[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

WO2017152858A1 - Forme cristalline de céritinib et procédé pour sa préparation - Google Patents

Forme cristalline de céritinib et procédé pour sa préparation Download PDF

Info

Publication number
WO2017152858A1
WO2017152858A1 PCT/CN2017/076179 CN2017076179W WO2017152858A1 WO 2017152858 A1 WO2017152858 A1 WO 2017152858A1 CN 2017076179 W CN2017076179 W CN 2017076179W WO 2017152858 A1 WO2017152858 A1 WO 2017152858A1
Authority
WO
WIPO (PCT)
Prior art keywords
crystal form
present
ray powder
powder diffraction
diffraction pattern
Prior art date
Application number
PCT/CN2017/076179
Other languages
English (en)
Chinese (zh)
Inventor
陈敏华
张炎锋
刁小娟
张晓宇
Original Assignee
苏州晶云药物科技有限公司
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 苏州晶云药物科技有限公司 filed Critical 苏州晶云药物科技有限公司
Publication of WO2017152858A1 publication Critical patent/WO2017152858A1/fr

Links

Images

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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the invention relates to the field of chemical medicine, in particular to crystal form II of chromatinib and a preparation method thereof.
  • Ceritinib is a new anticancer drug developed by Novartis. The drug was approved by the US Food and Drug Administration (FDA) on April 29, 2014. Coloritinib is an anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor that blocks the promotion of cancer cell protein for the treatment of crizotinib, but has a metastatic ALK positive non-small Patients with cell lung cancer (NSCLC).
  • ALK anaplastic lymphoma kinase
  • NSCLC metastatic ALK positive non-small Patients with cell lung cancer
  • rititinib is 5-chloro-N2-(2-isopropoxy-5-methyl-4-piperidin-4-yl-phenyl)-N4-[2-(propane-2-sulfonate) Acyl)-phenyl]-pyrimidine-2,4-diamine, the structural formula of which is as follows:
  • Drug polymorphism refers to the presence of two or more different crystalline forms of a drug. Polymorphism is widespread in medicine. Different crystal forms of the same drug have significant differences in solubility, melting point, density, stability, etc., which affect the stability, homogeneity, bioavailability, efficacy and safety of the drug to varying degrees.
  • WO2012082972A1 discloses two crystal forms A and Form B of chromatinib, but the patent does not relate to the hygroscopicity, stability and other physicochemical properties of the two crystal forms, and comprehensive system polycrystals are developed in drug development.
  • Type screening selecting the crystal form most suitable for development, is one of the important research contents that cannot be ignored. Based on this, it is necessary to further carry out the polymorphic screening of the compound of formula (1), and develop a crystal-free type with good stability, low wettability and suitable for industrial production, which provides more and better for the subsequent development of the drug. s Choice.
  • the invention provides a novel crystal form of the compound of the formula (1), and the crystal form provided by the invention has favorable properties such as good stability, low moisture absorption, process developability and easy handling, and the preparation method is simple and the cost is Low cost is of great value to the optimization and development of this drug in the future.
  • the X-ray powder diffraction pattern of Form II provided by the present invention has characteristic peaks at 2theta values of 5.03° ⁇ 0.20°, 10.05° ⁇ 0.20°, 14.40° ⁇ 0.20°, 18.11° ⁇ 0.20°, and 20.00° ⁇ 0.20°. .
  • the X-ray powder diffraction pattern of Form II provided by the present invention has characteristic peaks at 2theta values of 15.00 ° ⁇ 0.20 °, 21.85 ° ⁇ 0.20 °, 23.20 ° ⁇ 0.20 °, and 27.21 ° ⁇ 0.20 °.
  • the X-ray powder diffraction pattern of Form II provided by the present invention has a value of 2theta in 2theta There are characteristic peaks at 10.34° ⁇ 0.20° and 16.05° ⁇ 0.20°.
  • the X-ray powder diffraction pattern of Form II provided by the present invention comprises a value of 5.03° ⁇ 0.20°, 10.05° ⁇ 0.20°, 10.34° ⁇ 0.20°, 14.40° ⁇ 0.20°, 15.00° ⁇ 0.20° at 2theta. Characteristic peaks at 16.05° ⁇ 0.20°, 18.11° ⁇ 0.20°, 20.00° ⁇ 0.20°, 21.85° ⁇ 0.20°, 23.20° ⁇ 0.20°, and 27.21° ⁇ 0.20°.
  • the X-ray powder diffraction pattern of Form II provided by the present invention is substantially as shown in FIG.
  • thermogravimetric analysis when heated to 150 ° C, there is a mass loss gradient of about 1.0%, and the thermogravimetric analysis diagram is basically as shown in FIG. 3 .
  • Another object of the present invention is to provide a process for the preparation of Form II, which comprises adding a compound of the formula (I) and hydrochloric acid to one or more solvent systems selected from the group consisting of alcohols, ketones, nitriles
  • solvent systems selected from the group consisting of alcohols, ketones, nitriles
  • the cyclic ethers are stirred at room temperature and dried, and then redissolved in the solvent or a mixed solvent system thereof with water, followed by stirring with an aqueous solution of sodium hydroxide.
  • the solvent includes a single system of a saturated ketone, a lower alkyl alcohol, a hydrocarbyl nitrile and a cyclic ether solvent or a mixed system thereof.
  • the solvent is selected from the group consisting of acetone, acetonitrile or a mixture thereof.
  • the present invention also provides the crystalline form II of the compound of the formula (I) as a therapeutic anaplastic lymphoma Application in enzyme-mediated diseases of drugs.
  • the anaplastic lymphoma kinase-mediated diseases include anaplastic large cell lymphoma, non-Hodgkin's lymphoma, inflammatory myofibroblastic tumor, neuroblastoma, sarcoma, lung cancer, bronchial carcinoma, prostate Cancer, breast cancer, pancreatic cancer, gastrointestinal cancer, colon cancer, rectal cancer, colon cancer, colorectal adenoma, thyroid cancer, liver cancer, intrahepatic cholangiocarcinoma, hepatocellular carcinoma, adrenal cancer, glioma, glial Blastoma, endometrial cancer, melanoma, kidney cancer, renal pelvic cancer, small bowel cancer, bladder cancer, endometrial cancer, cervical cancer, vaginal cancer, ovarian cancer, multiple myeloma, esophageal cancer,
  • Another object of the invention is to provide a pharmaceutical composition or formulation comprising a therapeutically effective amount of Form II of a compound of formula (I) together with a pharmaceutically acceptable carrier, diluent or excipient.
  • a pharmaceutical composition or formulation is generally prepared by combining or contacting a therapeutically effective amount of Form II of a compound of Formula (I) with one or more pharmaceutical excipients, which are well known in the pharmaceutical arts. The way to prepare.
  • the present invention also provides the use of the crystalline form II of the compound of the formula (I) for the preparation of a pharmaceutical preparation for treating non-small cell lung cancer.
  • the crystal form provided by the present invention has good stability. It can well avoid drug storage and crystal transformation during development, thus avoiding changes in bioavailability and efficacy;
  • the crystal form provided by the invention has low wettability, meets the requirements of bioavailability and efficacy, does not require special drying conditions in the preparation process, simplifies the preparation process and post-treatment process of the drug, and is not easily affected by humidity, and the storage condition The requirements are not harsh, and it is convenient for long-term storage, which greatly reduces the cost of material storage and quality control;
  • the new crystal form provided by the invention can be directly obtained by desalting the hydrochloride salt, can be incorporated into the synthesis process, the preparation method is simple and reproducible, the process is controllable, the solvent is safe and the routine is easy to obtain, the cost is low, and the method is suitable for direct industrialization. produce.
  • phrases "effective therapeutic amount” or “therapeutically effective amount” as used herein refers to a biological response or drug response that is caused by a researcher, veterinarian, doctor or other clinician in a tissue, system, animal, individual or human. The amount of active compound or agent.
  • treating refers to one or more of the following: (1) preventing a disease; for example, a disease or condition that may be predisposed to a disease, disorder, or disorder, but has not yet suffered or manifested the disease. Preventing the disease, condition or disorder in the individual; (2) inhibiting the disease; for example, inhibiting the disease, condition or disorder in an individual who is suffering from or showing a disease or condition of the disease, condition or disorder; and (3) improving the disease A disease; for example, ameliorating the disease, condition or disorder (i.e., reversing the disease and/or condition) in an individual suffering from or showing a disease or condition of the disease, condition or disorder, e.g., reducing the severity of the disease.
  • a disease for example, a disease or condition that may be predisposed to a disease, disorder, or disorder, but has not yet suffered or manifested the disease.
  • Preventing the disease, condition or disorder in the individual (2) inhibiting the disease; for example, inhibiting the disease, condition or disorder in an individual who is suffering from or
  • polymorphic compound refers to different crystalline forms of the same compound and includes, but is not limited to, other solid molecular forms comprising hydrates and solvates of the same compound.
  • the phenomenon that a plurality of crystal forms are formed by the same drug molecule is called a drug polymorph, and a drug polymorph is a phenomenon commonly found in solid drugs.
  • X-ray powder diffraction pattern refers to an experimentally observed diffraction pattern or parameters derived therefrom.
  • the X-ray powder diffraction pattern was characterized by peak position and peak intensity.
  • the lower alkyl alcohol used in the present invention may be a C1-C3 alkyl alcohol.
  • the compound of the formula (I) and/or its salt as a raw material means a solid (crystalline or amorphous), semi-solid, wax or oil form.
  • the compound of the formula (I) and/or its salt as a raw material is in the form of a solid powder.
  • Figure 1 is an XRPD pattern of Form II of the present invention
  • Figure 2 is a DSC chart of Form II of the present invention.
  • Figure 3 is a TGA diagram of Form II of the present invention.
  • Figure 4 is a 1 H-NMR chart of Form II of the present invention.
  • Figure 5 is a DVS diagram of Form II of the present invention.
  • Figure 6 is an XRPD diagram of the DVS before and after the DVS hygroscopicity measurement of Form II of the present invention
  • Figure 7 is a comparison chart of XRPD of the Form II of the present invention placed at 25 ° C / 60% relative humidity for 30 days (the upper image shows the XRPD pattern before placement, and the lower image shows the XRPD pattern after placement);
  • Figure 8 is a comparison chart of XRPD of the Form II of the present invention placed at 40 ° C / 75% relative humidity for 30 days (the upper image shows the XRPD pattern before placement, and the lower figure shows the XRPD pattern after placement);
  • test methods described are generally carried out under conventional conditions or conditions recommended by the manufacturer; the raw materials of the colorizone are commercially available.
  • PSD particle size distribution
  • D10 indicates the particle size distribution (volume distribution) accounts for 10% of the particle size
  • D50 indicates the particle diameter corresponding to the particle size distribution (volume distribution), which is also called the median diameter.
  • D90 indicates the particle size distribution (volume distribution) accounts for 90% of the particle size
  • the X-ray powder diffraction pattern of the present invention was collected on a Panalytical Empyrean X-ray powder diffractometer.
  • the method parameters of the X-ray powder diffraction described in the present invention are as follows:
  • Scan range: from 3.0 to 40.0 degrees
  • the differential scanning calorimetry (DSC) map of the present invention was acquired on a TA Q2000.
  • the method parameters of the differential scanning calorimetry (DSC) described in the present invention are as follows:
  • thermogravimetric analysis (TGA) map of the present invention was taken on a TA Q5000.
  • the method parameters of the thermogravimetric analysis (TGA) described in the present invention are as follows:
  • the dynamic moisture adsorption (DVS) pattern of the present invention was collected on an Intrinsic dynamic moisture adsorber manufactured by SMS Corporation (Surface Measurement Systems Ltd.).
  • the method parameters of the dynamic moisture adsorber are as follows:
  • Relative humidity range 0%RH-95%RH
  • the X-ray powder diffraction data of Form II obtained in this example is shown in Table 1.
  • the XRPD pattern is shown in Fig. 1.
  • the DSC chart is shown in Fig. 2.
  • the TGA chart is shown in Fig. 3.
  • the 1 H-NMR chart is shown in Fig. 4.
  • the 1 H-NMR data is as follows: 1H-NMR (400 MHz, DMSO-d6) ⁇ 8.
  • the method for preparing the hydrochloride salt of the compound of the formula (1) is the same as in the first embodiment. 19.8 mg of the compound of the formula (1) hydrochloride was dissolved in 0.04 mL of acetonitrile and 0.4 mL of water, and 0.035 mL of a 1 mol/L sodium hydroxide aqueous solution was added thereto, and the mixture was stirred at 5 ° C for 24 hours, and the lower layer solid was centrifuged, and dried overnight at room temperature. The resulting solid was Form II.
  • the wetting weight gain is not less than 15%
  • Humidity Wet weight gain is less than 15% but not less than 2%
  • wetting gain is less than 2% but not less than 0.2%
  • wetting gain is less than 0.2%
  • the crystal form II prepared by the present invention was separately placed at 25 ° C / 60% relative humidity and 40 ° C / 75% relative humidity for 30 days and 90 days, respectively, and its XRPD was measured.
  • the experimental results are shown in Table 4.
  • the XRPD of the Form II of the present invention before and after being placed under the above two conditions for 30 days is shown in Figs. 7 and 8, respectively.
  • the crystalline form II of the compound of the formula (I) prepared in Example 1 and the amorphous form A of the patent WO2012082972A1 were respectively prepared into a saturated solution with high purity water, and the saturation was determined by high performance liquid chromatography after 1 hour, 4 hours and 24 hours. The amount of sample in the solution.
  • the experimental results are shown in Table 5.
  • the crystalline form II of the present invention has a higher solubility than the amorphous form A of the patent WO2012082972A1 after being placed in high-purity water for 1 hour, 4 hours and 24 hours.
  • the higher dissolution rate and solubility in water help to enhance the absorption and utilization of drugs in the organism and improve the efficacy.
  • Average particle size ( ⁇ m) Form II Crystal form A D10 5.47 3.68 D50 41.72 18.68 D90 197.1 102.5
  • the crystal form II of the present invention has a larger particle size and better fluidity than the crystal-free type A in the patent WO2012082972A1, and has excellent properties such as easy filtration in process production.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne la forme cristalline II du 5-chloro-N2-(2-isopropoxy-5-méthyl-4-pipéridin-4-yl-phényl)-N4-[2-(propane-2-sulfonyl) -phényl]-pyrimidine-2,4-diamine (céritinib) et la présente invention concerne également le procédé de préparation de la forme cristalline, la composition pharmaceutique comprenant la forme cristalline et le procédé de traitement de maladies avec la forme cristalline et la composition pharmaceutique. La forme cristalline fournie par la présente invention présente des performances avantageuses, telles qu'une bonne stabilité, une hygroscopicité relativement faible, une capacité d'utilisation et une forte aptitude au traitement du processus et le procédé de préparation est simple, est bon marché et a une valeur importante pour l'optimisation et la mise au point du médicament dans le futur.
PCT/CN2017/076179 2016-03-11 2017-03-09 Forme cristalline de céritinib et procédé pour sa préparation WO2017152858A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201610140386 2016-03-11
CN201610140386.5 2016-03-11

Publications (1)

Publication Number Publication Date
WO2017152858A1 true WO2017152858A1 (fr) 2017-09-14

Family

ID=59790059

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2017/076179 WO2017152858A1 (fr) 2016-03-11 2017-03-09 Forme cristalline de céritinib et procédé pour sa préparation

Country Status (1)

Country Link
WO (1) WO2017152858A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112645929A (zh) * 2019-10-11 2021-04-13 苏州泽璟生物制药股份有限公司 异丙磺酰基苯基嘧啶类化合物或其盐的多晶型物

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101616895A (zh) * 2006-12-08 2009-12-30 Irm责任有限公司 作为蛋白激酶抑制剂的化合物和组合物
CN103282359A (zh) * 2010-12-17 2013-09-04 诺华股份有限公司 5-氯-n2-(2-异丙氧基-5-甲基-4-哌啶-4-基-苯基)-n4-[2-(丙烷-2-磺酰基)-苯基]-嘧啶-2,4-二胺的结晶形式
CN103992262A (zh) * 2014-06-12 2014-08-20 苏州明锐医药科技有限公司 塞瑞替尼及其中间体的制备方法
CN104803908A (zh) * 2015-03-26 2015-07-29 药源药物化学（上海）有限公司 2-异丙氧基-5-甲基-4-(4-哌啶基)苯胺二盐酸盐的水合物、其制备方法及用途
CN105061397A (zh) * 2015-08-07 2015-11-18 武汉英普瑞医药科技有限公司 一种色瑞替尼的c型晶型及其制备方法与应用
CN105294650A (zh) * 2014-08-01 2016-02-03 江苏奥赛康药业股份有限公司 一种Ceritinib化合物及其药物组合物
CN105601614A (zh) * 2014-11-21 2016-05-25 奥浦顿（上海）医药科技有限公司 一种色瑞替尼晶型及其制备方法
WO2016098070A1 (fr) * 2014-12-19 2016-06-23 Novartis Ag Forme cristalline de la 5-chloro-n2-(2-isopropoxy-5-méthyl-4-pipéridin-4-yl-phényl)-n4-[2-(propane-2-sulfonyl)-phényl]-pyrimidine-2,4-diamine

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101616895A (zh) * 2006-12-08 2009-12-30 Irm责任有限公司 作为蛋白激酶抑制剂的化合物和组合物
CN103282359A (zh) * 2010-12-17 2013-09-04 诺华股份有限公司 5-氯-n2-(2-异丙氧基-5-甲基-4-哌啶-4-基-苯基)-n4-[2-(丙烷-2-磺酰基)-苯基]-嘧啶-2,4-二胺的结晶形式
CN103992262A (zh) * 2014-06-12 2014-08-20 苏州明锐医药科技有限公司 塞瑞替尼及其中间体的制备方法
CN105294650A (zh) * 2014-08-01 2016-02-03 江苏奥赛康药业股份有限公司 一种Ceritinib化合物及其药物组合物
CN105601614A (zh) * 2014-11-21 2016-05-25 奥浦顿（上海）医药科技有限公司 一种色瑞替尼晶型及其制备方法
WO2016098070A1 (fr) * 2014-12-19 2016-06-23 Novartis Ag Forme cristalline de la 5-chloro-n2-(2-isopropoxy-5-méthyl-4-pipéridin-4-yl-phényl)-n4-[2-(propane-2-sulfonyl)-phényl]-pyrimidine-2,4-diamine
CN104803908A (zh) * 2015-03-26 2015-07-29 药源药物化学（上海）有限公司 2-异丙氧基-5-甲基-4-(4-哌啶基)苯胺二盐酸盐的水合物、其制备方法及用途
CN105061397A (zh) * 2015-08-07 2015-11-18 武汉英普瑞医药科技有限公司 一种色瑞替尼的c型晶型及其制备方法与应用

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112645929A (zh) * 2019-10-11 2021-04-13 苏州泽璟生物制药股份有限公司 异丙磺酰基苯基嘧啶类化合物或其盐的多晶型物

Similar Documents

Publication Publication Date Title
RU2497820C2 (ru) Кристаллические формы и две сольватные формы солей молочной кислоты 4-амино-5-фтор-3-[5-(4-метилпиперазин-1-ил)-1 - н-бензимидазол-2-ил]хинолин-2(1н)она
WO2016184436A1 (fr) Nouvelle forme cristalline de sel de méthanesulfonate de lenvatinib et son procédé de préparation
WO2016124137A1 (fr) Phosphate de l'inhibiteur du récepteur du facteur de croissance épidermique, forme cristalline du phosphate et procédé de préparation
US10947233B2 (en) Crystals of azabicyclic compound
WO2018196687A1 (fr) Nouvelle forme cristalline de méthanesulfonate de lenvatinib et procédé de préparation correspondant
WO2011095059A1 (fr) Polymorphes du dasatinib, leurs procédés de préparation et leurs compositions pharmaceutiques
WO2016165650A1 (fr) Cocristal d'olaparib et d'urée et son procédé de préparation
JP6971390B2 (ja) 重水素化ａｚｄ９２９１の結晶形、製造方法および使用
TWI669304B (zh) Ｃ－Ｍｅｔ抑制劑結晶型游離鹼或其結晶型酸式鹽及其製備方法和應用
JP6830888B2 (ja) Ｊａｋ阻害剤の硫酸水素塩の結晶形およびその製造方法
TW201236684A (en) Pharmaceutically acceptable salts of (E)-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]-3-[(2R)-1-methylpyrrolidin-2-yl]prop-2-enamide, preparation process and pharmaceutical use there of
WO2017152707A1 (fr) Formes cristallines de sel de mésylate de dérivé de pyridinyl-aminopyrimidine, procédés de préparation et applications associés
WO2016090257A1 (fr) Sels et forme cristallines de 6-acétyl-8-cyclopentyl-5-méthyl-2((5-(pipérazin-1-yl) pyridin-2-yl)amino)pyrido [2,3-d] pyrimidin -7 (8h)-one (palbociclib)
JP2018516946A (ja) ヒストン脱アセチル化阻害剤の結晶形態
WO2018006870A1 (fr) Forme cristalline de galunisertib, son procédé de préparation et son utilisation
US9453011B2 (en) Crystal form of dabrafenib mesylate and preparation method thereof
WO2017152858A1 (fr) Forme cristalline de céritinib et procédé pour sa préparation
WO2017020869A1 (fr) Forme cristalline b de 2-[(2r)-2-méthyl-2-pyrrolidinyl]-1h-benzimidazole-7-carboxamide, procédé de préparation et utilisation
WO2017028802A1 (fr) Forme cristalline de dichlorhydrate de 5-[2,6-di(4-morpholinyl)-4-pyrimidinyl]-4-(trifluorométhyl)-2-pyridinamine et son procédé de préparation
TWI535724B (zh) 埃克替尼磷酸鹽的新晶型及其用途
US20220162185A1 (en) Crystalline and amorphous forms of n-(5-((4-ethylpiperazin-1-yl)methyl)pyridine-2-yl)-5-fluoro-4-(3-isopropyl-2-methyl-2h-indazol-5-yl)pyrimidin-2-amine and its salts, and preparation methods and therapeutic uses thereof
CN106029664A (zh) 一种酪氨酸激酶抑制剂的苹果酸盐的结晶形式及其制备方法
CN104788435A (zh) 一种蛋白酪氨酸激酶抑制剂的二苯磺酸盐的i型结晶
WO2018099451A1 (fr) Forme cristalline d'un composé
WO2017076358A1 (fr) Nouvelle forme cristalline de sel de composé imidazolyl-biphényl et son procédé de préparation

Legal Events

Date Code Title Description
NENP Non-entry into the national phase

Ref country code: DE

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 17762544

Country of ref document: EP

Kind code of ref document: A1

122 Ep: pct application non-entry in european phase

Ref document number: 17762544

Country of ref document: EP

Kind code of ref document: A1