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WO2025167361A1 - Forme cristalline a de 6- ((5,6-diphényl -1,2,4-triazine-3-yl) (isopropyl) amino)-n- (méthylsulfonyl) hexanamide, et son utilisation et son procédé de préparation - Google Patents

Forme cristalline a de 6- ((5,6-diphényl -1,2,4-triazine-3-yl) (isopropyl) amino)-n- (méthylsulfonyl) hexanamide, et son utilisation et son procédé de préparation

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Publication number
WO2025167361A1
WO2025167361A1 PCT/CN2024/141731 CN2024141731W WO2025167361A1 WO 2025167361 A1 WO2025167361 A1 WO 2025167361A1 CN 2024141731 W CN2024141731 W CN 2024141731W WO 2025167361 A1 WO2025167361 A1 WO 2025167361A1
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WO
WIPO (PCT)
Prior art keywords
compound
crystallization
solvent
formula
cooling
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/CN2024/141731
Other languages
English (en)
Chinese (zh)
Inventor
孙立杰
孙晓飞
郭志强
杨娴
曹柳
李磊
孟维迪
陈伟
侯海婷
左悦
朱树杰
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shijiazhuang No 4 Pharmaceutical Co Ltd
Hebei Guolong Pharmaceutical Co Ltd
Original Assignee
Shijiazhuang No 4 Pharmaceutical Co Ltd
Hebei Guolong Pharmaceutical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shijiazhuang No 4 Pharmaceutical Co Ltd, Hebei Guolong Pharmaceutical Co Ltd filed Critical Shijiazhuang No 4 Pharmaceutical Co Ltd
Publication of WO2025167361A1 publication Critical patent/WO2025167361A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
    • C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
    • C07D253/06—1,2,4-Triazines
    • C07D253/065—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members
    • C07D253/07—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members with hetero atoms, or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Definitions

  • the present application belongs to the field of pharmacy, and specifically relates to a crystalline form of the compound 6-((5,6-diphenyl-1,2,4-triazin-3-yl)(isopropyl)amino)-N-(methylsulfonyl)hexanamide, its pharmaceutical composition, use and preparation method.
  • Pulmonary arterial hypertension is a rare, incurable pulmonary vascular disease that can gradually lead to right heart failure and ultimately death.
  • PAH is characterized by pulmonary microvascular remodeling, which leads to a progressive increase in pulmonary artery resistance (PVR), which in turn causes right heart failure. This makes PAH a progressive and fatal disease. 75% of PAH patients die within 5 years of diagnosis, with an average survival of 1.9 years after symptom onset. It is often referred to as the "malignant tumor of the cardiovascular and pulmonary vascular system.”
  • PGI2 is an important endothelial relaxing factor that stimulates cyclic adenosine monophosphate (cAMP) production, causing pulmonary vascular smooth muscle relaxation and inhibiting smooth muscle growth. PGI2 deficiency can cause pulmonary hypertension, making PGI2 drugs the most active treatment for PAH.
  • PGI2 drugs include PGI2 analogs and PGI2 receptor agonists.
  • PGI2 analogs which share a native PGI2 backbone, are rapidly metabolized and have a very short biological half-life. They require frequent dosing or intravenous infusion, leading to poor patient compliance. Furthermore, PGI2 analogs have poor target selectivity, making it difficult to separate their therapeutic effects from other effects and prone to adverse reactions.
  • the compound of formula I also known as Compound I, has the chemical name 6-((5,6-diphenyl-1,2,4-triazin-3-yl)(isopropyl)amino)-N-(methylsulfonyl)hexanamide, and its structural formula is shown in Formula I. It is a PGI2 receptor agonist with a novel structure and good drugability. Compound I has strong target selectivity, and its agonist activity at the prostacyclin IP receptor is more than 1,000 times that of the other seven prostacyclin receptor targets.
  • IP receptor mainly activates the IP receptor to promote the production of cAMP in pulmonary artery smooth muscle cells, thereby inhibiting abnormal contraction of the pulmonary artery, inhibiting the proliferation of pulmonary artery smooth muscle cells, and reducing pulmonary artery pressure, thereby achieving the treatment of pulmonary hypertension.
  • IP receptor to promote the production of cAMP in pulmonary artery smooth muscle cells, thereby inhibiting abnormal contraction of the pulmonary artery, inhibiting the proliferation of pulmonary artery smooth muscle cells, and reducing pulmonary artery pressure, thereby achieving the treatment of pulmonary hypertension.
  • it has higher efficacy and safety.
  • Compound I exists in various crystalline forms. Extensive research has been conducted on the crystalline forms of Compound I to identify and prepare crystalline forms that meet pharmaceutical requirements. Based on these studies, this application provides Compound I Form A, which is non-hygroscopic and exhibits excellent storage stability, making it suitable for formulation development. This application also provides pharmaceutical compositions and uses of Compound I Form A, as well as a method for preparing Compound I Form A, which operates under mild process conditions and is suitable for large-scale production.
  • One object of the present application is to provide a crystalline form A of compound I, whose X-ray powder diffraction pattern expressed in 2 ⁇ angles has diffraction peaks at 9.50 ⁇ 0.2°, 11.05 ⁇ 0.2°, 15.54 ⁇ 0.2°, 16.23 ⁇ 0.2°, 18.23 ⁇ 0.2° and 22.13 ⁇ 0.2°.
  • the crystalline form A of compound 1 has an X-ray powder diffraction pattern expressed in 2 ⁇ angles at 6.38 ⁇ 0.2°, 9.50 ⁇ 0.2°, 11.05 ⁇ 0.2°, 13.11 ⁇ 0.2°, 15.54 ⁇ 0.2°, 16.23 ⁇ 0.2°, 18.23 ⁇ 0.2°, 18.96 ⁇ 0.2°, 19.42 ⁇ 0.2°, 20.52 ⁇ 0.2°, 21.43 ⁇ 0.2°, 22.13 ⁇ 0.2°, and 23.07 ⁇ 0.2°.
  • the crystalline form A of Compound I has an X-ray powder diffraction pattern expressed in 2 ⁇ angles as shown in FIG1 .
  • Form A of Compound 1 when Form A of Compound 1 is characterized by TGA/DSC, its TGA graph can confirm that Form A does not contain crystalline water or solvate.
  • Form A of Compound I when Form A of Compound I is characterized by TGA/DSC, its DSC chart shows that the melting point of Form A is 130°C-135°C.
  • the TGA/DSC graph of Form A of Compound 1 is shown in FIG2 .
  • the second object of the present application is to provide a preparation method for Compound I Form A, which comprises the following steps: heating and dissolving Compound I in a solvent, cooling to 25°C to 45°C, slowly cooling to crystallize or keeping warm to crystallize, continuing to cool to 0°C to 10°C to keep warm to crystallize, separating, and drying to obtain Form A.
  • the solvent is one or a mixed solvent of alcohols, ethers, esters, alkanes, ketones, acetonitrile, and water.
  • the solvent is one or a mixed solvent of methanol, ethanol, isopropanol, acetonitrile, tetrahydrofuran, methyl tert-butyl ether, ethyl acetate, dichloromethane, n-hexane, acetone, and water.
  • the solvent is one or a mixed solvent of isopropyl alcohol, ethanol or water.
  • the solvent is isopropyl alcohol.
  • the mass volume ratio (g/mL) of the compound I to the solvent is 1:4-15.
  • the heating and dissolving can be performed by heating and dissolving in a single solvent or a mixed solvent, or by first heating and dissolving in one solvent and then adding another one or more solvents.
  • the heating condition is heating under reflux.
  • the cooling to 25°C to 45°C can be performed in a variety of conventional ways, such as cooling in a water bath or a cold water bath, cooling by turning off the heating, or cooling at room temperature.
  • the temperature is lowered to 25°C to 45°C, and the cooling time is 0-50 minutes.
  • the temperature is lowered to 25°C to 45°C, preferably to 35°C to 45°C.
  • the crystallization is carried out by slowly cooling or keeping the temperature at room temperature after cooling to 25°C to 45°C, which can be natural slow cooling and crystallization at room temperature, or keeping the temperature at room temperature.
  • the crystallization by slow cooling or heat preservation can be performed by standing still or by stirring, such as paddle stirring, suspension stirring, etc.
  • the crystallization is carried out by slowly cooling or keeping warm, and the crystallization time is 1 to 24 hours, preferably 1 to 3 hours.
  • the continued cooling is performed in an ice bath or an ice salt bath.
  • the temperature is continuously lowered to 0°C to 10°C for crystallization, and the crystallization can be performed by standing still or under stirring, such as paddle stirring, suspension stirring, etc.
  • the temperature is continued to be lowered to 0°C to 10°C for crystallization, and the crystallization time is 1 to 24 hours, preferably 1 to 2 hours.
  • the separation can be performed by conventional methods, such as centrifugation or filtration.
  • the drying is a conventional drying method, such as vacuum drying.
  • the drying entails drying to constant weight.
  • the third object of the present application is to provide a second method for preparing Form A of Compound I, which comprises the following steps: dissolving Compound I in a solvent by heating, cooling to 0°C to 10°C, preserving the temperature for crystallization, separating, and drying to obtain Form A.
  • the solvent is one or a mixed solvent of alcohols, ethers, esters, alkanes, ketones, acetonitrile, and water.
  • the solvent is one or a mixed solvent of methanol, ethanol, isopropanol, acetonitrile, tetrahydrofuran, methyl tert-butyl ether, ethyl acetate, dichloromethane, n-hexane, acetone, and water.
  • the solvent is one or a mixed solvent of isopropyl alcohol, ethanol or water.
  • the solvent is isopropyl alcohol.
  • the mass volume ratio (g/mL) of the compound I to the solvent is 1:3.5-15.
  • the heating condition is heating under reflux.
  • the heating and dissolving can be performed by heating and dissolving in a single solvent or a mixed solvent, or by first heating and dissolving in one solvent and then adding another one or more solvents.
  • the cooling to 0°C to 10°C is performed in a cold water bath, an ice bath, or an ice salt bath.
  • the temperature is lowered to 0°C to 10°C, and the cooling time is 5-15 minutes.
  • the crystallization method in the heat preservation crystallization, can be static crystallization or crystallization under stirring, such as paddle stirring, suspension stirring, etc.
  • the crystallization time is 2 to 24 hours, preferably 2 to 5 hours.
  • the separation can be performed by conventional methods, such as centrifugation or filtration.
  • the drying is a conventional drying method, such as vacuum drying.
  • the drying entails drying to constant weight.
  • the fourth object of the present application is to provide a third method for preparing Compound I Form A, which comprises the following steps: heating and dissolving Compound I in a solvent, cooling to 10°C to 25°C, keeping warm for crystallization, continuing to cool to 0°C to 10°C, keeping warm for crystallization, separating, and drying to obtain Form A.
  • the solvent is one or a mixed solvent of alcohols, ethers, esters, alkanes, ketones, acetonitrile, and water.
  • the solvent is one or a mixed solvent of methanol, ethanol, isopropanol, acetonitrile, tetrahydrofuran, methyl tert-butyl ether, ethyl acetate, dichloromethane, n-hexane, acetone, and water.
  • the solvent is one or a mixed solvent of isopropyl alcohol, ethanol or water.
  • the solvent is isopropyl alcohol.
  • the mass volume ratio (g/mL) of the compound I to the solvent is 1:4-15.
  • the heating condition is heating under reflux.
  • the heating and dissolving can be performed by heating and dissolving in a single solvent or a mixed solvent, or by first heating and dissolving in one solvent and then adding another one or more solvents.
  • the cooling to 10°C to 25°C is performed in a cold water bath or a water bath.
  • the temperature is lowered to 10°C to 25°C, and the cooling time is 10 to 40 minutes.
  • the temperature is lowered to 10° C. to 25° C. and then kept warm for crystallization.
  • the crystallization can be performed by standing still or under stirring, such as paddle stirring, suspension stirring, etc.
  • the temperature is lowered to 10° C. to 25° C. and then kept warm for crystallization, and the crystallization time is 0 to 24 hours, preferably 1 to 3 hours.
  • the further cooling to 0°C to 10°C is performed in an ice bath or an ice salt bath.
  • the temperature is continuously lowered to 0°C to 10°C for crystallization, and the crystallization can be performed by standing still or under stirring, such as paddle stirring, suspension stirring, etc.
  • the temperature is continued to be lowered to 0°C to 10°C for crystallization, and the crystallization time is 1 to 24 hours, preferably 1 to 2 hours.
  • the separation can be performed by conventional methods, such as centrifugation or filtration.
  • the drying is a conventional drying method, such as vacuum drying.
  • the drying entails drying to constant weight.
  • the fifth object of the present application is to provide a pharmaceutical composition comprising a therapeutically effective dose of Compound I Form A and a pharmaceutically acceptable carrier and excipient.
  • the pharmaceutical composition can be formulated into a variety of dosage forms for easy administration, for example, oral preparations (such as tablets, capsules, granules, powders, solutions or suspensions, etc.); injectable preparations (such as injectable solutions or suspensions, or injectable dry powders that can be used immediately after adding a drug solvent before injection).
  • oral preparations such as tablets, capsules, granules, powders, solutions or suspensions, etc.
  • injectable preparations such as injectable solutions or suspensions, or injectable dry powders that can be used immediately after adding a drug solvent before injection.
  • the disease or condition is associated with PGI2 receptor agonism.
  • the disease or condition is selected from: pulmonary hypertension, cardiovascular and cerebrovascular diseases related to platelet aggregation, and diabetic nephropathy.
  • the seventh object of the present application is to provide a therapeutically effective dose of Compound I Form A or the pharmaceutical composition thereof for use in the preparation of a PGI2 receptor agonist drug.
  • room temperature or "RT” refers to an ambient temperature of 20 to 25°C (68-77°F).
  • Form A of Compound I of this application exhibits low hygroscopicity and good stability in accelerated and long-term stability studies, making it suitable for formulation development. Furthermore, experiments have shown that Form A has high bioavailability, indicating good drug absorption and enhancing efficacy. Furthermore, its preparation process is mild and suitable for large-scale production. Therefore, Form A offers significant advantages in terms of drugability and ease of industrial production, and is of great significance for drug development.
  • FIG1 shows the XRPD spectrum of Compound 1 Form A prepared in Example 1;
  • FIG2 shows the TGA/DSC spectrum of Compound 1 Form A prepared in Example 1;
  • FIG3 shows the 1 H-NMR spectrum of Compound I Form A prepared in Example 1;
  • FIG4 shows the IR spectrum of Compound 1 Form A prepared in Example 1;
  • FIG5 shows the XRPD superposition of Compound I Form A prepared in Example 1 at the end of the 6th month of the accelerated experiment, the end of the 6th month of the long-term experiment, and day 0;
  • FIG6 shows the average concentration-time curve of Compound I in plasma of Group 1 animals after intravenous administration in the bioavailability study of Experimental Example 7;
  • FIG7 shows the average concentration-time curve of Compound I in plasma after oral administration to the second group of animals in the bioavailability test of Experimental Example 7.
  • X-ray tube cathode: copper; tube voltage: 40 kV; tube current: 30 mA; scanning mode: one-dimensional scanning; scanning rate: 10°/min; scanning axis: ⁇ /2 ⁇ ; scanning range: 3-35°; step interval: 0.01°.
  • Form A has characteristic peaks at diffraction angles 2 ⁇ of 6.38 ⁇ 0.2°, 9.50 ⁇ 0.2°, 11.05 ⁇ 0.2°, 13.11 ⁇ 0.2°, 15.54 ⁇ 0.2°, 16.23 ⁇ 0.2°, 18.23 ⁇ 0.2°, 18.96 ⁇ 0.2°, 19.42 ⁇ 0.2°, 20.52 ⁇ 0.2°, 21.43 ⁇ 0.2°, 22.13 ⁇ 0.2°, and 23.07 ⁇ 0.2° as determined by X-ray powder diffraction.
  • thermogravimetric-differential scanning calorimetry (TGA/DSC) spectrum is shown in FIG2 .
  • Atmosphere AIR(80/20)--/NITROGEN/50/NITROGEN/20
  • the TGA graph can confirm that Form A does not contain crystalline water or solvate; the DSC graph can confirm that the melting point (extrapolated onset temperature) of Form A is 132.6 ⁇ 2°C.
  • Detection method Take an appropriate amount of this product (about 1-2 mg) and an appropriate amount of ground and dried potassium bromide, place them in an agate mortar, mix the sample and potassium bromide and grind them evenly, take an appropriate amount of the ground mixture and put it into a tablet pressing mold to press the tablet, and measure the infrared spectrum.
  • the infrared spectrum of the sample has characteristic peaks at 3243 ⁇ 5cm -1 , 2931 ⁇ 5cm -1 , 1706 ⁇ 5cm -1 , 1530 ⁇ 5cm -1 , 1488 ⁇ 5cm -1 , 1446 ⁇ 5cm -1 , 1430 ⁇ 5cm -1 , 1226 ⁇ 5cm -1 , 1125 ⁇ 5cm -1 , 1110 ⁇ 5cm -1 , 706 ⁇ 5cm - 1 , and 692 ⁇ 5cm -1 .
  • the thickness of the test sample is generally about 1 mm. Accurately weigh the weight (m 2 ).
  • Example 1 A stability study was conducted on the Compound I Form A sample prepared in Example 1. The sample was placed at 40°C ⁇ 2°C/75% RH ⁇ 5% RH for 6 months for an accelerated stability experiment, and at 30°C ⁇ 2°C/65% RH ⁇ 5% RH for 6 months for a long-term stability experiment. The XRPD spectra of the sample were measured on the 0th day, 1 month, 2 months, 3 months, and at the end of 6 months to determine the change in the crystal form. At the same time, its purity was determined by high performance liquid chromatography to examine the changes in related substances.
  • the stability test results of the 6-month accelerated test and the 6-month long-term test of the Form A sample are shown in Tables 2 and 3.
  • the XRPD overlay images at the end of the 6th month in the accelerated test and at the end of the 6th month and day 0 in the long-term test are shown in Figure 5.
  • a bioavailability test was conducted on the Compound I Form A sample prepared in Example 1.
  • the Compound I Form A sample was first prepared into an injection and a suspension using conventional methods.
  • the homogeneity and concentration of the drug formulations were analyzed using a validated HPLC-UV analytical method.
  • concentration of Compound I in plasma samples was determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method.
  • LC-MS/MS liquid chromatography-tandem mass spectrometry
  • the Compound I Form A samples prepared in Examples 2 to 33 have comparable properties to the Compound I Form A sample prepared in Example 1, including hygroscopicity, stability, and bioavailability.

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  • Diabetes (AREA)
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  • Urology & Nephrology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
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Abstract

La présente invention concerne une forme cristalline A du composé I 6- ((5,6-diphényl -1,2,4-triazine-3-yl) (isopropyl) amino)-N- (méthylsulfonyl) hexanamide, une composition pharmaceutique le comprenant, son utilisation et son procédé de préparation. La forme cristalline A du composé I de la présente demande présente des pics de diffraction dans un diagramme de diffraction des rayons X sur poudre au moins aux angles de diffraction 2θ suivants : 9,50 ± 0,2°, 11,05 ± 0,2°, 15,54 ± 0,2°, 16,23 ± 0,2°, 18,23 ± 0,2° et 22,13 ± 0,2°. La forme cristalline A du composé I de la présente invention présente les avantages d'une faible hygroscopicité, d'une bonne stabilité et similaire, et revêt une grande importance pour le développement de médicaments.
PCT/CN2024/141731 2024-02-06 2024-12-24 Forme cristalline a de 6- ((5,6-diphényl -1,2,4-triazine-3-yl) (isopropyl) amino)-n- (méthylsulfonyl) hexanamide, et son utilisation et son procédé de préparation Pending WO2025167361A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CN202410169645.1 2024-02-06
CN202410169645 2024-02-06
CN202410898621.XA CN118852041B (zh) 2024-02-06 2024-07-05 6-((5,6-二苯基-1,2,4-三嗪-3-基)(异丙基)氨基)-n-(甲基磺酰基)己酰胺晶型a及其用途和制备方法
CN202410898621.X 2024-07-05

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Publication Number Publication Date
WO2025167361A1 true WO2025167361A1 (fr) 2025-08-14

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PCT/CN2024/130940 Pending WO2025167237A1 (fr) 2024-02-06 2024-11-08 Composé de diphényltriazine, son procédé de préparation et son utilisation
PCT/CN2024/141731 Pending WO2025167361A1 (fr) 2024-02-06 2024-12-24 Forme cristalline a de 6- ((5,6-diphényl -1,2,4-triazine-3-yl) (isopropyl) amino)-n- (méthylsulfonyl) hexanamide, et son utilisation et son procédé de préparation
PCT/CN2024/141737 Pending WO2025167362A1 (fr) 2024-02-06 2024-12-24 Forme cristalline b de 6-((5,6-diphényl-1,2,4-triazin-3-yl)(isopropyl)amino)-n-(méthylsulfonyl)hexanamide, son utilisation et son procédé de préparation

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CN118598820B (zh) * 2024-02-06 2025-07-08 石家庄四药有限公司 一种二苯基三嗪类化合物及其制备方法和应用

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CN108530348B (zh) * 2018-04-08 2021-11-05 哈尔滨博达森虎医药科技有限公司 一种治疗慢性阻塞性肺疾病的药物及其制备方法
CN108863955B (zh) * 2018-08-03 2021-08-13 成都苑东生物制药股份有限公司 二苯基吡嗪类化合物或其药学上可接受的盐、异构体及其制备方法和用途
CN115583908B (zh) * 2021-07-05 2024-08-06 西北农林科技大学 一种吲哚甲酰胺类化合物及其制备方法和用途
CN118619893A (zh) * 2023-12-27 2024-09-10 石家庄四药有限公司 Pgi2受体激动剂化合物、药物组合物和应用
CN118598820B (zh) * 2024-02-06 2025-07-08 石家庄四药有限公司 一种二苯基三嗪类化合物及其制备方法和应用

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