Treatment for glomerular disease

Abstract

The present invention relates to the development of therapeutic compounds for the treatment of glomerular disease. In particular, the present invention relates to the use of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof, or a combination of the compound of formula (Ia) or the pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the compound of formula (Ia) or the pharmaceutically acceptable salt thereof in the treatment of glomerular diseases.

Description

Technical Field

[0001] The present invention relates to the development of therapeutic compounds for treating glomerular diseases. Specifically, the present invention relates to the use of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof, a combination of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof for treating glomerular diseases. Background Art

[0002] Glomerulus is the functional part of nephron, which is involved in filtering and removing waste from the body. Diseases affecting glomeruli are called glomerulopathy. It may be inflammatory or non-inflammatory in origin. Damage to glomerular function worsens renal function. Glomerulopathy is also associated with hematuria or proteinuria, endothelial dysfunction, glomerular filtration barrier or podocytes. Subsequently, the resulting proteinuria, hypoalbuminemia, edema and hyperlipidemia are called nephrotic / nephritic syndrome. Glomerulopathy can also be of genetic origin, such as IgAN, IgMAN, C3G, aHUS, iMN, Alport syndrome, autosomal dominant polycystic kidney disease and LN. If caused by systemic lupus erythematosus, inflammatory nephropathy associated with other diseases or inflammatory nephropathy aggravated by other diseases is lupus nephritis. In the presence of obesity, diabetes and other comorbidities, glomerulopathy may occur or accelerate. Scarring of blood vessels in the glomerulus or glomerulus also affects renal function and is called glomerulosclerosis. Focal segmental glomerulosclerosis (FSGS) or nodular glomerulosclerosis is a form of glomerulosclerosis. FSGC leads to end-stage renal disease and irreversibly leads to nephrotic syndrome. Glomerulopathy or glomerulosclerosis can occur without any known cause, or can be secondary to drugs, toxins or underlying diseases. It is reported that chronic hypoxia leads to anemia and is one of the complications and causes of kidney diseases (such as glomerulopathy and glomerulosclerosis) (1-3). Glomerulonephritis is also called glomerular disease. This is a type of kidney disease caused by damage to the glomeruli of a person due to excessive activation of the person's immune system. This damage means that the glomeruli cannot remove waste and fluids as they should.

[0003] Oxygen is an important factor in regulating acute and chronic inflammation. Oxygen levels in tissues are sensed by hypoxia-inducible factors (HIFs: HIF-1 and HIF-2) and regulated by prolyl hydroxylases (4). Activation of HIF prevents renal disease and ischemia-reperfusion injury (5,6). Inhibition of PHD stabilizes HIF, thereby increasing the availability of HIF at sites of inflammation. Hypoxia-inducible factor (HIF) regulates the secretion of erythropoietin (EPO) and inhibition of PHD increases EPO by stabilizing HIF. Thus, PHD inhibitors alleviate anemia, which improves oxygen to the kidneys and can delay the progression of glomerulopathy or glomerulosclerosis. HIF regulates inflammatory stimuli and inflammatory mediators (7,8). HIF has been reported to regulate inflammatory pathways mediated by nuclear factor-κB (NF-κB) and extracellular signal-regulated kinase (ERK) (9). Desidustat is a PHD inhibitor currently approved in India for the treatment of chronic kidney disease-related anemia. It is reported that in anemic animal models, desidustat treatment stabilizes HIF and thus induces erythropoiesis (10). In clinical trials, desidustat also improved hemoglobin (11). Desidustat treatment reduces IL-6 and IL-1β levels in ischemic states (12). These inflammatory markers are increased in renal dysfunction nephropathy or nephritis (13). It also reduces SOD and MDA, thereby reducing oxidative stress (12). The standard treatment for glomerulopathy or glomerulonephritis is steroids or anti-infective drugs that suppress inflammation. Other agents such as RAAS inhibitors, mineralocorticoid antagonists, SGLT2 inhibitors, complement system inhibitors, antidiabetic agents, antihyperlipidemic agents, diuretics, or other agents used to manage symptoms of glomerular disease or renal dysfunction or ESRD. Other investigational treatments can be used to slow the progression of these diseases or reverse these diseases, such as anti-inflammatory agents, NRF2 modulators, endothelin antagonists, immunomodulators, ACE inhibitors, discoidin domain receptor 1 inhibitors, osteopontin blockers, vasopressin receptor antagonists, gene editing therapy or stem cell therapy. Therefore, the compound of formula (Ia) can be used alone or in combination with the above-mentioned agents to treat glomerulopathy or glomerulonephritis and related diseases and related complications.

[0004] Some of the prolyl hydroxylase inhibitors have been disclosed in EP 661269, WO 2007070359, WO 2008076425, WO 2011007856, WO 2012106472, WO 2013043621, WO 2004108681, and WO2008002576 includes prolyl hydroxylase inhibitors. Pharmaceutical compositions for treating oxidative stress disorders and treating hemoglobin disorders are disclosed in WIPO publications WO 2014200773, WO 2017027810, and WO2019028150, respectively.

[0005] WO 2014102818 discloses compounds of the following general formula:

[0006]

[0007] It was found that the compound of formula (Ia) given below

[0008]

[0009] and pharmaceutically acceptable salts thereof are effective in treating glomerular diseases.

[0010] Purpose of the Invention

[0011] In one embodiment, the present invention provides a method of treating glomerular diseases using a compound of formula (Ia) or a pharmaceutically acceptable salt thereof.

[0012] In another embodiment, the present invention provides a method of treating glomerular diseases using a compound of formula (Ia) or a pharmaceutically acceptable salt thereof in combination with a suitable second therapeutic agent selected from a suitable factor B inhibitor or a suitable angiotensin II receptor antagonist or a suitable factor D inhibitor or a suitable C3 inhibitor or a suitable C5 inhibitor or a suitable C6 inhibitor or a suitable lectin pathway inhibitor or a suitable properdin inhibitor or a suitable C9 antibody and a multi-target complement inhibitor.

[0013] In another embodiment, the present invention provides a method of treating glomerular diseases using a combination of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof and a suitable factor B inhibitor.

[0014] In another embodiment, the present invention provides a method of treating glomerular diseases using a combination of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof and a suitable angiotensin II receptor antagonist.

[0015] In another embodiment, the present invention provides a suitable pharmaceutical composition for treating glomerular diseases, comprising a compound of formula (Ia) or a pharmaceutically acceptable salt thereof.

[0016] In another embodiment, the present invention provides a combination of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof and a suitable second therapeutic agent selected from a suitable factor B inhibitor or a suitable angiotensin II receptor antagonist or a suitable factor D inhibitor or a suitable C3 inhibitor or a suitable C5 inhibitor or a suitable C6 inhibitor or a suitable lectin pathway inhibitor or a suitable properdin inhibitor or a suitable C9 antibody and a multi-target complement inhibitor.

[0017] In another embodiment, the present invention provides a combination of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof and a suitable Factor B inhibitor.

[0018] In another embodiment, the present invention provides a combination of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof and a suitable angiotensin II receptor antagonist.

[0019] In another embodiment, the present invention provides a suitable pharmaceutical composition for treating glomerular diseases, comprising a compound of formula (Ia) or a pharmaceutically acceptable salt of a compound of formula (Ia) and a suitable factor B inhibitor.

[0020] In another embodiment, the present invention provides a suitable pharmaceutical composition for treating glomerular diseases, comprising a compound of formula (Ia) or a pharmaceutically acceptable salt of a compound of formula (Ia) and a suitable angiotensin II receptor antagonist.

[0021] In another embodiment, the present invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof for treating glomerular diseases.

[0022] In another embodiment, the present invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof in combination with a suitable factor B inhibitor for treating glomerular diseases.

[0023] In another embodiment, the present invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof in combination with a suitable angiotensin II receptor antagonist for treating glomerular diseases.

[0024] In one embodiment, the applied compound of formula (Ia) or a pharmaceutically acceptable salt thereof alone or a suitable combination of the compound of formula (Ia) or a pharmaceutically acceptable salt thereof can be further characterized by the reduction of the amount of urinary protein.

[0025] In another embodiment, the present invention provides a compound of formula (Ia) or a pharmaceutically acceptable salt thereof, administered alone or in combination with a suitable second therapeutic agent, for use in treating glomerular diseases.

[0026] In another embodiment, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof or a suitable combination of the compound of formula (Ia) or a pharmaceutically acceptable salt thereof of the present invention is used for treating glomerular disease in patients with diabetes. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 A. Effects of the compound of formula (Ia) and its combination with Iptacopan on serum creatinine (A) in LPS-treated mice;

[0028] Figure 1 B. Effects of the compound of formula (Ia) and its combination with ipracopan on serum urea (B) in LPS-treated mice;

[0029] Figure 1 C. Effects of the compound of formula (Ia) and its combination with ipracopan on urinary total protein (C) in mice treated with doxorubicin;

[0030] Figure 1 D. Effects of the compound of formula (Ia) and its combination with Fimasartan on urinary total protein (D) in mice induced by BSA overload.

[0031] Figure 2 A. Effect of the compound of formula (Ia) on urinary albumin (A) in rats with 5 / 6 nephrectomy;

[0032] Figure 2 B. Effect of the compound of formula (Ia) on serum creatinine (B) in rats with 5 / 6 nephrectomy;

[0033] Figure 2 C. Effect of the compound of formula (Ia) on serum urea (C) in rats with 5 / 6 nephrectomy;

[0034] Figure 2 D. Effect of the compound of formula (Ia) on urinary albumin (D) in db / db mice;

[0035] Figure 2 E. Effect of the compound of formula (Ia) on serum creatinine (E) in db / db mice;

[0036] Figure 2 F. Effect of the compound of formula (Ia) on serum urea (F) in db / db mice. Summary of the invention

[0037] The present invention relates to a compound of formula (Ia) or a pharmaceutically acceptable salt thereof or a combination of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof for treating glomerular diseases. The present invention also relates to a pharmaceutical composition comprising a compound of formula (Ia) or a pharmaceutically acceptable excipient for treating glomerular diseases. DETAILED DESCRIPTION

[0038] definition:

[0039] The term "treating" and variations thereof refer to slowing, stopping or delaying the progression of a disease or clinical symptom in a patient, as evidenced by a reduction or elimination of clinical or diagnostic symptoms of the disease, disorder or condition. The term "subject" refers to a mammal. The term "effective amount" in this context is the amount of a drug substance administered sufficient to produce the desired effect. The term "pharmaceutically acceptable" use includes both human and veterinary uses. The compound of formula (Ia) is deldostat.

[0040] Methods for treating glomerular diseases by compounds of formula (Ia)

[0041] In one embodiment, the present invention provides a method for treating a glomerular disease in a subject, comprising administering an effective amount of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof; wherein formula (Ia) is represented by:

[0042]

[0043] Glomerular diseases include nephrotic syndrome, focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous nephropathy (MN), IgA nephropathy (IgANephropathy, IgAN), C3 glomerulopathy (MPGN3), diabetic nephropathy, lupus nephritis and other conditions related to glomerular diseases.

[0044] The pharmaceutically acceptable salt of the compound of formula (Ia) is selected from metal salts, amine salts and amino acid salts.

[0045] The metal salt is selected from calcium, sodium, potassium, lithium, barium, strontium, magnesium, cesium, copper, cobalt, iron, manganese, lead, aluminum, cadmium, silver, zinc, ammonium, etc.; the amine salt is selected from methylamine, dimethylamine, ethylamine, diethylamine, n-propylamine, isopropylamine, diisopropylamine, N-methylisopropylamine, n-butylamine, tert-butylamine, 2-butylamine, 1,2-ethylenediamine, N-methylglucamine, N,N,N-trimethylethanolamine hydroxide (choline), tromethamine, cyclohexylamine, N-methylcyclohexylamine hexylamine, guanidine, N-(4-aminobutyl)guanidine, dicyclohexylamine, benzylamine, ethanolamine, diethanolamine, tris(hydroxymethyl)methylamine, hydroxylamine, methylamine, benzylamine, N-methylbenzylamine, N-ethylbenzylamine, 4-methoxybenzylamine, pyrrolidine, piperidine, piperazine, morpholine, 2-aminopyrimidine, 2-thienylethylamine, (2S)-3,3-dimethyl-2-butylamine, cyclopentylamine, cycloheptylamine, meglumine, benethamine, di Benzylamine, diphenylamine, α-naphthylamine, o-phenylenediamine, 1,3-diaminopropane, (S)-α-naphthylethylamine, (S)-3-methoxyphenylethylamine, (S)-4-methoxyphenylethylamine, (S)-4-chlorophenylethylamine, (S)-4-methylphenylethylamine, cinchonine, cinchonidine, (-)-quinine, triethanolamine, imidazole, ethylenediamine, epolamine, morpholine 4-(2-hydroxyethyl), NN-diethylethanolamine , dimethylethanolamine, hydrabamine, betaine, adamantane, L-adamantanamine, triphenylamine, glucosamine, N-methylpyrrolidine, urea, procaine, metformin, hexane-1,6-diamine, 2-(2-aminoethoxy)ethylamine, N-methylmorpholine and N-ethylmorpholine; wherein the amino acid salt is selected from alanine, lysine, arginine, histidine, threonine, proline, glutamine and glycine.

[0046] In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject at a dosage of 1 mg to 500 mg. In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject to provide a 1 mg to 150 mg dosage of the compound of formula (Ia) or a pharmaceutically acceptable salt thereof. In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject to provide a 25 mg, 50 mg, and 100 mg dosage of the compound of formula (Ia) or a pharmaceutically acceptable salt thereof to a subject.

[0047] In another embodiment, the compound of Formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject in an amount of about 1 mg to about 500 mg, about 50 mg to about 450 mg, about 100 mg to about 400 mg, about 150 mg to about 350 mg, about 200 mg to about 300 mg, about 1 mg to about 50 mg, about 1 mg to about 25 mg to a subject.

[0048] In certain embodiments, the compound of Formula (Ia) or a pharmaceutically acceptable salt thereof can be further characterized according to the dose of the compound administered to a subject, wherein the subject is an animal or a human.

[0049] In another embodiment, the present invention provides an effective amount of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof administered to a subject by oral, parenteral, intravenous or intramuscular administration.

[0050] Method for treating glomerular diseases by combining a compound of formula (Ia) or a pharmaceutically acceptable salt thereof with other suitable inhibitors

[0051] In one embodiment, the present invention provides a method of treating a glomerular disease in a subject, comprising administering a compound of formula (Ia), or a pharmaceutically acceptable salt thereof, in combination with a suitable second therapeutic agent selected from a suitable factor B inhibitor or a suitable angiotensin II receptor antagonist or a suitable factor D inhibitor or a suitable C3 inhibitor or a suitable C5 inhibitor or a suitable C6 inhibitor or a suitable lectin pathway inhibitor or a suitable properdin inhibitor or a suitable C9 antibody and a multi-target complement inhibitor.

[0052] The factor B inhibitor is iprosartan; the angiotensin II receptor antagonist is fimasartan, azilsartan, candesartan, eprosartan, losartan, olmesartan, telmisartan, valsartan; the factor D inhibitor is selected from Danicopan, ALXN2050, BCX9930; the C3 inhibitor is selected from pegcitacoplan and AMY 201; the C5 inhibitor is selected from eculizumab, vilobelimab, RA 101348, DF2593A, Tesidolumab, SOBI-002, Ravulizumab, Cemdsiran, ARC1905 and Avacopan; the C6 inhibitor is CP 010; the lectin pathway inhibitor is Narsoplimab; the properdin inhibitor is NM9401; the C9 antibody and multi-target complement inhibitor is MFHR1.

[0053] Method for treating glomerular diseases by combining a compound of formula (Ia) or a pharmaceutically acceptable salt thereof with a suitable factor B inhibitor

[0054] In one embodiment, the present invention provides a method of treating a glomerular disease in a subject comprising administering a compound of formula (Ia) or a pharmaceutically acceptable salt thereof in combination with a suitable Factor B inhibitor.

[0055] Glomerular diseases include nephrotic syndrome, focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous nephropathy (MN), IgA nephropathy (IgAN), C3 glomerulopathy (MPGN3), diabetic nephropathy, lupus nephritis and other conditions related to glomerular disease.

[0056] The pharmaceutically acceptable salt of the compound of formula (Ia) is selected from metal salts, amine salts and amino acid salts.

[0057] The metal salt is selected from calcium, sodium, potassium, lithium, barium, strontium, magnesium, cesium, copper, cobalt, iron, manganese, lead, aluminum, cadmium, silver, zinc, ammonium, etc.; the amine salt is selected from methylamine, dimethylamine, ethylamine, diethylamine, n-propylamine, isopropylamine, diisopropylamine, N-methylisopropylamine, n-butylamine, tert-butylamine, 2-butylamine, 1,2-ethylenediamine, N-methylglucamine, N,N,N-trimethylethanolamine hydroxide (choline), tromethamine, Cyclohexylamine, N-methylcyclohexylamine, guanidine, N-(4-aminobutyl)guanidine, dicyclohexylamine, benzylamine, ethanolamine, diethanolamine, tris(hydroxymethyl)methylamine, hydroxylamine, methylamine, benzylamine, N-methylbenzylamine, N-ethylbenzylamine, 4-methoxybenzylamine, pyrrolidine, piperidine, piperazine, morpholine, 2-aminopyrimidine, 2-thienylethylamine, (2S)-3,3-dimethyl-2-butylamine, cyclopentylamine, cycloheptylamine, meglumine, Benzylamine, dibenzylamine, diphenylamine, α-naphthylamine, o-phenylenediamine, 1,3-diaminopropane, (S)-α-naphthylethylamine, (S)-3-methoxyphenethylamine, (S)-4-methoxyphenethylamine, (S)-4-chlorophenethylamine, (S)-4-methylphenethylamine, cinchonine, cinchonidine, (-)-quinine, triethanolamine, imidazole, ethylenediamine, epoline, morpholine 4-(2-hydroxyethyl), NN-diethyl The invention relates to an amino acid salt selected from the group consisting of alanine, lysine, arginine, histidine, threonine, proline, glutamine and glycine.

[0058] The Factor B inhibitor used in combination with the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is ipracopan.

[0059] In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject at a dosage of 1 mg to 500 mg. In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject to provide a 1 mg to 150 mg dosage of the compound of formula (Ia) or a pharmaceutically acceptable salt thereof. In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject to provide a 25 mg, 50 mg, and 100 mg dosage of the compound of formula (Ia) or a pharmaceutically acceptable salt thereof to a subject.

[0060] In another embodiment, the compound of Formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject in an amount of about 1 mg to about 500 mg, about 50 mg to about 450 mg, about 100 mg to about 400 mg, about 150 mg to about 350 mg, about 200 mg to about 300 mg, about 1 mg to about 50 mg, about 1 mg to about 25 mg to a subject.

[0061] In another embodiment, iplomepam is administered to a subject in an amount of about 1 mg to about 500 mg, about 50 mg to about 450 mg, about 100 mg to about 400 mg, about 150 mg to about 350 mg, about 200 mg to about 300 mg. In a certain embodiment, iplomepam is administered in an amount of 200 mg.

[0062] In certain embodiments, the compound of Formula (Ia) or a pharmaceutically acceptable salt thereof can be further characterized according to the dose of the compound administered to a subject, wherein the subject is an animal or a human.

[0063] In another embodiment, the present invention provides an effective amount of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof administered to a subject by oral, parenteral, intravenous or intramuscular administration.

[0064] Method for treating glomerular diseases by combining a compound of formula (Ia) or a pharmaceutically acceptable salt thereof with a suitable angiotensin II receptor antagonist

[0065] In one embodiment, the present invention provides a method of treating a glomerular disease in a subject comprising administering a compound of formula (Ia) or a pharmaceutically acceptable salt thereof in combination with a suitable angiotensin II receptor antagonist.

[0066] Glomerular diseases include nephrotic syndrome, focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous nephropathy (MN), IgA nephropathy (IgAN), C3 glomerulopathy (MPGN3), diabetic nephropathy, lupus nephritis and other conditions related to glomerular disease.

[0067] The pharmaceutically acceptable salt of the compound of formula (Ia) is selected from metal salts, amine salts and amino acid salts.

[0068] The metal salt is selected from calcium, sodium, potassium, lithium, barium, strontium, magnesium, cesium, copper, cobalt, iron, manganese, lead, aluminum, cadmium, silver, zinc, ammonium, etc.; the amine salt is selected from methylamine, dimethylamine, ethylamine, diethylamine, n-propylamine, isopropylamine, diisopropylamine, N-methylisopropylamine, n-butylamine, tert-butylamine, 2-butylamine, 1,2-ethylenediamine, N-methylglucamine, N,N,N-trimethylethanolamine hydroxide (choline), tromethamine, Cyclohexylamine, N-methylcyclohexylamine, guanidine, N-(4-aminobutyl)guanidine, dicyclohexylamine, benzylamine, ethanolamine, diethanolamine, tris(hydroxymethyl)methylamine, hydroxylamine, methylamine, benzylamine, N-methylbenzylamine, N-ethylbenzylamine, 4-methoxybenzylamine, pyrrolidine, piperidine, piperazine, morpholine, 2-aminopyrimidine, 2-thienylethylamine, (2S)-3,3-dimethyl-2-butylamine, cyclopentylamine, cycloheptylamine, meglumine, Benzylamine, dibenzylamine, diphenylamine, α-naphthylamine, o-phenylenediamine, 1,3-diaminopropane, (S)-α-naphthylethylamine, (S)-3-methoxyphenethylamine, (S)-4-methoxyphenethylamine, (S)-4-chlorophenethylamine, (S)-4-methylphenethylamine, cinchonine, cinchonidine, (-)-quinine, triethanolamine, imidazole, ethylenediamine, epoline, morpholine 4-(2-hydroxyethyl), NN-diethyl The invention relates to an amino acid salt selected from the group consisting of alanine, lysine, arginine, histidine, threonine, proline, glutamine and glycine.

[0069] Angiotensin II receptor antagonists for use in combination with the compound of formula (Ia) or a pharmaceutically acceptable salt thereof are fimasartan, azilsartan, candesartan, eprosartan, losartan, olmesartan, telmisartan and valsartan.

[0070] In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject at a dosage of 1 mg to 500 mg. In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject to provide a 1 mg to 150 mg dosage of the compound of formula (Ia) or a pharmaceutically acceptable salt thereof. In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject to provide a 25 mg, 50 mg, and 100 mg dosage of the compound of formula (Ia) or a pharmaceutically acceptable salt thereof to a subject.

[0071] In another embodiment, the compound of Formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject in an amount of about 1 mg to about 500 mg, about 50 mg to about 450 mg, about 100 mg to about 400 mg, about 150 mg to about 350 mg, about 200 mg to about 300 mg, about 1 mg to about 50 mg, about 1 mg to about 25 mg to a subject.

[0072] In another embodiment, fimasartan is administered to a subject in an amount of about 1 mg to about 500 mg, about 50 mg to about 450 mg, about 100 mg to about 400 mg, about 150 mg to about 350 mg, about 200 mg to about 300 mg. In another embodiment, azilsartan is administered to a subject in an amount of about 1 mg to about 500 mg. In another embodiment, candesartan is administered to a subject in an amount of about 1 mg to about 200 mg. In another embodiment, eprosartan is administered to a subject in an amount of about 1 mg to about 1000 mg. In another embodiment, losartan is administered to a subject in an amount of about 1 mg to about 500 mg. In another embodiment, olmesartan is administered to a subject in an amount of about 1 mg to about 200 mg. In another embodiment, telmisartan is administered to a subject in an amount of about 1 mg to about 500 mg. In another embodiment, valsartan is administered to a subject in an amount of about 1 mg to about 500 mg.

[0073] In a certain embodiment, fimasartan is applied to a subject in an amount of about 60mg and 120mg. In another embodiment, azilsartan is applied to a subject in an amount of about 40mg and 80mg. In another embodiment, candesartan is applied to a subject in an amount of about 4mg, 8mg, 16mg and 32mg. In another embodiment, eprosartan is applied to a subject in an amount of about 400mg and 600mg. In another embodiment, losartan is applied to a subject in an amount of about 25mg, 50mg and 100mg. In another embodiment, olmesartan is applied to a subject in an amount of about 5mg, 20mg and 40mg. In another embodiment, telmisartan is applied to a subject in an amount of about 20mg, 40mg and 80mg. In another embodiment, valsartan is applied to a subject in an amount of about 40mg, 80mg, 160mg and 320mg.

[0074] In certain embodiments, the compound of Formula (Ia) or a pharmaceutically acceptable salt thereof can be further characterized according to the dose of the compound administered to a subject, wherein the subject is an animal or a human.

[0075] In another embodiment, the present invention provides an effective amount of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof administered to a subject by oral, parenteral, intravenous or intramuscular administration.

[0076] Pharmaceutical composition of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof for treating glomerular diseases

[0077] In one embodiment, the present invention provides a pharmaceutical composition for treating glomerular diseases, comprising a compound of formula (Ia) or a pharmaceutically acceptable salt thereof, optionally containing one or more pharmaceutically acceptable excipients.

[0078] Glomerular diseases include nephrotic syndrome, focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous nephropathy (MN), IgA nephropathy (IgAN), C3 glomerulopathy (MPGN3), diabetic nephropathy, lupus nephritis and other conditions related to glomerular disease.

[0079] The pharmaceutically acceptable salt of the compound of formula (Ia) is selected from metal salts, amine salts and amino acid salts.

[0080] The metal salt is selected from calcium, sodium, potassium, lithium, barium, strontium, magnesium, cesium, copper, cobalt, iron, manganese, lead, aluminum, cadmium, silver, zinc, ammonium, etc.; the amine salt is selected from methylamine, dimethylamine, ethylamine, diethylamine, n-propylamine, isopropylamine, diisopropylamine, N-methylisopropylamine, n-butylamine, tert-butylamine, 2-butylamine, 1,2-ethylenediamine, N-methylglucamine, N,N,N-trimethylethanolamine hydroxide (choline), tromethamine, Cyclohexylamine, N-methylcyclohexylamine, guanidine, N-(4-aminobutyl)guanidine, dicyclohexylamine, benzylamine, ethanolamine, diethanolamine, tris(hydroxymethyl)methylamine, hydroxylamine, methylamine, benzylamine, N-methylbenzylamine, N-ethylbenzylamine, 4-methoxybenzylamine, pyrrolidine, piperidine, piperazine, morpholine, 2-aminopyrimidine, 2-thienylethylamine, (2S)-3,3-dimethyl-2-butylamine, cyclopentylamine, cycloheptylamine, meglumine, Benzylamine, dibenzylamine, diphenylamine, α-naphthylamine, o-phenylenediamine, 1,3-diaminopropane, (S)-α-naphthylethylamine, (S)-3-methoxyphenethylamine, (S)-4-methoxyphenethylamine, (S)-4-chlorophenethylamine, (S)-4-methylphenethylamine, cinchonine, cinchonidine, (-)-quinine, triethanolamine, imidazole, ethylenediamine, epoline, morpholine 4-(2-hydroxyethyl), NN-diethyl The invention relates to an amino acid salt selected from the group consisting of alanine, lysine, arginine, histidine, threonine, proline, glutamine and glycine.

[0081] The pharmaceutically acceptable excipient is selected from at least one of the following: a diluent, a binder, a disintegrant, a lubricant, a glidant, a sweetener, a pH adjuster, a suspending agent or a viscosity adjuster, a flavoring agent, and an optional coating redimix.

[0082] Diluents include, but are not limited to, lactose monohydrate, lactose, microcrystalline cellulose, polymethacrylates selected from Eudragit, potassium chloride, sulfobutyl ether b-cyclodextrin, sodium chloride, spray-dried lactose, and preferably sulfobutyl ether b-cyclodextrin, combinations thereof, and other such substances known to those of ordinary skill in the art.

[0083] Binders include, but are not limited to, hypromellose 3Cps, carbomers selected from carbopol, gellan gum, gum arabic, hydrogenated vegetable oils, polymethacrylates selected from Eudragit, xanthan gum, lactose and zein, combinations thereof, and other such substances known to those of ordinary skill in the art.

[0084] Disintegrants include, but are not limited to, croscarmellose sodium, bicarbonate, chitin, gellan gum, polyclinic potassium, and docusate sodium, combinations thereof, and other such substances known to those of ordinary skill in the art.

[0085] Glidants include, but are not limited to, colloidal silicon dioxide, calcium silicate, magnesium silicate, silica hydrogel, corn starch, talc, combinations thereof, and other such materials known to those of ordinary skill in the art.

[0086] Lubricants include, but are not limited to, calcium stearate, magnesium stearate, mineral oil, stearic acid, zinc stearate, glyceryl behenate, hydrogenated vegetable oils, sodium stearyl fumarate and myristic acid, suitable combinations thereof, and other such materials known to those of ordinary skill in the art.

[0087] Suitable pH adjusting agents for maintaining the pH of the formulations according to the present invention include, but are not limited to, citric acid and other similar excipients and suitable combinations thereof, as well as other substances known to those of ordinary skill in the art.

[0088] Suspending agents or viscosity agents according to the present invention include, but are not limited to, microcrystalline cellulose and sodium carboxymethyl cellulose (Avicel CL 611) and other similar excipients, and suitable combinations thereof, as well as other substances known to those of ordinary skill in the art.

[0089] Sweeteners are selected from sucrose and all such substances known to those skilled in the art.

[0090] The flavoring agent is selected from the group consisting of cherry flavor, orange flavor, mango flavor and all such fruit flavors known to those of ordinary skill in the art.

[0091] The coating redimix is ​​selected from Opadry Pink, all such materials known to those skilled in the art.

[0092] In certain embodiments, the pharmaceutical composition of the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is as follows;

[0093]

[0094] The stable pharmaceutical composition according to the present invention may be in the form of a tablet or capsule or powder or a suspension in a liquid or an aerosol formulation or a solution, preferably in the form of a tablet or capsule or a suspension.

[0095] In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject at a dosage of 1 mg to 500 mg. In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject to provide a 1 mg to 150 mg dosage of the compound of formula (Ia) or a pharmaceutically acceptable salt thereof. In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject to provide a 25 mg, 50 mg, and 100 mg dosage of the compound of formula (Ia) or a pharmaceutically acceptable salt thereof to a subject.

[0096] In another embodiment, the compound of Formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject in an amount of about 1 mg to about 500 mg, about 50 mg to about 450 mg, about 100 mg to about 400 mg, about 150 mg to about 350 mg, about 200 mg to about 300 mg, about 1 mg to about 50 mg, about 1 mg to about 25 mg to a subject.

[0097] In certain embodiments, the compound of Formula (Ia) or a pharmaceutically acceptable salt thereof can be further characterized according to the dose of the compound administered to a subject, wherein the subject is an animal or a human.

[0098] In another embodiment, the present invention provides an effective amount of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof administered to a subject by oral, parenteral, intravenous or intramuscular administration.

[0099] Combination of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof with other suitable inhibitors

[0100] In one embodiment, the present invention provides a combination of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof and a suitable second therapeutic agent selected from a suitable factor B inhibitor or a suitable angiotensin II receptor antagonist or a suitable factor D inhibitor or a suitable C3 inhibitor or a suitable C5 inhibitor or a suitable C6 inhibitor or a suitable lectin pathway inhibitor or a suitable properdin inhibitor or a suitable C9 antibody and a multi-target complement inhibitor.

[0101] The factor B inhibitor is ipilimumab; the angiotensin II receptor antagonist is fimasartan, azilsartan, candesartan, eprosartan, losartan, olmesartan, telmisartan, valsartan; the factor D inhibitor is selected from Danicopan, ALXN2050, BCX9930; the C3 inhibitor is selected from pegcitacoplan and AMY 201; the C5 inhibitor is selected from eculizumab, virolizumab, RA101348, DF2593A, tertulumab, SOBI-002, ravlizumab, Cemdsiran, ARC1905 and avacopan; the C6 inhibitor is CP 010; the lectin pathway inhibitor is nasolizumab; the properdin inhibitor is NM9401; the C9 antibody and multi-target complement inhibitor is MFHR1. Combinations of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof with a suitable factor B inhibitor

[0102] In one embodiment, the present invention provides a combination of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof and a suitable Factor B inhibitor.

[0103] The factor B inhibitor used in combination with the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is ipracopan. Combination of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof with a suitable angiotensin II receptor antagonist

[0104] In one embodiment, the present invention provides a combination of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof and a suitable angiotensin II receptor antagonist.

[0105] Angiotensin II receptor antagonists for use in combination with the compound of formula (Ia) or a pharmaceutically acceptable salt thereof are fimasartan, azilsartan, candesartan, eprosartan, losartan, olmesartan, telmisartan and valsartan.

[0106] Pharmaceutical composition of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof and a suitable factor B inhibitor for treating glomerular diseases

[0107] In one embodiment, the present invention provides a pharmaceutical composition for treating glomerular diseases, comprising a compound of formula (Ia) or a pharmaceutically acceptable salt of a compound of formula (Ia) and a suitable factor B inhibitor, optionally containing one or more pharmaceutically acceptable excipients.

[0108] Glomerular diseases include nephrotic syndrome, focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous nephropathy (MN), IgA nephropathy (IgAN), C3 glomerulopathy (MPGN3), diabetic nephropathy, lupus nephritis and other conditions related to glomerular disease.

[0109] The pharmaceutically acceptable salt of the compound of formula (Ia) is selected from metal salts, amine salts and amino acid salts.

[0110] The metal salt is selected from calcium, sodium, potassium, lithium, barium, strontium, magnesium, cesium, copper, cobalt, iron, manganese, lead, aluminum, cadmium, silver, zinc, ammonium, etc.; the amine salt is selected from methylamine, dimethylamine, ethylamine, diethylamine, n-propylamine, isopropylamine, diisopropylamine, N-methylisopropylamine, n-butylamine, tert-butylamine, 2-butylamine, 1,2-ethylenediamine, N-methylglucamine, N,N,N-trimethylethanolamine hydroxide (choline), tromethamine, Cyclohexylamine, N-methylcyclohexylamine, guanidine, N-(4-aminobutyl)guanidine, dicyclohexylamine, benzylamine, ethanolamine, diethanolamine, tris(hydroxymethyl)methylamine, hydroxylamine, methylamine, benzylamine, N-methylbenzylamine, N-ethylbenzylamine, 4-methoxybenzylamine, pyrrolidine, piperidine, piperazine, morpholine, 2-aminopyrimidine, 2-thienylethylamine, (2S)-3,3-dimethyl-2-butylamine, cyclopentylamine, cycloheptylamine, meglumine, Benzylamine, dibenzylamine, diphenylamine, α-naphthylamine, o-phenylenediamine, 1,3-diaminopropane, (S)-α-naphthylethylamine, (S)-3-methoxyphenethylamine, (S)-4-methoxyphenethylamine, (S)-4-chlorophenethylamine, (S)-4-methylphenethylamine, cinchonine, cinchonidine, (-)-quinine, triethanolamine, imidazole, ethylenediamine, epoline, morpholine 4-(2-hydroxyethyl), NN-diethyl The invention relates to an amino acid salt selected from the group consisting of alanine, lysine, arginine, histidine, threonine, proline, glutamine and glycine.

[0111] The factor B inhibitor is ipratropium.

[0112] The pharmaceutically acceptable excipient is selected from at least one of the following: a diluent, a binder, a disintegrant, a lubricant, a glidant, a sweetener, a pH adjuster, a suspending agent or a viscosity adjuster, a flavoring agent and an optional coating redimix.

[0113] Diluents include, but are not limited to, lactose monohydrate, lactose, microcrystalline cellulose, polymethacrylates selected from Eudragit, potassium chloride, sulfobutyl ether b-cyclodextrin, sodium chloride, spray-dried lactose, and preferably sulfobutyl ether b-cyclodextrin, combinations thereof, and other such substances known to those of ordinary skill in the art.

[0114] Binders include, but are not limited to, hypromellose 3Cps, carbomer selected from Carbopol, gellan gum, gum arabic, hydrogenated vegetable oils, polymethacrylates selected from Eudragit, xanthan gum, lactose and zein, combinations thereof, and other such substances known to those of ordinary skill in the art.

[0115] Disintegrants include, but are not limited to, croscarmellose sodium, bicarbonate, chitin, gellan gum, polyclinic potassium, and docusate sodium, combinations thereof, and other such substances known to those of ordinary skill in the art.

[0116] Glidants include, but are not limited to, colloidal silicon dioxide, calcium silicate, magnesium silicate, silica hydrogel, corn starch, talc, combinations thereof, and other such materials known to those of ordinary skill in the art.

[0117] Lubricants include, but are not limited to, calcium stearate, magnesium stearate, mineral oil, stearic acid, zinc stearate, glyceryl behenate, hydrogenated vegetable oils, sodium stearyl fumarate and myristic acid, suitable combinations thereof, and other such materials known to those of ordinary skill in the art.

[0118] The coating redimix is ​​selected from Opadry Pink, all such materials known to those skilled in the art.

[0119] In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject at a dosage of 1 mg to 500 mg. In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject to provide a 1 mg to 150 mg dosage of the compound of formula (Ia) or a pharmaceutically acceptable salt thereof. In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject to provide a 25 mg, 50 mg, and 100 mg dosage of the compound of formula (Ia) or a pharmaceutically acceptable salt thereof to a subject.

[0120] In another embodiment, the compound of Formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject in an amount of about 1 mg to about 500 mg, about 50 mg to about 450 mg, about 100 mg to about 400 mg, about 150 mg to about 350 mg, about 200 mg to about 300 mg, about 1 mg to about 50 mg, about 1 mg to about 25 mg to a subject.

[0121] In another embodiment, iplomepam is administered to a subject in an amount of about 1 mg to about 500 mg, about 50 mg to about 450 mg, about 100 mg to about 400 mg, about 150 mg to about 350 mg, about 200 mg to about 300 mg. In a certain embodiment, iplomepam is administered in an amount of 200 mg.

[0122] In certain embodiments, the compound of Formula (Ia) or a pharmaceutically acceptable salt thereof can be further characterized according to the dose of the compound administered to a subject, wherein the subject is an animal or a human.

[0123] In another embodiment, the present invention provides an effective amount of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof administered to a subject by oral, parenteral, intravenous or intramuscular administration.

[0124] Pharmaceutical composition of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof and a suitable angiotensin II receptor antagonist for treating glomerular diseases

[0125] In one embodiment, the present invention provides a pharmaceutical composition for treating glomerular diseases, comprising a compound of formula (Ia) or a pharmaceutically acceptable salt of a compound of formula (Ia) and a suitable angiotensin II receptor antagonist, optionally containing one or more pharmaceutically acceptable excipients.

[0126] Glomerular diseases include nephrotic syndrome, focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous nephropathy (MN), IgA nephropathy (IgAN), C3 glomerulopathy (MPGN3), diabetic nephropathy, lupus nephritis and other conditions related to glomerular disease.

[0127] The pharmaceutically acceptable salt of the compound of formula (Ia) is selected from metal salts, amine salts and amino acid salts.

[0128] The metal salt is selected from calcium, sodium, potassium, lithium, barium, strontium, magnesium, cesium, copper, cobalt, iron, manganese, lead, aluminum, cadmium, silver, zinc, ammonium, etc.; the amine salt is selected from methylamine, dimethylamine, ethylamine, diethylamine, n-propylamine, isopropylamine, diisopropylamine, N-methylisopropylamine, n-butylamine, tert-butylamine, 2-butylamine, 1,2-ethylenediamine, N-methylglucamine, N,N,N-trimethylethanolamine hydroxide (choline), tromethamine, Cyclohexylamine, N-methylcyclohexylamine, guanidine, N-(4-aminobutyl)guanidine, dicyclohexylamine, benzylamine, ethanolamine, diethanolamine, tris(hydroxymethyl)methylamine, hydroxylamine, methylamine, benzylamine, N-methylbenzylamine, N-ethylbenzylamine, 4-methoxybenzylamine, pyrrolidine, piperidine, piperazine, morpholine, 2-aminopyrimidine, 2-thienylethylamine, (2S)-3,3-dimethyl-2-butylamine, cyclopentylamine, cycloheptylamine, meglumine, Benzylamine, dibenzylamine, diphenylamine, α-naphthylamine, o-phenylenediamine, 1,3-diaminopropane, (S)-α-naphthylethylamine, (S)-3-methoxyphenethylamine, (S)-4-methoxyphenethylamine, (S)-4-chlorophenethylamine, (S)-4-methylphenethylamine, cinchonine, cinchonidine, (-)-quinine, triethanolamine, imidazole, ethylenediamine, epoline, morpholine 4-(2-hydroxyethyl), NN-diethyl The invention relates to an amino acid salt selected from the group consisting of alanine, lysine, arginine, histidine, threonine, proline, glutamine and glycine.

[0129] Angiotensin II receptor antagonists are fimasartan, azilsartan, candesartan, eprosartan, losartan, olmesartan, telmisartan, and valsartan.

[0130] The pharmaceutically acceptable excipient is selected from at least one of the following: a diluent, a binder, a disintegrant, a lubricant, a glidant, a sweetener, a pH adjuster, a suspending agent or a viscosity adjuster, a flavoring agent and an optional coating redimix.

[0131] Diluents include, but are not limited to, lactose monohydrate, lactose, microcrystalline cellulose, polymethacrylates selected from Eudragit, potassium chloride, sulfobutyl ether b-cyclodextrin, sodium chloride, spray-dried lactose, and preferably sulfobutyl ether b-cyclodextrin, combinations thereof, and other such substances known to those of ordinary skill in the art.

[0132] Binders include, but are not limited to, hypromellose 3Cps, carbomer selected from Carbopol, gellan gum, gum arabic, hydrogenated vegetable oils, polymethacrylates selected from Eudragit, xanthan gum, lactose and zein, combinations thereof, and other such substances known to those of ordinary skill in the art.

[0133] Disintegrants include, but are not limited to, croscarmellose sodium, bicarbonate, chitin, gellan gum, polyclinic potassium, and docusate sodium, combinations thereof, and other such substances known to those of ordinary skill in the art.

[0134] Glidants include, but are not limited to, colloidal silicon dioxide, calcium silicate, magnesium silicate, silica hydrogel, corn starch, talc, combinations thereof, and other such materials known to those of ordinary skill in the art.

[0135] Lubricants include, but are not limited to, calcium stearate, magnesium stearate, mineral oil, stearic acid, zinc stearate, glyceryl behenate, hydrogenated vegetable oils, sodium stearyl fumarate and myristic acid, suitable combinations thereof, and other such materials known to those of ordinary skill in the art.

[0136] The coating redimix is ​​selected from Opadry Pink, all such materials known to those skilled in the art.

[0137] In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject at a dosage of 1 mg to 500 mg. In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject to provide a 1 mg to 150 mg dosage of the compound of formula (Ia) or a pharmaceutically acceptable salt thereof. In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject to provide a 25 mg, 50 mg, and 100 mg dosage of the compound of formula (Ia) or a pharmaceutically acceptable salt thereof to a subject.

[0138] In another embodiment, the compound of Formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject in an amount of about 1 mg to about 500 mg, about 50 mg to about 450 mg, about 100 mg to about 400 mg, about 150 mg to about 350 mg, about 200 mg to about 300 mg, about 1 mg to about 50 mg, about 1 mg to about 25 mg to a subject.

[0139] In another embodiment, fimasartan is administered to a subject in an amount of about 1 mg to about 500 mg, about 50 mg to about 450 mg, about 100 mg to about 400 mg, about 150 mg to about 350 mg, about 200 mg to about 300 mg. In another embodiment, azilsartan is administered to a subject in an amount of about 1 mg to about 500 mg. In another embodiment, candesartan is administered to a subject in an amount of about 1 mg to about 200 mg. In another embodiment, eprosartan is administered to a subject in an amount of about 1 mg to about 1000 mg. In another embodiment, losartan is administered to a subject in an amount of about 1 mg to about 500 mg. In another embodiment, olmesartan is administered to a subject in an amount of about 1 mg to about 200 mg. In another embodiment, telmisartan is administered to a subject in an amount of about 1 mg to about 500 mg. In another embodiment, valsartan is administered to a subject in an amount of about 1 mg to about 500 mg.

[0140] In a certain embodiment, fimasartan is applied to a subject in an amount of about 60mg and 120mg. In another embodiment, azilsartan is applied to a subject in an amount of about 40mg and 80mg. In another embodiment, candesartan is applied to a subject in an amount of about 4mg, 8mg, 16mg and 32mg. In another embodiment, eprosartan is applied to a subject in an amount of about 400mg and 600mg. In another embodiment, losartan is applied to a subject in an amount of about 25mg, 50mg and 100mg. In another embodiment, olmesartan is applied to a subject in an amount of about 5mg, 20mg and 40mg. In another embodiment, telmisartan is applied to a subject in an amount of about 20mg, 40mg and 80mg. In another embodiment, valsartan is applied to a subject in an amount of about 40mg, 80mg, 160mg and 320mg.

[0141] In certain embodiments, the compound of Formula (Ia) or a pharmaceutically acceptable salt thereof can be further characterized according to the dose of the compound administered to a subject, wherein the subject is an animal or a human.

[0142] In another embodiment, the present invention provides an effective amount of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof administered to a subject by oral, parenteral, intravenous or intramuscular administration.

[0143] Use of the compound of formula (Ia) or its pharmaceutically acceptable salt for treating glomerular diseases

[0144] In one embodiment, the present invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof for treating glomerular diseases.

[0145] Glomerular diseases include nephrotic syndrome, focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous nephropathy (MN), IgA nephropathy (IgAN), C3 glomerulopathy (MPGN3), diabetic nephropathy, lupus nephritis and other conditions related to glomerular disease.

[0146] The pharmaceutically acceptable salt of the compound of formula (Ia) is selected from metal salts, amine salts and amino acid salts.

[0147] The metal salt is selected from calcium, sodium, potassium, lithium, barium, strontium, magnesium, cesium, copper, cobalt, iron, manganese, lead, aluminum, cadmium, silver, zinc, ammonium, etc.; the amine salt is selected from methylamine, dimethylamine, ethylamine, diethylamine, n-propylamine, isopropylamine, diisopropylamine, N-methylisopropylamine, n-butylamine, tert-butylamine, 2-butylamine, 1,2-ethylenediamine, N-methylglucamine, N,N,N-trimethylethanolamine hydroxide (choline), tromethamine, Cyclohexylamine, N-methylcyclohexylamine, guanidine, N-(4-aminobutyl)guanidine, dicyclohexylamine, benzylamine, ethanolamine, diethanolamine, tris(hydroxymethyl)methylamine, hydroxylamine, methylamine, benzylamine, N-methylbenzylamine, N-ethylbenzylamine, 4-methoxybenzylamine, pyrrolidine, piperidine, piperazine, morpholine, 2-aminopyrimidine, 2-thienylethylamine, (2S)-3,3-dimethyl-2-butylamine, cyclopentylamine, cycloheptylamine, meglumine, Benzylamine, dibenzylamine, diphenylamine, α-naphthylamine, o-phenylenediamine, 1,3-diaminopropane, (S)-α-naphthylethylamine, (S)-3-methoxyphenethylamine, (S)-4-methoxyphenethylamine, (S)-4-chlorophenethylamine, (S)-4-methylphenethylamine, cinchonine, cinchonidine, (-)-quinine, triethanolamine, imidazole, ethylenediamine, epoline, morpholine 4-(2-hydroxyethyl), NN-diethyl The invention relates to an amino acid salt selected from the group consisting of alanine, lysine, arginine, histidine, threonine, proline, glutamine and glycine.

[0148] In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject at a dosage of 1 mg to 500 mg. In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject to provide a 1 mg to 150 mg dosage of the compound of formula (Ia) or a pharmaceutically acceptable salt thereof. In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject to provide a 25 mg, 50 mg, and 100 mg dosage of the compound of formula (Ia) or a pharmaceutically acceptable salt thereof to a subject.

[0149] In another embodiment, the compound of Formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject in an amount of about 1 mg to about 500 mg, about 50 mg to about 450 mg, about 100 mg to about 400 mg, about 150 mg to about 350 mg, about 200 mg to about 300 mg, about 1 mg to about 50 mg, about 1 mg to about 25 mg to a subject.

[0150] In certain embodiments, the compound of Formula (Ia) or a pharmaceutically acceptable salt thereof can be further characterized according to the dose of the compound administered to a subject, wherein the subject is an animal or a human.

[0151] In another embodiment, the present invention provides an effective amount of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof administered to a subject by oral, parenteral, intravenous or intramuscular administration.

[0152] Use of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof in combination with a suitable factor B for treating glomerular diseases

[0153] In one embodiment, the present invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof in combination with a suitable factor B inhibitor for treating glomerular diseases.

[0154] Glomerular diseases include nephrotic syndrome, focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous nephropathy (MN), IgA nephropathy (IgAN), C3 glomerulopathy (MPGN3), diabetic nephropathy, lupus nephritis and other conditions related to glomerular disease.

[0155] The pharmaceutically acceptable salt of the compound of formula (Ia) is selected from metal salts, amine salts and amino acid salts.

[0156] The metal salt is selected from calcium, sodium, potassium, lithium, barium, strontium, magnesium, cesium, copper, cobalt, iron, manganese, lead, aluminum, cadmium, silver, zinc, ammonium, etc.; the amine salt is selected from methylamine, dimethylamine, ethylamine, diethylamine, n-propylamine, isopropylamine, diisopropylamine, N-methylisopropylamine, n-butylamine, tert-butylamine, 2-butylamine, 1,2-ethylenediamine, N-methylglucamine, N,N,N-trimethylethanolamine hydroxide (choline), tromethamine, Cyclohexylamine, N-methylcyclohexylamine, guanidine, N-(4-aminobutyl)guanidine, dicyclohexylamine, benzylamine, ethanolamine, diethanolamine, tris(hydroxymethyl)methylamine, hydroxylamine, methylamine, benzylamine, N-methylbenzylamine, N-ethylbenzylamine, 4-methoxybenzylamine, pyrrolidine, piperidine, piperazine, morpholine, 2-aminopyrimidine, 2-thienylethylamine, (2S)-3,3-dimethyl-2-butylamine, cyclopentylamine, cycloheptylamine, meglumine, Benzylamine, dibenzylamine, diphenylamine, α-naphthylamine, o-phenylenediamine, 1,3-diaminopropane, (S)-α-naphthylethylamine, (S)-3-methoxyphenethylamine, (S)-4-methoxyphenethylamine, (S)-4-chlorophenethylamine, (S)-4-methylphenethylamine, cinchonine, cinchonidine, (-)-quinine, triethanolamine, imidazole, ethylenediamine, epoline, morpholine 4-(2-hydroxyethyl), NN-diethyl The invention relates to an amino acid salt selected from the group consisting of alanine, lysine, arginine, histidine, threonine, proline, glutamine and glycine.

[0157] A factor B inhibitor for use in combination with a compound of formula (Ia) or a pharmaceutically acceptable salt thereof is ipracopan, which is used to treat glomerular diseases.

[0158] In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject at a dosage of 1 mg to 500 mg. In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject to provide a dosage of 1 mg to 150 mg of the compound of formula (Ia) or a pharmaceutically acceptable salt thereof. In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject to provide a 25 mg, 50 mg, and 100 mg dosage of the compound of formula (Ia) or a pharmaceutically acceptable salt thereof to the subject.

[0159] In another embodiment, the compound of Formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject in an amount of about 1 mg to about 500 mg, about 50 mg to about 450 mg, about 100 mg to about 400 mg, about 150 mg to about 350 mg, about 200 mg to about 300 mg, about 1 mg to about 50 mg, about 1 mg to about 25 mg to a subject.

[0160] In another embodiment, iplomepam is administered to a subject in an amount of about 1 mg to about 500 mg, about 50 mg to about 450 mg, about 100 mg to about 400 mg, about 150 mg to about 350 mg, about 200 mg to about 300 mg. In a certain embodiment, iplomepam is administered in an amount of 200 mg.

[0161] In certain embodiments, the compound of Formula (Ia) or a pharmaceutically acceptable salt thereof can be further characterized according to the dose of the compound administered to a subject, wherein the subject is an animal or a human.

[0162] In another embodiment, the present invention provides an effective amount of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof administered to a subject via oral, parenteral, intravenous or intramuscular administration.

[0163] Use of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof in combination with a suitable angiotensin II receptor antagonist for treating glomerular diseases

[0164] In one embodiment, the present invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof in combination with a suitable angiotensin II receptor antagonist for treating glomerular diseases.

[0165] Glomerular diseases include nephrotic syndrome, focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous nephropathy (MN), IgA nephropathy (IgAN), C3 glomerulopathy (MPGN3), diabetic nephropathy, lupus nephritis and other conditions related to glomerular disease.

[0166] The pharmaceutically acceptable salt of the compound of formula (Ia) is selected from metal salts, amine salts and amino acid salts.

[0167] The metal salt is selected from calcium, sodium, potassium, lithium, barium, strontium, magnesium, cesium, copper, cobalt, iron, manganese, lead, aluminum, cadmium, silver, zinc, ammonium, etc.; the amine salt is selected from methylamine, dimethylamine, ethylamine, diethylamine, n-propylamine, isopropylamine, diisopropylamine, N-methylisopropylamine, n-butylamine, tert-butylamine, 2-butylamine, 1,2-ethylenediamine, N-methylglucamine, N,N,N-trimethylethanolamine hydroxide (choline), tromethamine, Cyclohexylamine, N-methylcyclohexylamine, guanidine, N-(4-aminobutyl)guanidine, dicyclohexylamine, benzylamine, ethanolamine, diethanolamine, tris(hydroxymethyl)methylamine, hydroxylamine, methylamine, benzylamine, N-methylbenzylamine, N-ethylbenzylamine, 4-methoxybenzylamine, pyrrolidine, piperidine, piperazine, morpholine, 2-aminopyrimidine, 2-thienylethylamine, (2S)-3,3-dimethyl-2-butylamine, cyclopentylamine, cycloheptylamine, meglumine, Benzylamine, dibenzylamine, diphenylamine, α-naphthylamine, o-phenylenediamine, 1,3-diaminopropane, (S)-α-naphthylethylamine, (S)-3-methoxyphenethylamine, (S)-4-methoxyphenethylamine, (S)-4-chlorophenethylamine, (S)-4-methylphenethylamine, cinchonine, cinchonidine, (-)-quinine, triethanolamine, imidazole, ethylenediamine, epoline, morpholine 4-(2-hydroxyethyl), NN-diethyl The invention relates to an amino acid salt selected from the group consisting of alanine, lysine, arginine, histidine, threonine, proline, glutamine and glycine.

[0168] Angiotensin II receptor antagonists used in combination with the compound of formula (Ia) or a pharmaceutically acceptable salt thereof are fimasartan, azilsartan, candesartan, eprosartan, losartan, olmesartan, telmisartan and valsartan, which are useful in the treatment of glomerular diseases.

[0169] In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject at a dosage of 1 mg to 500 mg. In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject to provide a 1 mg to 150 mg dosage of the compound of formula (Ia) or a pharmaceutically acceptable salt thereof. In certain embodiments, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used to be administered to a subject to provide a 25 mg, 50 mg, and 100 mg dosage of the compound of formula (Ia) or a pharmaceutically acceptable salt thereof to a subject.

[0170] In another embodiment, the compound of Formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject in an amount of about 1 mg to about 500 mg, about 50 mg to about 450 mg, about 100 mg to about 400 mg, about 150 mg to about 350 mg, about 200 mg to about 300 mg, about 1 mg to about 50 mg, about 1 mg to about 25 mg to a subject.

[0171] In another embodiment, fimasartan is administered to a subject in an amount of about 1 mg to about 500 mg, about 50 mg to about 450 mg, about 100 mg to about 400 mg, about 150 mg to about 350 mg, about 200 mg to about 300 mg. In another embodiment, azilsartan is administered to a subject in an amount of about 1 mg to about 500 mg. In another embodiment, candesartan is administered to a subject in an amount of about 1 mg to about 200 mg. In another embodiment, eprosartan is administered to a subject in an amount of about 1 mg to about 1000 mg. In another embodiment, losartan is administered to a subject in an amount of about 1 mg to about 500 mg. In another embodiment, olmesartan is administered to a subject in an amount of about 1 mg to about 200 mg. In another embodiment, telmisartan is administered to a subject in an amount of about 1 mg to about 500 mg. In another embodiment, valsartan is administered to a subject in an amount of about 1 mg to about 500 mg.

[0172] In a certain embodiment, fimasartan is applied to a subject in an amount of about 60mg and 120mg. In another embodiment, azilsartan is applied to a subject in an amount of about 40mg and 80mg. In another embodiment, candesartan is applied to a subject in an amount of about 4mg, 8mg, 16mg and 32mg. In another embodiment, eprosartan is applied to a subject in an amount of about 400mg and 600mg. In another embodiment, losartan is applied to a subject in an amount of about 25mg, 50mg and 100mg. In another embodiment, olmesartan is applied to a subject in an amount of about 5mg, 20mg and 40mg. In another embodiment, telmisartan is applied to a subject in an amount of about 20mg, 40mg and 80mg. In another embodiment, valsartan is applied to a subject in an amount of about 40mg, 80mg, 160mg and 320mg.

[0173] In certain embodiments, the compound of Formula (Ia) or a pharmaceutically acceptable salt thereof can be further characterized according to the dose of the compound administered to a subject, wherein the subject is an animal or a human.

[0174] In another embodiment, the present invention provides an effective amount of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof administered to a subject by oral, parenteral, intravenous or intramuscular administration.

[0175] Reduction in urine protein

[0176] In one embodiment, when administered to a subject, the compound of formula (Ia) or a pharmaceutically acceptable salt thereof, alone or in combination with a suitable other inhibitor, results in a decrease in the amount of urinary protein.

[0177] For example, in certain embodiments, there is a reduction in the amount of urine protein.

[0178] In certain embodiments, there is at least a 5% reduction in the amount of urine protein. In certain embodiments, there is at least a 10% reduction in the amount of urine protein. In certain embodiments, there is at least a 15% reduction in the amount of urine protein. In certain embodiments, there is at least a 20% reduction in the amount of urine protein. In certain embodiments, there is at least a 25% reduction in the amount of urine protein. In certain embodiments, there is at least a 30% reduction in the amount of urine protein. In certain embodiments, there is at least a 35% reduction in the amount of urine protein. In certain embodiments, there is at least a 40% reduction in the amount of urine protein. In certain embodiments, there is at least a 50% reduction in the amount of urine protein. In certain embodiments, there is at least a 60% reduction in the amount of urine protein. In certain embodiments, there is at least a 70% reduction in the amount of urine protein. In certain embodiments, there is at least a 80% reduction in the amount of urine protein. In certain embodiments, there is at least a 90% reduction in the amount of urine protein.

[0179] Dosage regimen

[0180] The method can be further characterized by a dosing regimen by which a compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered alone or in combination, and a pharmaceutical composition of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered alone or in combination.

[0181] In certain embodiments, the compound is administered to a subject once a day, twice a day, and three times a day. In another embodiment, the compound is administered to a subject for at least 1 week. In another embodiment, the compound is administered to a subject for at least 2 weeks. In another embodiment, the compound is administered to a subject for at least 3 weeks. In another embodiment, the compound is administered to a subject for at least 4 weeks. In another embodiment, the compound is administered to a subject for at least 6 weeks. In another embodiment, the compound is administered to a subject for at least 8 weeks. In another embodiment, the compound is administered to a subject for at least 10 weeks. In another embodiment, the compound is administered to a subject for at least 12 weeks. In another embodiment, the compound is administered to a subject for at least 14 weeks. In another embodiment, the compound is administered to a subject for at least 16 weeks.

[0182] In one embodiment, the present invention provides a method for treating glomerular disease in a patient with diabetes, comprising administering an effective amount of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof, or a combination of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof and a suitable factor B inhibitor or an angiotensin II receptor antagonist.

[0183] The scope of pharmaceutically acceptable salts, dosage forms, suitable factor B inhibitors, suitable angiotensin II receptor antagonists, and glomerular diseases are as defined anywhere in the specification.

[0184] In another embodiment, the present invention provides a combination of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof with other prolyl hydroxylase inhibitors, such as Roxadustat, Vadadustat, Molidustat, Daprodustat, and the like.

[0185] The compound of formula (Ia) was prepared according to the method disclosed in WO 2014102818.

[0186] Ipracolapam was prepared according to the method disclosed in WO2015009616.

[0187] Fimasartan was prepared according to the method disclosed in WO199955681.

[0188] Example

[0189] The effects of the compounds of formula (Ia) and combinations thereof in animal models of glomerular disease are shown below.

[0190] Animal Models of Glomerular Disease

[0191] Example 1: Effects of the compound of formula (Ia) and its combination on LPS-induced nephritis in C57 mice

[0192] Single dose lipopolysaccharide (LPS)-induced acute nephritis was produced in C57 mice, and the effects of the compound of formula (Ia) and the combination are shown below.

[0193] Male C57 mice were treated with vehicle / compound of formula (Ia) (15 mg / kg) and a combination of compound of formula (Ia) (15 mg / kg) and ipracol (20 mg / kg, twice daily) by oral route. The mice were bled 24 hours after LPS treatment and serum was obtained. Serum creatinine and urea levels were determined.

[0194] Sr.No. Compound Serum creatinine Serum urea 1 Formula (Ia) 34.1％±5.2％ 44.9％±5.2％ 2 Combination of formula (Ia) and ipracolpan 55.6％±4.8％ 65.6％±3.2％

[0195] Acute treatment with the compound of formula (Ia) reduced serum creatinine by 34.1 ± 5.2, while the combination of the compound of formula (Ia) and ipracopan reduced serum creatinine by 55.6% ± 4.8% relative to LPS-treated mice ( Figure 1 A). When compared to mice treated with LPS, the compound of formula (Ia) reduced serum urea by 44.9±5.2, while the combination of ipracopan and the compound of formula (Ia) reduced serum urea by 65.6%±3.2% ( Figure 1 B).

[0196] Example 2: Effects of the compound of formula (Ia) on renal dysfunction induced by 5 / 6 nephrectomy in male SD rats

[0197] Male SD rats were subjected to 5 / 6 nephrectomy to induce focal segmental glomerulosclerosis. After one week of recovery, the animals were treated with the compound of formula (Ia). Randomized rats were treated with the compound of formula (Ia) (15 mg / kg) for four weeks. At the end of the treatment, serum creatinine, serum urea and urine microalbumin were determined.

[0198] Sr.No. Compound Microalbumin Serum creatinine Serum urea 1 Formula (Ia) 35.9％±12.0％ 14.9％±3.2％ 15.9％±8.8％

[0199] When compared to diabetic mice, treatment with the compound of formula (Ia) reduced urinary microalbumin excretion by 35.9±12.0 ( Figure 2 A). It also reduced serum creatinine and urea by 14.9% ± 3.2% and 15.% ± 8.8%, respectively ( Figure 2 B to C).

[0200] Example 3: Effects of the compound of formula (Ia) or a combination thereof on doxorubicin-induced glomerulosclerosis in male Balb / c mice

[0201] Male Balb / c mice are treated with doxorubicin (10mg / kg, IV). After 5 weeks of treatment, mice are randomly divided into four groups based on protein excretion urine: doxorubicin, formula (Ia) compound (15mg / kg) and formula (Ia) compound (15mg / kg) and fimasartan (15mg / kg) by oral route. Processing continues for two weeks. These mice are kept in metabolic cages, and 24 hours of urine protein excretion is measured.

[0202] Sr.No. Compound Urine total protein 1 Formula (Ia) 47.8％±5.8％ 2 Combination of formula (Ia) and Fimasartan 64.4％±10.1％

[0203] After two weeks of treatment, the compound of formula (Ia) reduced the excretion of total protein in urine by 47.8 ± 5.8 relative to animals treated with doxorubicin. The combination of Fimasartan and the compound of formula (Ia) reduced proteinuria by 64.4% ± 10.1% relative to doxorubicin treatment. Figure 1 C.

[0204] Example 4: Effects of the compound of formula (Ia) or a combination thereof on cationic bovine serum albumin (cBSA)-induced nephritis in male C57 mice

[0205] Male C57 mice were treated with 2, 4, 6, 8 and 10 mg / kg of bovine serum albumin (BSA) by intraperitoneal route on days 1, 2, 3, 4 and 5, respectively. The next 5 days were treated with 10 mg / kg of BSA. On the same day, mice were treated with a combination of vehicle / compound of formula (Ia) (15 mg / kg) and compound of formula (Ia) (15 mg / kg) with ipracol (20 mg / kg, BID) by oral route and continued for 10 days. On the 11th day, mice were housed in metabolic cages and 24-hour urine protein excretion was measured.

[0206] Sr.No. Compound Urine total protein 1 Formula (Ia) 40.1％±7.6％ 2 Combination of formula (Ia) and ipracolpan 65.7％±7.8％

[0207] Compared to mice treated with BSA, treatment with the compound of formula (Ia) reduced total protein excretion by 40.1% ± 7.6%. Treatment with ipracopan combined with the compound of formula (Ia) reduced proteinuria by 65.7% ± 7.8% ( Figure 1 D).

[0208] Example 5: Diabetes-induced renal dysfunction and the effects of Formula I(a).

[0209] To induce diabetes-induced renal dysfunction, one kidney was removed from male db / db mice and they were treated with compounds of formula (Ia) and combinations for 8 weeks. At the end of treatment, renal dysfunction was assessed. Histological changes in renal disease were also assessed by biochemical changes in serum and urine.

[0210] Male db / db mice were randomized into groups and treated with the compound of formula (Ia) (15 mg / kg) for 8 weeks.

[0211] At the end of treatment, serum creatinine, serum urea, and urine microalbumin were measured.

[0212] Sr.No. Compound Urine microalbumin Serum creatinine Serum urea 1 Formula (Ia) 50.2％±3.2％ 28.4％±4.4％ 25.8％±4.8％

[0213] When compared to diabetic mice, treatment with the compound of formula (Ia) reduced urinary excretion of microalbumin by 50.2 ± 3.2 ( Figure 2 D). It also reduced serum creatinine and urea by 28.4%±4.4% and 25.8%±4.8%, respectively ( Figure 2 E to F).

[0214] The compound of formula (Ia) alone or in combination with ipracopam or fimasartan showed synergistic effects as described and illustrated in the above table.

[0215] References

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Claims

1. A method for treating a glomerular disease in a subject, comprising administering an effective amount of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof, wherein formula (Ia) is represented by:

2. The method of claim 1, wherein the glomerular disease is selected from nephrotic syndrome, focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous nephropathy (MN), IgA nephropathy (IgAN), C3 glomerulopathy (MPGN), diabetic nephropathy, and lupus nephritis.

3. The method of claim 1, wherein the pharmaceutically acceptable salt of the compound of formula (Ia) is selected from metal salts, amine salts and amino acid salts.

4. The method of claim 3, wherein the metal salt is selected from calcium, sodium, potassium, lithium, barium, strontium, magnesium, cesium, copper, cobalt, iron, manganese, lead, aluminum, cadmium, silver, zinc, ammonium, etc.; wherein the amine salt is selected from methylamine, dimethylamine, ethylamine, diethylamine, n-propylamine, isopropylamine, diisopropylamine, N-methylisopropylamine, n-butylamine, tert-butylamine, 2-butylamine, 1,2-ethylenediamine, N-methylglucamine, N,N,N-trimethylethanolamine hydroxide choline), tromethamine, cyclohexylamine, N-methylcyclohexylamine, guanidine, N-(4-aminobutyl)guanidine, dicyclohexylamine, benzylamine, ethanolamine, diethanolamine, tris(hydroxymethyl)methylamine, hydroxylamine, methylamine, benzylamine, N-methylbenzylamine, N-ethylbenzylamine, 4-methoxybenzylamine, pyrrolidine, piperidine, piperazine, morpholine, 2-aminopyrimidine, 2-thienylethylamine, (2S)-3,3-dimethyl-2-butylamine, cyclopentylamine, cyclopentylamine Heptylamine, meglumine, phenethylbenzylamine, dibenzylamine, diphenylamine, α-naphthylamine, o-phenylenediamine, 1,3-diaminopropane, (S)-α-naphthylethylamine, (S)-3-methoxyphenethylamine, (S)-4-methoxyphenethylamine, (S)-4-chlorophenethylamine, (S)-4-methylphenethylamine, cinchonine, cinchonidine, (-)-quinine, triethanolamine, imidazole, ethylenediamine, epoline, morpholine 4-(2-hydroxyethyl), NN -diethylethanolamine, dimethylethanolamine, hydrabamine, betaine, amantadine, L-amantadine, triphenylamine, glucosamine, N-methylpyrrolidine, urea, procaine, metformin, hexane-1,6-diamine, 2-(2-aminoethoxy)ethylamine, N-methylmorpholine and N-ethylmorpholine; wherein the amino acid salt is selected from alanine, lysine, arginine, histidine, threonine, proline, glutamine and glycine.

5. The method of claim 1, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to the subject in an amount of 1 mg to 500 mg, 50 mg to 450 mg, 100 mg to 400 mg, 150 mg to 350 mg, 200 mg to 300 mg, 1 mg to 50 mg, 1 mg to 25 mg to the subject.

6. The method of claim 1, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to the subject at a dose of 1 mg to 150 mg.

7. The method of claim 1, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to the subject at a dose of 25 mg, 50 mg and 100 mg.

8. The method of claim 1, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject, wherein the subject is an animal or a human.

9. The method of claim 1, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to the subject via oral, parenteral, intravenous or intramuscular administration.

10. A method for treating a glomerular disease in a subject, comprising administering a compound of formula (Ia) or a pharmaceutically acceptable salt thereof in combination with a suitable second therapeutic agent, wherein the suitable second therapeutic agent is selected from a suitable factor B inhibitor or a suitable angiotensin II receptor antagonist or a suitable factor D inhibitor or a suitable C3 inhibitor or a suitable C5 inhibitor or a suitable C6 inhibitor or a suitable lectin pathway inhibitor or a suitable properdin inhibitor or a suitable C9 antibody and a multi-target complement inhibitor.

11. The method of claim 10, wherein the suitable second therapeutic agent is a factor B inhibitor or an angiotensin II receptor antagonist.

12. The method of claim 10, wherein the glomerular disease is selected from nephrotic syndrome, focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous nephropathy (MN), IgA nephropathy (IgAN), C3 glomerulopathy (MPGN), diabetic nephropathy, and lupus nephritis.

13. The method of claim 10, wherein the pharmaceutically acceptable salt of the compound of formula (Ia) is selected from metal salts, amine salts and amino acid salts.

14. The method of claim 13, wherein the metal salt is selected from calcium, sodium, potassium, lithium, barium, strontium, magnesium, cesium, copper, cobalt, iron, manganese, lead, aluminum, cadmium, silver, zinc, ammonium, etc.; wherein the amine salt is selected from methylamine, dimethylamine, ethylamine, diethylamine, n-propylamine, isopropylamine, diisopropylamine, N-methylisopropylamine, n-butylamine, tert-butylamine, 2-butylamine, 1,2-ethylenediamine, N-methylglucamine, N,N,N-trimethylethanolamine hydroxide choline), tromethamine, cyclohexylamine, N-methylcyclohexylamine, guanidine, N-(4-aminobutyl)guanidine, dicyclohexylamine, benzylamine, ethanolamine, diethanolamine, tris(hydroxymethyl)methylamine, hydroxylamine, methylamine, benzylamine, N-methylbenzylamine, N-ethylbenzylamine, 4-methoxybenzylamine, pyrrolidine, piperidine, piperazine, morpholine, 2-aminopyrimidine, 2-thienylethylamine, (2S)-3,3-dimethyl-2-butylamine, cyclopentylamine, cyclopentylamine Heptylamine, meglumine, phenethylbenzylamine, dibenzylamine, diphenylamine, α-naphthylamine, o-phenylenediamine, 1,3-diaminopropane, (S)-α-naphthylethylamine, (S)-3-methoxyphenethylamine, (S)-4-methoxyphenethylamine, (S)-4-chlorophenethylamine, (S)-4-methylphenethylamine, cinchonine, cinchonidine, (-)-quinine, triethanolamine, imidazole, ethylenediamine, epoline, morpholine 4-(2-hydroxyethyl), NN -diethylethanolamine, dimethylethanolamine, hydrabamine, betaine, amantadine, L-amantadine, triphenylamine, glucosamine, N-methylpyrrolidine, urea, procaine, metformin, hexane-1,6-diamine, 2-(2-aminoethoxy)ethylamine, N-methylmorpholine and N-ethylmorpholine; wherein the amino acid salt is selected from alanine, lysine, arginine, histidine, threonine, proline, glutamine and glycine.

15. The method of claim 11, wherein the suitable factor B inhibitor is iprazosin and the suitable angiotensin II receptor antagonist is fimasartan, azilsartan, candesartan, eprosartan, losartan, olmesartan, telmisartan and valsartan.

16. The method of claim 10, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to the subject in an amount of 1 mg to 500 mg, 50 mg to 450 mg, 100 mg to 400 mg, 150 mg to 350 mg, 200 mg to 300 mg, 1 mg to 50 mg, 1 mg to 25 mg to the subject.

17. The method of claim 10, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to the subject at a dose of 1 mg to 150 mg.

18. The method of claim 10, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to the subject at a dose of 25 mg, 50 mg, and 100 mg.

19. The method of claim 11, wherein ipracopam is administered to the subject in an amount of 1 mg to 500 mg, 50 mg to 450 mg, 100 mg to 400 mg, 150 mg to 350 mg, 200 mg to 300 mg.

20. The method of claim 11, wherein ipracopam is administered to the subject in an amount of 200 mg.

21. The method of claim 11, wherein fimasartan is administered to the subject in an amount of 1 mg to 500 mg, 50 mg to 450 mg, 100 mg to 400 mg, 150 mg to 350 mg, 200 mg to 300 mg, azilsartan is administered to the subject in an amount of 1 mg to about 500 mg, candesartan is administered to the subject in an amount of 1 mg to 200 mg, eprosartan is administered to the subject in an amount of 1 mg to 1000 mg, losartan is administered to the subject in an amount of 1 mg to 500 mg, olmesartan is administered to the subject in an amount of 1 mg to 200 mg, telmisartan is administered to the subject in an amount of 1 mg to 500 mg, and valsartan is administered to the subject in an amount of about 1 mg to 500 mg.

22. The method of claim 11, wherein fimasartan is administered to the subject in an amount of 60 mg to 120 mg, azilsartan is administered to the subject in an amount of 40 mg and 80 mg, candesartan is administered to the subject in an amount of 4 mg, 8 mg, 16 mg, and 32 mg, eprosartan is administered to the subject in an amount of 400 mg and 600 mg, losartan is administered to the subject in an amount of 25 mg, 50 mg, and 100 mg, olmesartan is administered to the subject in an amount of 5 mg, 20 mg, and 40 mg, telmisartan is administered to the subject in an amount of 20 mg, 40 mg, and 80 mg, and valsartan is administered to the subject in an amount of 40 mg, 80 mg, 160 mg, and 320 mg.

23. The method of claim 10, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject, wherein the subject is an animal or a human.

24. The method of claim 10, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to the subject by oral, parenteral, intravenous or intramuscular administration.

25. The method of claim 1 or claim 10, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is used alone or in combination to reduce urine protein.

26. The method of claim 1 or claim 10, wherein the reduction in the amount of urine protein is at least 5%, wherein the reduction in the amount of urine protein is at least 10%, wherein the reduction in the amount of urine protein is at least 15%, wherein the reduction in the amount of urine protein is at least 20%, wherein the reduction in the amount of urine protein is at least 25%, wherein the reduction in the amount of urine protein is at least 30%, wherein the reduction in the amount of urine protein is at least 35%, wherein the reduction in the amount of urine protein is at least 40%, wherein the reduction in the amount of urine protein is at least 50%, wherein the reduction in the amount of urine protein is at least 60%, wherein the reduction in the amount of urine protein is at least 70%, wherein the reduction in the amount of urine protein is at least 80%, wherein the reduction in the amount of urine protein is at least 90%.

27. The method of any one of claims 1 or 10, wherein the compound is administered to the subject once daily, twice daily, or three times daily.

28. The method of any one of claims 1 or claim 10, wherein the compound is administered to the subject for at least 1 week, for at least 2 weeks, for at least 3 weeks, for at least 4 weeks, for at least 6 weeks, for at least 8 weeks, for at least 10 weeks, for at least 12 weeks, for at least 14 weeks, or for at least 16 weeks.

29. A pharmaceutical composition for treating glomerular diseases, comprising a compound of formula (Ia) or a pharmaceutically acceptable salt thereof, optionally containing one or more pharmaceutically acceptable excipients.

30. The composition for use according to claim 29, wherein the glomerular disease is selected from nephrotic syndrome, focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous nephropathy (MN), IgA nephropathy (IgAN), C3 glomerulopathy (MPGN), diabetic nephropathy and lupus nephritis.

31. The composition for use according to claim 29, wherein the pharmaceutically acceptable salt of the compound of formula (Ia) is selected from metal salts, amine salts and amino acid salts.

32. The composition for use according to claim 31, wherein the metal salt is selected from calcium, sodium, potassium, lithium, barium, strontium, magnesium, cesium, copper, cobalt, iron, manganese, lead, aluminum, cadmium, silver, zinc, ammonium, etc.; wherein the amine salt is selected from methylamine, dimethylamine, ethylamine, diethylamine, n-propylamine, isopropylamine, diisopropylamine, N-methylisopropylamine, n-butylamine, tert-butylamine, 2-butylamine, 1,2-ethylenediamine, N-methylglucosamine, N,N,N-trimethylethanol Amine hydroxide (choline), tromethamine, cyclohexylamine, N-methylcyclohexylamine, guanidine, N-(4-aminobutyl)guanidine, dicyclohexylamine, benzylamine, ethanolamine, diethanolamine, tris(hydroxymethyl)methylamine, hydroxylamine, methylamine, benzylamine, N-methylbenzylamine, N-ethylbenzylamine, 4-methoxybenzylamine, pyrrolidine, piperidine, piperazine, morpholine, 2-aminopyrimidine, 2-thienylethylamine, (2S)-3,3-dimethyl-2-butylamine, cyclopentyl Amine, cycloheptylamine, meglumine, phenethylbenzylamine, dibenzylamine, diphenylamine, α-naphthylamine, o-phenylenediamine, 1,3-diaminopropane, (S)-α-naphthylethylamine, (S)-3-methoxyphenethylamine, (S)-4-methoxyphenethylamine, (S)-4-chlorophenethylamine, (S)-4-methylphenethylamine, cinchonine, cinchonidine, (-)-quinine, triethanolamine, imidazole, ethylenediamine, epoline, morpholine 4-(2-hydroxyethyl), NN-diethylethanolamine, dimethylethanolamine, hydrazine, betaine, amantadine, L-amantadine, triphenylamine, glucosamine, N-methylpyrrolidine, urea, procaine, metformin, hexane-1,6-diamine, 2-(2-aminoethoxy)ethylamine, N-methylmorpholine and N-ethylmorpholine; wherein the amino acid salt is selected from alanine, lysine, arginine, histidine, threonine, proline, glutamine and glycine.

33. The composition for use according to claim 29, wherein the pharmaceutically acceptable excipient is selected from diluents, binders, disintegrants, lubricants, glidants, sweeteners, pH regulators, suspending agents or viscosity regulators, flavoring agents and optional coating redimix.

34. A composition for use according to claim 33, wherein the diluent is selected from the group consisting of monohydrate, lactose, microcrystalline cellulose, polymethacrylate, potassium chloride, sulfobutyl ether b-cyclodextrin, sodium chloride, spray-dried lactose and sulfobutyl ether b-cyclodextrin.

35. The composition for use according to claim 33, wherein the binder is selected from the group consisting of hypromellose 3Cps, carbomer, gellan gum, gum arabic, hydrogenated vegetable oil, polymethacrylate, xanthan gum, lactose and zein.

36. The composition for use according to claim 33, wherein the disintegrant is selected from the group consisting of cross-linked carboxymethylcellulose sodium, bicarbonate, chitosan, gellan gum, polyclinic potassium and docusate sodium.

37. The composition for use according to claim 33, wherein the composition is selected from colloidal silicon dioxide, calcium silicate, magnesium silicate, silica hydrogel, corn starch and talc.

38. A composition for use according to claim 33, wherein the lubricant is selected from calcium stearate, magnesium stearate, mineral oil, stearic acid, zinc stearate, glyceryl behenate, hydrogenated vegetable oil, sodium stearyl fumarate and myristic acid.

39. The composition for use according to claim 33, wherein the coating redimix is ​​Opadry Pink.

40. The composition for use according to claim 29, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject in an amount of 1 mg to 500 mg, 50 mg to 450 mg, 100 mg to 400 mg, 150 mg to 350 mg, 200 mg to 300 mg, 1 mg to 50 mg, 1 mg to 25 mg to the subject.

41. The composition for use according to claim 29, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject at a dose of 1 mg to 150 mg.

42. The composition for use according to claim 29, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject at a dose of 25 mg, 50 mg and 100 mg.

43. The composition for use according to claim 29, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject, wherein the subject is an animal or a human.

44. The composition for use according to claim 29, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject via oral, parenteral, intravenous or intramuscular administration.

45. A combination of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof and a suitable second therapeutic agent, wherein the suitable second therapeutic agent is selected from a suitable factor B inhibitor or a suitable angiotensin II receptor antagonist or a suitable factor D inhibitor or a suitable C3 inhibitor or a suitable C5 inhibitor or a suitable C6 inhibitor or a suitable lectin pathway inhibitor or a suitable properdin inhibitor or a suitable C9 antibody and a multi-target complement inhibitor.

46. ​​A combination according to claim 45, wherein the suitable second therapeutic agent is a suitable Factor B inhibitor or a suitable angiotensin II receptor antagonist.

47. A combination according to claim 46, wherein the suitable factor B inhibitor is iprazosin and the suitable angiotensin II receptor antagonist is fimasartan, azilsartan, candesartan, eprosartan, losartan, olmesartan, telmisartan and valsartan.

48. A pharmaceutical composition for treating glomerular diseases, comprising a compound of formula (Ia) or a pharmaceutically acceptable salt thereof and a suitable factor B inhibitor or a suitable angiotensin II receptor antagonist, optionally containing one or more pharmaceutically acceptable excipients.

49. The composition for use according to claim 48, wherein the glomerular disease is selected from nephrotic syndrome, focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous nephropathy (MN), IgA nephropathy (IgAN), C3 glomerulopathy (MPGN), diabetic nephropathy and lupus nephritis.

50. The composition for use according to claim 48, wherein the pharmaceutically acceptable salt of the compound of formula (Ia) is selected from metal salts, amine salts and amino acid salts.

51. The composition for use according to claim 50, wherein the metal salt is selected from calcium, sodium, potassium, lithium, barium, strontium, magnesium, cesium, copper, cobalt, iron, manganese, lead, aluminum, cadmium, silver, zinc, ammonium, etc.; wherein the amine salt is selected from methylamine, dimethylamine, ethylamine, diethylamine, n-propylamine, isopropylamine, diisopropylamine, N-methylisopropylamine, n-butylamine, tert-butylamine, 2-butylamine, 1,2-ethylenediamine, N-methylglucamine, N,N,N-trimethylethanol Amine hydroxide (choline), tromethamine, cyclohexylamine, N-methylcyclohexylamine, guanidine, N-(4-aminobutyl)guanidine, dicyclohexylamine, benzylamine, ethanolamine, diethanolamine, tris(hydroxymethyl)methylamine, hydroxylamine, methylamine, benzylamine, N-methylbenzylamine, N-ethylbenzylamine, 4-methoxybenzylamine, pyrrolidine, piperidine, piperazine, morpholine, 2-aminopyrimidine, 2-thienylethylamine, (2S)-3,3-dimethyl-2-butylamine, cyclopentyl Amine, cycloheptylamine, meglumine, phenethylbenzylamine, dibenzylamine, diphenylamine, α-naphthylamine, o-phenylenediamine, 1,3-diaminopropane, (S)-α-naphthylethylamine, (S)-3-methoxyphenethylamine, (S)-4-methoxyphenethylamine, (S)-4-chlorophenethylamine, (S)-4-methylphenethylamine, cinchonine, cinchonidine, (-)-quinine, triethanolamine, imidazole, ethylenediamine, epoline, morpholine 4-(2-hydroxyethyl), NN-diethylethanolamine, dimethylethanolamine, hydrazine, betaine, amantadine, L-amantadine, triphenylamine, glucosamine, N-methylpyrrolidine, urea, procaine, metformin, hexane-1,6-diamine, 2-(2-aminoethoxy)ethylamine, N-methylmorpholine and N-ethylmorpholine; wherein the amino acid salt is selected from alanine, lysine, arginine, histidine, threonine, proline, glutamine and glycine.

52. A composition for use according to claim 48, wherein the suitable factor B inhibitor is iprazosin and the suitable angiotensin II receptor antagonist is fimasartan, azilsartan, candesartan, eprosartan, losartan, olmesartan, telmisartan and valsartan.

53. The composition for use according to claim 48, wherein the pharmaceutically acceptable excipient is selected from diluents, binders, disintegrants, lubricants, glidants, sweeteners, pH regulators, suspending agents or viscosity regulators, flavoring agents and optional coating redimix.

54. A composition for use according to claim 53, wherein the diluent is selected from the group consisting of monohydrate, lactose, microcrystalline cellulose, polymethacrylate, potassium chloride, sulfobutyl ether b-cyclodextrin, sodium chloride, spray-dried lactose and sulfobutyl ether b-cyclodextrin.

55. The composition for use according to claim 53, wherein the binder is selected from the group consisting of hypromellose 3Cps, carbomer, gellan gum, gum arabic, hydrogenated vegetable oil, polymethacrylate, xanthan gum, lactose and zein.

56. The composition for use according to claim 53, wherein the disintegrant is selected from the group consisting of croscarmellose sodium, bicarbonate, chitosan, gellan gum, polyclinic potassium and docusate sodium.

57. The composition for use according to claim 53, wherein the glidant is selected from colloidal silicon dioxide, calcium silicate, magnesium silicate, silica hydrogel, corn starch and talc.

58. A composition for use according to claim 53, wherein the lubricant is selected from calcium stearate, magnesium stearate, mineral oil, stearic acid, zinc stearate, glyceryl behenate, hydrogenated vegetable oil, sodium stearyl fumarate and myristic acid.

59. The composition for use according to claim 53, wherein the coating redimix is ​​Opadry Pink.

60. The composition for use according to claim 48, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject in an amount of 1 mg to 500 mg, 50 mg to 450 mg, 100 mg to 400 mg, 150 mg to 350 mg, 200 mg to 300 mg, 1 mg to 50 mg, 1 mg to 25 mg to the subject.

61. The composition for use according to claim 48, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject at a dose of 1 mg to 150 mg.

62. The composition for use according to claim 48, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject at a dose of 25 mg, 50 mg and 100 mg.

63. The composition for use according to claim 52, wherein iprazosin is administered to a subject in an amount of 1 mg to 500 mg, 50 mg to 450 mg, 100 mg to 400 mg, 150 mg to 350 mg, 200 mg to 300 mg.

64. The composition for use according to claim 52, wherein ipracopan is administered to the subject in an amount of 200 mg.

65. The composition for use according to claim 52, wherein fimasartan is administered to a subject in an amount of 1 mg to 500 mg, 50 mg to 450 mg, 100 mg to 400 mg, 150 mg to 350 mg, 200 mg to 300 mg, azilsartan is administered to a subject in an amount of 1 mg to about 500 mg, candesartan is administered to a subject in an amount of 1 mg to 200 mg, eprosartan is administered to a subject in an amount of 1 mg to 1000 mg, losartan is administered to a subject in an amount of 1 mg to 500 mg, olmesartan is administered to a subject in an amount of 1 mg to 200 mg, telmisartan is administered to a subject in an amount of 1 mg to 500 mg, and valsartan is administered to a subject in an amount of about 1 mg to 500 mg.

66. The composition for use according to claim 52, wherein fimasartan is administered to a subject in an amount of 60 mg to 120 mg, azilsartan is administered to a subject in an amount of 40 mg and 80 mg, candesartan is administered to a subject in an amount of 4 mg, 8 mg, 16 mg and 32 mg, eprosartan is administered to a subject in an amount of 400 mg and 600 mg, losartan is administered to a subject in an amount of 25 mg, 50 mg and 100 mg, olmesartan is administered to a subject in an amount of 5 mg, 20 mg and 40 mg, telmisartan is administered to a subject in an amount of 20 mg, 40 mg and 80 mg, and valsartan is administered to a subject in an amount of 40 mg, 80 mg, 160 mg and 320 mg.

67. The composition for use according to claim 48, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject, wherein the subject is an animal or a human.

68. The composition for use according to claim 48, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject via oral, parenteral, intravenous or intramuscular administration.

69. Use of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof for treating glomerular diseases.

70. The use of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof according to claim 69, wherein the glomerular disease is selected from nephrotic syndrome, focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous nephropathy (MN), IgA nephropathy (IgAN), C3 glomerulopathy (MPGN), diabetic nephropathy and lupus nephritis.

71. Use of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof according to claim 69, wherein the pharmaceutically acceptable salt is selected from metal salts, amine salts and amino acid salts.

72. The use of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof according to claim 71, wherein the metal salt is selected from calcium, sodium, potassium, lithium, barium, strontium, magnesium, cesium, copper, cobalt, iron, manganese, lead, aluminum, cadmium, silver, zinc, ammonium, etc.; wherein the amine salt is selected from methylamine, dimethylamine, ethylamine, diethylamine, n-propylamine, isopropylamine, diisopropylamine, N-methylisopropylamine, n-butylamine, tert-butylamine, 2-butylamine, 1,2-ethylenediamine, N-methylglucosamine, N, N,N-trimethylethanolamine hydroxide (choline), tromethamine, cyclohexylamine, N-methylcyclohexylamine, guanidine, N-(4-aminobutyl)guanidine, dicyclohexylamine, benzylamine, ethanolamine, diethanolamine, tris(hydroxymethyl)methylamine, hydroxylamine, methylamine, benzylamine, N-methylbenzylamine, N-ethylbenzylamine, 4-methoxybenzylamine, pyrrolidine, piperidine, piperazine, morpholine, 2-aminopyrimidine, 2-thiopheneethylamine, (2S)-3,3-dimethyl-2 -Butylamine, cyclopentylamine, cycloheptylamine, meglumine, phenethylbenzylamine, dibenzylamine, diphenylamine, α-naphthylamine, o-phenylenediamine, 1,3-diaminopropane, (S)-α-naphthylethylamine, (S)-3-methoxyphenethylamine, (S)-4-methoxyphenethylamine, (S)-4-chlorophenethylamine, (S)-4-methylphenethylamine, cinchonine, cinchonidine, (-)-quinine, triethanolamine, imidazole, ethylenediamine, epoline, morpholine 4-(2-hydroxyethyl) yl), NN-diethylethanolamine, dimethylethanolamine, hydrabamine, betaine, amantadine, L-amantadine, triphenylamine, glucosamine, N-methylpyrrolidine, urea, procaine, metformin, hexane-1,6-diamine, 2-(2-aminoethoxy)ethylamine, N-methylmorpholine and N-ethylmorpholine; wherein the amino acid salt is selected from alanine, lysine, arginine, histidine, threonine, proline, glutamine and glycine.

73. The use of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof according to claim 69, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject in an amount of 1 mg to 500 mg, 50 mg to 450 mg, 100 mg to 400 mg, 150 mg to 350 mg, 200 mg to 300 mg, 1 mg to 50 mg, 1 mg to 25 mg to the subject.

74. The use of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof according to claim 69, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject at a dose of 1 mg to 150 mg.

75. The use of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof according to claim 69, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject at a dose of 25 mg, 50 mg and 100 mg.

76. The use of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof according to claim 69, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject, wherein the subject is an animal or a human.

77. The use of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof according to claim 69, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject by oral, parenteral, intravenous or intramuscular administration.

78. Use of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof in combination with a suitable factor B inhibitor or a suitable angiotensin II receptor antagonist for treating glomerular diseases.

79. Use of the combination according to claim 78, wherein the glomerular disease is selected from nephrotic syndrome, focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous nephropathy (MN), IgA nephropathy (IgAN), C3 glomerulopathy (MPGN), diabetic nephropathy and lupus nephritis.

80. Use of a combination according to claim 78, wherein the pharmaceutically acceptable salt of the compound of formula (Ia) is selected from metal salts, amine salts and amino acid salts.

81. The use of the combination according to claim 80, wherein the metal salt is selected from calcium, sodium, potassium, lithium, barium, strontium, magnesium, cesium, copper, cobalt, iron, manganese, lead, aluminum, cadmium, silver, zinc, ammonium, etc.; wherein the amine salt is selected from methylamine, dimethylamine, ethylamine, diethylamine, n-propylamine, isopropylamine, diisopropylamine, N-methylisopropylamine, n-butylamine, tert-butylamine, 2-butylamine, 1,2-ethylenediamine, N-methylglucamine, N,N,N-trimethylethanol Amine hydroxide (choline), tromethamine, cyclohexylamine, N-methylcyclohexylamine, guanidine, N-(4-aminobutyl)guanidine, dicyclohexylamine, benzylamine, ethanolamine, diethanolamine, tris(hydroxymethyl)methylamine, hydroxylamine, methylamine, benzylamine, N-methylbenzylamine, N-ethylbenzylamine, 4-methoxybenzylamine, pyrrolidine, piperidine, piperazine, morpholine, 2-aminopyrimidine, 2-thienylethylamine, (2S)-3,3-dimethyl-2-butylamine, cyclopentyl Amine, cycloheptylamine, meglumine, phenethylbenzylamine, dibenzylamine, diphenylamine, α-naphthylamine, o-phenylenediamine, 1,3-diaminopropane, (S)-α-naphthylethylamine, (S)-3-methoxyphenethylamine, (S)-4-methoxyphenethylamine, (S)-4-chlorophenethylamine, (S)-4-methylphenethylamine, cinchonine, cinchonidine, (-)-quinine, triethanolamine, imidazole, ethylenediamine, epoline, morpholine 4-(2-hydroxyethyl), NN-diethylethanolamine, dimethylethanolamine, hydrazine, betaine, amantadine, L-amantadine, triphenylamine, glucosamine, N-methylpyrrolidine, urea, procaine, metformin, hexane-1,6-diamine, 2-(2-aminoethoxy)ethylamine, N-methylmorpholine and N-ethylmorpholine; wherein the amino acid salt is selected from alanine, lysine, arginine, histidine, threonine, proline, glutamine and glycine.

82. Use of a combination according to claim 78, wherein the suitable factor B inhibitor is iprazosin and the suitable angiotensin II receptor antagonist is fimasartan, azilsartan, candesartan, eprosartan, losartan, olmesartan, telmisartan and valsartan.

83. The use of the combination according to claim 78, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject in an amount of 1 mg to 500 mg, 50 mg to 450 mg, 100 mg to 400 mg, 150 mg to 350 mg, 200 mg to 300 mg, 1 mg to 50 mg, 1 mg to 25 mg to the subject.

84. The use of a combination according to claim 78, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject at a dose of 1 mg to 150 mg.

85. Use of the combination according to claim 78, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject at a dose of 25 mg, 50 mg and 100 mg.

86. Use of the combination according to claim 82, wherein iprazosin is administered to a subject in an amount of 1 mg to 500 mg, 50 mg to 450 mg, 100 mg to 400 mg, 150 mg to 350 mg, 200 mg to 300 mg.

87. Use of the combination according to claim 82, wherein ipracopan is administered to the subject in an amount of 200 mg.

88. The use of the combination according to claim 82, wherein fimasartan is administered to a subject in an amount of 1 mg to 500 mg, 50 mg to 450 mg, 100 mg to 400 mg, 150 mg to 350 mg, 200 mg to 300 mg, azilsartan is administered to a subject in an amount of 1 mg to about 500 mg, candesartan is administered to a subject in an amount of 1 mg to 200 mg, eprosartan is administered to a subject in an amount of 1 mg to 1000 mg, losartan is administered to a subject in an amount of 1 mg to 500 mg, olmesartan is administered to a subject in an amount of 1 mg to 200 mg, telmisartan is administered to a subject in an amount of 1 mg to 500 mg, and valsartan is administered to a subject in an amount of about 1 mg to 500 mg.

89. The use of the combination according to claim 82, wherein fimasartan is administered to a subject in an amount of 60 mg to 120 mg, azilsartan is administered to a subject in an amount of 40 mg and 80 mg, candesartan is administered to a subject in an amount of 4 mg, 8 mg, 16 mg and 32 mg, eprosartan is administered to a subject in an amount of 400 mg and 600 mg, losartan is administered to a subject in an amount of 25 mg, 50 mg and 100 mg, olmesartan is administered to a subject in an amount of 5 mg, 20 mg and 40 mg, telmisartan is administered to a subject in an amount of 20 mg, 40 mg and 80 mg, and valsartan is administered to a subject in an amount of 40 mg, 80 mg, 160 mg and 320 mg.

90. The use of the combination according to claim 78, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject, wherein the subject is an animal or a human.

91. The use of the combination according to claim 78, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to a subject by oral, parenteral, intravenous or intramuscular administration.

92. A method for treating glomerular disease in a patient suffering from diabetes mellitus, comprising administering an effective amount of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof, or a combination of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof and a suitable factor B inhibitor or a suitable angiotensin II receptor antagonist.

93. The method of claim 92, wherein the glomerular disease is selected from nephrotic syndrome, focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous nephropathy (MN), IgA nephropathy (IgAN), C3 glomerulopathy (MPGN), diabetic nephropathy, and lupus nephritis.

94. The method of claim 92, wherein the pharmaceutically acceptable salt of the compound of formula (Ia) is selected from metal salts, amine salts and amino acid salts.

95. The method of claim 94, wherein the metal salt is selected from calcium, sodium, potassium, lithium, barium, strontium, magnesium, cesium, copper, cobalt, iron, manganese, lead, aluminum, cadmium, silver, zinc, ammonium, etc.; wherein the amine salt is selected from methylamine, dimethylamine, ethylamine, diethylamine, n-propylamine, isopropylamine, diisopropylamine, N-methylisopropylamine, n-butylamine, tert-butylamine, 2-butylamine, 1,2-ethylenediamine, N-methylglucamine, N,N,N-trimethylethanolamine, hydrogen Oxide (choline), tromethamine, cyclohexylamine, N-methylcyclohexylamine, guanidine, N-(4-aminobutyl)guanidine, dicyclohexylamine, benzylamine, ethanolamine, diethanolamine, tris(hydroxymethyl)methylamine, hydroxylamine, methylamine, benzylamine, N-methylbenzylamine, N-ethylbenzylamine, 4-methoxybenzylamine, pyrrolidine, piperidine, piperazine, morpholine, 2-aminopyrimidine, 2-thienylethylamine, (2S)-3,3-dimethyl-2-butylamine, cyclopentylamine, Cycloheptylamine, meglumine, phenethylbenzylamine, dibenzylamine, diphenylamine, α-naphthylamine, o-phenylenediamine, 1,3-diaminopropane, (S)-α-naphthylethylamine, (S)-3-methoxyphenethylamine, (S)-4-methoxyphenethylamine, (S)-4-chlorophenethylamine, (S)-4-methylphenethylamine, cinchonine, cinchonidine, (-)-quinine, triethanolamine, imidazole, ethylenediamine, epoline, morpholine 4-(2-hydroxyethyl), N N-diethylethanolamine, dimethylethanolamine, hydrazine, betaine, amantadine, L-amantadine, triphenylamine, glucosamine, N-methylpyrrolidine, urea, procaine, metformin, hexane-1,6-diamine, 2-(2-aminoethoxy)ethylamine, N-methylmorpholine and N-ethylmorpholine; wherein the amino acid salt is selected from alanine, lysine, arginine, histidine, threonine, proline, glutamine and glycine.

96. The method of claim 92, wherein the suitable factor B inhibitor is iprazosin and the suitable angiotensin II receptor antagonist is fimasartan, azilsartan, candesartan, eprosartan, losartan, olmesartan, telmisartan and valsartan.

97. The method of claim 92, wherein the compound of Formula (Ia) or a pharmaceutically acceptable salt thereof is administered to the subject in an amount of 1 mg to 500 mg, 50 mg to 450 mg, 100 mg to 400 mg, 150 mg to 350 mg, 200 mg to 300 mg, 1 mg to 50 mg, 1 mg to 25 mg to the subject.

98. The method of claim 92, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to the subject at a dose of 1 mg to 150 mg.

99. The method of claim 92, wherein the compound of formula (Ia) or a pharmaceutically acceptable salt thereof is administered to the subject at doses of 25 mg, 50 mg, and 100 mg.

100. The method of claim 96, wherein ipracopam is administered to the subject in an amount of 1 mg to 500 mg, 50 mg to 450 mg, 100 mg to 400 mg, 150 mg to 350 mg, 200 mg to 300 mg.

101. The method of claim 96, wherein ipracopam is administered to the subject in an amount of 200 mg.

102. The method of claim 96, wherein fimasartan is administered to the subject in an amount of 1 mg to 500 mg, 50 mg to 450 mg, 100 mg to 400 mg, 150 mg to 350 mg, 200 mg to 300 mg, azilsartan is administered to the subject in an amount of 1 mg to about 500 mg, candesartan is administered to the subject in an amount of 1 mg to 200 mg, eprosartan is administered to the subject in an amount of 1 mg to 1000 mg, losartan is administered to the subject in an amount of 1 mg to 500 mg, olmesartan is administered to the subject in an amount of 1 mg to 200 mg, telmisartan is administered to the subject in an amount of 1 mg to 500 mg, and valsartan is administered to the subject in an amount of about 1 mg to 500 mg.

103. The method of claim 96, wherein fimasartan is administered to the subject in an amount of 60 mg to 120 mg, azilsartan is administered to the subject in an amount of 40 mg and 80 mg, candesartan is administered to the subject in an amount of 4 mg, 8 mg, 16 mg, and 32 mg, eprosartan is administered to the subject in an amount of 400 mg and 600 mg, losartan is administered to the subject in an amount of 25 mg, 50 mg, and 100 mg, olmesartan is administered to the subject in an amount of 5 mg, 20 mg, and 40 mg, telmisartan is administered to the subject in an amount of 20 mg, 40 mg, and 80 mg, and valsartan is administered to the subject in an amount of 40 mg, 80 mg, 160 mg, and 320 mg.

104. A pharmaceutical composition for treating glomerular diseases, comprising a compound of formula (Ia) or a pharmaceutically acceptable salt thereof, sucrose, citric acid, microcrystalline cellulose and sodium carboxymethyl cellulose (Avicel CL 611), xanthan gum and one or more pharmaceutically acceptable excipients.

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