WO2024045633A1 - 一种Sotorasib新晶型及其制备方法与应用 - Google Patents
一种Sotorasib新晶型及其制备方法与应用 Download PDFInfo
- Publication number
- WO2024045633A1 WO2024045633A1 PCT/CN2023/088845 CN2023088845W WO2024045633A1 WO 2024045633 A1 WO2024045633 A1 WO 2024045633A1 CN 2023088845 W CN2023088845 W CN 2023088845W WO 2024045633 A1 WO2024045633 A1 WO 2024045633A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- sotorasib
- crystal form
- new crystal
- acetic acid
- solid
- Prior art date
Links
- NXQKSXLFSAEQCZ-SFHVURJKSA-N sotorasib Chemical compound FC1=CC2=C(N(C(N=C2N2[C@H](CN(CC2)C(C=C)=O)C)=O)C=2C(=NC=CC=2C)C(C)C)N=C1C1=C(C=CC=C1O)F NXQKSXLFSAEQCZ-SFHVURJKSA-N 0.000 title claims abstract description 65
- 229940073531 sotorasib Drugs 0.000 title claims abstract description 64
- 239000013078 crystal Substances 0.000 title claims abstract description 42
- 238000002360 preparation method Methods 0.000 title abstract description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 98
- 239000012453 solvate Substances 0.000 claims abstract description 15
- 239000007787 solid Substances 0.000 claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 238000002425 crystallisation Methods 0.000 claims description 3
- 230000008025 crystallization Effects 0.000 claims description 3
- 238000004090 dissolution Methods 0.000 claims description 3
- 239000013557 residual solvent Substances 0.000 claims description 3
- 230000004580 weight loss Effects 0.000 claims description 3
- 206010064571 Gene mutation Diseases 0.000 claims description 2
- 238000001514 detection method Methods 0.000 claims description 2
- 238000000113 differential scanning calorimetry Methods 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 102200006538 rs121913530 Human genes 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 238000002411 thermogravimetry Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 abstract description 5
- 238000009776 industrial production Methods 0.000 abstract description 3
- 238000012512 characterization method Methods 0.000 description 7
- 229910004373 HOAc Inorganic materials 0.000 description 5
- 239000012065 filter cake Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000000967 suction filtration Methods 0.000 description 5
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 238000001144 powder X-ray diffraction data Methods 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 229910002483 Cu Ka Inorganic materials 0.000 description 1
- 159000000021 acetate salts Chemical class 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- RDYMFSUJUZBWLH-UHFFFAOYSA-N endosulfan Chemical compound C12COS(=O)OCC2C2(Cl)C(Cl)=C(Cl)C1(Cl)C2(Cl)Cl RDYMFSUJUZBWLH-UHFFFAOYSA-N 0.000 description 1
- HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229940125459 lumakras Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940127554 medical product Drugs 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical group CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000011973 solid acid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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 invention belongs to the field of medical technology, specifically a new crystal form of Sotorasib and its preparation method and application.
- Sotorasib is a drug (trade name: Lumakras) developed by Amgen for the treatment of metastatic non-small cell lung cancer. It was approved by the FDA in May 2021. On January 29, 2021, the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China granted sotorasib Breakthrough Therapy Designation.
- CDE Center for Drug Evaluation
- NMPA National Medical Products Administration
- Sotorasib is a poorly water-soluble substance and its dosage form is generally oral tablets, so the study of its crystal form is of great significance.
- the originator Amgen's patent WO2020236947 discloses sotorasib amorphous, anhydrous Form I, II, III, hydrate Form I, II and various solvates;
- WO2020236948 discloses sotorasib hydrochloride Form I-VII, phosphate Form I, Methanesulfonate Form I.
- Teva's patent WO2021236920 discloses sotorasib anhydrous form IV, hydrate form H2, H3, H4, and succinate.
- the present invention provides a new crystal form of Sotorasib, which is different from various crystal forms disclosed in the prior art.
- the structure is confirmed by PXRD, NMR, DSC, TGA and GC characterization.
- This crystal form has stable chemical properties, is easy to store, and is suitable for making various preparations.
- the preparation process of the new crystal form is simple and easy, suitable for industrial production, and provides a new option for the development of Sotorasib formulations.
- the new crystal form of Sotorasib provided by the present invention is the acetic acid solvate of Sotorasib.
- the crystal forms of Sotorasib disclosed in the prior art include anhydrate, hydrate, and solvate, such as ethanolate, ethyl acetate, etc., while acetic acid is a weak acid and is generally considered to form an acetate salt with Sotorasib, such as now There are technologies that have been disclosed Sotorasib forms a salt with succinic acid.
- the inventor obtained the acetic acid solvate of Sotorasib by controlling the ratio, dissolution and crystallization conditions of acetic acid and Sotorasib. After relevant characterization, it was confirmed that it is a new crystal form of Sotorasib, which is different from the existing disclosed crystal form of Sotorasib. The models are all different.
- solvate is interpreted according to its accepted meaning, that is, it relates to solvent molecules incorporated into the crystal structure of Sotorasib.
- the X-ray powder diffraction of the above-mentioned new crystal form of Sotorasib at the diffraction angle 2 ⁇ is: 7.0° ⁇ 0.2°, 9.1° ⁇ 0.2°, 9.6° ⁇ 0.2°, 10.6° ⁇ 0.2°, 13.7° ⁇ 0.2°, 14.2 ° ⁇ 0.2°, 14.5° ⁇ 0.2°, 16.6° ⁇ 0.2°, 17.0° ⁇ 0.2°, 17.6° ⁇ 0.2°, 18.6° ⁇ 0.2°, 19.1° ⁇ 0.2°, 19.5° ⁇ 0.2°, 21.0° ⁇ 0.2°, 21.4° ⁇ 0.2°, 22.4° ⁇ 0.2°, 22.8° ⁇ 0.2°, 23.1° ⁇ 0.2°, 24.3° ⁇ 0.2°, 24.7° ⁇ 0.2°, 25.3° ⁇ 0.2°, 25.5° ⁇ 0.2° and one or more characteristic peaks at 28.5° ⁇ 0.2°.
- differential scanning calorimetry heat map of the new crystalline form of Sotorasib of the present invention includes an endotherm starting at 172-175°C.
- thermogravimetric analysis heat map of the new crystal form of Sotorasib of the present invention includes a weight loss of 9.7-10.2% when heated from 35-40°C to 195-200°C.
- gas phase detection residual solvent of the new crystal form of Sotorasib of the present invention contains 88,000 to 95,000 ppm acetic acid.
- the present invention also provides a preparation method of a new crystal form of Sotorasib, which includes the following steps:
- the mass-to-volume ratio of Sotorasib solid and acetic acid in step 1) is 1:1 to 1:3g/mL.
- step 1) and step 2) are both 30-50°C.
- the present invention also provides the use of the above-mentioned new crystal form of Sotorasib for preparing drugs for treating related diseases caused by KRAS G12C gene mutations.
- the present invention also provides a pharmaceutical composition, which contains an effective therapeutic amount of the above-mentioned new crystal form of Sotorasib and pharmaceutically acceptable excipients.
- the present invention has the following advantages:
- the invention provides a new crystal form of Sotorasib, which has stable chemical properties, is easy to preserve, and is suitable for being made into various preparations. Moreover, the preparation process is simple and easy, and is suitable for industrial production.
- Figure 1 is a 1 H NMR spectrum of the new crystal form of Sotorasib obtained in the present invention.
- Figure 2 is a 13 C NMR spectrum of the new crystal form of Sotorasib obtained in the present invention.
- Figure 3 is a PXRD pattern of the new crystal form of Sotorasib obtained in the present invention.
- Figure 4 is a DSC spectrum of the new crystal form of Sotorasib obtained in the present invention.
- Figure 5 is a TGA spectrum of the new crystal form of Sotorasib obtained in the present invention.
- Figure 6 is a PXRD pattern of the new crystal form of Sotorasib obtained in Comparative Example 1 of the present invention.
- the PXRD pattern was collected on a Bruker D2 Phaser X-ray diffractometer.
- the specific parameters are as follows:
- Anti-air scattering slit (knife edge): 1.0mm
- the PXRD pattern is shown in Figure 3, and the PXRD peak table is shown in Table 1.
- TGA contained a weight loss of approximately 10.1% when heated from approximately 39°C to approximately 197°C, see Figure 5. (1.0mol HOAc).
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (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
提供了Sotorasib的新晶型及其制备方法与应用,该晶型为Sotorasib的乙酸溶剂化物,化学性质稳定,容易保存,适合制成各种制剂。并且制备过程简单易行,适合工业化生产,为Sotorasib制剂开发提供了新的选择。
Description
本发明属于医药技术领域,具体说是Sotorasib的新晶型及其制备方法与应用。
Sotorasib,化学名为(1R)-6-氟-7-(2-氟-6-羟基苯基)-1-[4-甲基-2-(1-甲基乙基)-3-吡啶基]-4-[(2S)-2-甲基-4-(1-氧代-2-丙烯-1-基)-1-哌嗪基]-吡啶并[2,3-D]嘧啶-2(1H)-酮,其结构式如下:
Sotorasib是由安进公司开发的用于治疗转移性非小细胞肺癌的药物(制剂商品名:Lumakras),于2021年5月获FDA批准上市。2021年1月29日,中国国家药品监督管理局(NMPA)的药品审评中心(CDE)授予了sotorasib突破性疗法认定。
Sotorasib属水难溶性物质,剂型一般为口服片剂,因此对其晶型的研究具有十分重要的意义。原研安进公司的专利WO2020236947公开了sotorasib无定形,无水物Form I、II、III,水合物Form I、II以及多种溶剂合物;WO2020236948公开了sotorasib盐酸盐Form I-VII,磷酸盐Form I,甲磺酸盐Form I。另外,Teva的专利WO2021236920公开了sotorasib无水物Form IV,水合物Form H2、H3、H4,以及琥珀酸盐。
发明内容
本发明提供一种Sotorasib的新晶型,均不同于现有技术中公开的各种晶型,结构经PXRD、NMR、DSC、TGA和GC表征确认。该晶型化学性质稳定,容易保存,适合制成各种制剂。相比现有晶型,新晶型的制备过程简单易行,适合工业化生产,为Sotorasib制剂开发提供了新的选择。
本发明提供的Sotorasib的新晶型,为Sotorasib的乙酸溶剂化物。
现有技术中公开的Sotorasib晶型,有无水物、水合物,也有溶剂合物,如乙醇化物、乙酸乙酯化物等,而乙酸为弱酸,通常认为会与Sotorasib形成乙酸盐,例如现有技术中公开了
Sotorasib与琥珀酸成盐。
在本发明中,发明人通过控制乙酸与Sotorasib的配比、溶清和析晶条件,获得Sotorasib的乙酸溶剂化物,经过相关表征确认,为Sotorasib的一种新晶型,与现有公开的Sotorasib晶型均不相同。
在本发明中,术语“溶剂化物”依据其公认的含义进行解释,即它涉及掺入Sotorasib晶体结构中的溶剂分子。
上述的Sotorasib的新晶型,其X射线粉末衍射在衍射角2θ为:7.0°±0.2°、9.1°±0.2°、9.6°±0.2°、10.6°±0.2°、13.7°±0.2°、14.2°±0.2°、14.5°±0.2°、16.6°±0.2°、17.0°±0.2°、17.6°±0.2°、18.6°±0.2°、19.1°±0.2°、19.5°±0.2°、21.0°±0.2°、21.4°±0.2°、22.4°±0.2°、22.8°±0.2°、23.1°±0.2°、24.3°±0.2°、24.7°±0.2°、25.3°±0.2°、25.5°±0.2°和28.5°±0.2°的一处或多处特征峰处。
进一步地,本发明Sotorasib的新晶型的差示扫描量热法热图包含在172~175℃起始的吸热。
进一步地,本发明Sotorasib的新晶型的热重分析热图包含从35~40℃加热至195~200℃时9.7~10.2%的重量损失。
进一步地,本发明Sotorasib的新晶型的气相检测残留溶剂,含有88000~95000ppm的乙酸。
本发明还提供Sotorasib的新晶型的制备方法,包括以下步骤:
1)将Sotorasib固体用乙酸溶清并过滤;
2)将Sotorasib的乙酸溶液滴加到水和乙酸的溶剂化物中;
3)将析出的固体抽滤并烘干。
进一步地,步骤1)中的Sotorasib固体与乙酸的质量体积比为1:1~1:3g/mL。
进一步地,步骤1)和步骤2)中的Sotorasib固体溶清温度和析晶温度均为30~50℃。
本发明还提供上述Sotorasib的新晶型的用途,用于制备治疗KRAS G12C基因突变引起的相关疾病的药物。
本发明还提供一种药物组合物,包含有效治疗量的上述Sotorasib新晶型及药学上可接受的赋形剂。
通过实施上述技术方案,本发明具有如下的优点:
本发明提供一种Sotorasib的新晶型,化学性质稳定,容易保存,适合制成各种制剂。而且制备过程简单易行,适合工业化生产。
附图1为本发明所得Sotorasib的新晶型的1H NMR图谱;
附图2为本发明所得Sotorasib的新晶型的13C NMR图谱;
附图3为本发明所得Sotorasib的新晶型的PXRD图谱;
附图4为本发明所得Sotorasib的新晶型的DSC图谱;
附图5为本发明所得Sotorasib的新晶型的TGA图谱;
附图6为本发明对比例1所得Sotorasib的新晶型的PXRD图谱。
结合以下实施例对本发明做详细说明,所述实施例详细描述本发明的晶型的制备和使用方法。对本领域技术人员显而易见的是,对于材料和方法两者的许多改变可在不脱离本发明范围的情况下实施。
实施例1:
Sotorasib乙酸溶剂化物的制备
向5g Sotorasib固体加入10mL乙酸,升温至35℃溶清,过滤。将7mL乙酸和30mL水混合均匀,升温至35℃,再慢慢滴入上述所得滤液,30min滴完。滴完35℃保温搅拌1.0h,有较多固体析出。抽滤,滤饼用少量水洗涤,40℃真空干燥,得白色粉末4.8g,即乙酸溶剂化物。
1H NMR图谱见附图1,13C NMR图谱见附图2。产物核磁表征结果如下:
1H NMR(400MHz,DMSO-d6),δ11.96(1H,s),10.21(1H,s),8.39(1H,d),8.29(1H,t),7.27(1H,q),6.90(1H,d),6.91~6.82(1H,m),6.74~6.66(2H,m),6.23~6.18(1H,m),5.78~5.75(1H,dd),4.90(1H,s),4.39~4.31(2H,m),4.16~4.01(1H,m),3.70~3.49(2H,m),3.28~3.12(1H,m),2.71(1H,t),1.91(2.5H,s,HOAc),1.90(3H,s),1.34(3H,s),1.07(3H,s),0.93(3H,s)。
13C NMR(100MHz,DMSO-d6),δ172.5,165.5,163.9,163.0,161.9,159.4,157.4,157.3,154.3,153.7,151.2,150.0,148.8,145.8,144.9,144.7,132.1,132.0,131.3,128.4,128.2,123.7,123.4,123.2,112.2,110.3,110.2,110.1,110.1,106.3,106.1,105.8,105.8,51.9,51.5,49.4,45.9,45.1,44.1,42.1,40.6,40.4,39.5,39.3,30.3,22.4,22.1,21.5,17.5,16.0,15.3。
NMR 0.8mol HOAc。
PXRD图是在Bruker D2 Phaser型X-射线衍射仪上采集,具体参数如下:
光源:Cu Ka(1.5406A)
管压:30KV
管流:10mA
发散狭缝:1.0mm
接收狭缝:3.0mm
防空气散射狭缝(刀口):1.0mm
2θ扫描范围:2°~4°
扫描速率步时:0.2s/step
步长:0.02°
PXRD图谱见附图3,PXRD峰表见表1。
表1 PXRD峰值表
DSC吸热起始在约174℃,见附图4。TGA包含当从约39℃加热至约197℃时约10.1%的重量损失,见附图5。(1.0mol HOAc)。
通过GC测定残留溶剂:HOAc 93358ppm(1.0mol HOAc)。
实施例2:
Sotorasib乙酸溶剂化物的制备
向5g Sotorasib固体加入15mL乙酸,升温至50℃溶清,过滤。将8mL乙酸和40mL水混合均匀,升温至50℃,再慢慢滴入上述所得滤液,30min滴完。滴完50℃保温搅拌1.0h,有较多固体析出。抽滤,滤饼用少量水洗涤,40℃真空干燥,得白色粉末3.9g,即乙酸溶剂化物。
产物表征结果同实施例1。
实施例3:
Sotorasib乙酸溶剂化物的制备
向5g Sotorasib固体加入5mL乙酸,升温至40℃溶清,过滤。将7mL乙酸和30mL水混合均匀,升温至40℃,再慢慢滴入上述所得滤液,30min滴完。滴完40℃保温搅拌1.0h,有
较多固体析出。抽滤,滤饼用少量水洗涤,40℃真空干燥,得白色粉末4.7g,即乙酸溶剂化物。
产物表征结果同实施例1。
对比例1:
向5g Sotorasib固体加入10mL乙酸,升温至60℃溶清,过滤。将7mL乙酸和30mL水混合均匀,升温至60℃,再慢慢滴入上述所得滤液,30min滴完。滴完60℃保温搅拌1.0h,有较多固体析出。抽滤,滤饼用少量水洗涤,40℃真空干燥,得白色粉末4.2g。
产物PXRD表征结果同原研专利WO2020236947的无水Form I,详见附图6。
对比例2:
向5g Sotorasib固体加入5mL乙酸,升温至40℃溶清,过滤。将40mL水升温至40℃,再慢慢滴入上述所得滤液,30min滴完。滴完40℃保温搅拌1.0h,有较多固体析出。抽滤,滤饼用少量水洗涤,40℃真空干燥,得白色粉末4.4g。
产物PXRD表征结果同对比例1。
Claims (10)
- 一种S°torasib的新晶型,其特征在于,所述新晶型为Sotorasib的乙酸溶剂化物。
- 根据权利要求1所述的一种Sotorasib的新晶型,其特征在于,其X射线粉末衍射在衍射角2θ为:7.0°±0.2°、9.1°±0.2°、9.6°±0.2°、10.6°±0.2°、13.7°±0.2°、14.2°±0.2°、14.5°±0.2°、16.6°±0.2°、17.0°±0.2°、17.6°±0.2°、18.6°±0.2°、19.1°±0.2°、19.5°±0.2°、21.0°±0.2°、21.4°±0.2°、22.4°±0.2°、22.8°±0.2°、23.1°±0.2°、24.3°±0.2°、24.7°±0.2°、25.3°±0.2°、25.5°±0.2°和28.5°±0.2°的一处或多处特征峰处。
- 根据权利要求1所述的一种Sotorasib的新晶型,其特征在于,所述新晶型的差示扫描量热法热图包含在172~175℃起始的吸热。
- 根据权利要求1所述的一种Sotorasib的新晶型,其特征在于,所述新晶型的热重分析热图包含从35~40℃加热至195~200℃时9.7~10.2%的重量损失。
- 根据权利要求1所述的一种Sotorasib的新晶型,其特征在于,所述新晶型的气相检测残留溶剂,含有88000~95000ppm的乙酸。
- 一种如权利要求1-5任一项所述Sotorasib的新晶型的制备方法,其特征在于,包括以下步骤:1)将Sotorasib固体用乙酸溶清并过滤;2)将Sotorasib的乙酸溶液滴加到水和乙酸的溶剂化物中;3)将析出的固体抽滤并烘干。
- 根据权利要求6所述的一种Sotorasib的新晶型的制备方法,其特征在于,步骤1)中的Sotorasib固体与乙酸的质量体积比为1:1~1:3g/mL。
- 根据权利要求6所述的一种Sotorasib的新晶型的制备方法,其特征在于,步骤1)和步骤2)中的Sotorasib固体溶清温度和析晶温度均为30~50℃。
- 如权利要求1-5任一项所述Sotorasib的新晶型,用于制备治疗KRAS G12C基因突变引起的相关疾病的药物。
- 一种药物组合物,包含有效治疗量的如权利要求1-5任一项所述Sotorasib的新晶型,及药学上可接受的赋形剂。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202211067503.1A CN115368358A (zh) | 2022-09-01 | 2022-09-01 | 一种Sotorasib新晶型及其制备方法与应用 |
CN202211067503.1 | 2022-09-01 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2024045633A1 true WO2024045633A1 (zh) | 2024-03-07 |
Family
ID=84070310
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CN2023/088845 WO2024045633A1 (zh) | 2022-09-01 | 2023-04-18 | 一种Sotorasib新晶型及其制备方法与应用 |
Country Status (2)
Country | Link |
---|---|
CN (1) | CN115368358A (zh) |
WO (1) | WO2024045633A1 (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115368358A (zh) * | 2022-09-01 | 2022-11-22 | 浙江九洲药业股份有限公司 | 一种Sotorasib新晶型及其制备方法与应用 |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2019051291A1 (en) * | 2017-09-08 | 2019-03-14 | Amgen Inc. | KRAS G12C INHIBITORS AND METHODS OF USE |
CN110997668A (zh) * | 2017-05-22 | 2020-04-10 | 美国安进公司 | Kras g12c抑制剂及其使用方法 |
WO2020236948A1 (en) * | 2019-05-21 | 2020-11-26 | Amgen Inc. | Solid state forms |
WO2021236920A1 (en) * | 2020-05-20 | 2021-11-25 | Teva Pharmaceuticals International Gmbh | Solid state forms of amg-510 and process for preparation thereof |
CN114144414A (zh) * | 2019-05-21 | 2022-03-04 | 美国安进公司 | 固态形式 |
CN114605406A (zh) * | 2021-09-18 | 2022-06-10 | 都创(上海)医药开发有限公司 | Amg510化合物的晶型及其制备方法和用途 |
CN115368358A (zh) * | 2022-09-01 | 2022-11-22 | 浙江九洲药业股份有限公司 | 一种Sotorasib新晶型及其制备方法与应用 |
WO2022246069A1 (en) * | 2021-05-19 | 2022-11-24 | Teva Pharmaceuticals International Gmbh | Process for preparation of sotorasib and solid state form thereof |
WO2022269008A1 (en) * | 2021-06-24 | 2022-12-29 | Sandoz Ag | Crystalline form of sotorasib |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MX2023002248A (es) * | 2020-09-03 | 2023-05-16 | Revolution Medicines Inc | Uso de inhibidores de sos1 para tratar neoplasias malignas con mutaciones de shp2. |
CN113603636A (zh) * | 2021-07-12 | 2021-11-05 | 江苏弘和药物研发有限公司 | 一种Sotorasib中间体的制备方法 |
-
2022
- 2022-09-01 CN CN202211067503.1A patent/CN115368358A/zh active Pending
-
2023
- 2023-04-18 WO PCT/CN2023/088845 patent/WO2024045633A1/zh unknown
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110997668A (zh) * | 2017-05-22 | 2020-04-10 | 美国安进公司 | Kras g12c抑制剂及其使用方法 |
WO2019051291A1 (en) * | 2017-09-08 | 2019-03-14 | Amgen Inc. | KRAS G12C INHIBITORS AND METHODS OF USE |
WO2020236948A1 (en) * | 2019-05-21 | 2020-11-26 | Amgen Inc. | Solid state forms |
CN114144414A (zh) * | 2019-05-21 | 2022-03-04 | 美国安进公司 | 固态形式 |
WO2021236920A1 (en) * | 2020-05-20 | 2021-11-25 | Teva Pharmaceuticals International Gmbh | Solid state forms of amg-510 and process for preparation thereof |
WO2022246069A1 (en) * | 2021-05-19 | 2022-11-24 | Teva Pharmaceuticals International Gmbh | Process for preparation of sotorasib and solid state form thereof |
WO2022269008A1 (en) * | 2021-06-24 | 2022-12-29 | Sandoz Ag | Crystalline form of sotorasib |
CN114605406A (zh) * | 2021-09-18 | 2022-06-10 | 都创(上海)医药开发有限公司 | Amg510化合物的晶型及其制备方法和用途 |
CN115368358A (zh) * | 2022-09-01 | 2022-11-22 | 浙江九洲药业股份有限公司 | 一种Sotorasib新晶型及其制备方法与应用 |
Also Published As
Publication number | Publication date |
---|---|
CN115368358A (zh) | 2022-11-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN103974949B (zh) | 一种酪氨酸激酶抑制剂的二马来酸盐的i型结晶及制备方法 | |
CN110650963B (zh) | Gdc-0077的多晶型物和固体形式及其制备方法 | |
JP2018520205A (ja) | レンバチニブメシル酸塩の新規結晶形及びその製造方法 | |
WO2011095059A1 (zh) | 达沙替尼多晶型物及其制备方法和药物组合物 | |
JP6971390B2 (ja) | 重水素化azd9291の結晶形、製造方法および使用 | |
WO2010139981A2 (en) | Processes for preparing crystalline forms | |
WO2006052810A2 (en) | Combination of a src kinase inhibitor and a bcr-abl inhibitor for the treatment of proliferative diseases | |
CN105367552A (zh) | 来那替尼马来酸盐的新晶型及其制备方法 | |
WO2024045633A1 (zh) | 一种Sotorasib新晶型及其制备方法与应用 | |
WO2011023146A1 (en) | Imatinib mesylate polymorphs generated by crystallization in aqueous inorganic salt solutions | |
WO2018157803A1 (zh) | 维奈妥拉的晶型及其制备方法 | |
TW201638090A (zh) | 一種週期素依賴性蛋白激酶抑制劑的結晶形式及其製備方法 | |
CN106279127B (zh) | 阿法替尼酸加成盐及其晶型、其制备方法及药物组合物 | |
WO2021121146A1 (zh) | 氨基嘧啶类化合物甲磺酸盐的晶型a及其制备方法和应用 | |
WO2016101867A1 (zh) | 萘普替尼对甲苯磺酸盐的α晶型及制备方法和含有其的药物组合物 | |
JP2019055960A (ja) | 薬学的に活性な化合物の固体形態 | |
WO2020244612A1 (zh) | Cdk9抑制剂的多晶型物及其制法和用途 | |
WO2023193563A1 (zh) | 一种噻吩并吡啶化合物的晶型a、制备方法及其药物组合物 | |
WO2018214877A1 (zh) | 一种地佐辛晶型及其制备方法 | |
EP3475269A1 (en) | Solid state forms of neratinib and salts thereof | |
CN113045554A (zh) | 一种非索替尼晶型及其制备方法 | |
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 | |
WO2016101868A1 (zh) | 萘普替尼对甲苯磺酸盐的β晶型及制备方法和含有其的药物组合物 | |
JP6871255B2 (ja) | ゲフィチニブの結晶形aを製造する方法 | |
JP2022508864A (ja) | チロシンキナーゼ阻害剤のマレイン酸塩の結晶形及びその調製方法 |
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: 23858674 Country of ref document: EP Kind code of ref document: A1 |