Use of heterocyclic compound in preparation of drug for preventing or treating iga nephropathy

Abstract

Disclosed in the present invention is the use of a heterocyclic compound in the preparation of a drug for preventing or treating IgA nephropathy. Specifically disclosed in the present invention is the use of compound (A) or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating and / or preventing IgA nephropathy. The compound A of the present invention exhibits good therapeutic effects on IgA nephropathy.

Description

Use of heterocyclic compounds in the preparation of drugs for the prevention or treatment of IgA nephropathy

[0001] This application claims priority to Chinese Patent Application No. 2024114964716, filed on October 25, 2024, and Chinese Patent Application No. 2025115188261, filed on October 22, 2025. The full text of the aforementioned Chinese patent applications is incorporated herein by reference. Technical Field

[0002] This invention belongs to the field of medicine, specifically relating to the use of heterocyclic compounds in the preparation of drugs for the prevention or treatment of IgA nephropathy. Background Technology

[0003] Complement is a class of soluble pattern recognition molecules in the immune system that perform a variety of effector functions. Under natural conditions, complement components exist as inactive zymogens. Various specific and non-specific immunological mechanisms break down these inactive zymogens, producing active large and small fragments. The large fragments typically remain on the surface of pathogens or cells, causing their lysis or accelerating their clearance; the small fragments leave the cell surface and mediate various inflammatory responses. Complement activation consists of two closely related processes, forming a cascade of complement activation. Currently known complement activation pathways mainly include three: the classical pathway, the lectin pathway, and the alternative pathway. Although the initiation mechanisms and activation sequences of these three complement activation pathways differ, they share a common terminal pathway. The activation of the alternative pathway is independent of the antigen-antibody complex. Typically, C3b deposited on the cell surface binds to factor B, becoming readily broken down by factor D in serum. During this process, factor B is broken down into Ba and Bb. C3b and Bb then form a complex, becoming the C3 convertase C3bBb in the alternative pathway. In this process, complement factor B plays an early and central role in the activation of the alternative pathway within the complement cascade. Here, C3b is both a product of C3 convertase breakdown and a component of the alternative pathway C3 convertase, thus forming a feedback amplification mechanism where the classical and alternative pathways influence each other. Current research has found a correlation between various diseases, including hematologic, autoimmune, inflammatory, and neurodegenerative diseases, and complement system dysfunction.

[0004] IgA nephropathy (IgAN) is a complex, immune-related primary glomerulonephritis characterized by the deposition of IgA or IgA-dominant immune complexes in the glomeruli, accompanied by various pathological damage. In China, IgA nephropathy accounts for nearly half of all primary glomerulonephritis cases. It commonly affects young adults and is one of the most common causes of end-stage renal disease. IgA nephropathy presents with diverse clinical manifestations and is a multigenic, multifactorial, and complex disease; its exact pathogenesis remains unclear. Compared to conventional nephritis, such as glomerulonephritis, IgA nephropathy has a higher clinical incidence, more complex treatment, faster disease progression, and a worse prognosis.

[0005] Epidemiological studies have shown that poorly controlled small amounts of proteinuria can progress to massive proteinuria, and the rate of renal function decline in patients with persistent proteinuria ≥3g / 24h is 25 times faster than in patients with proteinuria <1g / 24h. Current guidelines recommend treatment with ACEIs / ARBs and / or glucocorticoids, which can reduce proteinuria to some extent, but clinical efficacy is unsatisfactory; more importantly, guidelines do not yet recommend effective treatments for hematuria. Therefore, the development and production of effective therapeutic drugs are clinically essential to alleviate or delay disease progression and improve patients' quality of life. IgA nephropathy has the highest incidence rate in Asian populations, with approximately 30% of IgA nephropathy patients progressing to end-stage renal failure. Reversing the disease or delaying its progression is crucial.

[0006] Therefore, there is an urgent need to explore more effective and safer drugs for the treatment of IgA nephropathy. Summary of the Invention

[0007] To address the aforementioned technical problems, this invention provides the use of a heterocyclic compound in the preparation of a medicament for treating and / or preventing IgA nephropathy. The compound of this invention is effective in treating and / or preventing IgA nephropathy.

[0008] The first aspect of this invention provides the use of compound A or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating and / or preventing IgA nephropathy, said compound A having the following structure:

[0009] A second aspect of the present invention provides a method for treating IgA nephropathy in a subject in need, comprising administering to the subject a therapeutically effective amount of compound A or a pharmaceutically acceptable salt thereof.

[0010] A third aspect of the present invention provides a compound A or a pharmaceutically acceptable salt thereof for treating IgA nephropathy.

[0011] In certain preferred embodiments of the present invention, certain technical features of the use described in the first aspect, the method described in the second aspect, and compound A or its pharmaceutically acceptable salt for treating IgA nephropathy described in the third aspect are independently defined as follows, and technical features not mentioned are the same as those described in any embodiment of the present invention (hereinafter referred to as "some embodiments of the present invention"). Other inventive items of the present invention are referred to using the same abbreviations as this invention and will not be described in detail hereafter.

[0012] In some embodiments of the present invention, the pharmaceutically acceptable salt is selected from hydrochloride, phosphate, hydrogen phosphate, sulfate, hydrogen sulfate, sulfite, acetate, oxalate, malonate, valerate, glutamate, oleate, stearate, laurate, p-toluenesulfonate, methanesulfonate, fumarate, hydroxyethylsulfonate, maleate, malate, tartrate, citrate, benzoate, bis(hydroxynaphthyl)ate, salicylate, vanillate, and succinate.

[0013] In some embodiments of the present invention, the pharmaceutically acceptable salt is a hydrochloride salt.

[0014] In some embodiments of the present invention, the pharmaceutically acceptable salt is a monohydrochloride salt.

[0015] In some embodiments of the present invention, compound A or a pharmaceutically acceptable salt thereof is compound B.

[0016] In some embodiments of the present invention, the IgA nephropathy includes primary IgA nephropathy and secondary IgA nephropathy.

[0017] In some embodiments of the present invention, the IgA nephropathy is primary IgA nephropathy.

[0018] In some embodiments of the present invention, the IgA nephropathy is secondary IgA nephropathy.

[0019] In some embodiments of the present invention, the primary IgA nephropathy includes primary IgA nephropathy caused by genetic factors or abnormal autoimmune regulation.

[0020] In some embodiments of the present invention, in the primary IgA nephropathy, eGFR ≥ 30 mL / min / 1.73 m 2 "eGFR" refers to glomerular filtration rate.

[0021] In some embodiments of the present invention, in the primary IgA nephropathy, eGFR ≥ 45 mL / min / 1.73 m 2 "eGFR" refers to glomerular filtration rate; patients with primary IgA nephropathy had undergone a qualified biopsy within 5 years prior to screening.

[0022] In some embodiments of the present invention, in the primary IgA nephropathy, 45 mL / min / 1.73 m2 > eGFR > 30 mL / min / 1.73 m2; "eGFR" refers to glomerular filtration rate; patients with primary IgA nephropathy have undergone a qualified biopsy within 2 years prior to screening, and renal tubulointerstitial fibrosis <50%.

[0023] In some embodiments of the present invention, the secondary IgA nephropathy includes diseases secondary to allergic purpura, viral hepatitis, cirrhosis, systemic lupus erythematosus, ankylosing spondylitis, rheumatoid arthritis, mixed connective tissue disease, polyarteritis nodosa, erythema nodosa, psoriasis, ulcerative colitis, Crohn's disease, tumors, AIDS, etc.

[0024] In some embodiments of the present invention, the secondary IgA nephropathy is secondary to one or more of the following: allergic purpura, viral hepatitis, cirrhosis, systemic lupus erythematosus, ankylosing spondylitis, rheumatoid arthritis, mixed connective tissue disease, polyarteritis nodosa, erythema nodosa, psoriasis, ulcerative colitis, Crohn's disease, tumors, and AIDS.

[0025] In one aspect of the present invention, the IgA nephropathy is IgA nephropathy caused by glomerular lesions;

[0026] The glomerular lesions are preferably one or more of the following: abnormal urinary albumin concentration, abnormal urinary albumin amount (e.g., total 24-hour urinary albumin), abnormal urinary albumin-creatinine ratio, IgA deposition, and C3 deposition;

[0027] The abnormal urinary albumin level is preferably ≥0.75g / 24h urinary protein during the screening period (24-hour urine sample) and / or ≥0.75g / 24h urinary protein level before the first administration of the study drug.

[0028] In one aspect of the present invention, the IgA nephropathy is IgA nephropathy caused by glomerular lesions;

[0029] The glomerular lesions are preferably C3 deposits and / or C5b-9 deposits.

[0030] In some embodiments of the present invention, in a first aspect, the drug is presented in the form of an oral dosage form or an injectable dosage form.

[0031] In some embodiments of the present invention, in a first aspect, the drug is presented in an oral dosage form, such as in tablet form.

[0032] In some embodiments of the present invention, in the second and third aspects, the compound A or a pharmaceutically acceptable salt thereof is administered in the form of a medicine containing the compound A or a pharmaceutically acceptable salt thereof;

[0033] The drug is preferably presented in oral or injectable form;

[0034] The drug is more preferably presented in an oral dosage form, such as in tablet form.

[0035] Unless otherwise specified, the dosage described in this invention, or the content of compound A or its pharmaceutically acceptable salt in the drug or pharmaceutical composition, is calculated based on the amount of the active ingredient (i.e., the amount of compound A). For example, when the drug or pharmaceutical composition contains compound A or its pharmaceutically acceptable salt, the dosage or content of compound A or its pharmaceutically acceptable salt is calculated based on the dosage or content of the active ingredient compound A. Similarly, when the salt of compound A in the drug or pharmaceutical composition is compound B, the content or dosage of compound B in the drug or pharmaceutical composition is calculated based on the content or dosage of the active ingredient compound A.

[0036] In some embodiments of the present invention, the dosage of the aforementioned drug (calculated based on the active ingredient) is any value or combination of any value within the range of 0.1-1000 mg, 0.1-800 mg, 10-800 mg, 100-800 mg, or 200-600 mg. For example, 10 mg, 50 mg, 100 mg, 150 mg, 200 mg, 205 mg, 210 mg, 215 mg, 220 mg, 225 mg, 230 mg, 235 mg, 240 mg, 245 mg, 250 mg, 255 mg, 260 mg, 265 mg, 270 mg, 275 mg, 280 mg, 285 mg, 290 mg, 295 mg, 300 mg, 305 mg, 310 mg, 3... 15mg, 320mg, 325mg, 330mg, 335mg, 340mg, 345mg, 350mg, 355mg, 360mg, 365mg, 370mg, 375mg, 380mg , 385mg, 390mg, 395mg, 400mg, 405mg, 410mg, 415mg, 420mg, 425mg, 430mg, 435mg, 440mg, 445mg, 450 mg, 455mg, 460mg, 465mg, 470mg, 475mg, 480mg, 485mg, 490mg, 495mg, 500mg, 505mg, 510mg, 515mg, 5 20mg, 525mg, 530mg, 535mg, 540mg, 545mg, 550mg, 555mg, 560mg, 565mg, 570mg, 575mg, 580mg, 585mg , 590mg, 595mg, 600mg, 705mg, 710mg, 715mg, 720mg, 725mg, 730mg, 735mg, 740mg, 745mg, 750mg, 755 mg, 760mg, 765mg, 770mg, 775mg, 780mg, 785mg, 790mg, 795mg, 800mg, 850mg, 900mg, 950mg, 1000mg.

[0037] In some embodiments of the present invention, the dosage of the aforementioned drug (calculated based on the active ingredient) is 0.1-2000 mg, preferably 50-2000 mg, for example 100 mg, 200 mg, 400 mg, 600 mg, 800 mg, 1200 mg or 1600 mg.

[0038] In some embodiments of the present invention, the dosage of the aforementioned drug (calculated based on the active ingredient) is 0.1 mg / kg to 300 mg / kg, preferably 1 mg / kg to 100 mg / kg, or any value within the range of 4 mg / kg to 20 mg / kg, or any combination of values ​​within the range, such as 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12 mg / kg, 13 mg / kg, 14 mg / kg, 15 mg / kg, 16 mg / kg, 17 mg / kg, etc. 18mg / kg, 19mg / kg, 20mg / kg, 21mg / kg, 22mg / kg, 23mg / kg, 24mg / kg, 25mg / kg, 26mg / kg, 27mg / kg, 28mg / kg, 29mg / kg, 30mg / kg, 31mg / kg, 32mg / kg, 33mg / kg, 34mg / kg, 35mg / kg, 36mg / kg, 37mg / kg, 38mg / kg, 39mg / kg, 40mg / kg, 41mg / kg, 42mg / kg, 43mg / kg, 44mg / kg, 45mg / kg, 46mg / kg, 47m g / kg, 48mg / kg, 49mg / kg, 50mg / kg, 55mg / kg, 60mg / kg, 65mg / kg, 70mg / kg, 75mg / kg, 80mg / kg, 85mg / kg, 90mg / kg, 95mg / kg, 100mg / kg, 105mg / k g, 110mg / kg, 115mg / kg, 120mg / kg, 125mg / kg, 130mg / kg, 135mg / kg, 140mg / kg, 145mg / kg, 150mg / kg, 155mg / kg, 160mg / kg, 165mg / kg, 170mg / kg , 175mg / kg, 180mg / kg, 185mg / kg, 190mg / kg, 195mg / kg, 200mg / kg, 205mg / kg, 210mg / kg, 215mg / kg, 220mg / kg, 225mg / kg, 230mg / kg, 235mg / kg , 240mg / kg, 245mg / kg, 250mg / kg, 255mg / kg, 260mg / kg, 265mg / kg, 270mg / kg, 275mg / kg, 280mg / kg, 285mg / kg, 290mg / kg, 295mg / kg, 300mg / kg.

[0039] In some embodiments of the present invention, the frequency of administration of the aforementioned drug may be once a day, twice a day, three times a day, once every other day, once a week, twice a week, three times a week, once every other week, once every two weeks, once every three weeks, once every four weeks, etc., preferably once a day or twice a day.

[0040] In some embodiments of the present invention, when the aforementioned drug is a tablet, each tablet contains 50-500 mg of compound A, preferably 50-200 mg, for example 100 mg.

[0041] In some embodiments of the present invention, the content of compound A or its pharmaceutically acceptable salt in the aforementioned drug is 100 mg to 800 mg, for example 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg or 800 mg, and the administration frequency may be once a day or twice a day.

[0042] In some embodiments of the present invention, the aforementioned drug is administered at a daily dose of 400 mg / day, 600 mg / day, 800 mg / day, or 1200 mg / day.

[0043] In some embodiments of the present invention, the aforementioned drug is administered at a dose of compound A of 200 mg / day, 400 mg / day, 600 mg / day, 800 mg / day, 1200 mg / day, or 1600 mg / day.

[0044] In some embodiments of the present invention, the content of compound B in the aforementioned drug is 200 mg, and the administration frequency is once or twice a day.

[0045] In some embodiments of the present invention, the content of compound B in the aforementioned drug is 400 mg, and the administration frequency is once or twice a day.

[0046] In some embodiments of the present invention, the content of compound B in the aforementioned drug is 400 mg, and the administration frequency is once a day.

[0047] In some embodiments of the present invention, the content of compound B in the aforementioned drug is 400 mg, and the administration frequency is twice a day.

[0048] In some embodiments of the present invention, the content of compound B in the aforementioned drug is 600 mg, and the administration frequency is once or twice a day.

[0049] In some embodiments of the present invention, the content of compound B in the aforementioned drug is 600 mg, and the administration frequency is once a day.

[0050] In some embodiments of the present invention, the content of compound B in the aforementioned drug is 600 mg, and the administration frequency is twice a day.

[0051] In some embodiments of the present invention, the content of compound B in the aforementioned drug is 800 mg, and the administration frequency is once or twice a day.

[0052] In some embodiments of the present invention, the content of compound B in the aforementioned drug is 800 mg, and the administration frequency is once a day.

[0053] In some embodiments of the present invention, the content of compound B in the aforementioned drug is 800 mg, and the administration frequency is twice a day.

[0054] In some embodiments of the present invention, the content of compound A in the aforementioned drug is 200 mg, preferably, the dosing frequency is once or twice a day; preferably, in the aforementioned drug, compound A is introduced in the form of compound A or compound B; more preferably, in the aforementioned drug, compound A is introduced in the form of compound B. (Hereinafter, "in the aforementioned drug, compound A is introduced in the form of compound A or compound B" means that the active pharmaceutical ingredient used in the preparation of the drug is the original form of compound A or the salt form of compound A (i.e., compound B); similar expressions have similar meanings and will not be repeated.)

[0055] In some embodiments of the present invention, the content of compound A in the aforementioned drug is 400 mg, preferably, the administration frequency is once a day or twice a day; preferably, in the aforementioned drug, compound A is introduced in the form of compound A or compound B; more preferably, in the aforementioned drug, compound A is introduced in the form of compound B.

[0056] In some embodiments of the present invention, the content of compound A in the aforementioned drug is 400 mg, preferably, the administration frequency is once a day; preferably, in the aforementioned drug, compound A is introduced in the form of compound A or compound B; more preferably, in the aforementioned drug, compound A is introduced in the form of compound B.

[0057] In some embodiments of the present invention, the content of compound A in the aforementioned drug is 400 mg, preferably, the administration frequency is twice a day; preferably, in the aforementioned drug, compound A is introduced in the form of compound A or compound B; more preferably, in the aforementioned drug, compound A is introduced in the form of compound B.

[0058] In some embodiments of the present invention, the content of compound A in the aforementioned drug is 600 mg, preferably, the administration frequency is once a day or twice a day; preferably, in the aforementioned drug, compound A is introduced in the form of compound A or compound B; more preferably, in the aforementioned drug, compound A is introduced in the form of compound B.

[0059] In some embodiments of the present invention, the content of compound A in the aforementioned drug is 600 mg, preferably, the administration frequency is once a day; preferably, in the aforementioned drug, compound A is introduced in the form of compound A or compound B; more preferably, in the aforementioned drug, compound A is introduced in the form of compound B.

[0060] In some embodiments of the present invention, the content of compound A in the aforementioned drug is 600 mg, preferably, the administration frequency is twice a day; preferably, in the aforementioned drug, compound A is introduced in the form of compound A or compound B; more preferably, in the aforementioned drug, compound A is introduced in the form of compound B.

[0061] In some embodiments of the present invention, the content of compound A in the aforementioned drug is 800 mg, preferably, the administration frequency is once a day or twice a day; preferably, in the aforementioned drug, compound A is introduced in the form of compound A or compound B; more preferably, in the aforementioned drug, compound A is introduced in the form of compound B.

[0062] In some embodiments of the present invention, the content of compound A in the aforementioned drug is 800 mg, preferably, the administration frequency is once a day; preferably, in the aforementioned drug, compound A is introduced in the form of compound A or compound B; more preferably, in the aforementioned drug, compound A is introduced in the form of compound B.

[0063] In some embodiments of the present invention, the content of compound A in the aforementioned drug is 800 mg, preferably, the administration frequency is twice a day; preferably, in the aforementioned drug, compound A is introduced in the form of compound A or compound B; more preferably, in the aforementioned drug, compound A is introduced in the form of compound B.

[0064] In some embodiments of the present invention, the dosage of the aforementioned drug (calculated based on the active ingredient) is 4 mg / kg to 20 mg / kg, and the frequency of administration may be once or twice a day.

[0065] In some embodiments of the present invention, the dosage of the aforementioned drug is 4 mg / kg-6 mg / kg, and the frequency of administration is once or twice a day.

[0066] In some embodiments of the present invention, the dosage of the aforementioned drug is 6 mg / kg-8 mg / kg, and the frequency of administration is once or twice a day.

[0067] In some embodiments of the present invention, the dosage of the aforementioned drug is 8 mg / kg-10 mg / kg, and the frequency of administration is once or twice a day.

[0068] A fourth aspect of the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of compound A as described above or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers; the pharmaceutical composition is used to prepare a medicament for treating and / or preventing IgA nephropathy.

[0069] The fifth aspect of the present invention provides a unit dose pharmaceutical composition comprising 50 mg to 800 mg of compound A or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, for use in preparing a medicament for treating and / or preventing IgA nephropathy.

[0070] A sixth aspect of the present invention provides a pharmaceutical composition for treating and / or preventing IgA nephropathy, the pharmaceutical composition comprising a therapeutically effective amount of compound A as described above or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers.

[0071] The seventh aspect of the present invention provides a unit dose pharmaceutical composition for treating and / or preventing IgA nephropathy, each unit dose comprising 50 mg to 800 mg of compound A or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers.

[0072] In some embodiments of the present invention, each unit dose contains, for example, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg or 800 mg of compound A or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, for the preparation of a medicament for the treatment and / or prevention of IgA nephropathy.

[0073] In some embodiments of the present invention, each unit dose contains 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg or 800 mg of compound A or a pharmaceutically acceptable salt thereof;

[0074] Preferably, each unit dose contains 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg or 800 mg of compound A.

[0075] In some embodiments of the present invention, each unit dose contains, for example, 50 mg, 100 mg, 200 mg or 400 mg of compound A or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, for the preparation of a medicament for the treatment and / or prevention of IgA nephropathy.

[0076] In some embodiments of the present invention, each unit dose contains 50 mg, 100 mg, 200 mg or 400 mg of compound A or a pharmaceutically acceptable salt thereof;

[0077] Preferably, each unit dose contains 50 mg, 100 mg, 200 mg or 400 mg of compound A.

[0078] In some embodiments of the present invention, the aforementioned drug, the aforementioned compound A or a pharmaceutically acceptable salt thereof, or the aforementioned pharmaceutical composition is administered in a manner selected from simultaneous administration, independently formulated and co-administered, or independently formulated and sequentially administered.

[0079] In some embodiments of the present invention, the aforementioned drug, the aforementioned compound A, or a pharmaceutically acceptable salt thereof, or the aforementioned pharmaceutical composition, is administered orally, parenterally, or transdermally, preferably orally, for example, via tablets. The parenterial administration is selected from injection administration, including but not limited to intravenous injection, subcutaneous injection, or intramuscular injection.

[0080] In some embodiments of the present invention, the aforementioned drug, the aforementioned compound A or a pharmaceutically acceptable salt thereof, or the aforementioned pharmaceutical composition, is used to treat glomerular lesions in a subject with IgA nephropathy, preferably, the treatment includes reducing proteinuria in the subject.

[0081] In some embodiments of the present invention, the aforementioned drug, the aforementioned compound A, or a pharmaceutically acceptable salt thereof, or the aforementioned pharmaceutical composition, is used to reduce IgA deposition in the kidney tissue of a subject with IgA nephropathy.

[0082] In some embodiments of the present invention, the aforementioned drug, the aforementioned compound A or a pharmaceutically acceptable salt thereof, or the aforementioned pharmaceutical composition, treats and / or prevents IgA nephropathy by treating and / or inhibiting glomerular lesions in subjects with IgA nephropathy;

[0083] The glomerular lesions are preferably one or more of the following: abnormal urinary albumin concentration, abnormal urinary albumin amount (e.g., total 24-hour urinary albumin), abnormal urinary albumin-creatinine ratio, IgA deposition, and C3 deposition;

[0084] The abnormal urinary albumin level is preferably ≥0.75g / 24h urinary protein during the screening period (24-hour urine sample) and / or ≥0.75g / 24h urinary protein level before the first administration of the study drug.

[0085] In some embodiments of the present invention, the aforementioned drug, the aforementioned compound A or a pharmaceutically acceptable salt thereof, or the aforementioned pharmaceutical composition, treats and / or prevents IgA nephropathy by treating and / or inhibiting glomerular lesions in subjects with IgA nephropathy;

[0086] The glomerular lesions are preferably C3 deposits and / or C5b-9 deposits.

[0087] In some embodiments of the present invention, the aforementioned drug, the aforementioned compound A or a pharmaceutically acceptable salt thereof, or the aforementioned pharmaceutical composition, treats and / or prevents IgA nephropathy by performing one or more of the following actions: reducing urinary albumin concentration, reducing urinary protein amount (e.g., total 24-hour urinary albumin), reducing urinary albumin-to-creatinine ratio, reducing IgA deposition, and reducing C3 deposition.

[0088] The reduction in urinary albumin concentration is preferably a reduction of 50%-70%, such as 56%, 62% or 63%.

[0089] The reduction in urinary protein is preferably a reduction of 50%-70% of the total 24-hour urinary albumin, for example, 57% or 60%.

[0090] The reduction in the urine albumin-creatinine ratio is preferably a reduction of 55%-70%, for example, 61% or 65%.

[0091] The reduction in IgA deposition is preferably a reduction of 50%-90% (calculated as the change in the area of ​​IgA-positive region / total glomerular area), for example, 54%, 81% or 85%.

[0092] The reduction of IgA deposition is preferably achieved by reducing the ratio of IgA-positive area to total glomerular area to below 8%, for example, 7.74%, 3.14%, or 2.47%.

[0093] The reduction in C3 deposition is preferably a reduction of 40%-80% (calculated as the change in the area of ​​C3-positive region / total glomerular area), for example 49%, 62% or 67%;

[0094] The reduction of C3 deposition is preferably achieved by reducing the area of ​​C3-positive regions to less than 5% of the total glomerular area, for example, 4.88%, 3.58%, or 3.10%.

[0095] In some embodiments of the present invention, the aforementioned drug, the aforementioned compound A or a pharmaceutically acceptable salt thereof, or the aforementioned pharmaceutical composition, treats and / or prevents IgA nephropathy by reducing C3 deposition and / or reducing C5b-9 deposition;

[0096] The reduction of C3 deposition is preferably a reduction of C3 deposition on mesangial cells, more preferably a reduction of 20%-40% of C3 deposition on mesangial cells, such as 28%, 32% or 31%;

[0097] The reduction of C5b-9 deposition is preferably a reduction of C5b-9 deposition on mesangial cells, more preferably a reduction of 35%-60% of C5b-9 deposition on mesangial cells, for example 43%, 46% or 54%.

[0098] In some embodiments of the present invention, IgA nephropathy subjects treated with the aforementioned drug, the aforementioned compound A or a pharmaceutically acceptable salt thereof, or the aforementioned drug composition, have improvements in one or more of the following biological indicators: reduced urinary albumin concentration, reduced urinary albumin amount (e.g., total 24-hour urinary albumin), reduced urinary albumin-to-creatinine ratio, reduced IgA deposition, and reduced C3 deposition.

[0099] The reduction in urinary albumin concentration is preferably a reduction of 50%-70%, for example, 56%, 62% or 63%;

[0100] The reduction in urinary protein is preferably a reduction of 50%-70% of the total 24-hour urinary albumin, for example, 57% or 60%.

[0101] The reduction in the urine albumin-creatinine ratio is preferably a reduction of 55%-70%, for example, 61% or 65%.

[0102] The reduction in IgA deposition is preferably a reduction of 50%-90% (calculated as the change in the area of ​​IgA-positive region / total glomerular area), for example, 54%, 81% or 85%.

[0103] The reduction in IgA deposition is preferably achieved by reducing the ratio of IgA-positive area to total glomerular area to below 8%, for example, 7.74%, 3.14%, or 2.47%.

[0104] The reduction in C3 deposition is preferably a reduction of 40%-80% (calculated as the change in the area of ​​C3-positive region / total glomerular area), for example, 49%, 62% or 67%.

[0105] The reduction in C3 deposition is preferably achieved by reducing the area of ​​C3-positive regions to less than 5% of the total glomerular area, for example, 4.88%, 3.58%, or 3.10%.

[0106] In some embodiments of the present invention, IgA nephropathy subjects treated with the aforementioned drug, compound A, or a pharmaceutically acceptable salt thereof, or the aforementioned pharmaceutical composition, exhibit improvements in the following biological indicators:

[0107] C3 deposition is reduced and / or C5b-9 deposition is reduced;

[0108] The reduction in C3 deposition is preferably a reduction in C3 deposition on mesangial cells, more preferably a reduction of 20%-40% in C3 deposition on mesangial cells, such as 28%, 32% or 31%;

[0109] The reduction in C5b-9 deposition is preferably a reduction in C5b-9 deposition on mesangial cells, more preferably a reduction of 35%-60% in C5b-9 deposition on mesangial cells, such as 43%, 46% or 54%.

[0110] Unless otherwise specified, the terms used in this invention may be defined as follows:

[0111] The term "pharmaceutically acceptable" refers to molecular entities and compositions that are physiologically tolerable when administered to humans and generally do not produce allergic or similar inappropriate reactions, such as gastrointestinal upset, dizziness, etc.

[0112] The term "effective amount" or "therapeutic effective amount" refers to the amount of the compound described in this invention sufficient to achieve the intended application (including, but not limited to, the treatment of diseases as defined below). Therapeutic effective amounts can vary depending on factors such as the intended application (in vitro or in vivo), the subject being treated, and the condition of the disease, such as the subject's weight and age, the severity of the disease, and the route of administration, which can be readily determined by those skilled in the art. Specific dosages will vary depending on factors such as the particular compound selected, the administration regimen, whether it is administered in combination with other compounds, the timing of administration, the tissue to which the drug is administered, and the physical delivery system used.

[0113] The term "pharmaceutically acceptable carrier" includes any and all solvents, dispersion media, coatings, surfactants, antioxidants, preservatives (e.g., antimicrobial agents, antifungal agents), isotonic agents, absorption delay agents, salts, preservatives, pharmaceuticals, pharmaceutical stabilizers, binders, excipients, disintegrants, lubricants, sweeteners, flavorings, dyes, and the like and combinations thereof, which are considered for use in therapeutic or pharmaceutical compositions unless any conventional carrier is incompatible with the active ingredient.

[0114] Without violating common sense in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain various preferred embodiments of the present invention.

[0115] The reagents and raw materials used in this invention are all commercially available.

[0116] Beneficial effects: The compounds of this invention have therapeutic effects on IgA nephropathy. Attached Figure Description

[0117] Figure 1 shows the 24-hour urinary albumin content at the study endpoint in the BSA / LPS / CCL4 combined-induced SD rat nephropathy model.

[0118] Figure 2 shows the deposition of IgA in the glomeruli of a BSA / LPS / CCL4-induced nephropathy model in SD rats.

[0119] Figure 3 shows the deposition of C3 in the glomeruli of a BSA / LPS / CCL4-induced nephropathy model in SD rats.

[0120] Figure 4 shows the deposition of complement component C3 on mesangial cells;

[0121] Figure 5 shows the deposition of complement component C5b-9 on mesangial cells. Detailed Implementation

[0122] The technical solution of the present invention will be further described in detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative and explanatory of the present invention, and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are covered within the scope of protection intended by the present invention.

[0123] Unless otherwise stated, the raw materials and reagents used in the following examples are commercially available products or can be prepared by known methods.

[0124] Preparation Example 1: Preparation of Compound A

[0125] The preparation of compound A was carried out by referring to the preparation method of compound I in Preparation Example 1, pages 19-23 of the specification WO2023143293A1.

[0126] Preparation of the monohydrochloride salt of compound A in Example 2

[0127] Compound B was prepared by referring to the preparation method of compound I monohydrochloride (Formula I-1) in Example 1, page 24 of the specification WO2023143293A1.

[0128] Test Example 1: In vivo test

[0129] Methods: The efficacy of compound B was evaluated in a BSA / LPS / CCL4-induced SD rat nephropathy model (primary IgA nephropathy model).

[0130] A total of 69 male Sprague Dawley rats were used in this experiment and randomly divided into two groups: a normal control group (G1) and a model group. Before drug administration, the animals in the model group were further randomly divided into subgroups (G2-G6).

[0131] The model was established by combined induction of BSA / LPS / CCL4 after unilateral nephrectomy.

[0132] On the first day of the experiment, rats in the model group underwent unilateral nephrectomy under aseptic conditions throughout the procedure. Modeling began on the eighth day. BSA (400 mg / kg) was administered orally every two days via gavage at a volume of 10 mL / kg; LPS (0.5 mg / kg) was administered intraperitoneally once a week at a volume of 10 mL / kg; and CCl4 (CCl4 to olive oil volume ratio of 1:4) was administered intraperitoneally once a week at a dose of 0.3 μL / g. The modeling period lasted ten weeks. Drug administration began four weeks after combined BSA / LPS / CCl4 induction.

[0133] Dosage was calculated based on the active ingredient, and all administration was oral: Group 1 (G1) of the normal control group and Group 2 (G2) of the model group received the solvent; Group 3 (G3) received dexamethasone at a dose of 0.3 mg / kg via gavage once daily; Group 4 (G4) received compound B at a dose of 5 mg / kg via gavage twice daily; Group 5 (G5) received compound B at a dose of 15 mg / kg via gavage twice daily; Group 6 (G6) received compound B at a dose of 50 mg / kg via gavage twice daily. The treatment period was six weeks; for Groups G4-G6, the dosage was calculated based on the content of active ingredient compound A.

[0134] Unless otherwise specified, "solvent" refers to a 0.5% methylcellulose (MC) solution.

[0135] Detection indicators: body weight, food intake, urine output, urine albumin level, and pathological and immunofluorescence detection of kidney tissue.

[0136] Table 1. Drug administration details for each group

[0137] Results: Compared with the normal control group (G1), the IgAN model (G2) rats showed significantly lower body weight, significantly higher urinary albumin concentration, higher 24-hour urinary albumin total, and significantly higher ACR; the percentage of inflammatory infiltration area in the kidney tissue and the number of glomerular mesangial cells were significantly increased; and the deposition levels of IgA and C3 in the glomeruli of the model animals were significantly increased. In conclusion, the IgAN model was successfully established.

[0138] Compared with the model group (G2), compound B significantly reduced the urinary albumin concentration, 24-hour total urinary albumin (see Figure 1 and Table 2), and ACR (urinary albumin-creatinine ratio, see Table 3) in a dose-dependent manner in the model animals at three weeks of administration and at the end of the study; it also significantly reduced the deposition of IgA (see Figure 2 and Table 4) and C3 in the glomeruli of the model animals (see Figure 3 and Table 5).

[0139] Table 2. Statistical mean ± standard error of urinary albumin data at the study endpoint; *p<0.05, **p<0.01, ***p<0.001 vs G2; Kruskal-Wallis Test

[0140] Table 3. Statistics of ACR data at the finish line

[0141] Mean ± standard error; **p<0.01, ***p<0.001 vs G2; Kruskal-Wallis Test

[0142] Table 4. Statistical mean ± standard error of IgA deposition data in kidney tissue; ***p<0.001 vs G2; Kruskal-Wallis Test

[0143] Table 5. Statistical mean ± standard error of C3 deposition data in kidney tissue; **p<0.01, ***p<0.001; One-way ANOVA

[0144] Therefore, compound B showed significant efficacy in improving urinary protein and IgA and C3 deposition in kidney tissue in the IgAN rat model, and can be used for the treatment of IgA nephropathy.

[0145] Test Example 2: The compound of the present invention is used to treat primary IgA nephropathy.

[0146] The following is a multicenter, randomized, double-blind, placebo-controlled, parallel-design phase II clinical trial evaluating the efficacy and safety of compound B of the present invention in patients with primary IgA nephropathy.

[0147] Compound B of the present invention exhibits excellent safety and efficacy in patients with primary IgA nephropathy, particularly at doses of 200 mg, 400 mg, 600 mg or 800 mg once or twice daily.

[0148] Test Example 3: Evaluating the efficacy of compound B in an in vitro IgAN model

[0149] Experimental Principle: Abnormal IgA immune complexes from IgAN patients bind to mesangial cell receptors, leading to IgA deposition in mesangial cells. MBL and L-ficolin can directly recognize and bind to abnormal IgA, activating the lectin pathway and further activating the alternative pathway to participate in complement pathway amplification. 90% of IgAN patients have C3 deposition in their mesangial cells, forming the attack complex (C5b-9) on these cells, which can directly damage them. This experiment aims to investigate the inhibitory effect of compound B on the mesangial cell C3 deposition and attack complex (C5b-9) formation induced by the activation of the complement pathway following abnormal IgA deposition in patients.

[0150] Experimental materials: Human primary glomerular mesangial cells, purchased from ScienCell;

[0151] Modeling method: The cell suspension concentration was adjusted to 10^5 cells / mL. 100 μL of cell suspension was added to each well of a 96-well plate. When the cells grew to 70%-80% confluence, they were starved for 8 hours in serum-free and growth factor-free MCM medium. IgA from IgAN patients was added to a final concentration of 100 μg / mL. The blank control group was added to PBS and incubated for 48 hours in a serum-free state to allow patient IgA to deposit on mesangial cells. The original medium was then discarded. The blank control group (PBS) and the model group (IgAN-pIgA) were incubated for 1 hour in MCM medium containing 11% serum to activate the complement pathway. Different dose groups were incubated for 1 hour in MCM medium containing 0.2 μM, 0.4 μM, and 0.8 μM compound B, respectively.

[0152] Detection indicators: Detection of complement components C3 (C3c is the C3 antibody epitope) and C5b-9 deposition on mesangial cells.

[0153] Experimental results: Cell-based ELISA results showed that compound B significantly reduced the deposition of complement component C3 on mesangial cells in the concentration range of 200 nM to 800 nM (Figure 4 and Table 6); compound B significantly reduced the deposition of complement component C5b-9 on mesangial cells in the concentration range of 200 nM to 800 nM (Figure 5 and Table 7).

[0154] Table 6. C3 deposition of complement component on mesangial cells.

[0155] Note: Mean ± Standard Deviation: ###P<0.001 vs. blank control group; ***P<0.001 vs. model group; One-way ANOVA

[0156] Table 7. Deposition of complement component C5b-9 on mesangial cells.

[0157] Note: Mean ± Standard Deviation; ##P<0.001 vs. Blank Control Group; ***P<0.001 vs. Model Group; One-way ANOVA.

[0158] The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiments. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. Use of compound A or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the treatment and / or prevention of IgA nephropathy, said compound A having the following structure:

2. The use according to claim 1, characterized in that, The pharmaceutically acceptable salts are selected from hydrochloride, phosphate, hydrogen phosphate, sulfate, hydrogen sulfate, sulfite, acetate, oxalate, malonate, valerate, glutamate, oleate, stearate, laurate, p-toluenesulfonate, methanesulfonate, fumarate, hydroxyethylsulfonate, maleate, malate, tartrate, citrate, benzoate, bis(hydroxynaphthyl)ate, salicylate, vanillate, and succinate. Preferably, the pharmaceutically acceptable salt is a hydrochloride salt; More preferably, the pharmaceutically acceptable salt is a monohydrochloride salt.

3. The use according to claim 1, characterized in that, The pharmaceutically acceptable salt of compound A is compound B.

4. The use according to claim 1, characterized in that, It meets one or more of the following conditions: (1) The IgA nephropathy includes primary IgA nephropathy and secondary IgA nephropathy, preferably primary IgA nephropathy; Preferably, the primary IgA nephropathy includes primary IgA nephropathy caused by genetic factors or abnormal autoimmune regulation. Preferably, in the primary IgA nephropathy, eGFR ≥ 30 mL / min / 1.73 m 2 "eGFR" refers to glomerular filtration rate. Preferably, the secondary IgA nephropathy is secondary to one or more of the following: allergic purpura, viral hepatitis, cirrhosis, systemic lupus erythematosus, ankylosing spondylitis, rheumatoid arthritis, mixed connective tissue disease, polyarteritis nodosa, erythema nodosa, psoriasis, ulcerative colitis, Crohn's disease, tumors, and AIDS. (2) The IgA nephropathy mentioned above is IgA nephropathy caused by glomerular lesions; The glomerular lesions are preferably one or more of the following: abnormal urinary albumin concentration, abnormal urinary albumin amount, abnormal urinary albumin-creatinine ratio, IgA deposition, and C3 deposition. The preferred abnormality in urinary albumin level is ≥0.75g / 24h urinary protein during the screening period and / or ≥0.75g / 24h urinary protein level in the 24 hours before the first administration of the study drug; (3) The IgA nephropathy mentioned above is IgA nephropathy caused by glomerular lesions; The glomerular lesions are preferably C3 deposits and / or C5b-9 deposits.

5. The use according to claim 1, characterized in that, The drug is presented in an oral or injectable form; preferably, it is presented in an oral form, such as in tablet form. Preferably, the dosage of the drug (calculated based on the active ingredient) is 0.1-2000 mg, more preferably 50-2000 mg, for example 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 1200 mg or 1600 mg; Preferably, the frequency of administration of the drug is once a day, twice a day, three times a day, once every other day, once a week, twice a week, three times a week, once every other week, once every two weeks, once every three weeks, or once every four weeks; more preferably, the frequency of administration of the drug is selected from once a day or twice a day.

6. The use according to claim 1, characterized in that, It meets one or more of the following conditions: (1) The dosage of the drug (calculated based on the active ingredient) is 0.1 mg / kg to 300 mg / kg, preferably 1 mg / kg to 100 mg / kg or 4 mg / kg to 20 mg / kg; (2) When the drug is a tablet, each tablet contains 50-500 mg of compound A, preferably 50-200 mg, for example 100 mg; (3) The content of compound A or its pharmaceutically acceptable salt in the drug is 100mg to 800mg, for example 100mg, 200mg, 300mg, 400mg, 500mg, 600mg, 700mg or 800mg, and the preferred frequency of administration is once or twice a day. (4) The drug is administered at a dose of compound A of 200 mg / day, 400 mg / day, 600 mg / day, 800 mg / day, 1200 mg / day or 1600 mg / day.

7. The use according to claim 1, characterized in that, It meets one or more of the following conditions: (1) The content of compound A in the drug is 200 mg, preferably, the frequency of administration is once a day or twice a day; preferably, in the drug, compound A is introduced in the form of compound A or compound B; more preferably, in the drug, compound A is introduced in the form of compound B; (2) The content of compound A in the drug is 400 mg. Preferably, the frequency of administration is once a day or twice a day. Preferably, in the drug, compound A is introduced in the form of compound A or compound B. More preferably, in the drug, compound A is introduced in the form of compound B. (3) The content of compound A in the drug is 600 mg. Preferably, the frequency of administration is once a day or twice a day. Preferably, in the drug, compound A is introduced in the form of compound A or compound B. More preferably, in the drug, compound A is introduced in the form of compound B. (4) The content of compound A in the drug is 800 mg. Preferably, the frequency of administration is once a day or twice a day. Preferably, in the drug, compound A is introduced in the form of compound A or compound B. More preferably, in the drug, compound A is introduced in the form of compound B. (5) The dosage of the drug (calculated based on the active ingredient) is 4 mg / kg to 20 mg / kg, and the frequency of administration may be once a day or twice a day; Preferably, the dosage of the drug is 4 mg / kg-6 mg / kg, and the frequency of administration is once or twice a day; Preferably, in some embodiments, the dosage of the drug is 6 mg / kg-8 mg / kg, and the frequency of administration is once or twice a day; Preferably, the dosage of the drug is 8 mg / kg-10 mg / kg, and the frequency of administration is once or twice a day.

8. The use according to claim 1, characterized in that, It meets one or more of the following conditions: (1) The administration method of the drug is selected from simultaneous administration, independently prepared and co-administered, or independently prepared and sequentially administered; (2) The route of administration of the drug is oral, parenteral, or transdermal, preferably oral, for example, via tablets; the parenteral administration is selected from injection, including but not limited to intravenous injection, subcutaneous injection, or intramuscular injection. (3) The drug is used to treat glomerular lesions in subjects with IgA nephropathy, preferably, the treatment includes reducing proteinuria in the subjects; (4) The drug is used to reduce IgA deposition in the kidney tissue of subjects with IgA nephropathy; (5) The drug treats and / or prevents IgA nephropathy by treating and / or inhibiting glomerular lesions in subjects with IgA nephropathy; The glomerular lesions are preferably one or more of the following: abnormal urinary albumin concentration, abnormal urinary albumin amount, abnormal urinary albumin-creatinine ratio, IgA deposition, and C3 deposition. The preferred abnormality in urinary albumin level is ≥0.75g / 24h urinary protein during the screening period and / or ≥0.75g / 24h urinary protein level in the 24 hours before the first administration of the study drug; (6) The drug treats and / or prevents IgA nephropathy by exerting one or more of the following effects: reducing urinary albumin concentration, reducing urinary protein amount, reducing urinary albumin-creatinine ratio, reducing IgA deposition, and reducing C3 deposition; The reduction in urinary albumin concentration is preferably a reduction of 50%-70%, such as 56%, 62% or 63%. The reduction in urinary protein is preferably a reduction of 50%-70% of the total 24-hour urinary albumin, for example, 57% or 60%. The reduction in the urine albumin-creatinine ratio is preferably a reduction of 55%-70%, for example, 61% or 65%. The reduction in IgA deposition is preferably a reduction of 50%-90%, for example, 54%, 81% or 85%; The reduction of IgA deposition is preferably achieved by reducing the ratio of IgA-positive area to total glomerular area to below 8%, for example, 7.74%, 3.14%, or 2.47%. The reduction in C3 deposition is preferably a reduction of 40%-80%, for example, 49%, 62% or 67%; The reduction of C3 deposition is preferably achieved by reducing the area of ​​C3-positive regions to less than 5% of the total glomerular area, for example, 4.88%, 3.58%, or 3.10%. (7) Subjects with IgA nephropathy who received the drug treatment showed improvement in one or more of the following biological indicators: reduced urinary albumin concentration, reduced urinary albumin amount, reduced urinary albumin-creatinine ratio, reduced IgA deposition, and reduced C3 deposition. The reduction in urinary albumin concentration is preferably a reduction of 50%-70%, for example, 56%, 62% or 63%; The reduction in urinary protein is preferably a reduction of 50%-70% of the total 24-hour urinary albumin, for example, 57% or 60%. The reduction in the urine albumin-creatinine ratio is preferably a reduction of 55%-70%, for example, 61% or 65%. The reduction in IgA deposition is preferably a reduction of 50%-90%, for example, 54%, 81% or 85%; The reduction in IgA deposition is preferably achieved by reducing the ratio of IgA-positive area to total glomerular area to below 8%, for example, 7.74%, 3.14%, or 2.47%. The reduction in C3 deposition is preferably a reduction of 40%-80%, for example, 49%, 62% or 67%; The reduction in C3 deposition is preferably achieved by reducing the area of ​​C3-positive regions to less than 5% of the total glomerular area, for example, 4.88%, 3.58%, or 3.10%. (8) The drug treats and / or prevents IgA nephropathy by treating and / or inhibiting glomerular lesions in subjects with IgA nephropathy; the glomerular lesions are preferably C3 deposition and / or C5b-9 deposition; (9) The drug treats and / or prevents IgA nephropathy by reducing C3 deposition and / or reducing C5b-9 deposition; The reduction of C3 deposition is preferably a reduction of C3 deposition on mesangial cells, more preferably a reduction of 20%-40% of C3 deposition on mesangial cells, such as 28%, 32% or 31%; The reduction of C5b-9 deposition is preferably a reduction of C5b-9 deposition on mesangial cells, more preferably a reduction of 35%-60% of C5b-9 deposition on mesangial cells, such as 43%, 46% or 54%. (10) Subjects with IgA nephropathy who received the drug treatment showed improvement in the following biological indicators: reduced C3 deposition and / or reduced C5b-9 deposition; The reduction in C3 deposition is preferably a reduction in C3 deposition on mesangial cells, more preferably a reduction of 20%-40% in C3 deposition on mesangial cells, such as 28%, 32% or 31%; The reduction in C5b-9 deposition is preferably a reduction in C5b-9 deposition on mesangial cells, more preferably a reduction of 35%-60% in C5b-9 deposition on mesangial cells, such as 43%, 46% or 54%.

9. A pharmaceutical composition for treating and / or preventing IgA nephropathy, said pharmaceutical composition comprising a therapeutically effective amount of compound A or a pharmaceutically acceptable salt thereof as described in any one of claims 1-8, and one or more pharmaceutically acceptable carriers.

10. A unit dose pharmaceutical composition for treating and / or preventing IgA nephropathy, each unit dose comprising 50 mg to 800 mg of compound A or a pharmaceutically acceptable salt thereof as described in any one of claims 1-8, and one or more pharmaceutically acceptable carriers; Preferably, each unit dose of the pharmaceutical composition contains 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg or 800 mg of compound A or a pharmaceutically acceptable salt thereof. More preferably, each unit dose contains 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg or 800 mg of compound A.

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