WO2019206336A1 - 一种三唑并嘧啶类化合物的晶型、盐型及其制备方法 - Google Patents

一种三唑并嘧啶类化合物的晶型、盐型及其制备方法 Download PDF

Info

Publication number
WO2019206336A1
WO2019206336A1 PCT/CN2019/084822 CN2019084822W WO2019206336A1 WO 2019206336 A1 WO2019206336 A1 WO 2019206336A1 CN 2019084822 W CN2019084822 W CN 2019084822W WO 2019206336 A1 WO2019206336 A1 WO 2019206336A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
reaction
crystal form
added
preparation
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.)
Ceased
Application number
PCT/CN2019/084822
Other languages
English (en)
French (fr)
Chinese (zh)
Inventor
陈新海
于衍新
陈鑫德
张丽
陈兆国
谢程
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.)
Medshine Discovery Inc
Original Assignee
Medshine Discovery Inc
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 Medshine Discovery Inc filed Critical Medshine Discovery Inc
Priority to DK19793622.2T priority Critical patent/DK3766884T3/da
Priority to JP2021508055A priority patent/JP7406691B2/ja
Priority to ES19793622T priority patent/ES2908424T3/es
Priority to US17/044,127 priority patent/US11649239B2/en
Priority to CN201980023228.3A priority patent/CN112105617B/zh
Priority to EP19793622.2A priority patent/EP3766884B1/en
Priority to PL19793622.2T priority patent/PL3766884T3/pl
Publication of WO2019206336A1 publication Critical patent/WO2019206336A1/zh
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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 invention relates to a crystal form of a [1,2,4]triazolo[1,5-c]pyrimidine compound and a process for the preparation thereof, and a process for preparing a drug for treating a disease associated with A 2A receptors Applications.
  • the adenosine A 2A receptor is widely distributed in human tissues. This receptor is highly expressed in tissues such as spleen, thymus, white blood cells, platelets, GABA-type neurons and olfactory bulbs. It is also expressed in the heart, lungs, blood vessels, and other parts of the brain. Adenosine A 2A receptors are commonly co-existing with other GPCRs and become heterodimers. For example, A 2A receptors can form heterodimers with dopamine D 2 , cannabinoid CB 1 , glutamic acid mGluR5 , etc. .
  • Adenosine A 2A receptors play an important role in regulating vasodilation, supporting the formation of new blood vessels, protecting body tissues from damage caused by inflammation, and adenosine A 2A receptors also affect the indirect pathways of the basal ganglia. The degree of activity.
  • the decomposition of cellular tissues and the environment of hypoxia cause a large amount of decomposition of ATP, which leads to extracellular adenosine enrichment, and the concentration is abnormally high, which is 10-20 times of the normal value.
  • Binding of high concentrations of adenosine to the A2A receptor activates the adenosine signaling pathway.
  • This signaling pathway is a mechanism that protects the body's tissues through immunosuppression in the event of damage to the body's tissues.
  • adenosine signaling pathway leads to long-term inhibition of the innate immune response, which produces immune tolerance, which in turn leads to the loss of controlled growth of adenosine and A2A receptors in white blood cells (such as lymphocytes).
  • white blood cells such as lymphocytes.
  • the combination of T lymphocytes, natural killer cells, dendritic cells, etc. inhibits the effector functions that these white blood cells should have in the immune system.
  • Binding of adenosine to the A2A receptor increases the expression of CD39, CD73 and CTLA4 (T cell checkpoints), resulting in more Treg cells with greater immunosuppression.
  • Blocking the A 2A receptor adenosine signaling pathway can reduce the inhibition of the immune system and enhance the immune function of T cells, and is therefore considered to be a promising negative feedback mechanism to inhibit tumor growth.
  • the present invention provides Form A of Compound 1, the X-ray powder diffraction pattern having characteristic diffraction peaks at the following 2 theta angles: 11.30 ⁇ 0.2 °, 16.90 ⁇ 0.2 °, 22.52 ⁇ 0.2 °.
  • the X crystal form of the above Compound 1 has an X-ray powder diffraction pattern having characteristic diffraction peaks at the following 2 ⁇ angles: 8.08 ⁇ 0.2°, 11.30 ⁇ 0.2°, 14.00 ⁇ 0.2°, 16.90 ⁇ 0.2°. , 18.30 ⁇ 0.2 °, 22.52 ⁇ 0.2 °, 23.15 ⁇ 0.2 °, 25.26 ⁇ 0.2 °.
  • the X-form analysis data of the A crystal form of the above Compound 1 is shown in Table 1.
  • the crystalline form of Form A of Compound 1 above has a differential scanning calorimetry curve having an onset of endothermic peak at 198.61 °C ⁇ 2 °C.
  • the A crystal form of the above compound 1 has a DSC pattern as shown in FIG.
  • the A crystal form of the above compound 1 has a thermogravimetric analysis curve having a weight loss of 0.4423% at 199.80 ° C ⁇ 3 ° C.
  • the T crystal of Form A of Compound 1 above is shown in Figure 3.
  • the present invention also provides the use of the above crystalline form A of Compound 1 for the preparation of a medicament for treating an A 2A receptor-related disorder.
  • Compound A has stable crystal form properties, low hygroscopicity, and good pharmaceutical prospects.
  • the crystal form A of the present invention has good stability and is easy to be used as a medicine; it has a significant inhibitory effect on the high concentration of adenosine and A 2A receptor binding activation adenosine signaling pathway in the tumor microenvironment, and passes through the CT-26 mouse.
  • the colorectal cancer model found that the A crystal form of Compound 1 had a significant inhibitory effect on tumors.
  • intermediate compounds of the present invention can be prepared by a variety of synthetic methods well known to those skilled in the art, including the specific embodiments listed below, combinations thereof with other chemical synthesis methods, and those skilled in the art.
  • Well-known equivalents, preferred embodiments include, but are not limited to, embodiments of the invention.
  • DMF dimethylformamide
  • Pd(PPh 3 ) 4 stands for tetrakis(triphenylphosphine)palladium
  • EtOH stands for ethanol
  • NaOH stands for sodium hydroxide
  • MTBE stands for methyl tert-butyl ether.
  • XRPD X-ray powder diffractometer
  • DSC Differential Scanning Calorimeter
  • Samples (0.5 to 1 mg) were placed in a DSC aluminum pan for testing at 25 ° C - 300 or 350 ° C, 10 ° C / min.
  • TGA Thermal Gravimetric Analyzer
  • a sample (2 to 5 mg) was placed in a TGA platinum pot for testing, and the sample was heated from room temperature to 300 degrees or weight loss by 20% at a heating rate of 10 ° C/min under 25 mL/min of N 2 .
  • Figure 1 is an XRPD spectrum of Cu-K ⁇ radiation of Form A of Compound 1;
  • Figure 2 is a DSC spectrum of Form A of Compound 1;
  • Figure 3 is a TGA spectrum of Form A of Compound 1.
  • step 1
  • the reaction solution was stirred at 70 ⁇ 5 ° C for 16 hours.
  • the reaction was monitored by HPLC and LCMS.
  • the reaction solution was cooled to room temperature, and the solvent was evaporated evaporated evaporated.
  • step 1
  • reaction solution was cooled to 20 ° C, then the reaction solution was closed and stirred, and the discharged reaction solution was slowly added to the mixed solution of water (16.8 L) and methanol (16.8 L) in the reaction vessel at a temperature of 15-25 ° C while maintaining the internal temperature. As the quenching proceeds, a yellow solid is formed, filtered, and the filter cake is collected and dried. Compound g (1480.72 g, yield 74.90%) was obtained as a yellow solid compound.
  • the reaction mixture was concentrated to dryness m vacuo. mjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj Stir well, the compound solution was filtered through silica gel (3Kg 200-300 mesh), and the filter cake was washed with 20 L of detergent (ethyl acetate: 15 L, n-heptane 5 L). The spin-dried solid was added to 1.0 L of ethyl acetate, heated to 75 ° C to dissolve completely, and the temperature was kept constant. n-Heptane (3.0 L) was slowly added dropwise to precipitate a white solid, which was then cooled to 20 ° C and filtered.
  • the A 2a stable cell line was constructed by Shanghai WuXi PharmaTech, host cell CHO.
  • Fluo-4 Direct kit (Invitrogen, Cat. No. F10471). After the fluorescent detection reagent (specifically binding to calcium ions and causing an increase in fluorescence signal) in the kit is incubated with the cells for a suitable period of time, the addition of the compound stimulates the cells to cause changes in intracellular calcium flux, thereby causing changes in the fluorescent signal, which can be reflected The strength of the agonistic or inhibitory activity of the compound.
  • test compound was dissolved in DMSO to prepare a 10 mM mother liquor.
  • the test compound was diluted to 0.2 mM with DMSO, and the reference compound CGS-15943 was diluted with DMSO to 0.015 mM.
  • 10 points of serial dilutions were performed with ECHO, 900 nl was transferred to the compound plate (Greiner-781280), and 30 ul of compound dilution buffer was added.
  • the final starting concentration of the test compound was 1 uM and CGS-15943 was 0.075 ⁇ M.
  • cryopreserved A 2A cells were resuspended in culture medium to 1 ⁇ 10 6 cells/ml after resuscitation, and 20 ⁇ l/well was seeded into 384-well polylysine-coated cell plates (Greiner-781946), 5% CO 2 , 37 Incubate overnight in a °C incubator.
  • the prepared cell plates from the previous day were taken out from the incubator, and 20 ⁇ l of 2X Fluo-4 DirectTM buffer was added to each well, 5% CO 2 , incubated in a 37 ° C incubator for 50 minutes, and allowed to stand at room temperature for 10 minutes.
  • Agonist NECA dilution NECA with a starting concentration of 0.15 mM was subjected to 10-point 3-fold serial dilution with Echo, followed by transfer of 900 nL to the corresponding compound plate; then 30 ⁇ l of compound dilution buffer was added to the corresponding compound plate. The final starting concentration was 750 nM.
  • the rodent pharmacological characteristics of the compound after intravenous injection and oral administration were tested by a standard protocol.
  • the candidate compound was formulated into a clear solution, and the mice were administered a single intravenous injection and a uniform suspension to the mice for single oral administration.
  • the vehicle was intravenously injected with 5% DMSO/95% 10% Cremophor EL, and the oral vehicle was 1% Tween 80, 9% PEG400, 90% water.
  • mice Female, 7 weeks, weighing approximately 16-20 grams, were maintained in an environment maintained in an SPF animal house and in a single ventilated cage (5 mice per cage). All cages, bedding and water are disinfected prior to use. All animals are free to access a standard certified commercial laboratory diet. A total of 80 were purchased from Shanghai Slack Laboratory Animals Co., Ltd. The anti-PD-1 antibody was purchased from BioXcell and cloned as RMP-14 under the accession number BP0146. 0.1 mL of 3 ⁇ 10 5 CT26 cells were subcutaneously inoculated into the right back of each mouse, and administered in random groups.
  • CT26 cells were subcutaneously inoculated on the right back BALB/c nude mice of each mouse for in vivo efficacy.
  • the test compound was orally administered daily for 22 days, and the anti-PD-1 antibody was administered once a week for three weeks.
  • the anti-tumor efficacy is determined by dividing the average tumor-increased volume of the treated animals by the average tumor-increased volume of the untreated animals. (BID means twice daily)
  • the single crystal of Compound A (50mg/Kg, BID) has antitumor effect; the combination of Compound A Form A (50mg/Kg, BID) and anti-PD-1 (5mg/Kg, QW) Significantly combined with anti-tumor effect.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Psychology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
PCT/CN2019/084822 2018-04-28 2019-04-28 一种三唑并嘧啶类化合物的晶型、盐型及其制备方法 Ceased WO2019206336A1 (zh)

Priority Applications (7)

Application Number Priority Date Filing Date Title
DK19793622.2T DK3766884T3 (da) 2018-04-28 2019-04-28 Krystalform og salttype af triazolopyrimidinforbindelse og fremstillingsfremgangsmåde dertil
JP2021508055A JP7406691B2 (ja) 2018-04-28 2019-04-28 トリアゾロピリミジン系化合物の結晶形、塩のタイプおよびその調製方法
ES19793622T ES2908424T3 (es) 2018-04-28 2019-04-28 Forma cristalina y tipo de sal del compuesto triazolopirimidina y método de preparación de la misma
US17/044,127 US11649239B2 (en) 2018-04-28 2019-04-28 Crystal form a of (5-amino-8-(2-methyl-6-(trifluoromethyl)pyridin-4-yl)-7-phenyl-[1,2,4]triazolo[1,5-c]pyrimidin-2-yl)methanol (compound 1)
CN201980023228.3A CN112105617B (zh) 2018-04-28 2019-04-28 一种三唑并嘧啶类化合物的晶型、盐型及其制备方法
EP19793622.2A EP3766884B1 (en) 2018-04-28 2019-04-28 Crystal form and salt type of triazolopyrimidine compound and preparation method therefor
PL19793622.2T PL3766884T3 (pl) 2018-04-28 2019-04-28 Postać krystaliczna i rodzaj soli związku triazolopirymidynowego oraz sposób jej wytwarzania

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201810399876 2018-04-28
CN201810399876.6 2018-04-28

Publications (1)

Publication Number Publication Date
WO2019206336A1 true WO2019206336A1 (zh) 2019-10-31

Family

ID=68294924

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2019/084822 Ceased WO2019206336A1 (zh) 2018-04-28 2019-04-28 一种三唑并嘧啶类化合物的晶型、盐型及其制备方法

Country Status (9)

Country Link
US (1) US11649239B2 (https=)
EP (1) EP3766884B1 (https=)
JP (1) JP7406691B2 (https=)
CN (1) CN112105617B (https=)
DK (1) DK3766884T3 (https=)
ES (1) ES2908424T3 (https=)
PL (1) PL3766884T3 (https=)
PT (1) PT3766884T (https=)
WO (1) WO2019206336A1 (https=)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020052631A1 (en) * 2018-09-12 2020-03-19 Dizal (Jiangsu) Pharmaceutical Co., Ltd. Triazolo-pyrimidine compounds and uses thereof
US20210094957A1 (en) * 2018-04-28 2021-04-01 Medshine Discovery Inc. Crystal form and salt type of triazolopyrimidine compound and preparation method thereof
CN114585625A (zh) * 2019-08-26 2022-06-03 因赛特公司 作为a2a/a2b抑制剂的三唑并嘧啶
EP3883576A4 (en) * 2018-11-20 2022-06-22 Merck Sharp & Dohme Corp. SUBSTITUTED AMINOTRIAZOLOPYRIMIDINES AND AMINO-TRIAZOLOPYRAZINE ADENOSINE RECEPTOR ANTAGONISTS, PHARMACEUTICAL COMPOSITIONS AND THEIR USE
WO2025108116A1 (zh) * 2023-11-22 2025-05-30 英诺湖医药(杭州)有限公司 用于治疗癌症的化合物

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998042711A1 (en) * 1997-03-24 1998-10-01 Kyowa Hakko Kogyo Co., Ltd. [1,2,4]TRIAZOLO[1,5-c]PYRIMIDINE DERIVATIVES
CN1596258A (zh) * 2001-11-30 2005-03-16 先灵公司 腺A2α受体拮抗剂
WO2018184590A1 (zh) * 2017-04-07 2018-10-11 南京明德新药研发股份有限公司 作为A 2A受体抑制剂的[1,2,4]三唑并[1,5-c]嘧啶衍生物

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004029056A1 (ja) 2002-09-24 2004-04-08 Kyowa Hakko Kogyo Co., Ltd. [１，２，４]トリアゾロ[１，５−ｃ]ピリミジン誘導体
PL3766884T3 (pl) * 2018-04-28 2022-07-18 Medshine Discovery Inc. Postać krystaliczna i rodzaj soli związku triazolopirymidynowego oraz sposób jej wytwarzania

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998042711A1 (en) * 1997-03-24 1998-10-01 Kyowa Hakko Kogyo Co., Ltd. [1,2,4]TRIAZOLO[1,5-c]PYRIMIDINE DERIVATIVES
CN1596258A (zh) * 2001-11-30 2005-03-16 先灵公司 腺A2α受体拮抗剂
WO2018184590A1 (zh) * 2017-04-07 2018-10-11 南京明德新药研发股份有限公司 作为A 2A受体抑制剂的[1,2,4]三唑并[1,5-c]嘧啶衍生物

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP3766884A4 *

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20210094957A1 (en) * 2018-04-28 2021-04-01 Medshine Discovery Inc. Crystal form and salt type of triazolopyrimidine compound and preparation method thereof
US11649239B2 (en) * 2018-04-28 2023-05-16 Medshine Discovery Inc. Crystal form a of (5-amino-8-(2-methyl-6-(trifluoromethyl)pyridin-4-yl)-7-phenyl-[1,2,4]triazolo[1,5-c]pyrimidin-2-yl)methanol (compound 1)
WO2020052631A1 (en) * 2018-09-12 2020-03-19 Dizal (Jiangsu) Pharmaceutical Co., Ltd. Triazolo-pyrimidine compounds and uses thereof
US10858365B2 (en) 2018-09-12 2020-12-08 Dizal (Jiangsu) Pharmaceutical Co., Ltd. Triazolo-pyrimidine compounds and uses thereof
JP2022500402A (ja) * 2018-09-12 2022-01-04 ディザル（ジァンスー）ファーマシューティカル・カンパニー・リミテッド トリアゾロ−ピリミジン化合物およびそれらの使用
US11629147B2 (en) 2018-09-12 2023-04-18 Dizal (Jiangsu) Pharmaceutical Co., Ltd. Triazolo-pyrimidine compounds and uses thereof
JP2024123079A (ja) * 2018-09-12 2024-09-10 ディザル（ジァンスー）ファーマシューティカル・カンパニー・リミテッド トリアゾロ－ピリミジン化合物およびそれらの使用
JP7572353B2 (ja) 2018-09-12 2024-10-23 ディザル（ジァンスー）ファーマシューティカル・カンパニー・リミテッド トリアゾロ－ピリミジン化合物およびそれらの使用
EP3883576A4 (en) * 2018-11-20 2022-06-22 Merck Sharp & Dohme Corp. SUBSTITUTED AMINOTRIAZOLOPYRIMIDINES AND AMINO-TRIAZOLOPYRAZINE ADENOSINE RECEPTOR ANTAGONISTS, PHARMACEUTICAL COMPOSITIONS AND THEIR USE
US12414952B2 (en) 2018-11-20 2025-09-16 Merck Sharp & Dohme Llc Substituted amino triazolopyrimidine and amino triazolopyrazine adenosine receptor antagonists, pharmaceutical compositions and their use
CN114585625A (zh) * 2019-08-26 2022-06-03 因赛特公司 作为a2a/a2b抑制剂的三唑并嘧啶
WO2025108116A1 (zh) * 2023-11-22 2025-05-30 英诺湖医药(杭州)有限公司 用于治疗癌症的化合物

Also Published As

Publication number Publication date
US11649239B2 (en) 2023-05-16
EP3766884B1 (en) 2022-02-09
ES2908424T3 (es) 2022-04-29
CN112105617B (zh) 2022-04-05
PT3766884T (pt) 2022-03-31
CN112105617A (zh) 2020-12-18
DK3766884T3 (da) 2022-03-28
EP3766884A4 (en) 2021-03-31
PL3766884T3 (pl) 2022-07-18
JP2021522335A (ja) 2021-08-30
JP7406691B2 (ja) 2023-12-28
US20210094957A1 (en) 2021-04-01
EP3766884A1 (en) 2021-01-20

Similar Documents

Publication Publication Date Title
WO2019206336A1 (zh) 一种三唑并嘧啶类化合物的晶型、盐型及其制备方法
JP5492565B2 (ja) Ｊａｎｕｓキナーゼ阻害剤としての置換複素環
CA3098336C (en) Crystal form of c-met inhibitor and salt form thereof and preparation method therefor
AU2016369835B2 (en) Pyrido[1,2-a]pyrimidone analog, crystal form thereof, intermediate thereof and preparation method therefor
EP3686199B9 (en) Fused ring derivative as a2a receptor inhibitor
CN110546145A (zh) 一种氮杂芳基衍生物、其制备方法和在药学上的应用
WO2020061996A1 (zh) 氘代azd9291化合物的新晶型及其用途
WO2021063276A1 (zh) 大环类衍生物及其制备方法和用途
JP2024543921A (ja) ＡＸＬキナーゼ阻害剤のモノ－ｐ－トルエンスルホン酸塩およびその結晶形
JP2022518605A (ja) ジアリールチオヒダントイン化合物結晶
CN117800953A (zh) 一种2-芳香胺基嘧啶类化合物及其制备方法与应用
HK40040486B (zh) 一种三唑并嘧啶类化合物的晶型、盐型及其制备方法
WO2023093859A1 (zh) Axl激酶抑制剂的盐、其制备方法和用途
HK40040486A (en) Crystal form and salt type of triazolopyrimidine compound and preparation method therefor
WO2022063229A1 (zh) 含芳氨基喹唑啉的化合物的盐及其制备方法和应用
JP7652987B2 (ja) ピリミジン誘導体およびその薬学的に許容される塩の多形体ならびに使用
CN116685588B (zh) 吡啶并吡咯类化合物的晶型、制备方法及其应用
JP7536036B2 (ja) Ａ２ａ受容体アンタゴニストの塩形態、結晶形態及びその製造方法
WO2023040876A1 (zh) 氮杂芳环类化合物及其药学上可接受的盐的多晶型物、药物组合物和应用

Legal Events

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

Ref document number: 19793622

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2021508055

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2019793622

Country of ref document: EP

Effective date: 20201014