] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 7.5 mg / kg, 15 mg / kg, or 30 mg / kg. When the subject is a human, in a preferred embodiment, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 1 mg / kg, 2.5 mg / kg, or 5 mg / kg.

[0440] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment method for lumbar disc herniation, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least 7 consecutive days (preferably at least 14 days, more preferably at least 21 days, and more preferably at least 28 days).

[0441] In a preferred embodiment, as a treatment method for lumbar disc herniation, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared with other compounds of the present invention, when compound I-1 is administered to the subject, it can significantly reduce TNF-α and IL-6 levels in the nucleus pulposus tissue and significantly reduce PLA2 activity in the nucleus pulposus tissue.

[0442] The present invention also relates to a method for preventing and / or treating polycystic ovary syndrome, comprising the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof.

[0443] The dosage of the compound represented by the general formula (I) of this invention administered as a treatment for polycystic ovary syndrome is a pharmaceutically acceptable effective dosage, i.e., a therapeutically effective dose. The term "therapeutically effective dose" refers to a quantity of the compound sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or sufficient to delay or minimize one or more symptoms associated with the disease or disorder. Typically, the effective dosage varies from subject to subject. In this invention, the terms "subject" and "test subject" may be used interchangeably and refer to animals such as mammals, including but not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In certain embodiments, the subject is a human.

[0444] In a preferred embodiment, when the subject is a mouse, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 7.5 mg / kg, 15 mg / kg, or 30 mg / kg. When the subject is a human, in a preferred embodiment, the subject is administered 1 to 200 mg / kg of the compound represented by the general formula (I) of the present invention, for example, 1 mg / kg, 2.5 mg / kg, or 5 mg / kg.

[0445] The frequency of administration of the compound represented by general formula (I) of the present invention, administered as a treatment for polycystic ovary syndrome, is preferably once a day, twice a day, three times a day, once every two days, once every three days, or once a week. In a preferred embodiment, the compound is administered once a day for at least 7 consecutive days (preferably at least 14 days, more preferably at least 21 days, and more preferably at least 28 days).

[0446] In a preferred embodiment, as a treatment method for polycystic ovary syndrome, a therapeutically effective dose of I-1 (TJ01-013) is administered to the subject. Compared with other compounds of the present invention, when compound I-1 is administered to the test subject, it can significantly reduce T, LH, and FSH levels and significantly improve ovarian function.

[0447] term In this specification, the term "alkyl" refers to a linear or branched saturated aliphatic hydrocarbon group. 1-6 The term "alkyl" refers to linear or branched alkyl groups having 1 to 6 carbon atoms. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, and their various branched isomers. 1-4 The term "alkyl" refers to a linear or branched alkyl group having 1 to 4 carbon atoms. 1-4 When alkyl is at the end of the molecule, non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and tert-butyl. Alternatively, when two parts of the molecule are connected via alkyl, non-limiting examples include -CH2-, -CH2-CH2-, -CH(CH3)-, -CH2-CH2-CH2-, -CH(C2H5)-, and -C(CH3)2-,C 1-4 Yes, C 1-4 Each hydrogen atom in the alkyl carbon may be substituted with substituents further listed herein.

[0448] As used herein, the term “alkenyl” refers to a straight or branched hydrocarbon chain containing at least one carbon-carbon double bond. Each hydrogen in the alkenyl carbon may be substituted with substituents further listed herein. 2~6 An "alkenyl" refers to a straight or branched hydrocarbon chain of 1 to 6 carbon atoms containing at least one carbon-carbon double bond. When it appears at the end of a molecule, non-limiting examples include -CH=CH2, -CH=CH-CH3, -CH2-CH=CH2, -CH=CH-CH2-CH3, and -CH=CH-CH=CH2, or when two parts of a molecule are connected via the alkenyl, a non-limiting example is -CH=CH-. 2~6 Each hydrogen atom in the alkenyl carbon may be substituted with substituents further listed herein.

[0449] As used herein, the term "alkynyl" refers to a linear or branched hydrocarbon chain containing at least one carbon-carbon triple bond. Each hydrogen atom in the alkynyl carbon may be substituted with substituents further listed herein. 2~6 An "alkynyl" refers to a linear or branched hydrocarbon chain of 1 to 6 carbon atoms containing at least one carbon-carbon triple bond. When it appears at the end of a molecule, non-limiting examples include -C≡CH, -CH2-C≡CH, -CH2-CH2-C≡CH, -CH2-C≡C-CH3, or when two parts of a molecule are connected via the alkynyl, a non-limiting example is -C≡C-. 2~6 Each hydrogen atom in the alkynyl carbon may be substituted with substituents further listed herein.

[0450] As used herein, the term "alkoxy" refers to a group having the structure "-O-alkyl," where alkyl is as defined above. 1-6The term "alkoxy" refers to alkoxy molecules having 1 to 6 carbon atoms. Non-exclusive examples include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, isobutoxy, and n-pentyloxy.

[0451] As used herein, the term "amine group" means a group formed by the substitution of at least one hydrogen atom of an amino group with an alkyl group, for example, an amine group In TIFF2026509562000093.tif16170, R 3-11 and R 3-12 Either one of them is alkyl, and the other is hydrogen, or R 3-11 and R 3-12 All are alkyl groups, R 3-11 and R 3-12 If all of them are alkyl, R 3-11 and R 3-12 They may combine to form a ring.

[0452] As used herein, the term "haloalkyl" refers to an alkyl group in which one or more hydrogen atoms (e.g., 1, 2, 3, 4, or 5) are substituted with halogens, where alkyl is defined above.

[0453] As used herein, "(O)" means This refers to TIFF2026509562000094.tif13170. In certain embodiments, -CH2C(O)R 3-2 teeth This refers to TIFF2026509562000095.tif15170.

[0454] As used herein, the term "haloalkoxy" refers to an alkoxy in which one or more hydrogen atoms are substituted with halogens, where alkoxy is defined above.

[0455] As used herein, the terms “aryl,” “aryl ring,” and “aromatic ring” are interchangeable and refer to all-carbon monocyclic rings, all-carbon non-condensed polycyclic rings (where the rings are connected by covalent bonds and are not condensed), or all-carbon condensed polycyclic rings (i.e., rings sharing pairs of adjacent carbon atoms) groups in which at least one ring is aromatic, i.e., a ring-forming conjugated π-electron system.

[0456] As used herein, the term "heteroaryl" refers to an aryl compound in which at least one of the ring carbon atoms constituting the aryl compound is replaced by a heteroatom that is a non-carbon atom such as S, N, or O.

[0457] As used herein, the term "monocyclic heteroaryl" refers to a heteroaryl having only one aromatic ring, where heteroaryl is defined as described above. The term "5-membered or 6-membered monocyclic heteroaryl" refers to a monocyclic heteroaryl having 5 or 6 ring atoms, of which 1, 2, or 3 ring atoms are heteroatoms selected from nitrogen, oxygen, or S(=O)m' (where m' is an integer between 0 and 2). Non-exclusive examples include thiophene, furan, thiazole, isothiazole, imidazole, oxazole, pyrrole, pyrazole, 20-triazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, 1,3,4-triazole, tetrazole, isoxazole, oxadiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, thiadiazole, pyridine, pyridazine, pyrimidine, and pyrazine.

[0458] As used herein, the term "condensed ring heteroaryl" refers to at least two aromatic rings in which two ring atoms are adjacent to each other, where heteroaryl is as defined above. The term "condensed bicyclic heteroaryl" refers to a condensed ring heteroaryl having two aromatic rings, where condensed ring heteroaryl is as defined above. The term "8-10 membered condensed bicyclic heteroaryl" refers to a condensed bicyclic heteroaryl having 8-10 ring atoms, of which 1, 2, 3, 4, or 5 ring atoms are heteroatoms selected from nitrogen, oxygen, or S(=O)m' (where m' is an integer from 0 to 2), and non-limiting examples include benzo[d]isoxazole, 1H-indole, isoindole, 1H-benzo[d]imidazole, benzo[d]isothiazole, 1H-benzo[d][1,2,3]triazole, benzo[d]oxazole This includes sazole, benzo[d]thiazole, indazole, benzofuran, benzo[b]thiophene, quinoline, isoquinoline, quinazoline, quinoxaline, sinnoline, pyrido[3,2-d]pyrimidine, pyrido[2,3-d]pyrimidine, pyrido[3,4-d]pyrimidine, pyrido[4,3-d]pyrimidine, 1,8-naphthiridine, 1,7-naphthiridine, 1,6-naphthiridine, 1,5-naphthiridine, pyrazolo[1,5-a]pyrimidine, imidazo[1,2-b]pyridazine, and others.

[0459] To further clarify the objectives, technical solutions, and advantages of the embodiments of the present invention, the invention will be described below based on specific embodiments. It should be understood that these embodiments are used solely for illustrative purposes and do not limit the scope of the invention. Experimental methods in the following embodiments that do not specify particular experimental conditions generally follow conventional conditions or conditions recommended by the manufacturer. Unless otherwise specified, percentages and parts refer to weight percentages and parts by weight. The experimental materials and reagents used in the following embodiments can be obtained from commercial sources unless otherwise specified.

[0460] Unless otherwise specified, the technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art to which this application pertains. It should be noted that the terms used herein are intended solely to describe specific embodiments and not to limit the exemplary embodiments of this application.

[0461] Example 1: Alleviation of premature ovarian failure and delay of ovarian dysfunction progression. 1) Chemotherapy-induced POF mouse model Infertility associated with premature ovarian failure is one of the most serious side effects of chemotherapy in young cancer patients, but there is no established effective treatment for gonadotoxic damage to the ovaries. Cyclophosphamide (Cy), a commonly used chemotherapy drug, can cause severe ovarian damage and is known as a risk factor for POF. Cyclophosphamide can cause primordial follicle failure.

[0462] Eight-week-old C57BL / 6J mice (body weight approximately 20-25g) were randomly assigned to one of four groups based on body weight after one week of adaptive feeding: a control group (n=8), a model group (Cy + 0.5% CMC-Na solvent administration, n=8), a TJ01-013 group (Cy + TJ01-013, 30 mg / kg TJ01-013 forced oral administration, n=8), and an I-14-1 group (Cy + I-14-1, 30 mg / kg I-14-1 forced oral administration, n=8). The model group and the TJ01-013 group received a single intraperitoneal administration of cyclophosphamide (75 mg / kg, 200-300 μl), while the control group received a single intraperitoneal administration of an equal volume of physiological saline. Samples were collected 12 days after administration, and the mice's body weight, ovarian weight, and serum E2 and FSH levels were measured.

[0463] 2) Measurement of the ovarian organ index Body weight and bilateral ovarian wet weight were measured for each mouse group using electronic and analytical balances. The testicular organ index for each mouse group was calculated based on mouse body weight (g) and bilateral ovarian wet weight (mg). See formula below: Testicular organ dilution = bilateral ovarian wet weight (mg) / mouse body weight (g).

[0464] As shown in Figure 1, no significant change was observed in the body weight of mice 14 days after chemotherapy, but ovarian weight significantly decreased with chemotherapy. Ovarian weight significantly increased after administration of TJ01-013 and I-14-1. Similarly, the ovarian index (ratio of ovarian weight to body weight) also significantly decreased with chemotherapy, but the ovarian index significantly increased after administration of TJ01-013 and I-14-1, and the effect of TJ01-013 was superior to that of I-14-1.

[0465] 3) Detection of serum hormone levels using Elisa.

[0466] At the end of the experiment, blood was collected from the orbit, allowed to stand at room temperature for 45 minutes, and then centrifuged at 12000g for 10 minutes. The supernatant (serum) was collected, and serum E2, FSH, and BDNF levels were measured using the ELISA method.

[0467] As shown in Figure 2, compared to the normal model group, serum FSH concentration was significantly increased after chemotherapy modeling, but serum FSH levels significantly decreased after TJ01-013 and I-14-1 treatment. As shown in Figure 3, serum E2 levels significantly decreased after chemotherapy modeling and significantly increased after I-14-1 and TJ01-013 treatment, suggesting that TJ01-013 and I-14-1 treatment significantly improved mouse ovarian function.

[0468] 4) ELISA detection of BDNF in ovarian tissue.

[0469] Brain-derived neurotrophic factor (BDNF) is a widely studied neurotrophic factor and is now also known as an ovarian endocrine factor. Numerous pieces of evidence suggest that BDNF plays a role in follicular development. After the experiment, the mice were euthanized, their ovaries were removed and pulverized, and BDNF levels in the ovarian tissue were measured using ELISA.

[0470] As shown in Figure 4, the results indicated that BDNF levels in ovarian tissue significantly decreased after chemotherapy modeling, and significantly increased after TJ01-013 and I-14-1 treatment, suggesting that TJ01-013 and I-14-1 treatment significantly improved mouse ovarian function.

[0471] TJ0113 shows superior improvements to FSH concentration, serum E2 levels, and BDNF levels compared to I-14-1, with its superiority being particularly pronounced in its effect on serum FSH concentration.

[0472] Example 2: Treatment of ovarian dysfunction due to natural aging 1) Modeling of spontaneously aging POF (NA-POF) A natural aging model (NA-POF) simulated the conditions for progressive ovarian degeneration. Female C57BL / 6J mice were purchased at 9-10 months of age and reared until 12 months of age. The mice were then randomly divided into three groups: a control group (forced oral administration of 0.5% CMC-Na, n=8), a TJ01-013 group (forced oral administration of TJ01-013, 30 mg / kg TJ01-013, n=8), and an I-14-1 group (forced oral administration of I-14-1, 30 mg / kg I-14-1, n=8). The drugs were administered daily for a total of 30 days. At the end of the experiment, the mice's body weight, ovarian weight, ovarian organ index, and serum hormone levels E2 and FSH were measured.

[0473] 2) Measurement of ovarian organ index Body weight and bilateral ovarian wet weight were measured for each mouse group using electronic and analytical balances. The ovarian organ index for each mouse group was calculated based on mouse body weight (g) and bilateral ovarian wet weight (mg). See the formula below: Ovarian organ dilution = bilateral ovarian wet weight (mg) / mouse body weight (g).

[0474] As shown in Figure 71, there were no significant changes in body weight of mice after natural aging and treatment with TJ01-013 and I-14-1. However, ovarian weight significantly decreased with aging, and significantly increased after administration of TJ01-013 and I-14-1. Similarly, the ovarian index significantly decreased with aging, and significantly increased after administration of TJ01-013. While no significant increase was observed with I-14-1 administration, an increasing trend was observed.

[0475] 3) Detection of serum hormone levels using Elisa.

[0476] At the end of the experiment, blood was collected from the orbit, allowed to stand at room temperature for 45 minutes, and then centrifuged at 12,000 g for 10 minutes. The supernatant (serum) was collected, and the E2 and FSH levels in the serum were measured using the ELISA method.

[0477] As shown in Figure 6, serum FSH levels were significantly reduced after treatment with TJ01-013 following aging. As shown in Figure 7, serum E2 levels were significantly increased after treatment with both TJ01-013 and I-14-1 following aging. These results indicate that both TJ01-013 and I-14-1 can improve, to some extent, the decline in ovarian function due to aging in mice, with TJ01-013 being more effective.

[0478] Example 3: Treatment of lupus nephritis 1) Modeling and Therapeutic Administration MRL / lpr mice are the most classic animal model of lupus and immune-related diseases. The MRL / lpr animal model eventually progresses to systemic lupus erythematosus-like disease characterized by generalized lymphadenopathy, skin lesions, alopecia, infiltrative arthritis, and immune complex deposition glomerulonephritis. Onset typically occurs between 14 and 16 weeks of age. Considering that the pathogenesis of SLE is sex-related, with a male-to-female incidence ratio of approximately 1:9, female MRL / lpr mice were selected for this study.

[0479] Ten-week-old female MRL / lpr mice were selected and housed in an SPF environment with a 12-hour light-dark cycle and a temperature maintained at 24-26°C. The mice were randomly divided into three groups according to their body weight: a model group (Control, n=8, forced oral administration of 0.5% CMC-Na), a TJ01-013 10 mg / kg administration group (10 mg / kg, n=8, forced oral administration of 10 mg / kg TJ01-013), and a TJ01-013 30 mg / kg administration group (30 mg / kg, n=8, forced oral administration of 30 mg / kg TJ01-013). After one week of adaptive feeding, the drugs were administered daily from week 11, and random urinary protein and urinary creatinine concentrations were monitored every two weeks from week 11 onward. The urinary protein / creatinine concentration ratio (uPCR) of the mice was calculated. The drug was administered for a total of 10 weeks. At the end of administration, blood was drawn from the orbit and serum was collected. Serum creatinine, urea nitrogen, serum ANA, and anti-dsDNA concentrations were measured.

[0480] 2) Detection of urinary protein and urinary creatinine concentrations Levels of urinary protein and urinary creatinine were detected using Coomassie brilliant blue staining. The results are shown in Figure 8. The uPCR trends, continuously monitored after 10 weeks of administration, were essentially the same in both the normal group and the TJ01-013 treatment group, and were significantly lower in both groups than in the MRL / lpr model group. This indicates that TJ01-013 treatment can reduce the occurrence of proteinuria.

[0481] 3) Detection of serum creatinine and urea nitrogen Serum creatinine and urea nitrogen were detected using a biochemical analyzer. The results are shown in Figure 9. Serum creatinine and urea nitrogen levels in MRL / lpr model mice were significantly increased compared to normal mice, and after administration of TJ01-013, serum creatinine and urea nitrogen levels in mice were significantly decreased compared to the model group, indicating that TJ01-013 treatment can significantly reduce renal function.

[0482] 4) Detection of serum ANA and anti-dsDNA concentrations Serum ANA and anti-dsDNA levels were detected by ELISA. The results are shown in Figures 10-11. Serum ANA and dsDNA levels in MRL / lpr model mice were significantly increased compared to normal mice, and after TJ01-013 administration, serum ANA and dsDNA levels were significantly decreased compared to the model group, indicating that TJ01-013 treatment can significantly reduce systemic lupus erythematosus-specific antibody levels.

[0483] 5) Detection of inflammatory factor levels in kidney tissue Kidney tissue was placed in a homogenizer and thoroughly cut with clean scissors. 400 μl of the lysate was added to the homogenizer and homogenized. The mixture was then placed on ice and repeated several times until the kidney tissue was as finely ground as possible. After 30 minutes of lysis, the lysate was pipetteed into a 1.5 ml centrifuge tube and centrifuged at 12000 rpm at 4°C for 10 minutes. The supernatant was stored at -20°C. Inflammatory factors TNFα and IL-6 in kidney tissue proteins were detected using ELISA.

[0484] The results are shown in Figure 12. Levels of TNFα and IL-6 in the kidney tissue of MRL / lpr model mice were significantly increased compared to normal mice, and after TJ01-013 treatment, levels of TNFα and IL-6 were significantly decreased compared to the model group, indicating that TJ01-013 treatment can significantly reduce the level of inflammation in kidney tissue.

[0485] Example 4: Treatment of sarcopenia 1) Modeling and grouping After weighing male mice, they were assigned to one of the following groups based on body weight: a blank group (normal, n=8), a model control group (control, forced oral administration of 0.5% CMC-Na, n=8), a TJ01-013 group (forced oral administration of TJ01-013 30 mg / kg, n=8), and an I-14-1 group (forced oral administration of I-14-1 30 mg / kg, n=8). Sarcopenia was induced in both the model control and treatment groups by continuous administration of hydrocortisone into the muscles of both hind limbs for 7 days, followed by continuous subcutaneous administration of D-galactose into the neck for 40 days. After modeling, the mice were administered the drugs daily for 30 days. At the end of the experiment, muscle strength was evaluated by tensile and swimming tests.

[0486] 2) Muscle strength evaluation experiment: Swimming experiment: A 50cm diameter container was filled with 37°C warm water, and mice were placed in the container for a 20-minute pre-swimming experiment. The water level was maintained so that the mice's feet did not touch the bottom of the container. After allowing the mice to exercise for a while, the time it took them to move their hind limbs within 5 minutes was measured.

[0487] Tensile Test: The tensile gauge was fixed vertically, a coarse rope was tied to the tip of the curved needle, and a mouse was allowed to grasp it by its tail. As the mouse exerted force to climb upward, the tail was pulled downward to create resistance, and the tensile force was recorded. This procedure was repeated three times, and the average value was calculated.

[0488] The above experiment was repeated at the same time of day three days before the end of the experiment, the experimental results were collected, and the average value was calculated.

[0489] As shown in Figure 13, compared to normal mice, sarcopenic mice had significantly shorter swimming times, and after administration of TJ01-013, swimming time significantly increased. An increasing trend in swimming time was observed after administration of I-14-1. As shown in Figure 14, compared to normal mice, sarcopenic mice had significantly lower tensile strength, and after administration of TJ01-013 and I-14-1 to sarcopenic mice, tensile strength levels significantly increased. These results suggest that administration of TJ01-013 and I-14-1 can alleviate the progression of sarcopenia and treat sarcopenia.

[0490] Example 5: Treatment of acute alcoholic liver injury 1) Modeling Eight-week-old C57BL / 6J mice were randomly divided into three groups after one week of adaptive feeding: a blank control group (Normal, n=8), a model control group (ETOH, n=8), a positive control group (ETOH+NAC, n=8), and a TJ01-013 administration group (ETOH+TJ01-013, n=8). Mice were force-fed orally at a dose of 5 ml / kg for three consecutive days, based on body weight. The blank and model control groups were administered 0.5% CMC-Na solvent, the positive control group was administered 400 mg / kg N-acetylcysteine ​​(NAC), and the TJ01-013 administration group was administered 10 mg / kg TJ01-013. Four hours after the final dose, all groups except the blank group were force-fed orally twice with 50% alcohol (10 ml / kg) at 12-hour intervals. The blank group was administered the same amount of physiological saline. Two hours after the final alcohol administration, blood was collected from the orbit, left at room temperature for one hour, and then centrifuged at 4°C. The supernatant was used to measure relevant serum indicators. Mice were sacrificed by dislocation, and their livers were promptly removed.

[0491] 2) Measurement of liver function indicators: aspartate aminotransferase (AST), alanine aminotransferase (ALT), triacylglycerol (TG), and cholesterol (TC) content. Using pre-prepared mouse serum, AST and ALT levels were measured according to the operating procedures of the biochemical analyzer. The liver was then crushed, the supernatant was extracted, and the TG and TC content in the liver tissue was analyzed, followed by significance analysis.

[0492] AST, ALT, TG, and TC are widely used indicators in clinical diagnosis of liver disease. When hepatocytes are damaged, the permeability of the hepatocyte membrane increases, and various enzymes are released into the bloodstream. As shown in Figure 15, ALT and AST levels were significantly increased in the model control group compared to the normal group, and TJ01-013 administration significantly suppressed ALT levels. Although there was no significant difference in the inhibitory effect on AST compared to the model group, there was an inhibitory trend, and the inhibitory trend on NAC was superior to that of the positive control. As shown in Figure 16, TG and TC levels in the liver tissue of the model control group were also significantly increased compared to the normal group, and TJ01-013 administration significantly suppressed TG and TC levels. These results suggest that TJ01-013 has some reversal effect on acute alcoholic liver injury and is significantly superior to the positive control drug.

[0493] Example 6: Treatment of chronic alcoholic liver disease 1) Modeling Eight-week-old C57BL / 6J male mice were randomly assigned to four groups based on body weight: a normal control group (PF, no subsequent alcohol-induced modeling, n=8), a model control group (AF, n=8), a positive drug administration group (AF + Metadoxine, n=8), and a TJ01-013 administration group (AF + TJ01-013, n=8). The experiment was divided into five steps: a 3-day environmental adaptation period (granular feed), a 3-day liquid feed adaptation period (normal or low-fat liquid feed without ethanol), a transition period to liquid feed containing ethanol (normal liquid feed containing 1% to 4% ethanol, 2 days each), and a modeling period (4 consecutive weeks of liquid feed containing ethanol). Administration began during the modeling period, with forced oral administration at a dose of 5 ml / kg based on mouse body weight. The normal control group and the model control group were orally administered 0.5% CMC-Na solvent for four consecutive weeks. The positive control group received 65 mg / kg Metadoxine, and the TJ01-013 administration group received 10 mg / kg TJ01-013. After administration, the mice were euthanized by dislocation after enucleation and blood collection. The livers were immediately removed, fixed with 4% paraformaldehyde, and used for tissue staining.

[0494] 2) Liver function indicators such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), triacylglycerol (TG), and cholesterol (TC) content were measured.

[0495] Using pre-prepared mouse serum, AST, ALT, TG, and TC were measured according to the operating procedures of the biochemical analyzer. The liver was crushed, the supernatant was extracted, and the TG and TC content in the liver tissue was analyzed, followed by significance analysis.

[0496] As shown in Figure 17, ALT and AST levels were significantly increased in the model control group compared to the normal group. Administration of the positive control drug and TJ01-013 significantly decreased ALT and AST levels, and the inhibitory effect on ALT and AST with TJ01-013 administration was superior to that of the positive control. These results suggest that TJ01-013 has some mitigating effect on biochemical indicators associated with chronic alcoholic liver disease.

[0497] 3) HE staining analysis of liver tissue After collecting blood from the mouse eyeballs, the mice were anesthetized by cardiac perfusion using PBS, fixed to a foam board with a needle, the skin of the chest and abdomen and the ribs were cut to expose the heart, a needle was inserted into the left ventricle of the mouse, the pericardium was cut, and the liver was perfused with PBS at a perfusion rate of 7 rpm until it turned white. After stopping the perfusion, the liver was removed, the liver capsule was peeled off, and the liver was fixed in 4% paraformaldehyde and immersed for 72 hours. Next, tissue embedding, sectioning, and HE staining were performed. The specific procedures are as follows: tissue embedding The tissue embedding steps were as follows: Ethanol dehydration: The tissue was dehydrated stepwise in ethanol solutions of different concentrations: 75%, 85%, 95%, 100%, and 100%, for 40 minutes each time. Clearing: The tissue was immersed sequentially in three xylene solutions for 30 minutes in each solution. Paraffin immersion: The tissue was immersed sequentially in three paraffin baths for 1 hour in the first bath, 1.5 hours in the second bath, and 2 hours in the third bath. Embedding: Liquid paraffin was poured into a mold box, and the paraffin-soaked tissue block was placed flat on the bottom with the cut surface facing downwards. After the paraffin hardened, the embedding frame was removed, and after complete cooling and hardening, the paraffin block was trimmed, and the paraffin around the tissue was properly retained for sectioning.

[0498] Section preparation The pre-cooled paraffin block was fixed in a paraffin microtome so that the cut surface of the paraffin block was parallel to the knife blade, the knife was tilted at a normal 15 degrees, and the rotary pusher was rotated to adjust the section thickness to 3 μm, cutting the section into uniform thickness sections. Holding a brush in the left hand, the microtome handle was rotated with the right hand, and when the section emerged, it was gently lifted with the brush, and the paraffin section was lightly tweezed with forceps and placed in a section spreading box facing forward, with the water temperature at approximately 40°C. After flattening, the section was removed. To mount the section, one end of the slide was held with the left hand, water was added vertically to mount the section, and the section was pressed with forceps using the right hand to mount it at two-thirds of the way down the slide glass. After mounting the section, it was left to dry slightly in the air, baked in a 60°C baking machine for 1 hour, and then baked in an oven for 2 hours.

[0499] Deparaffinization and rehydration of paraffin sections Paraffin sections were deparaffinized using a gradient method in the following order: xylene I for 15 minutes, xylene II for 15 minutes, anhydrous ethanol I for 10 minutes, anhydrous ethanol II for 10 minutes, 95% alcohol for 10 minutes, and 85% alcohol for 10 minutes.

[0500] HE staining The paraffin sections were stained with hematoxylin for 5-10 minutes, rinsed with tap water, separated with 1% hydrochloric acid alcohol for a few seconds, rinsed with tap water, then returned to blue with saturated lithium carbonate solution for 1 minute, rinsed with running water for a few seconds, immersed in eosin staining solution for a few seconds, and rinsed with running water.

[0501] Dehydration, sealing, and image acquisition Paraffin sections were immersed in 75% ethanol for 2 minutes, then 85% ethanol for 2 minutes, then anhydrous ethanol for 2 minutes, then anhydrous ethanol for 2 minutes, and finally xylene for 2 minutes until clear. The sections were removed from the xylene and sealed with neutral gum. They were examined under a microscope, images were collected, and analyzed.

[0502] As shown in Figure 18, the results of the liver tissue HE staining analysis experiment showed that chronic alcoholic fatty liver disease leads to blurring of hepatocyte structure and severe histological abnormalities, and that administration of TJ01-013 can alleviate the severe liver tissue abnormalities caused by chronic alcoholic liver disease.

[0503] 3) Oil red staining of liver tissue Kidney tissue was fixed with 4% paraformaldehyde for 48 hours, dehydrated with sucrose, and then sections were prepared using a cryostat. The tissue was warmed to room temperature and rinsed with distilled water to remove the embedding medium. Next, the tissue was rinsed with 60% isopropanol for 2 minutes and stained with Oil Red O standard solution for 2-5 minutes. Under a microscope, staining with 60% isopropanol was prepared, immediately washed with water, counterstained with hematoxylin, and then washed with running water until blue. The sections were then mounted with glycerol gelatin and observed under a microscope.

[0504] As shown in Figure 19, microscopic examination of liver tissue after oil red staining revealed a significant increase in fat levels in the chronic alcoholic fatty liver model group, suggesting that TJ01-013 administration can reduce fat accumulation due to chronic alcoholic liver disease.

[0505] Example 7: Treatment of drug-induced liver injury 1) Modeling APAP-induced liver injury is a common model of drug-induced liver injury. Eight-week-old male C57BL / 6J mice were randomly assigned to five groups (n=8) based on body weight: normal control group (n=8), model control group (APAP, n=8), positive drug administration group (APAP + silymarin, 50 mg / kg, n=8), low-dose TJ01-013 administration group (APAP + 13L, 10 mg / kg, n=8), and high-dose TJ01-013 administration group (APAP + 13H, 30 mg / kg, n=8). Mice were force-administered orally at a dose of 5 ml / kg based on body weight. The blank and model groups received 0.5% CMC-Na orally for three consecutive days. The positive drug administration group received 50 mg / kg silymarin, the low-concentration TJ01-013 administration group received 10 mg / kg TJ01-013, and the high-concentration TJ01-013 administration group received 30 mg / kg TJ01-013. Four hours after the final dose, all groups except the normal control group received 500 mg / kg APAP (10 ml / kg) orally, and the normal control group received the same amount of physiological saline. Six hours after modeling with APAP, blood was collected from the orbit, left at room temperature for 1 hour, and then centrifuged at 4°C. The supernatant was used to measure relevant serum indicators.

[0506] 2) Liver function indicators such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline fostatase (ALP), and cholesterol (CHOL) levels were measured.

[0507] The aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline fostatase (ALP), and cholesterol (CHOL) content were measured according to the operating procedures of the biochemical analyzer.

[0508] As shown in Figure 20, ALT and AST levels were significantly increased in the model control group compared to the normal group, and administration of the positive control drug and TJ01-013 all significantly decreased ALT and AST levels. As shown in Figure 21, serum ALP levels were also significantly increased in the model control group compared to the normal group, and administration of the positive control drug and TJ01-013 significantly suppressed ALP levels. These results suggest that TJ01-013 has some mitigating effect on APAP-induced drug-induced liver injury.

[0509] Example 8: Treatment of oligospermia 1) Modeling Male C57BL / 6J mice were numbered according to their body weight and randomly assigned to three groups using a random number table: a normal control group (n=8), a model control group (n=8), a TJ01-013 treatment group (TJ01-013, n=8), and an I-14-1 treatment group (I-14-1, n=8). Of these, the normal control group received 2 ml / d of physiological saline via subperitoneal injection for 5 consecutive days, while the model control group and the treatment group received 2 mg / d of 0.1% cyclophosphamide via subperitoneal injection for 5 consecutive days to create an oligospermia model. From day 6, the normal control group and the model control group were forcibly administered 0.5% CMC-Na at a dose of 5 ml / kg for 30 consecutive days, the TJ01-013 treatment group received 30 mg / kg of TJ01-013, and the I-14-1 treatment group received 30 mg / kg of I-14-1 at a dose of 5 ml / kg. After administration, the mice were weighed, blood was collected from the orbits, and the mice were euthanized. Both testes and epididymis were removed, and connective tissue such as fat was removed. Moisture was wiped off with filter paper, and the wet weight of the testes was measured using an analytical balance. 2) Measurement of serum hormones After collecting blood from the eyeballs, the blood was left at room temperature for 30 minutes and then centrifuged at 12,000 rpm for 10 minutes. The supernatant was collected to obtain serum. Using a biochemical analyzer, the levels of the sex hormones testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in the serum were measured.

[0510] The results are shown in Figure 22. Compared to the normal control group, serum FSH, LH, and T levels in the model group were significantly increased, serum FSH and T levels were significantly decreased after administration of TJ01-013 and I-14-1, serum LH levels were significantly decreased after administration of TJ01-013, and LH levels showed a decreasing trend after administration of I-14-1. These results suggest that TJ01-013 and I-14-1 can improve sex hormone levels in mouse serum, and that the effect of TJ01-013 is superior to that of I-14-1.

[0511] 3) Measurement of the testicular organ index Body weight and bilateral testicular wet weight were measured using electronic and analytical balances for each mouse group. The testicular organ index for each mouse group was calculated based on mouse body weight (g) and bilateral testicular wet weight (mg). See formula below: As shown in Figure 23, compared to the normal control group, the wet testicular weight of the model group mice decreased, and increased after administration of TJ01-013 and I-14-1. Although no significant difference was observed between the groups, a certain trend was observed. Compared to the normal control group, the testicular organ index of the model group mice decreased significantly, and increased after administration of TJ01-013 and I-14-1. A significant difference was observed, indicating that TJ01-013 and I-14-1 treatment can improve testicular quality in oligospermia, and that the effect of TJ01-013 is superior to that of I-14-1.

[0512] 4) Measurement of sperm density Collection of mouse semen: One excised mouse epididymis was immersed in 1 ml of pre-prepared 37°C physiological saline. The epididymis was finely chopped with ophthalmic scissors and incubated in a 37°C water bath for 15 minutes. After the sperm had completely emerged from the epididymal tissue, the suspension was mixed using a vortex mixer to prepare a sperm suspension. This suspension was placed in a 37°C water bath. Sperm count was measured using a hemocytometer.

[0513] As shown in Figure 24, the sperm density of the model group was significantly lower than that of the normal control group, indicating a significant decrease in the reproductive function of the model mice. The sperm density of the TJ01-013 and I-14-1 treatment groups was statistically significantly higher than that of the model control group. These results suggest that TJ01-013 and I-14-1 are effective in treating oligospermia and increasing sperm count, with TJ01-013 being more effective than I-14-1.

[0514] Example 9: Treatment of rheumatoid arthritis 1) Modeling Eight-week-old C57BL / 6J mice were randomly assigned to four groups after one adaptive feeding: a normal control group (n=8), a positive control group (n=8), a positive control group (Dex, dexamethasone group, 0.2 mg / kg, n=8), and a TJ01-013 administration group (TJ01-013, 30 mg / kg, n=8). Modeling was performed on all mice except the normal control group. The mice were treated with a 1:1 mixture of bovine type II collagen and complete Freund's adjuvant, emulsified on ice at 4°C to produce an antigen, and 0.1 ml was intradermally injected into the base of the mouse tail. Booster immunization was performed 21 days after the initial modeling. The normal control group was simultaneously injected with the same amount of physiological saline. Forced oral administration was performed for 14 consecutive days starting 28 days after the initial immunization.

[0515] 2) Arthritis score The arthritis index (AI) scoring was performed on mice every four days after the initial immunization. The severity of arthritis in each limb was evaluated on a scale from 0 to 4, with 4 being the most severe. The sum of the scores for the four feet of each mouse was used as the mouse AI score, with a maximum score of 16. AI score criteria: 0: No redness or swelling, 1: Redness of the little toe joint, 2: Redness of the little toe and metatarsal joints, 3: Redness of the entire foot including the ankle joint, 4: Redness or malformation of the entire foot including the ankle joint. The results are shown in Figure 25. After the initial immunization, the AI ​​score of the model group mice was significantly higher than that of the normal group, and the AI ​​score of the hormone Dex intervention group mice was significantly lower than that of the model control group, and this difference became increasingly pronounced. Administration of TJ01-013 could also significantly reduce the AI ​​score of the model mice.

[0516] 3) Assessment of immune function The number of swollen joints in the mice's limbs was assessed every four days following the initial immunization. Since each limb consists of five phalangeal joints and one ankle or wrist joint, the maximum number of swollen joints in each mouse's four limbs was 24. The thickness of the hind paw pads was also measured using calipers. The hind paw pad thickness was the average of the thicknesses of both limbs. At the end of the experiment, the mice were sacrificed, and the body weight, thymus, and spleen weight of each mouse were weighed to calculate the immune organ index. Formula: Immune organ index + immune organ weight (mg) / body weight (g) As shown in Figures 26 and 27, after initial immunization, the number of swollen joints and the thickness of the hind paw pads in the model group were significantly higher than in the normal control group, and administration of dexamethasone Dex and TJ01-013 significantly reduced the number of swollen joints and the thickness of the hind paw pads. The results are shown in Figure 28. The organ index of the thymus and spleen in the model control mice was significantly higher than in the normal control group, and administration of Dex and TJ01-013 significantly reduced the organ index of the thymus and spleen in the model mice. These results suggest that TJ01-013 can significantly alleviate the symptoms of rheumatoid arthritis.

[0517] Example 10: Treatment of cataracts SD rats that had their eyes closed for 10 days were randomly assigned to four groups: a normal control group (n=10), a model control group (Vehicle, n=10), an I-14-1 administration group (I-14-1 1 mg / kg, n=10), and a TJ01-013 high-concentration administration group (TJ01-013 10 mg / kg, n=10). For all groups except the normal control group, a model was created by preparing a 3 mmol / L solution of sodium selenite powder in sterile saline and administering it at a single intraperitoneal injection at a dose of 10 ml / kg. The normal control group received the same amount of saline intraperitoneally. The administration cycle began on the day of modeling. The treatment group received daily intraperitoneal injections of the corresponding doses of I-14-1 and TJ01-013 for 10 consecutive days, while the model group and normal control group received daily intraperitoneal injections of lysozyme (5% DMSO + 20% PEG400 + 65% sterile saline). For the endpoint, all animals had their eyes open, and the fundus was observed using an ophthalmoscope, and lens opacity was observed and scored using a slit-lamp microscope.

[0518] The results are shown in Figure 29. TJ01-013 and I-14-1 can alleviate rat lens opacity caused by selenite, and TJ01-013 has a higher alleviation effect.

[0519] Example 11: Treatment of Cushing's syndrome Seven-week-old male C57BL / 6J mice were randomly assigned to four groups based on body weight after one week of adaptive feeding: a normal control group (n=10), a model control group (n=10), an I-14-1 15 mg / kg dose group (I-14-1, n=10), and a TJ01-013 15 mg / kg dose group (TJ01-013, n=10). All groups except the normal control group were given drinking water containing 100 μg / mL of corticosterone for two weeks to create a Cushing's syndrome mouse model. Normal control mice were housed as usual. Administration was started simultaneously with the modeling group. The normal control and model control groups were administered the solvent (0.5% CMC-Na), while the dose groups received I-14-1 and TJ01-013 at corresponding concentrations, administered at a dose of 10 ml / kg for 14 days. After administration, blood was collected from the mouse orbits, placed in an anticoagulant tube, centrifuged at 12,000 rpm for 10 minutes, and the supernatant was collected. Blood glucose and insulin levels were then measured.

[0520] The results are shown in Figure 30. Compared to the normal control group, the blood glucose levels in the model control group were significantly increased, and TJ01-013 treatment was able to lower blood glucose levels, with a significant difference compared to the model group. Compared to the normal control group, the plasma insulin levels in the model control group were significantly increased, and both TJ01-013 and I-14-1 treatments were able to lower plasma insulin levels, with a significant difference compared to the model group. These results suggest that TJ01-013 and I-14-1 can alleviate Cushing's syndrome, and that TJ01-013 is more effective.

[0521] Example 12: Treatment of Hashimoto's disease Five-week-old male SD rats were randomly assigned to five groups based on body weight after one week of adaptive feeding: normal control (n=10), model control (n=10), TJ01-013 7.5 mg / kg dose group (7.5 mg / kg, n=10), TJ01-013 15 mg / kg dose group (15 mg / kg, n=10), and TJ01-013 30 mg / kg dose group (30 mg / kg, n=10). All groups except the normal control were fed iodine solution 0.64 g / L. Fourteen days after iodine solution administration, 0.2 ml of oil-in-water emulsion Tg containing total Freund's adjuvant (CFA) was administered subcutaneously twice at multiple sites on both legs at two-day intervals as a primary immunization. Two weeks later, as a booster immunization, 0.2 ml of oil-in-water emulsion Tg supplemented with complete Freund's adjuvant (CFA) was subcutaneously injected four times at multiple sites on the back at 7-day intervals. This was administered from the initial immunization. The normal control group and the model control group received the solvent (0.5% CMC-Na), while the TJ01-013 administration group received TJ01-013 at the corresponding concentration at a dose of 10 ml / kg for a total of 6 weeks. After administration, blood was collected from the retroocular vein of the rats. The blood was left at room temperature for 30 minutes, then centrifuged at 6000 rpm for 110 minutes, and the upper layer serum was collected. Serum levels of TGAb, TPO-Ab, TSH, and FT3 were measured by enzyme-linked immunosorbent assay (ELISA).

[0522] TSH promotes thyroid growth and is an important indicator of thyroid function. TSH primarily stimulates the metabolism of target organ epithelial cells, promoting intracellular nucleic acid and protein synthesis, thereby causing adenomatous hypertrophy. Since serum FT3 content is not affected by thyroid-binding proteins, it serves as a basic indicator for detecting thyroid dysfunction. As shown in Figure 31, serum TSH levels were significantly increased in the model group compared to the normal control group, and TJ01-013 administration in each dose group could lower serum TSH levels. Compared to the normal control group, FT3 levels were significantly decreased in the model group, and TJ01-013 administration could improve FT3 levels.

[0523] Thyroglobulin (TGAb), upon entering the bloodstream, generates complement, which then binds to and damages follicular epithelial cells. Serum TGAb and TPOAb levels are highly useful in the diagnosis of Hashimoto's disease. As shown in Figure 32, serum TGAb levels were significantly increased in the model group compared to the normal control group, and high-dose TJ01-013 30 mg / kg administration could lower serum TGAb levels. Compared to the normal control group, TPO-Ab levels were significantly increased in the model group, and TPO-Ab levels could be lowered with administration of 15 mg / kg and 30 mg / kg TJ01-013.

[0524] Example 13: Treatment of chronic obstructive pulmonary disease After one week of adaptive feeding, five-week-old male SD rats were randomly assigned to five groups based on body weight: normal (n=10), model control (n=10), TJ01-013 7.5 mg / kg (7.5 mg / kg, n=10), TJ01-013 15 mg / kg (15 mg / kg, n=10), and TJ01-013 30 mg / kg (30 mg / kg, n=10). This model was replicated by injecting lipopolysaccharide into the airways in combination with passive smoking, which is recognized as a model of chronic obstructive pulmonary disease. Excluding the normal control group, the remaining groups were anesthetized on day 1 of modeling by intraperitoneal injection of pentobarbital sodium. The rats were fixed to a rat table, their neck hairs were removed and disinfected, an incision of approximately 0.5 cm was made in the center of the neck, the subcutaneous tissue and fascia were separated, the rat's trachea was exposed, the rat's head was raised to a 45-degree angle, a 1 ml syringe containing 0.2 ml of LPS at a concentration of 1 mg / mL was selected and slowly injected into the rat's airway. After injection was complete, the rat was lifted by its tail and slowly rotated, shaking to ensure uniform distribution of the drug in the rat's airway and both lungs, and finally the surgical wound was sutured. On day 2 postoperatively, the rats were exposed to passive smoking. Tobacco was placed in a fumigation box, and approximately 10 cigarettes were consumed for 1 hour once a day. To avoid uneven distribution of smoke in the airway and lung tissue, the fumigation box was tapped once at approximately 5-minute intervals during smoking. Of these, the normal control group underwent sham surgery and did not undergo fumigation. From the second day of modeling, the normal control group and the model control group were orally administered the solvent (0.5% CMC-Na), and the TJ01-013 administration group was administered TJ01-013 at the corresponding concentration at a volume of 10 ml / kg for a total of 3 weeks. After administration, blood was collected from the posterior bulbar vein of the rats, allowed to stand at room temperature for 30 minutes, then centrifuged at 6000 rpm for 10 minutes, and the upper layer of serum was collected. The levels of TNFα and CXCL1 in the serum were detected by enzyme-linked immunosorbent assay (ELISA).

[0525] The results are shown in Figure 33. Serum TNFα and CXCL1 levels in the model rats were significantly higher compared to the normal control group. Both 15 mg / kg and 30 mg / kg administration of TJ01-013 reduced serum CXCL1 levels, and 30 mg / kg administration of TJ01-013 also reduced serum TNFα levels, with a significant difference. These results suggest that TJ01-013 administration can suppress the increase in inflammatory indicators caused by chronic obstructive pulmonary disease and alleviate symptoms.

[0526] Example 14: Treatment of tinnitus Seven-week-old male C57BL / 6 mice with normal hearing were screened for tinnitus absence using the acoustic startle (AS) response and the gap pre-pulse inhibition of the acoustic startle (GPIAS). Mice were randomly assigned to five groups: normal (n=10), model control (n=10), TJ01-013 7.5 mg / kg (n=10), TJ01-013 15 mg / kg (n=10), and TJ01-013 30 mg / kg (n=10). All groups except the normal control group were modeled using intraperitoneal injection of 450 mg / kg of sodium salicylate. In the normal control group, a corresponding amount of physiological saline was intraperitoneally injected, and drug administration was started on the day of modeling. Of these, the normal control group and the model control group were forcibly administered the solvent (0.5% CMC-Na) orally, while the TJ01-013 administration group was administered an equivalent concentration of TJ01-013 at a volume of 10 ml / kg. After 4 consecutive days of administration, acoustic startle was measured again 3 hours after the final administration. The behavioral test, the AS response and GPLAS response pair, is a behavioral test to detect the presence of tinnitus. Before starting the test, all mice were placed in a transparent box for 1 minute and adapted for 3 consecutive days. The background noise given in the experiment was narrowband noise of 8 kHz and 16 kHz with a bandwidth of 1 kHz in order to understand the frequency range in which tinnitus occurs. During the GPIAS experiment, each mouse was placed in a transparent box in a dark room, and the transparent box was placed on a highly sensitive piezoelectric transducer that generates a voltage proportional to the magnitude of the response induced by sound generated by a digital signal processor. The output of the platform was amplified, sampled, saved to a computer, and analyzed offline. GPIAS consisted of 100 tests with a front gap (gap tests) and 100 tests without a front gap (no-gap tests), with random pairing used for the front-gap and front-gap tests.The severity of tinnitus was calculated as the ratio (Ratio = gap / no gap × 100%) of the amplitude of the response induced by a stimulus with a front gap to the amplitude of the response induced by a stimulus without a front gap.

[0527] As shown in Figure 85, the AS response amplitude ratio in the tinnitus model group injected with sodium salicylate was significantly higher than that of the solvent group during 8kHz and 16kHz noise exposure, indicating successful modeling. The AS response amplitude ratio in the TJ0113 administration group was significantly lower than that of the model group and showed dose-dependent properties, suggesting that TJ0113 significantly improved tinnitus in mice.

[0528] Example 15: Treatment of Psoriasis Eight-week-old male C57BL / 6J mice were randomly assigned to five groups based on body weight after one week of adaptive feeding: a normal control group (n=10), a model control group (n=10), a TJ01-013 7.5 mg / kg dose group (7.5 mg / kg, n=10), a TJ01-013 15 mg / kg dose group (15 mg / kg, n=10), and a TJ01-013 30 mg / kg dose group (30 mg / kg, n=10). Two days prior to the experiment, the backs of the mice were shaved in an area of ​​approximately 2.5 cm x 4 cm and depilated using 2% sodium sulfide. The control group received daily application of 60 mg of petrolatum to their shaved backs. The model group and the TJ01-013 dose group received daily application of 60 mg of imiquimod cream to their shaved backs. Administration began on the first day of modeling and continued for 10 days. The normal control group received an intraperitoneal injection of a corresponding amount of physiological saline. Drug administration was started on the day of modeling. Of these, the normal control group and the model control group received forced oral administration of the solvent (0.5% CMC-Na), while the TJ01-013 administration group received TJ01-013 at an equivalent concentration at a dose of 10 ml / kg. After administration, skin tissue was collected from the backs of the mice and tissue sections were prepared. The thickness was measured at four locations on each section, and the average value was calculated. Skin thickness was used as an indicator of the severity of psoriasis-like symptoms.

[0529] As shown in Figure 35, the skin thickness of the model group was significantly thicker compared to the normal control group, and after treatment with TJ01-013, the skin thickness was significantly reduced compared to the model control group, suggesting that TJ01-013 can significantly alleviate psoriasis-like symptoms in mice in a dose-dependent manner.

[0530] Example 16: Significant therapeutic effect on chronic eczema Balb / c mice aged 6-8 weeks were randomly assigned to five groups based on body weight after one week of adaptive feeding: a normal control group (n=10), a model control group (n=10), a TJ01-013 7.5 mg / kg dose group (7.5 mg / kg, n=10), a TJ01-013 15 mg / kg dose group (15 mg / kg, n=10), and a TJ01-013 30 mg / kg dose group (30 mg / kg, n=10). Two days prior to the experiment, the backs of the mice were shaved in an area of ​​approximately 2.5 cm x 4 cm and depilated using 2% sodium sulfide. All groups except the normal control group were sensitized by applying 60 μL of 6% DNCB (2,4-dinitrochlorobenzene) to the depilated area as an initial treatment. Two weeks later, approximately 3cm x 4cm of hair was removed from the back of each mouse, and 100μL of 0.2% DNCB was applied once a week for four consecutive weeks. The behavioral status of the mice in each group was observed, and the appearance of clear eczema-like skin symptoms such as scabs, rough skin, and dark red spots indicated successful modeling. After successful modeling, drug administration was started. The normal group and the model control group were orally administered the solvent (0.5% CMC-Na), while the TJ01-013 administration group was administered TJ01-013 at the corresponding concentration at a dose of 10ml / kg. The administration cycle was 14 days, and after the end of administration, skin indicators such as transepidermal water loss (TEWL) and stratum corneum water content (SCH) were measured in each mouse group at weeks 0, 1, and 2 of administration using a GPSkinBarrier detector.

[0531] The results are shown in Figure 36. According to the transepidermal water loss (TEWL) index in mice, the significant increase from pre-administration levels in both the DNCB-treated modeling group and the TJ0113 protection group indicates successful modeling. On the other hand, the TJ0113 protection group showed improved protective effects as TEWL decreased with increasing administration duration and dosage. As shown in Figure 37, the significant decrease from pre-administration levels in both the DNCB-treated modeling group and the TJ0113 protection group, according to the mouse stratum corneum water content (SCH) index, indicates successful modeling. On the other hand, the increase in stratum corneum water content with increasing administration duration and dosage in the TJ0113 protection group indicates improved protective effects. These results suggest that TJ0113 has a significant therapeutic effect on eczema.

[0532] Example 17: Treatment of Non-Alcoholic Fatty Liver Disease (NASH) Male SD rats weighing 200-300g were randomly assigned to four groups: a model control group (n=10), a TJ01-013 3mg / kg dose group (3mg / kg, n=10), a TJ01-013 10mg / kg dose group (10mg / kg, n=10), and a TJ01-013 30mg / kg dose group (30mg / kg, n=10). The model and treatment groups were fed a choline-deficient / high-fat diet (CD / HFD) for four consecutive weeks, followed by weekly sodium nitrite administration for three consecutive weeks to induce fatty liver and hepatic fibrosis. The administration cycle began with an initial intraperitoneal administration of sodium nitrite, followed by forced oral administration once daily for eight consecutive weeks. The model group was simultaneously subjected to forced oral administration of the solvent (0.5% CMC-Na). At the endpoint, the liver was removed and histopathological scoring (non-alcoholic fatty liver NAS score) was performed.

[0533] Tissue embedding, sectioning, and Masson staining are performed, and the specific procedures are as follows:

[0534] (a) Tissue embedding Ethanol dehydration: The tissue was dehydrated in stages with ethanol solutions of different concentrations: 75%, 85%, 95%, 100%, and 100%, for 40 minutes each time. Clearing: The tissue was immersed sequentially in three xylene solutions for 30 minutes in each solution. Paraffin immersion: The tissue was immersed sequentially in three paraffin baths for 1 hour in the first bath, 1.5 hours in the second bath, and 2 hours in the third bath. Embedding: Liquid paraffin was poured into a mold box, and the paraffin-soaked tissue block was placed flat on the bottom with the cut surface facing downwards. After the paraffin hardened, the embedding frame was removed, and after complete cooling and hardening, the paraffin block was trimmed, and the paraffin around the tissue was properly retained for sectioning.

[0535] (b) Sectioning The pre-cooled paraffin block was fixed in a paraffin microtome so that the cut surface of the paraffin block was parallel to the knife blade, the knife was tilted at a normal 15 degrees, and the rotary pusher was rotated to adjust the section thickness to 3 μm, cutting the section into uniform thickness sections. Holding a brush in the left hand, the microtome handle was rotated with the right hand, and when the section emerged, it was gently lifted with the brush, and the paraffin section was lightly tweezed with forceps and placed in a section spreading box facing forward, with the water temperature at approximately 40°C. After flattening, the section was removed. To mount the section, one end of the slide was held with the left hand, water was added vertically to mount the section, and the section was pressed with forceps using the right hand to mount it at two-thirds of the way down the slide glass. After mounting the section, it was left to dry slightly in the air, baked in a 60°C baking machine for 1 hour, and then baked in an oven for 2 hours.

[0536] (c) Deparaffinization of paraffin sections Paraffin sections were deparaffinized using a gradient method in the following order: xylene I for 15 minutes, xylene II for 15 minutes, anhydrous ethanol I for 10 minutes, anhydrous ethanol II for 10 minutes, 95% alcohol for 10 minutes, and 85% alcohol for 10 minutes.

[0537] (d)masson staining Paraffin sections were stained with hematoxylin for 5-10 minutes, rinsed with tap water, stained with Masson-Ponceau acidic fuchsin solution for 5-10 minutes, immersed for a while in 2% glacial acetic acid solution, stained with 1% phosphomolybdic acid for 3-5 minutes, then stained directly with aniline blue for 5 minutes without washing, and immersed for a while in 0.2% glacial acetic acid solution.

[0538] (e) Dehydration, sealing and image acquisition Paraffin sections were immersed in 75% ethanol for 2 minutes, then 85% ethanol for 2 minutes, then anhydrous ethanol for 2 minutes, then anhydrous ethanol for 2 minutes, and finally xylene for 2 minutes until clear. The sections were removed from the xylene and sealed with neutral gum. They were examined under a microscope, images were collected, and analyzed.

[0539] Tissue embedding, sectioning, and Masson staining are performed, and the specific procedures are as follows:

[0540] The tissue was embedded in embedding solution, and frozen sections were prepared to a thickness of approximately 6–10 μm. The sections were lightly washed with distilled water, rinsed with 60% isopropyl alcohol for 20–30 seconds, and then stained with oil red stain for 5–10 minutes. Excess stain was removed with 60% isopropyl alcohol, washed with distilled water, and the nuclei were lightly stained with Mayer hematoxylin. Differentiation was performed with 1% hydrochloric acid and alcohol. After rinsing with running water for 10 minutes, the sections were mounted with mounting solution and observed under a microscope.

[0541] The results are shown in Figure 38. Administration of TJ01-013 alleviated fatty degeneration in liver tissue. As shown in Figures 39 and 40, administration of TJ01-013 reduced the levels of inflammation and fibrosis in liver tissue. These experimental results suggest that administration of TJ01-013 can alleviate the symptoms of NASH to some extent.

[0542] Example 18: Treatment of cholecystitis and liver dysfunction Male SD rats weighing 200-300g were randomly assigned to five groups: a normal control group (Sham, n=10), a model control group (Vehicle, n=10), a TJ01-013 3mg / kg dose group (3mg / kg, n=10), a TJ01-013 10mg / kg dose group (10mg / kg, n=10), and a TJ01-013 30mg / kg dose group (30mg / kg, n=10). Modeling was performed by bacterial infection and common bile duct ligation as described below: rats in the model and dose groups were anesthetized with ether, laparotomy was performed to expose the gallbladder, bile was aspirated with a 1mL syringe, the bile duct was ligated, and bacteria (0.1mL, Escherichia coli 1*10⁴CFU / mL) were injected directly above the ligation site. The needle incision site was ligated, the abdomen was closed, and the modeling was completed. A purulent inflammatory response occurred within one week. In the sham surgery group, sterile saline was injected into the common bile duct without ligation. The administration cycle began on the day of modeling, with the administration group receiving each dose of TJ0113 and the model group receiving the solvent (0.5% CMC-Na) daily for 10 consecutive days. For the endpoint, blood was collected by autopsy and aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) were measured.

[0543] The results are shown in Figure 41. Compared to the sham surgery group, liver-related biochemical indicators such as ALT, AST, and TBIL were significantly increased in the modeling group, and all of these decreased after TJ01-013 administration. Among these, the 10 mg / kg dose group showed a significant difference, suggesting that TJ01-013 administration can alleviate liver damage caused by cholecystitis.

[0544] Example 19: Treatment of age-related macular degeneration Four-month-old C57BL / 6 mice were randomly assigned to four groups: a normal control group (n=10), a model control group (n=10), an I-14-110 mg / kg dose group (3 mg / kg, n=10), and a TJ01-013-10 mg / kg dose group (10 mg / kg, n=10). A mouse model of age-related macular degeneration was created by combining chronic light exposure and hydroquinone administration as follows: Model and treatment mice were placed in an LED light fixture with a wavelength of 400-750 nm for 12 hours a day, and a light intensity of 2500 lx was ensured at the head using an illuminometer. The mice were also fed a diet containing 8 g / (kg·bw) of hydroquinone based on purified synthetic base. The control group mice were given the same diet without hydroquinone to maintain their normal circadian rhythm. The animals were reared for 3.5 months, during which the administration cycle began 1.5 months after modeling and continued for 2 months. The treatment group received TJ01-013 and I-14-110 mg / kg. The model group received daily forced oral administration of the solvent (0.5% CMC-Na). For endpoints, changes in retinal function and structure were observed in the mice of each group using electroretinography (ERG), light microscopy, and electron microscopy. Retinal cell apoptosis was observed using the TUNEL method, and the expression and distribution of retinal and choroidal vascular endothelial growth factor (VEGF) and CD31 were measured using immunofluorescence.

[0545] Table 1. Group-based comparison of measurement results using electroretinography (ERG). TIFF2026509562000097.tif46170

[0546] Optical microscopy of the retinal structure revealed that the normal group had a regular retinal structure, uniform cell morphology, and continuous, orderly retinal pigment epithelium. Compared to the normal group, the model group showed looser retinal layer arrangement, fewer photoreceptor cells, and atrophy of the retinal pigment epithelium. Bruch's membrane structure was disrupted, vascular proliferation was visible, and thickening was observed in some areas, while thinning was observed in others. The number of photoreceptor cells was significantly lower compared to the normal group. These phenomena were improved to some extent in the TJ01-013 and I-14-1 administered groups.

[0547] Retinal electron microscopy revealed that the retinal photoreceptor discs of normal mice were clearly organized and neatly arranged, and the pigment epithelial cells possessed abundant mitochondria, numerous and long apical microvilli, and a uniformly thick and orderly Bruch's membrane. The photoreceptor discs of the model mice were loose and deformed, showing changes such as separation, fragmentation, and concentration. The number of pigment granules in the retinal pigment epithelium was reduced, and the apical microvilli were sparser and shorter compared to the normal group. Deposits were observed beneath the retinal pigment epithelium (RPE). The thickness of Bruch's membrane was irregular and non-uniform, with some discontinuous sections, and endothelial cell proliferation was observed. The above phenomena were improved to some extent in the TJ01-013 and I-14-1 administered groups.

[0548] As a result, I-14-1 and TJ01-013 were able to mitigate age-related macular degeneration in a mouse model induced by a combination of chronic light exposure and hydroquinone administration, including improved retinal photosensitivity and restoration of normal retinal structure, demonstrating that the effect of TJ01-013 was superior to that of I-14-1.

[0549] Example 20: Treatment of retinitis pigmentosa, delay of retinitis pigmentosa progression 1. Modeling Sixteen-week-old Pde6aD670G / D670G mice were fed an adaptive diet for one week. The mechanism of disease in this mouse model is that the hydrolysis rate of cyclic acylglycosides is reduced or ineffective, resulting in the accumulation of large amounts of cGMP in cells, causing CNG channels to remain constantly open and leading to rod cell death. Based on body weight, mice were randomly assigned to three groups: a model group (Control, forced oral administration of 0.5% CMC-Na, n=8), a TJ01-013 administration group (TJ01-013, 30 mg / kg TJ01-013 forced oral administration, n=8), and an I-14-1 administration group (I-14-1, 30 mg / kg I-14-1 forced oral administration, n=8). A normal control group was also established using normal C57BL / 6J mice of the same age (WT, forced oral administration of 0.5% CMC-Na, n=8). The experiment involved administering the drug for a total of eight weeks, and after the completion of administration, confocal laser scanning microscopy imaging and retinal immunofluorescence staining were performed.

[0550] 2. Confocal laser scanning microscopy imaging After anesthetizing the mice, a custom-made bottle cap was used to fix the anterior part of the anesthetized mice's heads in a relaxed state within the imaging device. During imaging, a hydration gel was used to keep the mice's corneas constantly moist. The infrared mode of the Spectralis was used to locate the large blood vessels in the retina and focus on the fundus. By pushing the handle forward, uniform illumination was achieved across the entire field of view. Retinal fundus images, centered on the optic nerve of the mice, were acquired. After the retinal scan, the acquired images were statistically analyzed using imageJ software.

[0551] As shown in Figure 42, the thickness of the photoreceptor layer was measured and compared. In the model group, the thickness of the photoreceptor layer was significantly reduced compared to the control group, and a statistically significant difference was observed. After administration of TJ01-013 and I-14-1, the thickness of the photoreceptor layer increased by a statistically significant amount, and the therapeutic effect of TJ01-013 was significantly superior to that of I-14-1.

[0552] 3. Retinal immunofluorescence staining After the experiment, the mice were euthanized, and their eyeballs were immersed in 4% paraformaldehyde for 5 minutes. The eyes were then removed under a microscope, the anterior end of the eye was excised, and the retina was extracted and seeded into a 96-well cell culture plate. The plate was immersed in PBST for 15 minutes three times, fixed with 4% paraformaldehyde for 20 minutes, and then immersed in PBST for 10 minutes three times. GFAP antibody was diluted in the specified volume of PBST solution according to the instructions, added to the 96-well cell culture plate, and incubated overnight at 4°C. After washing with PBST, Hoechst was added, and the plate was incubated at room temperature for 15 minutes. After washing with PBST, the retina was transferred to a pre-treated glass slide. Using forceps, the retina was positioned with the ganglion cell side on the glass slide and the photoreceptor layer side away from the glass slide, and the entire retina was unfolded. One drop of fluorescent protective mounting medium was added to the retinal section on the glass slide, and the slide was covered with a coverslip, minimizing the formation of air bubbles. The retina was observed under a confocal microscope.

[0553] As shown in Figure 43, compared to the control group, the retinal microglia density in the retinitis pigmentosa mouse model increased significantly, with a statistically significant difference observed. After administration of TJ01-013 and I-14-1, the retinal microglia density decreased by a statistically significant margin, and the therapeutic effect of TJ01-013 was superior to that of I-14-1.

[0554] Experimental Example 21: Treatment of Multiple Sclerosis Multiple sclerosis (MS) is an autoimmune demyelinating disease with a complex etiology that affects the central nervous system. It is characterized by multiple lesions, relapsing, and a high rate of disability, severely impacting patients' daily lives. The pathogenesis is still not fully understood, but it is thought to be caused by various factors, including immune factors, environmental factors, and genetic factors. Currently, it is believed that the etiology involves an abnormal immune attack that disrupts the blood-brain barrier, allowing multiple inflammatory factors and immune cells to invade the central nervous system. These cells act on microglia and immune cells in the central nervous system, triggering an inflammatory response that leads to demyelination, neuronal cell death, and axonal damage. Current treatment for multiple sclerosis mainly focuses on anti-inflammatory therapy, but these therapies are only effective during relapses and remissions. Therefore, developing treatments for multiple sclerosis is an urgent task.

[0555] The UP model can be used to simulate multiple sclerosis by inducing demyelinating symptoms in mice through dietary supplementation with CUP. CUP is a copper chelating agent that, when added to the animal's diet, ultimately induces apoptosis of oligodendrocytes, leading to demyelinating.

[0556] 1. Modeling After one week of adaptive feeding, 7-8 week old C57BL / 6 female mice were randomly assigned to four groups based on body weight: a normal control group (0.5% CMC-Na forced oral administration, n=8), a model group (0.5% CMC-Na forced oral administration, n=8), a TJ01-013 group (TJ01-013, 30 mg / kg TJ01-013 forced oral administration, n=8), and an I-14-1 group (I-14-1, 30 mg / kg I-14-1 forced oral administration, n=8). The normal control group was given a basic diet for 12 weeks, while the model group, TJ01-013 group, and I-14-1 group were given a 0.2% CUP diet throughout the entire period. Administration in all groups began 6 weeks after modeling and continued for a total of 12 weeks, with a dose of 5 ml / kg.

[0557] 2. Behavioral testing (1) Elevated cross maze test The elevated cross maze consisted of two open arms (35cm x 6cm), two closed arms (35cm x 6cm x 14cm), and an intermediate area (6cm x 6cm), and was located 70cm above the ground. Mice were placed in the intermediate area facing the open arms and moved around a 50cm x 50cm open field for 5 minutes before the test began. During the test, the activity time, distance, and number of times mice entered the open arms were statistically recorded. After each mouse was tested, the maze was wiped with 75% alcohol. The experimental results are shown in Figure 44. Compared to the control group, the number of times mice in the model group entered the open arms was significantly increased. After administration of TJ01-013 and I-14-1, the number of times mice entered the open arm decreased significantly, with statistically significant differences between the two, and the therapeutic effect of TJ01-013 was significantly superior to that of I-14-1. As shown in Figure 45, compared to the control group, the distance walked by mice in the model group in the open arm increased significantly, and after administration of TJ01-013 and I-14-1, the distance walked by mice in the open arm decreased, and TJ01-013 treatment was significantly superior to I-14-1, with statistically significant differences. As shown in Figure 46, compared to the control group, the time spent in the open arm by mice in the model group increased significantly, and after administration of TJ01-013 and I-14-1, the time spent in the open arm by mice decreased significantly, with statistically significant differences between the two, and TJ01-013 treatment was significantly superior to I-14-1.

[0558] (2) Water Maze Test Mice were placed in a tank 70 cm in diameter and 30 cm high, with the water temperature set to approximately 22-24°C. The tank was divided into four quadrants, and a 5 cm diameter platform, placed 1 cm below the water surface, was placed in the target quadrant. Before the formal test, the mice were allowed to acclimate for one day and then learn for four days. During learning, the mice were guided to enter the water facing the wall of the tank and be given 60 seconds to find the platform, or to learn on the platform for 30 seconds otherwise. The time the mice spent finding the platform during the learning period was recorded. On the day of the test, the platform was removed, and the number of times the mice crossed the platform after entering from the quadrant opposite the target quadrant was recorded to measure the mice's spatial learning and memory abilities. As shown in Figure 47, compared to the normal group, the number of times mice crossed the platform was significantly reduced in the model group. After administration of TJ01-013 and I-14-1, the number of times mice crossed the platform increased, and TJ01-013 treatment was significantly superior to I-14-1, showing a statistically significant difference.

[0559] Experimental Example 22: Treatment of Hypothyroidism Hypothyroidism, also known as hypothyroidism, is a condition characterized by insufficient or deficient production of thyroid hormones by the tissues. It is more common in women than men and its prevalence increases with age. In modern medicine, hypothyroidism is caused by various factors, but the majority of cases are thought to be caused by autoimmune thyroiditis, radioactive iodine therapy to the thyroid gland, or thyroid surgery. In modern medicine, thyroid hormone replacement therapy is often used to treat hypothyroidism. However, long-term use of thyroid hormones may directly stimulate the action of osteoclasts on bone resorption, potentially increasing the risk of osteoporosis, coronary artery disease, and heart failure. Therefore, finding safer and more effective treatments for the prevention and treatment of hypothyroidism is an urgent task.

[0560] (1) Modeling 7-8 week old SD rats were randomly assigned to one week of adaptive feeding and then, based on body weight, into four groups: a normal control group (0.5% CMC-Na forced oral administration, n=8), a model group (0.5% CMC-Na forced oral administration, n=8), a TJ01-013 group (TJ01-013, 30 mg / kg TJ01-013 forced oral administration, n=8), and an I-14-1 group (I-14-1, 30 mg / kg I-14-1 forced oral administration, n=8). The model group, TJ01-013 group, and I-14-1 group were administered 0.1% propylthiouracil at a dose of 10 ml / kg for 15 consecutive days, while the normal control group received 0.1% physiological saline. After modeling, blood was drawn from the eyeballs, serum was centrifuged at 3000 rpm, and thyroid function was measured to confirm successful modeling. After 4 weeks of continuous administration, administration was discontinued, blood was drawn and serum was separated, and triiodothyronine T3, tetraiodothyronine T4, free triiodothyronine FT3, free tetraiodothyronine FT4, thyroid-stimulating hormone (TSH), and IgG levels were measured.

[0561] (2) Measurement of serum hormones Enzyme-linked immunosorbent assay (ELISA) utilizes the immobilization and enzymatic labeling of antigens or antibodies. During measurement, the sample reacts with the antigen or antibody on the surface of a solid support. The antigen-antibody complex formed on the solid support is separated from other substances by washing. Next, the enzymatically labeled antigen or antibody is added and bound to the solid support through a reaction. Upon addition of the substrate for the enzymatic reaction, the enzyme catalyzes the substrate to produce a colored product. The amount of the product directly correlates with the amount of the test substance in the sample, and this was quantitatively analyzed using a microplate reader.

[0562] The results are shown in Figure 48. Compared to the normal group, T3 and T4 levels in the model group were significantly lower, and after administration of TJ01-013 and I-14-1, T3 and T4 levels significantly increased. The therapeutic effect of TJ01-013 was significantly superior to that of I-14-1, with a statistically significant difference. As shown in Figure 49, compared to the normal group, serum FT3 and FT4 levels in the model group were significantly lower, and after administration of TJ01-013 and I-14-1, FT3 and FT4 levels significantly increased. The therapeutic effect of TJ01-013 was superior to that of I-14-1. As shown in Figure 50, compared to the normal group, serum FSH levels in the model group were significantly increased, and after administration of TJ01-013 and I-14-1, FSH levels decreased, with a significant difference observed. The therapeutic effect of TJ01-013 was significantly superior to that of I-14-1. As shown in Figure 51, compared to the normal group, serum IgG levels in the model group were significantly increased, and after administration of TJ01-013 and I-14-1, IgG levels decreased, showing a statistically significant difference. The therapeutic effect of TJ01-013 was significantly superior to that of I-14-1.

[0563] Experimental Example 23: Treatment of Atrophic Gastritis Chronic atrophic gastritis (CAG) is a common clinical condition whose incidence and prevalence increase with age. It is characterized by a decrease in proper glands due to recurrent damage to the gastric mucosal epithelium, sometimes accompanied by intestinal metaplasia or pseudopyloric metaplasia, and its symptoms are generally nonspecific. Those who do experience symptoms may have nonspecific indigestion symptoms such as upper abdominal bloating and pain, and may also be accompanied by nausea, loss of appetite, acid reflux, stomach heaviness, and a bitter taste in the mouth. Recurrence is common. Currently, there is no established effective treatment that can alleviate all clinical symptoms.

[0564] (1) Modeling After one week of adaptive feeding, 7-8 week old SD rats were randomly assigned to four groups based on body weight: a normal control group (0.5% CMC-Na forced oral administration, n=8), a model group (0.5% CMC-Na forced oral administration, n=8), a TJ01-013 administration group (TJ01-013, 30 mg / kg TJ01-013 forced oral administration, n=8), and an I-14-1 administration group (I-14-1, 30 mg / kg I-14-1 forced oral administration, n=8). Modeling was performed using the Hp strain. Frozen Helicobacter pylori Hp cells were removed from a -80°C freezer, slowly thawed at room temperature, spread uniformly, and cultured on Columbia blood agar. When the Hp strain reached the logarithmic growth phase, physiological saline was added to prepare a bacterial suspension, and the bacterial concentration was measured using the turbidimetric method at 1 × 10⁻⁶. 12 The concentration was adjusted to cfu / ml.

[0565] After one week of adaptive feeding, rats were randomly assigned to two groups: a normal control group (0.5% CMC-Na forced oral administration, n=8) and a modeling group of 24 rats. The control group was given a normal diet and drinking water, while the model group was modeled using a multifactorial composite method. Rats were given 120 mg / L of MNNG solution daily and fed a diet containing ranitidine 0.03 g / kg. Two days after feeding, the rats were fasted for one day. On the first day of feeding, 1...

Claims

1. The use of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or prodrug thereof in the preparation of a medicament for treating at least one disease selected from reproductive system disorders, autoimmune disorders, dermatitis, eye disorders, muscle or bone degenerative disorders, neurological disorders, anemia, adrenal disorders, chronic gastritis, myocarditis, periodontitis, hypothyroidism, alopecia, liver disorders, tinnitus, and chronic obstructive pulmonary disease. (Here, Z is or it is a sulfur atom, R 1 is hydrogen, C 1～6 Alkyl, And here, R 11 and R 12 Each is independently C 1～6 Alkyl or C 1～6 It is a cycloalkyl group, and n is 1 to 4. R 2 is hydrogen, C 1～6 alkyl, 3- to 6-membered cycloalkyl, 3- to 6-membered epoxyalkyl, phenyl, C 2－1 alkyl substituted with at least one hydrogen by R 1～6 alkyl, phenyl substituted with at least one hydrogen by R 2－1 , where R 2－1 is hydroxyl, halogen, amino or C 1～6 alkoxy, R 3 teeth Here, R 3－1 is hydrogen, hydroxyl, C 1～6 Alkyl, C 1～6 Alkoxy, C 3～6 Cycloalkyl, 3-6 member epoxyalkyl, amino, C 1～6 Amine group, -CH 2 C(O)R 3－2 , -CH 2 C(O)OR 3－2 , -CH 2 C(O)N(R) 3－2 R 3－2a ) and R 3－2 and R 3－2a Each is independently hydrogen and C 1～6 Alkyl or 3-6 membered cycloalkyl, m is 1 to 6, and Ar is a phenyl, naphthyl, 5- or 6-membered monocyclic heteroaryl, 8- to 10-membered condensed bicyclic heteroaryl, with at least one hydrogen atom being R 3－3 Phenyl substituted with R, at least one hydrogen atom is R 3－3 Naphthyl substituted with R, at least one hydrogen atom is R 3－3 A 5-membered or 6-membered monocyclic heteroaryl substituted with R, at least one hydrogen atom is R 3－3 It is an 8-10 member condensed bicyclic heteroaryl substituted with the R 3－3 is hydrogen, halogen, C 1～6 Alkyl, 3-6 membered cycloalkyl, hydroxyl, C 1～6 Alkoxy, 3-6 member epoxyalkyl, C 1～6 Haloalkyl, C 2～6 Alkenil, C 2～6 Alkinyl, -N(R 3－3a R 3－3b ) or phenyl, R 3－3a and R 3－3b Each is independently hydrogen and C 1～6 Alkyl or 3-6 membered cycloalkyl, R 4 teeth Here, R 4－1 R is phenyl, naphthyl, with at least one hydrogen atom 4－11 Phenyl substituted with R, 5-membered or 6-membered monocyclic heteroaryl, at least one hydrogen atom is R 4－11 5-membered or 6-membered monocyclic heteroaryls substituted with R, 8-10 membered fused bicyclic heteroaryls, at least one hydrogen atom is R 4－11 It is an 8-10 member condensed bicyclic heteroaryl substituted with R, 4－11 Hydrogen, halogen, nitro, nitrile, hydroxyl, C 1～6 Alkyl, C 3～6 Cycloalkyl, C 1～6 Alkoxy, -N(R 4－1a R 4－1b ), phenyl, C 1～6 Haloalkyl, C 1～6 Haloalkoxy, -C(O)OR 4－12 , -C(O)R 4－12 , -C(O)N(R 4－1a R 4－1b ), -S(O) 2 R 4－12 , -S(O)R 4－12 , -OC(O)R 4－12 , -OC(O)OR 4－12 or And R 4－12 , R 4－1a and R 4－1b Each is independently hydrogen and C 1～6 Alkyl, C 3～6 Cycloalkyl, C 2～6 Alkenil, C 2～6 Alkynyl, a C atom in which at least one hydrogen atom is substituted with a halogen. 1～6 Alkyl, C in which at least one hydrogen is substituted with a halogen. 2～6 Alkenyls, C12C 3～6 Cycloalkyl, C in which at least one hydrogen is substituted with a halogen. 2～6 It is an alkynyl and also R 4－1a and R 4－1b They can bond with each other to form a ring, R 4－2 is C 1～6 alkyl, C 3～6 cycloalkyl, C in which at least one hydrogen is substituted with hydroxyl 1～6 alkyl, C 3～6 epoxyalkyl, or R 2 is C 1～6 alkyl and R 4－2 is C 1～6 alkyl, when R 4－2 and R 2 are bonded to form a 4- to an 8-membered ring, R 4－3 is C 1～6 Alkyl or C 1～6 It is an alkoxy, R 5 is present in a number of from 0 to 5, and R 5 is, in each occurrence, independently of the others, hydrogen, halogen, nitro, nitrile, -N ＋ (R 5－1 ) 3 , C 1～6 haloalkyl, -C(O)OR 5－1 , -C(O)R 5－1 , -C(O)N(R 5－1 R 5－1a ), -S(O) 2 R 5－1 , -S(O)R 5－1 , -S(O) 2 N(R 5－1 R 5－1a ), -S(O)N(R 5－1 R 5－1a ), -N = C(R 5－1 R 5－1a )]] 5－1a 1～6 alkyl, phenyl, phenyl in which at least one hydrogen is replaced by R 5－1 , C 1～6 alkoxy, -N(R 5－1 R 5－1a ), -N(R 5－1 )C(O)R 5－1a , -N(R 5－1 )C(O)OR 5－1a , -N(R 5－1 )C(O)N(R 5－1a R 5－1b ), -OC(O)R 5－1 , -OC(O)OR 5－1 , -OC(O)N(R 5－1 R 5－1a ) or -SR 5－1 , where R 5－1 , R 5－1a and R 5－1b are each independently hydrogen, C 1～6 alkyl, C 2～6 alkenyl, C 2～6 alkynyl, C 1～6 alkyl in which at least one hydrogen is replaced by halogen, C 2～6 alkenyl in which at least one hydrogen is replaced by halogen or C 2～6 alkynyl in which at least one hydrogen is replaced by halogen.).

2. The above is or it is a sulfur atom, R 1 is hydrogen, C 1～4 Alkyl, And here, R 11 and R 12 Each is independently C 1～4 Alkyl or C 1～4 It is a cycloalkyl group, and n is 1 or 2. R 2 is hydrogen, C 1～4 Alkyl, 3-6 member cycloalkyl, 3-6 member epoxyalkyl, phenyl, at least one hydrogen R 2－1 C replaced by 1～4 Alkyl, at least one hydrogen is R 2－1 It is a phenyl substituted with, where R 2－1 is hydroxyl, halogen, amino or C 1～4 It is an alkoxy, R 3 teeth Here, R 3－1 is hydrogen, hydroxyl, C 1～4 Alkyl, C 1～4 Alkoxy, -N(R 3－2 R 3－2a ) and R 3－2 and R 3－2a Each is independently hydrogen or C 1～4 It is alkyl, m is 1 to 4. Ar is phenyl, a 5-membered or 6-membered monocyclic heteroaryl, with at least one hydrogen atom being R 3－3 A 5-membered or 6-membered monocyclic heteroaryl substituted with the R 3－3 Hydrogen, halogen, C 1～4 Alkyl, hydroxyl, C 1～4 Alkoxy, C 1～4 Haloalkyl or -N(R) 3－3a R 3－3b ) and R 3－3a and R 3－3b Each is independently hydrogen or C 1～4 It is alkyl, R 4 teeth Here, R 4－1 Phenyl, with at least one hydrogen atom R 4－11 Phenyl substituted with R, 5-membered or 6-membered monocyclic heteroaryl, at least one hydrogen atom is R 4－11 A 5-membered or 6-membered monocyclic heteroaryl substituted with the R 4－11 Hydrogen, halogen, nitro, C 1～4 Alkyl, C 3～6 Cycloalkyl, C 1～4 Alkoxy, -N(R 4－1a R 4－1b ), phenyl, C 1～4 Haloalkyl, C 1～4 Haloalkoxy or And R 4－1a and R 4－1b Each is independently hydrogen and C 1～4 Alkyl or C 3～6 It is cycloalkyl and R 4－1a and R 4－1b They can bond with each other to form a ring, R 4－2 is C 1～4 Alkyl, C 3～5 Cycloalkyl, C in which at least one hydrogen is substituted with a hydroxyl group. 1～4 Alkyl, C 3～5 It is epoxyalkyl, or R 2 C 1～4 Alkyl and R 4－2 C 1～4 If it is alkyl, R 4－2 and R 2 They combine to form a 4-8 membered ring. R 4－3 is C 1～4 Alkyl or C 1～4 It is an alkoxy, R 5 In each appearance, hydrogen, halogen, nitro, nitrile, and -N appear independently. ＋ (R 5－1 ) 3 , C 1～4 Haloalkyl, -C(O)OR 5－1 , -C(O)R 5－1 , -C(O)N(R 5－1 R 5－1a ), -S(O) 2 R 5－1 , -S(O)R 5－1 -N=C(R 5－1 R 5－1a ), hydroxyl, C 1～4 Alkyl, phenyl, at least one hydrogen is R 5－1 Phenyl substituted with C 1～4 Alkoxy, -N(R 5－1 R 5－1a ), -N(R 5－1 ) C(O)R 5－1a or -OC(O)R 5－1 And here, R 5－1 , R 5－1a and R 5－1b Each is independently hydrogen and C 1～4 Alkyl, C in which at least one hydrogen is substituted with a halogen. 1～4 The use according to claim 1, characterized in that it is alkyl.

3. The above is or it is a sulfur atom, and / or, R 1 is hydrogen, And here, R 11 and R 12 Each of these is independently methyl, ethyl, n-propyl, or isopropyl, where n is 1. and / or, R 2 These are hydrogen, methyl, ethyl, n-propyl, isopropyl, ethyl with one hydrogen substituted with a hydroxyl, n-propyl with one hydrogen substituted with a hydroxyl, phenyl, and / or, R 3 teeth Here, R 3－1 is hydrogen, hydroxyl, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, sec-butoxy, or isobutoxy. m is 1, Ar is a phenyl, 5-membered or 6-membered nitrogen-containing monocyclic heteroaryl. and / or, R 4 teeth Here, R 4－1 Phenyl, with at least one hydrogen atom R 4－11 Phenyl substituted with R, 5-membered or 6-membered monocyclic heteroaryl, at least one hydrogen atom is R 4－11 5-membered or 6-membered monocyclic heteroaryls substituted with R, 8-10 membered fused bicyclic heteroaryls, at least one hydrogen atom is R 4－11 It is an 8-10 member condensed bicyclic heteroaryl substituted with the R 4－11 Halogen, nitro, methyl, ethyl, n-propyl, isopropyl, Fluoromethyl, fluoroethyl, fluoro-n-propyl, fluoroisopropyl, chloromethyl, chloroethyl, chloro-n-propyl, chloroisopropyl, bromomethyl, bromoethyl, bromo-n-propyl, bromoisopropyl, iodomethyl, iodoethyl, iodo-n-propyl, iodoisopropyl, fluoromethoxy, fluoroethoxy, fluoro-n-propoxy, fluoroisopropoxy, chloromethoxy, chloroethoxy, chloro-n-propoxy, chloroisopropoxy, bromomethoxy, bromoethoxy, bromo-n-propoxy, bromoisopropoxy, iodomethoxy, iodoethoxy, iodo-n-propoxy, iodoisopropoxy or R 4－2 These include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, ethyl with one hydrogen substituted with hydroxyl, n-propyl with one hydrogen substituted with hydroxyl, and n-butyl with one hydrogen substituted with hydroxyl. or phenyl, or R 2 is methyl, ethyl, or n-propyl, and R 4－2 If R is methyl or ethyl, 4－2 and R 2 They combine to form a 4-8 membered ring. R 4－3 These are methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, or isopropoxy. and / or, R 5 In each appearance, hydrogen, halogen, nitro, nitrile, and -N appear independently. ＋ (R 5－1 ) 3 Fluoromethyl, fluoroethyl, fluoro-n-propyl, fluoroisopropyl, chloromethyl, chloroethyl, chloro-n-propyl, chloroisopropyl, bromomethyl, bromoethyl, bromo-n-propyl, bromoisopropyl, -C(O)OR 5－1 , -C(O)R 5－1 , -C(O)N(R 5－1 R 5－1a ), -S(O) 2 R 5－1 , -S(O)R 5－1 -N=C(R 5－1 R 5－1a ), hydroxyl, methyl, ethyl, n-propyl, isopropyl, phenyl, at least one hydrogen R 5－1 Phenyl, methoxy, ethoxy, n-propoxy, isopropoxy, -N(R) substituted 5－1 R 5－1a ), -N(R 5－1 ) C(O)R 5－1a , -OC(O)R 5－1 And here, R 5－1 , R 5－1a and R 5－1b The use according to claim 1, characterized in that each of them is independently hydrogen, methyl, ethyl, n-propyl, isopropyl, fluoromethyl, fluoroethyl, fluoro-n-propyl, fluoroisopropyl, chloromethyl, chloroethyl, chloro-n-propyl, chloroisopropyl, bromomethyl, bromoethyl, bromo-n-propyl, or bromoisopropyl.

4. Z is or it is a sulfur atom, and / or, R 1 is hydrogen, and / or, R 2 is hydrogen, methyl, or phenyl, and / or, R 3 teeth and / or, R 4 teeth Here, R 4－1 Phenyl, with at least one hydrogen atom R 4－11 Phenyl substituted with R, a 5-membered monocyclic heteroaryl, at least one hydrogen is R 4－11 A 5-membered monocyclic heteroaryl, a 9-membered condensed bicyclic heteroaryl, or naphthyl substituted with, where R 4－11 bromine, fluorine, chlorine, methyl, nitro, phenyl, trifluoromethyl, Methoxy, cyclopropyl, trifluoromethoxy, nitro or R 4－2 is methyl, ethyl, or phenyl, or R 2 is methyl, ethyl, or n-propyl, and R 4－2 If R is methyl or ethyl, 4－2 and R 2 They combine to form a 4-6 membered ring. R 4－3 These are methoxy, ethoxy, n-propoxy, or isopropoxy. and / or, R 5 In each appearance, halogen, nitro, nitrile, carboxyl, and -NHC(O)CH are independently present. 3 The use according to claim 1, characterized in that it is methoxy or hydroxyl.

5. The use according to claim 1, characterized in that the compound is selected from any one of the following compounds.

6. Z is And R 1 is hydrogen, and R 2 is hydrogen, and R 3 is hydrogen And R 4 teeth, And, Here, R 3-1 R is hydrogen, hydroxyl, 4-1 Phenyl, with at least one hydrogen atom R 4-11 A phenyl substituted with R 4-11 The use according to claim 1, characterized in that is halogen-substituted methyl, halogen-substituted ethyl, methyl, ethyl, or halogen.

7. R 3-1 is hydroxyl, and / or R 4-1 The use according to claim 6, characterized in that the material is phenyl, phenyl in which at least one hydrogen atom is substituted with trifluoromethyl, or phenyl in which at least one hydrogen atom is substituted with a halogen.

8. The compound represented by the general formula I is The use according to claim 7, characterized in that it is the same as described above.

9. The aforementioned reproductive system disorders include premature ovarian failure, ovarian dysfunction, polycystic ovary syndrome, oligospermia, and erectile dysfunction. The aforementioned autoimmune diseases include systemic lupus erythematosus nephritis, rheumatoid arthritis, multiple sclerosis, and Hashimoto's disease. The aforementioned skin diseases include psoriasis, melasma, vitiligo, and chronic eczema. The aforementioned eye diseases include cataracts, age-related macular degeneration, and retinitis pigmentosa. The aforementioned degenerative diseases of muscle or bone include sarcopenia and lumbar disc herniation. The aforementioned neurological disorders include epilepsy and stroke. The aforementioned anemia includes β-thalassemia, The aforementioned adrenal diseases include primary aldosteronism and Cushing's syndrome. The aforementioned chronic gastritis includes chronic atrophic gastritis, and / or The use according to claim 1, characterized in that the liver injury is acute alcoholic liver injury, chronic alcoholic liver injury, drug-induced liver injury, non-alcoholic fatty liver, or liver injury due to cholecystitis.

10. The aforementioned use is, (a1) Preparation of a medicine for the prevention and / or treatment of premature ovarian failure, and / or (a2) Prevention and / or treatment of premature ovarian failure, and / or (b1) Preparation of medicines for the prevention and / or treatment of ovarian insufficiency, and / or (b2) Prevention and / or treatment of ovarian insufficiency, and / or (c1) Preparation of medicines for the prevention and / or treatment of systemic lupus erythematosus nephritis, and / or (c2) Prevention and / or treatment of systemic lupus erythematosus nephritis, and / or (d1) Preparation of medicines for the prevention and / or treatment of sarcopenia, and / or (d2) Prevention and / or treatment of sarcopenia, and / or (e1) Preparation of medicines for the prevention and / or treatment of liver damage, and / or (e2) Prevention and / or treatment of liver damage, and / or (f1) Preparation of medicines for the prevention and / or treatment of oligospermia, and / or (f2) Prevention and / or treatment of oligospermia, and / or (g1) Preparation of medicines for the prevention and / or treatment of rheumatoid arthritis, and / or (g2) Prevention and / or treatment of rheumatoid arthritis, and / or (h1) Preparation of medicines for the prevention and / or treatment of cataracts, and / or (h2) Prevention and / or treatment of cataracts, and / or (i1) Preparation of medicines for the prevention and / or treatment of Cushing's syndrome, and / or (i2) Prevention and / or treatment of Cushing's syndrome, and / or (j1) Preparation of medicines for the prevention and / or treatment of Hashimoto's disease, and / or (j2) Prevention and / or treatment of Hashimoto's disease, and / or (k1) Preparation of pharmaceuticals for the prevention and / or treatment of chronic obstructive pulmonary disease, and / or (k2) Prevention and / or treatment of chronic obstructive pulmonary disease, and / or (l1) Preparation of medicines for the prevention and / or treatment of tinnitus, and / or (l2) Prevention and / or treatment of tinnitus, and / or (m1) Preparation of medicines for the prevention and / or treatment of psoriasis, and / or (m2) Prevention and / or treatment of psoriasis, and / or (n1) Preparation of medicines for the prevention and / or treatment of chronic eczema, and / or (n2) Prevention and / or treatment of chronic eczema, and / or (o1) Preparation of medicines for the prevention and / or treatment of age-related macular degeneration, and / or (o2) Prevention and / or treatment of age-related macular degeneration, (p1) Preparation of medicines for the prevention and / or treatment of retinitis pigmentosa, and / or (p2) Prevention and / or treatment of retinitis pigmentosa, (q1) Preparation of a medicine for the prevention and / or treatment of multiple sclerosis, and / or (q2) Prevention and / or treatment of multiple sclerosis, (r1) Preparation of pharmaceuticals for the prevention and / or treatment of hypothyroidism, and / or (r2) Prevention and / or treatment of hypothyroidism, (s1) Preparation of a medicine for the prevention and / or treatment of chronic atrophic gastritis, and / or (s2) Prevention and / or treatment of chronic atrophic gastritis, (t1) Preparation of medicines for the prevention and / or treatment of myocarditis, and / or (t2) Prevention and / or treatment of myocarditis, (u1) Preparation of medicines for the prevention and / or treatment of alopecia, and / or (u2) Prevention and / or treatment of alopecia, (v1) Preparation of a medicine for the prevention and / or treatment of primary aldosteronism, and / or (v2) Prevention and / or treatment of primary aldosteronism, (w1) Preparation of medicines for the prevention and / or treatment of erectile dysfunction, and / or (w2) Prevention and / or treatment of erectile dysfunction, (x1) Preparation of medicines for the prevention and / or treatment of periodontitis, and / or (x2) Prevention and / or treatment of periodontitis, (y1) Preparation of medicines for the prevention and / or treatment of stroke, and / or (y2) Prevention and / or treatment of stroke, (z1) Preparation of medicines for the prevention and / or treatment of epilepsy, and / or (z2) Prevention and / or treatment of epilepsy, (Aa1) Preparation of medicines for the prevention and / or treatment of melasma, and / or (Aa2) Prevention and / or treatment of melasma, and / or (Ab1) Preparation of medicines for the prevention and / or treatment of vitiligo, and / or (Ab2) Prevention and / or treatment of vitiligo, and / or (Ac1) Preparation of medicines for the prevention and / or treatment of β-thalassemia, and / or (Ac2) Prevention and / or treatment of β-thalassemia, and / or (Ad1) Preparation of medicines for the prevention and / or treatment of lumbar disc herniation, and / or (Ad2) Prevention and / or treatment of lumbar disc herniation, and / or (Ae1) Preparation of medicines for the prevention and / or treatment of polycystic ovary syndrome, and / or (Ae2) The use according to claim 1, characterized by comprising the prevention and / or treatment of polycystic ovary syndrome.

11. The present invention comprises the step of administering to a subject a therapeutically effective amount of a compound represented by general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof, for the following conditions: (a) premature ovarian failure, and / or (b) ovarian dysfunction, and / or (c) systemic lupus erythematosus nephritis, and / or (d) sarcopenia, and / or (e) liver dysfunction, and / or (f) oligospermia, and / or (g) rheumatoid arthritis, and / or (h) cataracts, and / or (i) Cushing's syndrome, and / or (j) Hashimoto's disease, and / or (k) chronic obstructive pulmonary disease, and / or (l) tinnitus, and / or (m) psoriasis, and / or (n) chronic eczema. Methods for preventing and / or treating (o) age-related macular degeneration, and / or (p) retinitis pigmentosa, and / or (q) multiple sclerosis, and / or (r) hypothyroidism, and / or (s) chronic atrophic gastritis, and / or (t) myocarditis, and / or (u) alopecia, and / or (v) primary aldosteronism, and / or (w) erectile dysfunction, and / or (x) periodontitis, and / or (y) stroke, and / or (z) epilepsy, and / or (Aa) melasma, and / or (Ab) vitiligo, and / or (Ac) β-thalassemia, and / or (Ad) lumbar disc herniation, and / or (Ae) polycystic ovary syndrome.

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