WO2024140425A1 - Forme cristalline d'aprocitentan, son procédé de préparation et son utilisation - Google Patents
Forme cristalline d'aprocitentan, son procédé de préparation et son utilisation Download PDFInfo
- Publication number
- WO2024140425A1 WO2024140425A1 PCT/CN2023/140806 CN2023140806W WO2024140425A1 WO 2024140425 A1 WO2024140425 A1 WO 2024140425A1 CN 2023140806 W CN2023140806 W CN 2023140806W WO 2024140425 A1 WO2024140425 A1 WO 2024140425A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- crystal form
- csvi
- crystalline
- present
- crystalline form
- Prior art date
Links
- 239000013078 crystal Substances 0.000 title claims abstract description 66
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- DKULOVKANLVDEA-UHFFFAOYSA-N ACT-132577 Chemical compound C=1C=C(Br)C=CC=1C=1C(NS(=O)(=O)N)=NC=NC=1OCCOC1=NC=C(Br)C=N1 DKULOVKANLVDEA-UHFFFAOYSA-N 0.000 title abstract description 4
- 229940070148 aprocitentan Drugs 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 24
- 239000003814 drug Substances 0.000 claims abstract description 21
- 229940079593 drug Drugs 0.000 claims abstract description 20
- 229940118365 Endothelin receptor antagonist Drugs 0.000 claims abstract description 4
- 230000009977 dual effect Effects 0.000 claims abstract description 4
- 239000002308 endothelin receptor antagonist Substances 0.000 claims abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 35
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical group OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 27
- 206010020772 Hypertension Diseases 0.000 claims description 27
- 239000007787 solid Substances 0.000 claims description 13
- 230000005855 radiation Effects 0.000 claims description 10
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 9
- 239000012453 solvate Substances 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 208000015658 resistant hypertension Diseases 0.000 abstract 1
- 238000002411 thermogravimetry Methods 0.000 description 9
- 239000008186 active pharmaceutical agent Substances 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 230000008859 change Effects 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 239000011888 foil Substances 0.000 description 5
- 238000001179 sorption measurement Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 4
- 229910052782 aluminium Inorganic materials 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 229910016860 FaSSIF Inorganic materials 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 208000001647 Renal Insufficiency Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 201000006370 kidney failure Diseases 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000003760 magnetic stirring Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000010907 mechanical stirring Methods 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 230000004584 weight gain Effects 0.000 description 2
- 235000019786 weight gain Nutrition 0.000 description 2
- UHEIKHWCXFBABC-UHFFFAOYSA-N 5-(4-bromophenyl)-6-[2-(5-bromopyrimidin-2-yl)oxyethoxy]pyrimidine-4-sulfonamide Chemical compound C=1C=C(Br)C=CC=1C=1C(S(=O)(=O)N)=NC=NC=1OCCOC1=NC=C(Br)C=N1 UHEIKHWCXFBABC-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102000002045 Endothelin Human genes 0.000 description 1
- 108050009340 Endothelin Proteins 0.000 description 1
- 229910005429 FeSSIF Inorganic materials 0.000 description 1
- 101001121408 Homo sapiens L-amino-acid oxidase Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100026388 L-amino-acid oxidase Human genes 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical group CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 206010063897 Renal ischaemia Diseases 0.000 description 1
- 101100012902 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) FIG2 gene Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 239000012159 carrier gas Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 238000007667 floating Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003517 fume Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 238000009522 phase III clinical trial Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000001932 seasonal effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000004441 surface measurement Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
Definitions
- WO2021088645A1 discloses Compound I crystalline form CSI, which discloses that crystalline form CSI is a more thermodynamically stable crystalline form than WO2018154101A1 crystalline form A.
- WO2021237004A1 discloses compound I crystalline forms T9, T10, T12, P1, P2, methanesulfonic acid cocrystal, ethanesulfonic acid cocrystal
- Crystal form T1 is a methyl acetate solvate
- crystal form T10 is an ether solvate
- crystal form T12 is an anhydrous form
- crystal forms P1 and P2 are piperazine cocrystals.
- the main purpose of the present invention is to provide a new crystal form of compound I and a preparation method and use thereof.
- the X-ray powder diffraction pattern of the crystalline form CSVI has characteristic peaks at any one, any two, any three, or four, or five, or six, or seven, or eight, or nine of the diffraction angle 2 ⁇ values of 15.0° ⁇ 0.2°, 17.2° ⁇ 0.2°, 18.2° ⁇ 0.2°, 18.7° ⁇ 0.2°, 20.5° ⁇ 0.2°, 20.9° ⁇ 0.2°, 23.6° ⁇ 0.2°, 24.6° ⁇ 0.2°, 25.8° ⁇ 0.2°, 26.5° ⁇ 0.2°, and 30.7° ⁇ 0.2°.
- the X-ray powder diffraction pattern of Form CSVI is substantially as shown in FIG. 1 .
- Form CSVI is a benzyl alcohol solvate containing about 0.5 molar equivalents of benzyl alcohol.
- the stirring temperature is preferably -20°C to 10°C, and more preferably 4°C.
- the present invention provides the use of the crystalline form CSVI for preparing other crystalline forms or co-crystals of compound I and its salts.
- the present invention provides use of crystalline CSVI in preparing a drug for treating refractory hypertension.
- the crystalline form CSVI of the present invention has higher solubility, especially in FaSSIF, the solubility is
- the crystal form CSVI provided by the present invention has higher solubility, which is beneficial to improve the absorption of the drug in the human body and improve the bioavailability; in addition, higher solubility can reduce the dosage of the drug while ensuring the efficacy of the drug, thereby reducing the side effects of the drug and improving the safety of the drug.
- Crystal form CSVI has better humidity stability. After experiencing humidity changes from 0% RH to 95% RH to 0% RH, the crystal form of crystal form CSI remains unchanged.
- the crystalline CSVI API provided by the present invention has good stability.
- the crystalline CSVI API was placed under 25°C/60%RH conditions, and the crystal form did not change for 6 months, and the chemical purity was maintained at more than 99.7%. This indicates that the crystalline CSVI API has good stability under long-term conditions.
- the crystalline CSVI API was placed under 40°C/75%RH conditions, and the crystal form did not change for 6 months, and the chemical purity was more than 99.7%, and the purity remained basically unchanged during storage. This indicates that the crystalline CSVI API has good stability under accelerated conditions.
- the crystalline CSVI provided by the present invention has low hygroscopicity. Test results show that the weight gain of the crystalline CSVI under 80% RH is 0.07%, and it is almost non-hygroscopic.
- the low hygroscopic crystal form has no strict requirements on the environment, reduces the cost of material production, storage and quality control, and has strong economic value.
- Figure 1 is the XRPD diagram of crystalline form CSVI
- Figure 2 is the TGA graph of crystalline CSVI
- Figure 4 is a comparison of XRPD images of CSVI before and after the 0%RH-95%RH-0%RH change (from top to bottom: before DVS, after DVS)
- the X-ray powder diffraction pattern of the present invention was collected on a Bruker D8 ADVANCE X-ray powder diffractometer.
- the method parameters of the X-ray powder diffraction are as follows:
- thermogravimetric analysis (TGA) graph of the present invention is collected on TA Q500.
- the method parameters of the thermogravimetric analysis (TGA) of the present invention are as follows:
- the dynamic moisture adsorption (DVS) graph of the present invention is collected on an Intrinsic dynamic moisture adsorption instrument produced by SMS (Surface Measurement Systems Ltd.).
- the instrument control software is DVS-Intrinsic control software.
- the method parameters of the dynamic moisture adsorption instrument are as follows:
- Relative humidity range 0%RH-95%RH
- the nuclear magnetic resonance hydrogen spectrum data ( 1 H NMR) were collected from a Bruker Avance II DMX 400M HZ nuclear magnetic resonance spectrometer. 1-5 mg of sample was weighed and dissolved in 0.5 mL of deuterated chloroform to prepare a 2-10 mg/mL solution.
- the "stirring” is accomplished by conventional methods in the art, such as magnetic stirring or mechanical stirring, with a stirring speed of 50-1800 rpm, wherein the magnetic stirring is preferably 300-900 rpm, and the mechanical stirring is preferably 100-300 rpm.
- the "drying” can be carried out at room temperature or higher.
- the drying temperature is from room temperature to about 80°C, or to 60°C, or to 40°C.
- the drying time can be more than 0.5 hours, or overnight.
- the drying is carried out in a fume hood, a forced air oven, or a vacuum oven.
- the relative intensity of the diffraction peaks in the X-ray powder diffraction pattern is related to the preferred orientation of the crystal, and the diffraction peak intensity shown in the present invention is illustrative rather than for absolute comparison. Therefore, those skilled in the art will understand that the X-ray powder diffraction pattern of the crystal form protected by the present invention does not have to be completely consistent with the X-ray powder diffraction pattern in the embodiments referred to herein, and any crystal form having an X-ray powder diffraction pattern that is the same or similar to the characteristic peaks in these patterns belongs to the scope of the present invention. Those skilled in the art can compare the X-ray powder diffraction pattern listed in the present invention with the X-ray powder diffraction pattern of an unknown crystal form to confirm whether the two sets of patterns reflect the same or different crystal forms.
- the “characteristic peak” refers to a representative diffraction peak used to identify crystals.
- the 2 ⁇ value of the characteristic peak can usually have an error of ⁇ 0.2°.
- solvate is a crystalline form containing stoichiometric or non-stoichiometric amounts of solvent.
- the crystalline form CSVI of the present invention is pure and substantially free of any other crystalline forms.
- substantially free when used to refer to a new crystalline form means that the crystalline form contains less than 20% (by weight) of other crystalline forms, particularly less than 10% (by weight) of other crystalline forms, more preferably less than 5% (by weight) of other crystalline forms, and more preferably less than 1% (by weight) of other crystalline forms.
- the compound I used in the following examples can be prepared according to the prior art, for example, according to the method described in WO2018154101A1.
- the obtained solid was the crystalline form CSVI of the present invention, and its X-ray powder diffraction pattern was shown in FIG1 , and the X-ray powder diffraction data were shown in Table 3. Its TGA was shown in FIG2 , and when it was heated to 150°C, it had a mass loss of about 10.1%.
- Open Place the sample in a glass vial, cover the vial with a layer of aluminum foil and make a hole in the foil.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
La présente invention concerne une nouvelle forme cristalline d'aprocitentan (appelée " composé I "), son procédé de préparation, une composition pharmaceutique contenant la forme cristalline, et l'utilisation de la forme cristalline dans la préparation de médicaments antagonistes du récepteur de l'endothéline double et de médicaments pour le traitement de l'hypertension résistante.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211724353 | 2022-12-30 | ||
| CN202211724353.7 | 2022-12-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2024140425A1 true WO2024140425A1 (fr) | 2024-07-04 |
Family
ID=91716398
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CN2023/140806 WO2024140425A1 (fr) | 2022-12-30 | 2023-12-22 | Forme cristalline d'aprocitentan, son procédé de préparation et son utilisation |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2024140425A1 (fr) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015087228A1 (fr) * | 2013-12-10 | 2015-06-18 | Mylan Laboratories Ltd. | Procédé pour la préparation de cabazitaxel et de ses solvates |
| CN110325186A (zh) * | 2017-02-27 | 2019-10-11 | 爱杜西亚药品有限公司 | 用于治疗内皮素相关疾病的4-嘧啶磺酰胺衍生物与活性成分的组合 |
| CN112679441A (zh) * | 2019-10-18 | 2021-04-20 | 普济生物科技（台州）有限公司 | 阿普昔腾坦的晶型、制备方法及其用途 |
| WO2021237004A1 (fr) * | 2020-05-21 | 2021-11-25 | Teva Pharmaceuticals International Gmbh | Formes à l'état solide d'aprocitentan et leur procédé de préparation |
| CN114630668A (zh) * | 2019-11-07 | 2022-06-14 | 苏州科睿思制药有限公司 | 一种Aprocitentan晶型及其制备方法和用途 |
-
2023
- 2023-12-22 WO PCT/CN2023/140806 patent/WO2024140425A1/fr unknown
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015087228A1 (fr) * | 2013-12-10 | 2015-06-18 | Mylan Laboratories Ltd. | Procédé pour la préparation de cabazitaxel et de ses solvates |
| CN110325186A (zh) * | 2017-02-27 | 2019-10-11 | 爱杜西亚药品有限公司 | 用于治疗内皮素相关疾病的4-嘧啶磺酰胺衍生物与活性成分的组合 |
| CN110381948A (zh) * | 2017-02-27 | 2019-10-25 | 爱杜西亚药品有限公司 | 4-嘧啶磺酰胺衍生物的结晶形式 |
| CN112679441A (zh) * | 2019-10-18 | 2021-04-20 | 普济生物科技（台州）有限公司 | 阿普昔腾坦的晶型、制备方法及其用途 |
| CN114630668A (zh) * | 2019-11-07 | 2022-06-14 | 苏州科睿思制药有限公司 | 一种Aprocitentan晶型及其制备方法和用途 |
| WO2021237004A1 (fr) * | 2020-05-21 | 2021-11-25 | Teva Pharmaceuticals International Gmbh | Formes à l'état solide d'aprocitentan et leur procédé de préparation |
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