WO2023165501A1 - Forme cristalline d'azd5305, son procédé de préparation et son utilisation - Google Patents

Forme cristalline d'azd5305, son procédé de préparation et son utilisation Download PDF

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Publication number
WO2023165501A1
WO2023165501A1 PCT/CN2023/078931 CN2023078931W WO2023165501A1 WO 2023165501 A1 WO2023165501 A1 WO 2023165501A1 CN 2023078931 W CN2023078931 W CN 2023078931W WO 2023165501 A1 WO2023165501 A1 WO 2023165501A1
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WO
WIPO (PCT)
Prior art keywords
crystal form
azd5305
water
present application
solvent
Prior art date
Application number
PCT/CN2023/078931
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English (en)
Chinese (zh)
Inventor
盛晓霞
盛晓红
曹雅晴
Original Assignee
杭州领业医药科技有限公司
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Publication of WO2023165501A1 publication Critical patent/WO2023165501A1/fr

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    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • 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
    • 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
    • C07D401/14—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 three or more hetero rings
    • 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

Definitions

  • This application relates to the field of chemical synthesis of medicines. Specifically, the application relates to the crystal form of AZD5305 and its preparation method and use.
  • AZD5305 is a second-generation PARP inhibitor developed by AstraZeneca. It is a selective PARP1 inhibitor and is clinically used as a single drug or in combination with other anti-tumor drugs to treat solid tumors.
  • the chemical name of AZD5305 is: 5-[4-[(7-ethyl-6-oxo-5H-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl]-N-methylpyridine-2-carboxamide, The structure is as shown in formula (I):
  • WO2021013735A1 discloses Form A, the crystalline form of AZD5305.
  • the inventors of the present application have found through research that Form A cannot maintain the original crystal form in water at room temperature, and that the DVS weight gain of Form A is about 5.7% under the environment of 0%RH to 80%RH. %, it can be seen that the Form A of the prior art has poor stability, high hygroscopicity, and low drug development value.
  • the present application provides a crystal form of AZD5305, which has at least one of the following improved characteristics: good stability, low hygroscopicity, good solubility, good dissolution, high purity, good fluidity, good processability such as good compressibility 1.
  • the tablet after tableting is more stable, has good crystal morphology, good compression resistance, can be stored stably, and avoids crystal transformation of the drug during the development process and storage.
  • the preparation method is simple and reliable, and has a large development value. value.
  • One aspect of the present application is to provide a crystal form 2 of AZD5305, using Cu-K ⁇ radiation, the X-ray powder diffraction (XRPD) spectrum of the crystal form 2 expressed at 2 ⁇ angle is at 9.1° ⁇ 0.2°, 19.1° At least one of ⁇ 0.2°, 19.5° ⁇ 0.2° and 20.3° ⁇ 0.2° has a characteristic peak; preferably at least three have characteristic peaks.
  • XRPD X-ray powder diffraction
  • the XRPD pattern of the crystal form 2 further has a characteristic peak at least one of 12.3° ⁇ 0.2°, 18.9° ⁇ 0.2°, 20.8° ⁇ 0.2° and 21.1° ⁇ 0.2°2 ⁇ .
  • the XRPD pattern of the crystal form 2 is further at 22.6° ⁇ 0.2°, 16.6° ⁇ 0.2°, 18.5° ⁇ 0.2°, 23.2° ⁇ 0.2°, 24.4° ⁇ 0.2°, 25.0° At least one of ⁇ 0.2° and 26.5° ⁇ 0.2° 2 ⁇ has a characteristic peak.
  • the XRPD pattern of the crystal form 2 has characteristics at 9.1° ⁇ 0.2°, 18.9° ⁇ 0.2°, 19.1° ⁇ 0.2°, 20.3° ⁇ 0.2° and 20.8° ⁇ 0.2°2 ⁇ peak.
  • the XRPD pattern of the crystal form 2 is further at 12.3° ⁇ 0.2°, 16.6° ⁇ 0.2°, 18.5° ⁇ 0.2°, 19.5° ⁇ 0.2° and 21.1° ⁇ 0.2°2 ⁇ At least one characteristic peak.
  • the XRPD pattern of the crystal form 2 is further at 22.6° ⁇ 0.2°, 23.2° ⁇ 0.2°, 24.4° ⁇ 0.2°, 25.0° ⁇ 0.2° and 26.5° ⁇ 0.2°2 ⁇ At least one characteristic peak.
  • the XRPD pattern of the crystal form 2 has a diffraction peak at the position of the following table at 2 ⁇ :
  • the crystalline form 2 has an XRPD pattern substantially as shown in FIG. 1 .
  • the Fourier transform infrared spectrum (FT-IR) of the crystal form 2 is at 3414cm -1 ⁇ 2cm -1 , 1570cm -1 ⁇ 2cm -1 , 1527cm -1 ⁇ 2cm -1 , 932cm -1 ⁇ 2cm -1 , 922cm -1 ⁇ 2cm -1 and 634cm -1 ⁇ 2cm -1 at least one has a characteristic peak; more preferably at 1647cm -1 ⁇ 2cm -1 , 1583cm -1 ⁇ 2cm -1 , 1249cm -1 ⁇ 2cm -1 , 1230cm -1 ⁇ 2cm -1 , 675cm -1 ⁇ 2cm -1 and 626cm -1 ⁇ 2cm -1 at least one of the characteristic diffraction peaks.
  • FT-IR Fourier transform infrared spectrum
  • the FT-IR characterization of the crystal form 2 is basically shown in FIG. 4 .
  • the TGA characterization of the crystal form 2 is basically shown in Figure 2, and there is about 2.2% weight loss before heating to 120°C.
  • the DSC characterization of the crystal form 2 is basically shown in FIG. 3 .
  • the DVS characterization of the crystal form 2 is basically shown in Figure 5, and the weight gain is about 1.2% under the environment of 0% RH to 80% RH.
  • the crystal form 2 is a hydrate.
  • the number of water molecules in the hydrate is 0.1-2;
  • the number of water molecules in the hydrate is 0.1-1;
  • the Form 2 is a hemihydrate.
  • the AZD5305 crystal form 2 described in this application has the following beneficial effects:
  • the AZD5305 crystal form 2 of the present application keeps the crystal form unchanged for 5 months under accelerated (40°C/75%RH, open) and high humidity (room temperature/97%RH, open) conditions, and has good crystal stability and the AZD5305 Form A of the prior art is transformed into a mixed crystal of Form A and Form 2 in 5 months under accelerated (40°C/75%RH, exposure) conditions, indicating that the AZD5305 Form 2 of the present application has more Good stability is conducive to drug storage, ensures the controllable quality of raw materials and preparations, minimizes the quality change of drugs caused by crystal form changes, and ensures the efficacy of drugs.
  • the tablet made of the AZD5305 crystal form 2 of the present application has a cumulative dissolution rate of more than 85% in pH4.5 acetate buffer solution for 120 minutes, which is comparable to the tablet made by the prior art Form A.
  • the AZD5305 crystal form 2 of the present application and the prior art have considerable solubility in water, and the solubility after 24 hours is >25ug/mL; the AZD5305 crystal form 2 of the present application and the Form A of the prior art are acetate at pH 4.5 It also has a considerable solubility in the buffer, and the solubility is >200ug/mL after 24 hours.
  • the AZD5305 crystal form 2 of the present application has a weight gain of about 1.2% under the environment of 0%RH to 80%RH, while the Form A of the prior art has a weight gain of about 5.7% under the same conditions, indicating that the crystal form 2 has Lower hygroscopicity.
  • Hygroscopicity may affect the stability, processability, and quality uniformity of the drug, and ultimately affect the quality of the pharmaceutical preparation, as well as the preparation, post-processing and storage of the drug. Crystal forms with low hygroscopicity do not have strict requirements on storage conditions. It reduces the cost of material storage and quality control, and has high economic value.
  • the AZD5305 crystal form 2 of the present application has better compressibility, and good compressibility can effectively improve problems such as unqualified hardness/friability and splitting in the tableting process.
  • the preparation has good processability and improves the appearance of the tablet. Improve the quality of tablets, expand the selection of excipients, and reduce costs.
  • the AZD5305 crystal form 2 of the present application has good crystallinity.
  • the AZD5305 crystal form 2 of the present application has a uniform particle size distribution, can be directly applied to the preparation process, avoids the complicated pretreatment process of the raw material drug, simplifies the process, reduces the production cost, improves the uniformity of the pharmaceutical preparation, and makes the quality of the pharmaceutical preparation better. controllable.
  • the preparation method is simple and suitable for industrial production.
  • the preparation method of AZD5305 crystal form 2 mainly uses crystal slurry, which is the most common crystal form, which is very easy to realize in industrialization, and the solvent used at the same time contains a lot of water, and water is the cheapest and most environmentally friendly Solvent, low preparation cost.
  • Another aspect of the present application provides a method for preparing crystal form 2 of AZD5305, the preparation method comprising any one of the following methods:
  • AZD5305 is prepared in solvent 1 as a suspension, crystal slurry, and separated to obtain crystal form 2;
  • the solvent 1 is water or a water-containing mixed solvent, and the water-containing mixed solvent is selected from nitriles, alcohols, acetone, tetrahydrofuran, 1,4-dioxane, DMSO, DMF
  • the mixing of any one or combination thereof with water more preferably the mixing of acetonitrile and/or tetrahydrofuran and water;
  • the alcohols are selected from any one of methanol, ethanol, propanol or a combination thereof;
  • the mass volume ratio (mg/mL) of said AZD5305 to solvent 1 ⁇ 5 More preferably 10:1-50:1, most preferably 15:1-30:1;
  • the water content of the solvent 1 calculated by volume ratio is ⁇ 5%; more preferably ⁇ 50%;
  • the temperature of the crystal slurry is room temperature
  • the number of days of the magma slurry is ⁇ 2 days; more preferably 2-10 days;
  • the drying temperature is 10°C-50°C, and the time is 1h-48h;
  • the drying temperature is 30° C.
  • the drying time is 24 hours.
  • the solvent 2 is water or a water-containing mixed solvent
  • the water-containing mixed solvent is selected from methanol, ethanol, propanol, acetone, tetrahydrofuran, 1,4-dioxane, tetrahydrofuran, Any one or combination of acetonitrile mixed with water,
  • the solvent 2 is a mixed solvent of methanol and water
  • the water content of the solvent 2 is ⁇ 5%
  • the volatilization temperature is ⁇ 15°C, more preferably 20-50°C; most preferably 30-50°C.
  • Another aspect of the present application is to provide a pharmaceutical composition, which comprises a therapeutically effective amount of the AZD5305 crystal form 2 described in the present application, and at least one pharmaceutically acceptable carrier.
  • the pharmaceutically acceptable carrier is an excipient commonly used in preparations in the art, including but not limited to binders, surfactants, diluents, anti-adhesive agents, hydrophilic or hydrophobic polymers Any of polymers, stabilizers or stabilizers, disintegrants, antioxidants, defoamers, fillers, glidants/lubricants, adsorbents, preservatives, plasticizers, sweeteners, and A mixture of two or more.
  • the filler or diluent is selected from lactose, microcrystalline cellulose, starch, pregelatinized starch, calcium sulfate, calcium hydrogen phosphate, calcium carbonate, mannitol Any one or a combination thereof;
  • the disintegrating agent is selected from any one of sodium carboxymethyl starch, cross-linked carmellose sodium, low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone or Its combination;
  • the lubricant/glidant is selected from one or a combination of magnesium stearate, talcum powder, micronized silica gel.
  • the pharmaceutical composition may also include one or more pH adjusters or buffers, for example: acids such as acetic acid, boric acid, citric acid, fumaric acid, maleic acid, tartaric acid, apple Any one of acid, lactic acid, phosphoric acid, hydrochloric acid or a combination thereof; or a base such as any one of sodium hydroxide, sodium phosphate, sodium borate, sodium citrate, sodium acetate, sodium lactate, tris, or composition; or buffers such as citrate/dextrose, sodium bicarbonate, ammonium chloride, and the like; such buffers used as bases may have counterions other than sodium, such as potassium, magnesium, calcium, ammonium, and other counterions ions; and other amounts necessary to maintain the pH of a component within an acceptable range, solutions or solids comprising such acids, bases and buffers.
  • acids such as acetic acid, boric acid, citric acid, fumaric acid, maleic acid, tartaric acid, apple Any one of acid, lactic acid, phosphoric acid
  • the pharmaceutical composition can be prepared using techniques known in the art.
  • the crystal form 2 of AZD5305 of the present application is mixed with at least one pharmaceutically acceptable carrier, or by Prepare dosage forms by direct mixing, granulating, tableting or dissolving processes.
  • the administration routes of the pharmaceutical composition include oral administration, subcutaneous injection, intravenous administration, intramuscular injection, transdermal administration, rectal administration and nasal cavity administration.
  • Another aspect of the present application is to provide a preparation prepared from the above pharmaceutical composition, and the preparation form is selected from oral solid preparations, external preparations and injections.
  • the preparation forms are tablets, capsules, pills, suppositories, granules, fine granules, powder/powder, sustained-release preparations, quick-release preparations, solutions, suspensions, elixirs, Aerosol etc.
  • the preparation form is a tablet.
  • Another aspect of the present application is also to provide a use of the AZD5305 crystal form 2 described in the present application or the pharmaceutical composition described in the present application in the preparation of pharmaceutical preparations for treating cancer.
  • the cancer is selected from breast cancer, ovarian cancer, prostate cancer, blood cancer, digestive tract cancer, lung cancer, bladder cancer, cervical cancer and endometrial cancer; preferably, the prostate cancer It is selected from metastatic prostate cancer, the digestive tract is selected from colorectal cancer, gastric cancer, cholangiocarcinoma, pancreatic cancer, and the lung cancer is selected from non-small cell lung cancer and small cell lung cancer.
  • the cancer is BRCA1 or BRCA2 deficient phenotype.
  • the cancer is a PARP inhibitor-related cancer, especially a PARP1 inhibitor-related cancer.
  • Another aspect of the present application is to provide a method for treating or preventing diseases, which includes administering to the patient an effective amount of the AZD5305 crystal form 2 described in the present application or any one of the pharmaceutical compositions described herein or combination; preferably, the disease is cancer.
  • the cancer is selected from breast cancer, ovarian cancer, prostate cancer, blood cancer, digestive tract cancer, lung cancer, bladder cancer, cervical cancer and endometrial cancer; preferably, the prostate cancer It is selected from metastatic prostate cancer, the digestive tract is selected from colorectal cancer, gastric cancer, cholangiocarcinoma, pancreatic cancer, and the lung cancer is selected from non-small cell lung cancer and small cell lung cancer.
  • the cancer is BRCA1 or BRCA2 deficient phenotype.
  • the cancer is a PARP inhibitor-related cancer, especially a PARP1 inhibitor-related cancer.
  • the method can be administered once a day, twice a day, three times a day or more; a single dose can be 0.1mg-500mg/kg/day, and the specific dosage will be determined according to the actual situation of the patient .
  • the method is administered twice a day, and the single dose is oral administration of 10, 50, 100, 150, 200, 250, 300, 350, 400, 450 or 500 mg of the crystal form 2 of AZD5305 ; more preferably 300 or 400 mg.
  • Another aspect of the present application is to provide a combination of the AZD5305 crystal form 2 described in the present application or the pharmaceutical composition described in the present application and other drugs.
  • the other drugs are selected from antitumor drugs.
  • the other drugs are selected from Paclitaxel, Carboplatin, T-Dxd and Dato-DXd.
  • room temperature in this application refers to a temperature of 10-30°C.
  • the "separation" can use conventional methods in the art, such as centrifugation or filtration. Wherein, vacuum filtration is generally carried out with suction filtration at a pressure less than atmospheric pressure at room temperature.
  • drying can be accomplished by conventional techniques in the art, such as drying at room temperature, air blowing or reduced pressure, or under reduced pressure or without reduced pressure.
  • the drying apparatus and method are not limited, and can be fume hood, blast oven, spray dryer, fluidized bed drying or vacuum oven; it can also be carried out under reduced or no reduced pressure.
  • the “relative intensity (I%)” is expressed as a specific value in a specific XRPD pattern. Based on the anisotropic characteristics of crystals and the principle of X-ray powder diffraction, the relative intensity value of the diffraction peaks of the same crystal form will fluctuate with the preferred orientation of the sample. The common sense that this fluctuation does not affect the judgment of the same crystal form should be regarded as accepted by those skilled in the art.
  • ratios involved in this application are mass-volume ratios between liquids and solids, and volume ratios between liquids and liquids.
  • Figure 1 is the XRPD pattern of AZD5305 crystal form 2 prepared in Example 1 of the present application;
  • Fig. 2 is the TGA diagram of the AZD5305 crystal form 2 prepared in Example 1 of the present application;
  • Fig. 3 is the DSC diagram of AZD5305 crystal form 2 prepared in Example 1 of the present application;
  • Fig. 4 is the FT-IR diagram of AZD5305 crystal form 2 prepared in Example 1 of the present application;
  • Figure 5 is the DVS diagram of AZD5305 crystal form 2 prepared in Example 1 of the present application.
  • Fig. 6 is an XRPD comparison chart of AZD5305 crystal form 2 prepared in Example 1 of the present application placed under accelerated conditions for 14 days;
  • Figure 7 is the XRPD comparison chart of AZD5305 crystal form 2 prepared in Example 1 of the present application placed under accelerated and high humidity conditions for 5 months;
  • Fig. 8 is the XRPD comparison chart of prior art Form A placed under accelerated and high-humidity conditions for 5 months;
  • Fig. 9 is an XRPD comparison chart of AZD5305 crystal form 2 prepared in Example 1 of the present application during solubility investigation;
  • Fig. 10 is the XRPD comparison chart of Form A in the prior art during solubility investigation
  • Figure 11 is the XRPD comparison chart of the transformation of Form A to AZD5305 crystal form 2 in water;
  • Figure 12 is the XRPD comparison chart of the transformation of Form A to AZD5305 crystal form 2 in 20% water;
  • Figure 13 is the XRPD comparison chart of the AZD5305 crystal form 2 of the present application mixed with auxiliary materials before and after tableting (the upper part is after tableting, and the lower part is before tableting).
  • X-ray powder diffraction (XRPD) data were collected from a Bruker D8 Advance diffractometer. The parameters are as follows: Cu target; wavelength is Current and voltage: 40KV, 40mA; angle range: 3-40°2 ⁇ .
  • FT-IR Fourier transform infrared spectroscopy
  • DSC Differential thermal analysis
  • TGA Thermogravimetric analysis
  • Polarized light microscopy (PLM) data were collected from XP-500E.
  • the parameters are as follows: eyepiece 10 times; objective lens 4 times.
  • HPLC determination method chromatograph model: Ultimate3000, chromatographic column: C18 3 ⁇ m (150*4.6mm), column temperature: 30°C, flow rate 1.0mL/min, detection wavelength: 315nm, injection volume: 10 ⁇ L, running time: 25min, Mobile phase: mobile phase A: 0.1% TFA aqueous solution, mobile phase B: pure acetonitrile, the operating gradient is as follows:
  • the starting material AZD5305 can be obtained commercially, or can be prepared by existing techniques, such as the method mentioned in WO2021013735A1.
  • Embodiment 4 investigation of crystal form stability
  • Embodiment 5 Solubility investigation
  • the AZD5305 crystal form 2 of the present application and the Form A of the prior art have considerable solubility, and the solubility in water after 24 hours is >25ug/mL; the crystal form of the AZD5305 crystal form 2 of the present application remains unchanged before and after the solubility measurement, Its XRPD spectrum is shown in Figure 9, while the Form A of the prior art is converted to the crystal form 2 of the present application, and its XRPD spectrum is shown in Figure 10;
  • the AZD5305 crystal form 2 of the present application and the Form A of the prior art have considerable solubility, and the solubility in the pH4.5 acetate buffer after 24 hours is >200ug/mL;
  • the applied AZD5305 crystal form 2 remains unchanged before and after the solubility measurement, and its XRPD spectrum is shown in Figure 11, while the Form A of the prior art is converted to the crystal form 2 of the present application, and its XRPD spectrum is shown in Figure 12 .
  • Embodiment 6 magma competition experiment
  • Form A was slurried in water, turned into mixed crystals in 8 hours, and completely turned into Form 2 in 24 hours, and its XRPD pattern is shown in Figure 11.
  • Embodiment 7 the preparation of tablet
  • the components were mixed, granulated and compressed to prepare tablets.
  • Embodiment 8 Examination of compressibility
  • Embodiment 9 the chemical stability investigation of tablet
  • Embodiment 10 Dissolution investigation of tablet
  • Dissolution medium pH4.5 acetate buffer
  • Dissolution method slurry method

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

Abstract

La présente demande relève du domaine de la synthèse chimique de produits pharmaceutiques. En particulier, la présente invention concerne une forme cristalline d'AZD5305, son procédé de préparation et son utilisation. La forme cristalline fournie par la présente invention présente au moins l'une des caractéristiques améliorées suivantes : une bonne stabilité, une faible hygroscopicité, une bonne solubilité, une bonne performance de dissolution, une pureté élevée, une bonne fluidité, une bonne pharmacopotentialité telle qu'une bonne compressibilité et une stabilité supérieure dans des formulations de comprimés après la formation de comprimés, une bonne morphologie cristalline, une bonne résistance au stress et une stabilité au stockage qui peut éviter la transition cristalline de médicaments dans le processus de développement et de stockage. La présente invention concerne un procédé de préparation simple et fiable et a une grande valeur de développement.
PCT/CN2023/078931 2022-03-01 2023-03-01 Forme cristalline d'azd5305, son procédé de préparation et son utilisation WO2023165501A1 (fr)

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CN202210184678.4 2022-03-01

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021013735A1 (fr) * 2019-07-19 2021-01-28 Astrazeneca Ab Inhibiteurs de parp1

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021013735A1 (fr) * 2019-07-19 2021-01-28 Astrazeneca Ab Inhibiteurs de parp1

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
JOHANNES, J.W. ET AL.: "Discovery of 5‑{4-[(7-Ethyl-6-oxo‑5,6-dihydro‑1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}‑N‑methylpyridine-2-carboxamide (AZD5305):A PARP1−DNA Trapper with High Selectivity for PARP1 over PARP2 and Other PARPs", JOURNAL OF MEDICINAL CHEMISTRY, vol. 64, no. 19, 27 September 2021 (2021-09-27), pages 14498 - 14512, XP093028792, DOI: 10.1021/acs.jmedchem.1c01012 *

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