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WO2026008074A1 - Forme cristalline d'un inhibiteur du facteur b du complément, son procédé de préparation et son utilisation - Google Patents

Forme cristalline d'un inhibiteur du facteur b du complément, son procédé de préparation et son utilisation

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Publication number
WO2026008074A1
WO2026008074A1 PCT/CN2025/107219 CN2025107219W WO2026008074A1 WO 2026008074 A1 WO2026008074 A1 WO 2026008074A1 CN 2025107219 W CN2025107219 W CN 2025107219W WO 2026008074 A1 WO2026008074 A1 WO 2026008074A1
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WIPO (PCT)
Prior art keywords
crystal form
compound
diseases
formula
ray powder
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Pending
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PCT/CN2025/107219
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English (en)
Chinese (zh)
Inventor
苏进财
李雪飞
张道俊
赵金红
马昌友
代清宇
吴舰
徐丹
朱春霞
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Nanjing Chia Tai Tianqing Pharmaceutical Co Ltd
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Nanjing Chia Tai Tianqing Pharmaceutical Co Ltd
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Application filed by Nanjing Chia Tai Tianqing Pharmaceutical Co Ltd filed Critical Nanjing Chia Tai Tianqing Pharmaceutical Co Ltd
Publication of WO2026008074A1 publication Critical patent/WO2026008074A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Definitions

  • This invention belongs to the field of biotechnology, specifically relating to the crystal form of complement factor B inhibitors, their preparation methods, and their uses.
  • the complement system is part of the host's innate immune system, involved in lysing exogenous cells, enhancing antigen phagocytosis, agglutinating antigen carriers, and attracting macrophages and neutrophils. It is a crucial component of the body's innate immune response against infections from exogenous pathogens, bacteria, and parasites, and also a vital link between innate and adaptive immunity. Complement is composed of plasma proteins, including soluble proteins, membrane-bound proteins, and complement receptors. It is primarily produced by membrane proteins expressed in the liver or on cell surfaces, and functions in plasma, tissues, or cells. The complement system is an important regulator of inflammatory responses and tissue damage, composed of more than 20 serum proteins and cell surface proteins.
  • the complement system includes intrinsic complement components and various regulatory proteins. Intrinsic complement components include C1–C9, with C3 being the most abundant.
  • the complement system is activated primarily through three pathways: the classical pathway (CP), the lectin pathway (LP), and the alternative pathway (AP).
  • CP classical pathway
  • LP lectin pathway
  • AP alternative pathway
  • the complement pathway In healthy individuals under normal physiological conditions, the complement pathway remains at a low level of activation to monitor for invasion by foreign pathogens.
  • Complement proteins are distributed on the surface of apoptotic cells, and complement activation is tightly regulated, serving only to eliminate apoptotic cells without further activating other innate or adaptive immune responses.
  • the complement system In the event of infection by foreign pathogens, the complement system is fully activated, producing inflammatory responses, opsonization, or phagocytosis, destroying pathogens and ultimately activating adaptive immune responses. Both ineffective and excessive complement stimulation can be harmful to the human body and are associated with increased susceptibility to infectious and non-infectious diseases.
  • Complement dysfunction or overactivation has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer.
  • activation of the alternative pathway in the complement cascade contributes to the production of C3a and C5a (both potent anaphylatoxins), which also play a role in many inflammatory diseases. Therefore, in some cases, it is desirable to reduce the response of complement pathways (including alternative complement pathways).
  • Complement factor B is a key protein involved in AP pathway activation. Inhibiting FB activity can prevent AP pathway activation without interfering with the CP and LP pathways, thus avoiding the increased infection risk due to complement system inhibition.
  • PCT/CN2024/071419 provides a class of complement factor B inhibitors.
  • the crystal structure of a pharmaceutically active ingredient often affects its chemical stability. Different crystal forms, preparation methods, and storage conditions can lead to changes in the crystal structure of the compound, sometimes even resulting in other crystal forms. Therefore, in-depth research on the polymorphism of compounds to obtain chemically stable crystal forms is of great significance for developing drugs suitable for industrial production and with good biological activity.
  • the purpose of this invention is to provide a crystal form of the compound shown in Formula I, its preparation method, and its uses.
  • the present invention provides a crystal form of the compound represented by Formula I, wherein the structure of Formula I is as follows:
  • the chemical name of the compound shown in Formula I is 4-((3R,4R)-4-((5-methoxy-7-methyl-1H-indol-4-yl)oxy)-1-(2,2,2-trifluoroethyl)piperidin-3-yl)benzoic acid.
  • a crystal form B of the compound of Formula I is provided, whose X-ray powder diffraction pattern has diffraction peaks at 2 ⁇ of 9.5° ⁇ 0.2°, 15.1° ⁇ 0.2°, 20.5° ⁇ 0.2° and 22.3° ⁇ 0.2°.
  • the crystal form B has X-ray powder diffraction patterns with diffraction peaks at 2 ⁇ of 9.5° ⁇ 0.2°, 13.0° ⁇ 0.2°, 15.1° ⁇ 0.2°, 17.8° ⁇ 0.2°, 20.5° ⁇ 0.2° and 22.3° ⁇ 0.2°.
  • the crystal form B has X-ray powder diffraction patterns with diffraction peaks at 2 ⁇ of 9.5° ⁇ 0.2°, 10.2° ⁇ 0.2°, 13.0° ⁇ 0.2°, 15.1° ⁇ 0.2°, 17.8° ⁇ 0.2°, 20.5° ⁇ 0.2°, 22.3° ⁇ 0.2° and 24.1° ⁇ 0.2°.
  • the crystal form B has X-ray powder diffraction patterns with diffraction peaks at 2 ⁇ of 9.5° ⁇ 0.2°, 10.2° ⁇ 0.2°, 13.0° ⁇ 0.2°, 15.1° ⁇ 0.2°, 16.9° ⁇ 0.2°, 17.8° ⁇ 0.2°, 18.5° ⁇ 0.2°, 20.5° ⁇ 0.2°, 22.3° ⁇ 0.2°, and 24.1° ⁇ 0.2°.
  • the crystal form B has X-ray powder diffraction patterns with diffraction peaks at 2 ⁇ of 9.5° ⁇ 0.2°, 10.2° ⁇ 0.2°, 13.0° ⁇ 0.2°, 15.1° ⁇ 0.2°, 16.9° ⁇ 0.2°, 17.8° ⁇ 0.2°, 18.5° ⁇ 0.2°, 20.5° ⁇ 0.2°, 22.3° ⁇ 0.2°, 23.3° ⁇ 0.2°, 23.5° ⁇ 0.2°, and 24.1° ⁇ 0.2°.
  • the 2 ⁇ of the X-ray powder diffraction pattern of crystal form B is detailed in the table below:
  • Table 1 X-ray powder diffraction data of crystal form B
  • the X-ray powder diffraction of crystal form B expressed at a 2 ⁇ angle, has an XRPD pattern as shown in Figure 2.
  • the crystal form B has an endothermic peak at an initial temperature of 180°C to 190°C in the thermal analysis diagram obtained by differential scanning calorimetry (DSC).
  • DSC differential scanning calorimetry
  • the crystal form B has an endothermic peak at an initial temperature of 183°C to 188°C in the thermal analysis diagram obtained by differential scanning calorimetry (DSC).
  • the crystal form B shows no weight loss before 150°C in the measured TGA graph.
  • the crystal form B has a TGA pattern as shown in Figure 4.
  • the crystal form A has X-ray powder diffraction patterns with diffraction peaks at 2 ⁇ of 8.8° ⁇ 0.2°, 9.5° ⁇ 0.2°, 14.9° ⁇ 0.2°, 20.5° ⁇ 0.2°, 21.7° ⁇ 0.2° and 24.3° ⁇ 0.2°.
  • the crystal form A has X-ray powder diffraction patterns with diffraction peaks at 2 ⁇ of 8.8° ⁇ 0.2°, 9.1° ⁇ 0.2°, 9.5° ⁇ 0.2°, 14.9° ⁇ 0.2°, 20.5° ⁇ 0.2°, 21.7° ⁇ 0.2°, 24.0° ⁇ 0.2° and 24.3° ⁇ 0.2°.
  • the crystal form A has X-ray powder diffraction patterns with diffraction peaks at 2 ⁇ of 8.8° ⁇ 0.2°, 9.1° ⁇ 0.2°, 9.5° ⁇ 0.2°, 14.9° ⁇ 0.2°, 15.6° ⁇ 0.2°, 17.7° ⁇ 0.2°, 20.5° ⁇ 0.2°, 21.7° ⁇ 0.2°, 24.0° ⁇ 0.2°, and 24.3° ⁇ 0.2°.
  • the crystal form A has X-ray powder diffraction patterns with diffraction peaks at 2 ⁇ of 8.8° ⁇ 0.2°, 9.1° ⁇ 0.2°, 9.5° ⁇ 0.2°, 12.1° ⁇ 0.2°, 14.9° ⁇ 0.2°, 15.6° ⁇ 0.2°, 17.4° ⁇ 0.2°, 17.7° ⁇ 0.2°, 20.5° ⁇ 0.2°, 21.7° ⁇ 0.2°, 24.0° ⁇ 0.2°, and 24.3° ⁇ 0.2°.
  • the 2 ⁇ of the X-ray powder diffraction pattern of crystal form A is detailed in the table below:
  • the X-ray powder diffraction pattern of crystal form A expressed at a 2 ⁇ angle, has the pattern shown in Figure 7.
  • the present invention also provides a method for preparing the crystal form of the compound shown in Formula I, including but not limited to the antisolvent addition method, the anti-antisolvent addition method, the solvent evaporation method, the gas-solid diffusion method, the suspension and stirring method, and the cooling crystallization method.
  • the method for preparing the crystal form of the compound shown in Formula I includes the following steps: weighing an appropriate amount of the compound, adding a corresponding positive solvent to dissolve it, adding an antisolvent to the solution, stirring, and cooling to crystallize.
  • the positive solvent includes one or more of methanol, ethanol, acetone, 2-butanone, ethyl acetate, isopropyl acetate, acetonitrile, chloroform, benzene, propanol, N,N-dimethylformamide, and ethyl formate; preferably one or more of methanol, ethanol, acetone, 2-butanone, ethyl acetate, isopropyl acetate, and acetonitrile.
  • the antisolvent includes one or more of n-hexane, n-heptane, water, cyclohexane, methyl tert-butyl ether, and isopropyl ether; preferably one or two of n-heptane and water.
  • the preparation method of the compound crystal form B shown in Formula I includes the following steps: weighing an appropriate amount of the compound, dissolving it in a corresponding positive solvent, optionally adding seed crystals, adding an antisolvent to the solution, stirring, and cooling to crystallize.
  • the preparation method of the compound crystal form B shown in Formula I includes the following steps: weighing an appropriate amount of the compound, adding a corresponding positive solvent to dissolve it, heating to dissolve it completely, optionally adding seed crystals, adding an antisolvent to the solution, stirring, and cooling to crystallize.
  • the positive solvent is one or more of ethanol, acetone, ethyl acetate or isopropyl acetate.
  • the antisolvent is selected from n-heptane or water.
  • the preparation method of the compound crystal form A shown in Formula I includes the following steps: weighing an appropriate amount of compound crystal form B, adding a corresponding positive solvent to dissolve it, adding an antisolvent to the solution, stirring, and cooling to crystallize.
  • this application provides a crystal form composition of crystal form B, wherein the weight of crystal form B accounts for more than 50% of the weight of the crystal form composition; preferably more than 80%; further preferably more than 90%; even more preferably more than 95%; and most preferably more than 98%.
  • the present invention also provides a pharmaceutical composition containing a therapeutically effective amount of the crystal form of the compound shown in Formula I.
  • the pharmaceutical composition contains a therapeutically effective amount of crystal form B of the compound represented by Formula I.
  • the pharmaceutical composition contains a therapeutically effective amount of crystal form A of the compound represented by Formula I.
  • the present invention also provides a pharmaceutical composition
  • a pharmaceutical composition comprising a therapeutically effective amount of the crystal form of the compound represented by Formula I and a pharmaceutically acceptable carrier.
  • the pharmaceutical composition contains a therapeutically effective amount of crystal form B of the compound represented by Formula I and a pharmaceutically acceptable carrier.
  • the pharmaceutical composition contains a therapeutically effective amount of crystal form A of the compound represented by Formula I and a pharmaceutically acceptable carrier.
  • the pharmaceutical composition can be administered via any suitable route or method, such as oral or parenteral (e.g., intravenous) administration.
  • the therapeutically effective amount of the aforementioned compound crystal form is from about 1 mg to 1 g/kg body weight/day.
  • the present invention also provides the use of the crystal form of the aforementioned compound or pharmaceutical compositions thereof in the preparation of medicaments for the prevention and/or treatment of complement factor B-mediated diseases or disease states.
  • the present invention also provides a method for preventing and/or treating complement factor B-mediated diseases or disease states, comprising administering an effective amount of the crystal form of the aforementioned compound or a pharmaceutical composition thereof to a subject in need.
  • the present invention also provides crystal forms of the aforementioned compounds of the present invention or pharmaceutical compositions of the present invention for the prevention and/or treatment of complement factor B-mediated diseases or disease states.
  • the present invention also provides the crystal form as described above, or the crystal form prepared as described above, or the composition as described above, for therapeutic purposes.
  • the present invention also provides the crystal form as described above, or the crystal form prepared as described above, or the composition as described above, for the prevention and/or treatment of complement factor B-mediated diseases or disease states.
  • the complement factor B-mediated disease or disease state is selected from one or more of ophthalmic diseases, autoimmune diseases (including arthritis), kidney-related diseases, respiratory diseases, and cardiovascular diseases.
  • the complement factor B-mediated disease or disease state is arthritis.
  • the crystal form prepared by this invention especially crystal form B, has good stability, for example, crystal form stability and thermal stability.
  • the "X-ray powder diffraction pattern" in this invention is obtained using Cu-K ⁇ radiation measurements. It should be noted that in X-ray powder diffraction (XRPD), the diffraction pattern obtained from a crystalline compound is often characteristic of a specific crystal, and the relative intensities of the bands (especially at low angles) can vary due to the dominant orientation effects resulting from differences in crystallization conditions, particle size, and other measurement conditions. Therefore, the relative intensities of diffraction peaks are not characteristic of the specific crystal. When determining whether it is the same as a known crystal, more attention should be paid to the relative positions of the peaks than their relative intensities. Furthermore, for any given crystal, the peak positions may have slight errors, which is well known in the field of crystallography.
  • the peak positions can shift, and the measurement error of the 2 ⁇ value is sometimes about ⁇ 0.5° and sometimes about ⁇ 0.2°. Therefore, this error should be taken into account when determining each crystal structure.
  • the shift of the key characteristic peak 2 ⁇ is within ⁇ 0.5°, especially within ⁇ 0.2°, it can be identified as the same crystal form.
  • DSC Differential scanning calorimetry determines the transition temperatures of a crystal when it absorbs or releases heat due to changes in its crystal structure or melting.
  • the error in thermal transition temperature and melting point is typically within about 5 °C, usually within about 3 °C, in continuous analysis.
  • DSC peak or melting point ⁇ 5 °C.
  • DSC provides an auxiliary method for distinguishing different crystal forms. Different crystal forms can be identified based on their different transition temperature characteristics. It should be noted that for mixtures, their DSC peaks or melting points may fluctuate over a wider range. Furthermore, since decomposition occurs during the melting process, the melting temperature is related to the heating rate.
  • Thermogravimetric analysis is a thermal analysis technique that measures the relationship between the mass of a sample and temperature change under programmed temperature control.
  • TGA Thermogravimetric analysis
  • Dynamic water vapor adsorption is a method that uses a microbalance (with an accuracy of one part per million) to weigh the change in weight of a sample before and after adsorption and desorption at a certain relative partial pressure to determine the amount of water vapor or organic vapor adsorbed or desorbed by the sample. It is often used to detect the hygroscopicity of drugs.
  • object refers to animals, including but not limited to primates (e.g., humans), cattle, pigs, sheep, goats, horses, dogs, cats, rabbits, rats, or mice.
  • primates e.g., humans
  • objects e.g., humans
  • pigs e.g., sheep
  • goats horses
  • dogs e.g., cats
  • rabbits rat
  • mice e.g., mice
  • patient e.g., to refer to mammals or humans.
  • ⁇ dose or “therapeutic effective dose” refers to a sufficient amount of a drug or agent that is non-toxic but achieves the desired effect.
  • pharmaceutically acceptable carrier refers to carriers that do not cause significant irritation to the body and do not impair the biological activity and properties of the active compound. This includes, but is not limited to, any diluents, disintegrants, binders, glidants, and wetting agents approved by the National Medical Products Administration for use in humans or animals.
  • DMSO Dimethyl sulfoxide
  • DMSO-d6 Deuterated dimethyl sulfoxide.
  • HPLC High Performance Liquid Chromatography.
  • V/V Volume/Volume.
  • Tris Tris(hydroxymethyl)aminomethane.
  • Tris buffer salt Tris-hydroxymethylaminomethane buffer salt.
  • MgCl2 Magnesium chloride.
  • PBS Phosphate Buffered Salt
  • Figure 1 shows the crystal structure of compound 1a-2 in Experimental Example 1;
  • Figure 2 shows the X-ray powder diffraction pattern of crystal form B of compound I
  • FIG. 3 shows the differential scanning calorimetry (DSC) curve of crystal form B of compound I.
  • Figure 4 shows the thermogravimetric analysis diagram of crystal form B of compound I
  • Figure 5 shows the dynamic water adsorption diagram of crystal form B of compound I
  • Figure 6 shows the superimposed X-ray powder diffraction patterns of compound B of formula I before and after DVS characterization
  • Figure 7 shows the X-ray powder diffraction pattern of crystal form A of compound I.
  • reaction conditions such as reactants, solvents, bases, amounts of compounds used, reaction temperatures, and reaction times are not limited to the examples below.
  • the compounds of the present invention can also be conveniently prepared by combining various synthetic methods described in this specification or known in the art, such combinations being readily performed by those skilled in the art.
  • the raw materials and equipment used in the specific embodiments of the present invention are all known products and can be obtained by purchasing commercially available products.
  • Example 1 4-((3S,4S)-4-((5-methoxy-7-methyl-1H-indol-4-yl)oxy)-1-(2,2,2-trifluoroethyl)piperidin-3-yl)benzoic acid and 4-((3R,4R)-4-((5-methoxy-7-methyl-1H-indol-4-yl)oxy)-1-(2,2,2-trifluoroethyl)piperidin-3-yl)benzoic acid Preparation of acids and 4-((3S,4R)-4-((5-methoxy-7-methyl-1H-indol-4-yl)oxy)-1-(2,2,2-trifluoroethyl)piperidin-3-yl)benzoic acid and 4-((3R,4S)-4-((5-methoxy-7-methyl-1H-indol-4-yl)oxy)-1-(2,2,2-trifluoroethyl)piperidin-3-yl)
  • the mixture was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to prepare slurry.
  • Example 1a 4-((3S,4S)-4-((5-methoxy-7-methyl-1H-indol-4-yl)oxy)-1-(2,2,2-trifluoroethyl)piperidin-3-yl)benzoic acid and 4-((3R,4R)-4-((5-methoxy-7-methyl-1H-indol-4-yl)oxy)-1-(2,2,2-trifluoroethyl)piperidin-3-yl)benzoic acid
  • the solution was diluted with water (100 mL) and extracted with ethyl acetate (3 ⁇ 500 mL). The organic phases were separated and dried over anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure to prepare slurry. The slurry was purified by column chromatography (mobile phase: dichloromethane/methanol 5/1 (V/V)) to give 1.7 g of the enantiomer of the title compound.
  • Example 1 X-ray single-crystal diffraction experiments in Example 1 confirmed the absolute configuration of 1a-2 as 4-((3R,4R)-4-((5-methoxy-7-methyl-1H-indol-4-yl)oxy)-1-(2,2,2-trifluoroethyl)piperidin-3-yl)benzoic acid.
  • Example 1b ( ⁇ )-rel-(3S,4R)-4-(4-((5-methoxy-7-methyl-1H-indol-4-yl)oxy)-1-(2,2,2-trifluoroethyl)piperidin-3-yl)benzoic acid
  • biotin-labeled complement factor B at a final concentration of 25 nM was incubated with different concentrations of the compound in buffer (PBS containing 10 mM MgCl2 and 0.05% Chaps) at 4°C for 30 minutes.
  • Cy5 fluorescently labeled probes and europium chelate-labeled streptavidin (PerkinElmer, AD0060) at final concentrations of 75 nM and 0.225 nM, respectively, were added, and the reaction was carried out at 4°C for 2 hours.
  • TR-FRET time-dependent fluorescence energy transfer
  • Sample collection At each set time point, 40 ⁇ L of whole blood was collected from the experimental animals via the orbital cavity. The whole blood sample was placed in an anticoagulant tube containing EDTA-K2. The whole blood sample was centrifuged at 1500g for 10 min to separate the plasma. The supernatant plasma sample was collected into a sample tube for LC-MS/MS analysis.
  • Plasma concentrations were processed using a non-compartmental model of WinNonlin TM Version 6.3 (Pharsight, Mountain View, CA) pharmacokinetic software.
  • the pharmacokinetic parameters Cl, T ⁇ sub>1/2 ⁇ /sub> , C ⁇ sub>max ⁇ /sub>, and AUC ⁇ sub>0-24 ⁇ /sub> were calculated using the linear logarithmic trapezoidal method. The results are shown in the table below.
  • Arthritis score AUC After the experiment, GraphPad Prism 8.4.3 software was used to analyze the mean arthritis score of each group of animals at each time point. The Area under curve of XY analyses was selected to calculate the arthritis score AUC of each group of animals. The larger the AUC, the greater the severity of arthritis. The AUC experimental results are shown in Table 8.
  • the compound of the present invention can significantly improve the severity of arthritis lesions in the model animals, and the AUC score is significantly lower than that of LNP023.
  • Test solution Take an appropriate amount of crystal form B of compound of formula I, accurately weigh it, dissolve and dilute it with solvent to prepare a solution containing about 0.5 mg per ml.
  • Control solution Accurately measure an appropriate amount of the test solution and dilute it with a solvent to prepare a solution containing approximately 0.5 ⁇ g per 1 ml.
  • Octadecylsilane-bonded silica gel was used as the stationary phase (Inertsil ODS-3V 4.6mm ⁇ 250mm, 5 ⁇ m or equivalent column); 0.1% phosphoric acid solution was used as mobile phase A, and acetonitrile was used as mobile phase B, with gradient elution performed according to the table below; the flow rate was 1.0 ml per minute; the column temperature was 40°C; the detection wavelength was 236 nm; and the injection volume was 10 ⁇ l.
  • the XRPD results of crystal form B are shown in Figure 2; the DSC results are shown in Figure 3; the TGA results are shown in Figure 4; the DVS results are shown in Figure 5; and the XRPD overlay before and after DVS characterization is shown in Figure 6.
  • test results of influencing factors show that: after being placed under high temperature (40°C) and relative humidity (75%) for 30 days, all indicators of crystal form B meet the requirements and there is no significant change compared with before placement. After being placed under high temperature (60°C) for 30 days, all indicators of crystal form B meet the requirements and there is no significant change compared with before placement. After being placed under light for 30 days, all indicators of crystal form B meet the requirements and there is no significant change compared with before placement. After being placed under relative humidity (92.5%) for 30 days, all indicators of crystal form B meet the requirements and there is no significant change compared with before placement.
  • Accelerated testing was conducted in accordance with (Chinese Pharmacopoeia 2020 Edition, Part IV, General Chapter 9001, Guidelines for Stability Testing of Active Pharmaceutical Ingredients and Preparations).
  • Test conditions 40°C ⁇ 2°C, 75%RH ⁇ 5%RH;
  • Packaging conditions are as follows: inner packaging (pharmaceutical low-density polyethylene bag); outer packaging (polyester/aluminum/polyethylene pharmaceutical composite bag + paper drum).
  • Test conditions 30°C ⁇ 2°C, 65%RH ⁇ 5%RH;
  • Packaging conditions Inner packaging (pharmaceutical low-density polyethylene bag); outer packaging (polyester/aluminum/polyethylene pharmaceutical composite bag + paper drum).
  • the crystal form B of compound I exhibits good stability under various influencing factors, accelerated experimental conditions, and long-term experimental conditions.
  • a saturated solution of compound I was prepared at approximately 50 °C using ethanol/water (1:2, v/v) in 1 mL. The solution was then transferred to room temperature and allowed to stand for one day to yield needle-like crystals.

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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention appartient au domaine technique de la biologie. L'invention concerne une forme cristalline d'un inhibiteur du facteur B du complément, son procédé de préparation et son utilisation. Plus particulièrement, la présente invention concerne une forme cristalline d'un composé représenté par la formule I, son procédé de préparation et son utilisation. La forme cristalline préparée par la présente invention présente une bonne stabilité, par exemple, une stabilité de forme cristalline et une stabilité thermique.
PCT/CN2025/107219 2024-07-05 2025-07-05 Forme cristalline d'un inhibiteur du facteur b du complément, son procédé de préparation et son utilisation Pending WO2026008074A1 (fr)

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CN202410909721 2024-07-05
CN202410909721.8 2024-07-05

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105579444A (zh) * 2013-07-15 2016-05-11 诺华股份有限公司 哌啶基吲哚衍生物和它们作为补体因子b抑制剂的用途
CN116496249A (zh) * 2022-01-26 2023-07-28 上海美悦生物科技发展有限公司 补体因子b抑制剂的盐型、晶型及其制备方法和应用
CN118026998A (zh) * 2022-11-11 2024-05-14 上海医药工业研究院有限公司 哌啶取代的苯甲酸类化合物、其药物组合物和应用
CN118108700A (zh) * 2020-08-07 2024-05-31 诺华股份有限公司 补体因子b抑制剂及其药物组合物、制备方法和用途
WO2024149261A1 (fr) * 2023-01-09 2024-07-18 南京正大天晴制药有限公司 Inhibiteur du facteur b du complément
WO2025068951A1 (fr) * 2023-09-29 2025-04-03 Novartis Ag Inhibiteurs du facteur b du complément et leurs utilisations

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105579444A (zh) * 2013-07-15 2016-05-11 诺华股份有限公司 哌啶基吲哚衍生物和它们作为补体因子b抑制剂的用途
CN118108700A (zh) * 2020-08-07 2024-05-31 诺华股份有限公司 补体因子b抑制剂及其药物组合物、制备方法和用途
CN116496249A (zh) * 2022-01-26 2023-07-28 上海美悦生物科技发展有限公司 补体因子b抑制剂的盐型、晶型及其制备方法和应用
CN118026998A (zh) * 2022-11-11 2024-05-14 上海医药工业研究院有限公司 哌啶取代的苯甲酸类化合物、其药物组合物和应用
WO2024149261A1 (fr) * 2023-01-09 2024-07-18 南京正大天晴制药有限公司 Inhibiteur du facteur b du complément
WO2025068951A1 (fr) * 2023-09-29 2025-04-03 Novartis Ag Inhibiteurs du facteur b du complément et leurs utilisations

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