WO2013156772A1 - Crystalline forms of (s) -4-amino-n- (1- (4 - chlorophenyl) - 3 - hydroxypropyl) -1- (7h - pyrrolo [2, 3-d] pyrimidi n-4-yl) piperidine-4-carboxamide - Google Patents

Crystalline forms of (s) -4-amino-n- (1- (4 - chlorophenyl) - 3 - hydroxypropyl) -1- (7h - pyrrolo [2, 3-d] pyrimidi n-4-yl) piperidine-4-carboxamide Download PDF

Info

Publication number
WO2013156772A1
WO2013156772A1 PCT/GB2013/050973 GB2013050973W WO2013156772A1 WO 2013156772 A1 WO2013156772 A1 WO 2013156772A1 GB 2013050973 W GB2013050973 W GB 2013050973W WO 2013156772 A1 WO2013156772 A1 WO 2013156772A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
crystalline form
ray powder
powder diffraction
diffraction pattern
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/GB2013/050973
Other languages
English (en)
French (fr)
Inventor
Gary Peter Tomkinson
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.)
AstraZeneca UK Ltd
AstraZeneca AB
Original Assignee
AstraZeneca UK Ltd
AstraZeneca AB
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
Priority to CA2869936A priority Critical patent/CA2869936C/en
Priority to EP13718618.5A priority patent/EP2847194B1/en
Priority to JP2015506302A priority patent/JP2015514741A/ja
Priority to CN201380020297.1A priority patent/CN104203953B/zh
Priority to HK15106857.2A priority patent/HK1206337B/en
Priority to BR112014025586-5A priority patent/BR112014025586B1/pt
Priority to RU2014143529A priority patent/RU2652377C3/ru
Priority to KR1020147031099A priority patent/KR20150002767A/ko
Priority to ES13718618.5T priority patent/ES2650797T3/es
Application filed by AstraZeneca UK Ltd, AstraZeneca AB filed Critical AstraZeneca UK Ltd
Priority to MX2014012642A priority patent/MX2014012642A/es
Priority to US14/394,918 priority patent/US9487525B2/en
Priority to SG11201405963YA priority patent/SG11201405963YA/en
Publication of WO2013156772A1 publication Critical patent/WO2013156772A1/en
Priority to IL234966A priority patent/IL234966A0/en
Anticipated expiration legal-status Critical
Priority to US15/291,370 priority patent/US10039766B2/en
Ceased legal-status Critical Current

Links

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
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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

Definitions

  • the present invention discloses certain new solid state forms of ( ) S)-4-amino-N-(l- (4-chlorophenyl)-3-hydroxypropyl)-l-(7H-pyrrolo[2,3-ii]pyrimidin-4-yl)piperidine-4- carboxamide, processes for preparing such forms, pharmaceutical compositions comprising them, and the use of such forms in therapy.
  • Compound (I) in crystalline form is in the form of Form B and is substantially free of Form C.
  • Form A of Compound (I) provides X-ray powder diffraction patterns substantially the same as the X-ray powder diffraction patterns shown in Figure 1 and has ten peaks [angle 2-theta (2 ⁇ ) values] shown in Table A. It will be understood that the 2-theta values of the X-ray powder diffraction pattern may vary slightly from one machine to another or from one sample to another, and so the values quoted are not to be construed as absolute.
  • Form B of Compound (I) was prepared by the method described hereinafter in 'Example and analysed using a Bruker D8 X-ray powder diffractometer, the X-ray powder diffraction pattern of Figure 3.1 was obtained (using 1.54A X-rays, i.e. CuKa radiation).
  • Form B of Compound (I) which has an X-ray powder diffraction pattern substantially the same as the X-ray powder diffraction pattern shown in Figure 3.1.
  • Form B of Compound (I) which has an X-ray powder diffraction pattern substantially the same as the X-ray powder diffraction pattern shown in Figure 3.2.
  • a crystalline form, Form B of Compound (I), which has an X-ray powder diffraction pattern with at least two specific peaks at 2-theta 15.0° and 19.2° wherein said values may be plus or minus 0.2° 2-theta.
  • a crystalline form, Form B of Compound (I), which has an X-ray powder diffraction pattern with specific peaks at 2- theta 10.0, 5.0, 15.0, 19.2, 17.1, 12.3, 24.4, 30.2, 32.2 and 23.3° wherein said values may be plus or minus 0.2° 2-theta.
  • Form B of Compound (I) which has an X-ray powder diffraction pattern as shown in Figure 3.1.
  • Form B of Compound (I) which has an X-ray powder diffraction pattern as shown in Figure 3.2.
  • Form B of Compound (I) [prepared by the method of Example 3, below] shows a melting endotherm with an onset of 168.5°C and a peak at 171.0°C ( Figure 7). Accordingly, the Form B prepared by the method of Example 1 has a slightly lower melting point from the Form B as prepared by Example 3. It is speculated that this small difference in melting point arises because the Form B as prepared by the method of Example 3 is even more highly crystalline than the Form B as produced by the method of Example 1.
  • Form B of Compound (I) may be a high melting solid with an onset of melting at about 162.3° C and a peak at about 167.1°C.
  • Form B of Compound (I) may be a high melting solid with an onset of 168.5°C and a peak at 171.0°C.
  • the Form B of Compound (I) has a melting point peak (as measured by DSC) within the range from 165°C to 173°C.
  • Form B of Compound (I) provides X-ray powder diffraction patterns substantially the same as the X-ray powder diffraction patterns shown in Figures 3.1 and 3.2 and has the ten (angle 2-theta values) shown in Tables B-l and B-2. It will be understood that the 2- theta values of the X-ray powder diffraction pattern may vary slightly from one machine to another or from one sample to another, and so the values quoted are not to be construed as absolute. Indeed, such variation is evident in Figures 3.1 and 3.2, and the corresponding Tables B-l and B-2.
  • Form C of Compound (I) is characterised in providing at least one of the following 2 ⁇ values measured using CuKa radiation: 23.2 and 16.2.
  • Compound (I) Form C is characterised in providing an X-ray powder diffraction pattern, substantially as shown in Figure 5.
  • Ten X-Ray powder diffraction peaks (using 1.54A X-rays, i.e. CuKa radiation) are shown in Table C:
  • Form C of Compound (I) which has an X-ray powder diffraction pattern substantially the same as the X-ray powder diffraction pattern shown in Figure 5.
  • Form C of Compound (I) provides X-ray powder diffraction patterns substantially the same as the X-ray powder diffraction patterns shown in Figure 5 and has the ten (angle 2-theta values) shown in Table C. It will be understood that the 2-theta values of the X-ray powder diffraction pattern may vary slightly from one machine to another or from one sample to another, and so the values quoted are not to be construed as absolute.
  • an X-ray powder diffraction pattern may be obtained which has one or more measurement errors depending on measurement conditions (such as equipment or machine used).
  • intensities in an X-ray powder diffraction pattern may fluctuate depending on measurement conditions. Therefore it should be understood that the Forms of the present invention are not limited to the crystals that provide X-ray powder diffraction patterns identical to the X-ray powder diffraction pattern shown in the Figures, and any crystals providing X-ray powder diffraction patterns substantially the same as those shown in the Figures fall within the scope of the present invention.
  • a person skilled in the art of X-ray powder diffraction is able to judge the substantial identity of X-ray powder diffraction patterns.
  • a measurement error of a diffraction angle in an X-ray powder diffractogram is approximately plus or minus 0.2° 2-theta, and such degree of a
  • composition which comprises Compound (I) in crystalline form, as defined hereinbefore in association with a pharmaceutically-acceptable diluent or carrier.
  • compositions of the invention may be in a form suitable for oral use (for example as tablets, lozenges, hard or soft capsules, aqueous or oily suspensions, emulsions, dispersible powders or granules, syrups or elixirs), for topical use (for example as creams, ointments, gels, or aqueous or oily solutions or suspensions), for administration by inhalation (for example as a finely divided powder or a liquid aerosol), for administration by insufflation (for example as a finely divided powder) or for parenteral administration (for example as a sterile aqueous or oily solution for intravenous, subcutaneous, intramuscular or intramuscular dosing or as a suppository for rectal dosing).
  • oral use for example as tablets, lozenges, hard or soft capsules, aqueous or oily suspensions, emulsions, dispersible powders or granules, syrups or elixir
  • compositions of the invention may be obtained by conventional procedures using conventional pharmaceutical excipients, well known in the art.
  • compositions intended for oral use may contain, for example, one or more colouring, sweetening, flavouring and/or preservative agents.
  • a suitable formulation of Compound (I) in crystalline form is that where the compound is filled into a white hypromellose (FIPMC) hard capsule with no other excipients.
  • the strength of the drug product can range from 5 to 165 mg.
  • composition of this capsule is as follows:
  • Form B is a tablet formulation, particularly a film-coated tablet formulation.
  • Various sizes of tablets can be manufactured from a granule (described below) using conventional mixing, dry granulation, compression and film coating processes, according to Good Manufacturing Practice standards.
  • tablets containing from 50 mg to 500 mg of Compound (I) may be prepared using the above-mentioned composition using the methods described herein.
  • Granule preparation Form B of Compound (I), microcrystalline cellulose, mannitol, croscarmellose sodium and intragranular magnesium stearate were mixed in a blender at 16 revolutions/minute for 5 minutes to achieve a uniform distribution of the Compound (I) within the mixture. This mixture was then fed through a roller compactor to produce a ribbon which was milled and passed through 1mm screen to achieve uniform particle size of granule.
  • Tablet core preparation The remaining extragranular magnesium stearate was added to the granules and the mixture was blended at 30 revolutions/minute for 1 minute. This mixture was then compressed into tablet cores using conventional tabletting equipment using standard concave punches to achieve the desired tablet sizes.
  • Film-coating of tablet cores The compressed tablet cores were coated with an aqueous (purified water) suspension containing the OpadryTM II film coating components, using a perforated drum coater.
  • the OpadryTM II film-coating material is available from ColorconTM whose website is www.colorcon.com.
  • a pharmaceutical composition which comprises Compound (I) in crystalline form as described herein (particularly as Form B), in association with microcrystalline cellulose, mannitol, croscarmellose sodium and magnesium stearate.
  • a pharmaceutical tablet i.e. suitable for oral administration to a human patient which comprises from 50 to 500 mg of Compound (I) in crystalline form (particularly as Form B) as described herein, in association with one or more pharmaceutically acceptable excipients.
  • a pharmaceutical tablet i.e. suitable for oral administration to a human patient
  • a pharmaceutical tablet which comprises from 0.5 to 2% by weight of magnesium stearate, from 2 to 5% by weight of croscarmellose sodium, from 15 to 60% by weight of Compound (I) in crystalline form (particularly as Form B) as described herein, microcrystalline cellulose and mannitol, wherein the relative weights of microcrystalline cellulose and mannitol within the pharmaceutical tablet composition are in a ratio of between 3 : 1 and 1 : 1.
  • a pharmaceutical tablet i.e. suitable for oral administration to a human patient
  • a pharmaceutical tablet which comprises from 0.5 to 2% by weight of magnesium stearate, from 2 to 5% by weight of croscarmellose sodium, from 15 to 60% by weight of Compound (I) in crystalline form (particularly as Form B) as described herein, microcrystalline cellulose and mannitol, wherein the relative weights of microcrystalline cellulose and mannitol within the tablet are in a ratio of from 3 : 1 to 1 : 1 and wherein the amount of Compound (I) in crystalline form within the tablet is from 50 to 500 mg.
  • a pharmaceutical tablet i.e. suitable for oral administration to a human patient which comprises greater than 55% by weight of Compound (I) in crystalline form as described herein (particularly as Form B). In one embodiment there is provided a pharmaceutical tablet (i.e. suitable for oral administration to a human patient) which comprises 50-70% by weight of Compound (I) in crystalline form as described herein (particularly as Form B).
  • Such tablet may comprise microcrystalline cellulose (particularly between 20 and 30% by weight of the total tablet).
  • Such tablet may comprise mannitol (particularly between 5 and 12% by weight of the total tablet).
  • Such tablet may comprise croscarmellose sodium (particularly between 2 and 5% by weight of the total tablet).
  • Such tablet may comprise magnesium stearate (particularly between 0.5 and 2% by weight of the total tablet).
  • Such tablet may include a film-coating around the core of the tablet (particularly where the film coating comprises 1 to 5% by weight of the total tablet).
  • Compound (I) in crystalline form will normally be administered to a warm-blooded animal at a unit dose within the range 5-5000 mg/m 2 body area of the animal, i.e.
  • a unit dose form such as a tablet or capsule will usually contain, for example 1-500 mg of active ingredient.
  • Particular daily doses could be 400mg b.i.d for monotherapy and 320mg b.i.d (continuous) or 360mg b.i.d (intermittent) for combination with another chemo- therapeutic.
  • the daily dose will necessarily be varied depending upon the host treated, the particular route of administration, and the severity of the illness being treated. Accordingly the practitioner who is treating any particular patient may determine the optimum dosage.
  • the term “therapy” also includes “prophylaxis” unless there are specific indications to the contrary.
  • the terms “therapeutic” and “therapeutically” should be construed accordingly.
  • treatment is intended to have its normal everyday meaning of dealing with a disease in order to entirely or partially relieve one, some or all of its symptoms, or to correct or compensate for the underlying pathology.
  • prophylaxis is intended to have its normal everyday meaning and includes primary prophylaxis to prevent the development of the disease and secondary prophylaxis whereby the disease has already developed and the patient is temporarily or permanently protected against exacerbation or worsening of the disease or the development of new symptoms associated with the disease.
  • Compound (I) in crystalline form is expected to be useful in the treatment of diseases or medical conditions mediated alone or in part by PKB activity, for example cancer.
  • the types of cancers which may be susceptible to treatment using Compound (I) in crystalline form of the present invention include, but are not limited to, ovarian cancer, cervical cancer, colorectal cancer, breast cancer, pancreatic cancer, glioma, glioblastoma, melanoma, prostate cancer, leukaemia, lymphoma, Non-Hodgkins lymphoma, gastric cancer, lung cancer, hepatocellular cancer, gastric cancer, gastrointestinal stromal tumour (GIST), glioma, thyroid cancer, bile duct cancer, endometrial cancer, renal cancer, anaplastic large cell lymphoma, acute myeloid leukaemia (AML), multiple myeloma, melanoma and mesothelioma.
  • AML acute myeloid leukaemia
  • Breast cancer, and more specifically luminal breast cancer may be particularly susceptible to treatment using compounds of the present invention.
  • Compound (I) in crystalline form may be useful in the treatment of breast cancer, including oestrogen receptor positive breast cancer, prostate cancer including castrate resistant prostate cancer and metastatic castrate resistant prostate cancer and gastric cancer.
  • Compound (I) in crystalline form may be useful in the treatment of breast cancer particularly oestrogen receptor positive breast cancer.
  • Compound (I) in crystalline form may be useful in the treatment of prostate cancer in particular castrate resistant prostate cancer.
  • Compound (I) in crystalline form may be useful in the treatment of prostate cancer in particular metastatic castrate resistant prostate cancer.
  • Compound (I) in crystalline form may be useful in the treatment of gastric cancer.
  • Compound (I) in crystalline form will be administered to a mammal, more particularly a human being.
  • Compound (I) in crystalline form will be administered to a mammal, more particularly a human being.
  • Compound (I) in crystalline form as defined hereinbefore for use as a medicament.
  • Compound (I) in crystalline form as defined hereinbefore for use in the treatment of a disease mediated through PKB.
  • Compound (I) in crystalline form as defined hereinbefore for use in the treatment of cancer there is provided Compound (I) in crystalline form as defined hereinbefore for use in the treatment of breast cancer, including oestrogen receptor positive breast cancer, prostate cancer including castrate resistant prostate cancer and metastatic castrate resistant prostate cancer and gastric cancer.
  • a method of treating a human suffering from a disease in which inhibition of PKB is beneficial comprising the steps of administering to a person in need thereof of a therapeutically effective amount of Compound (I) in crystalline form as defined hereinbefore.
  • a method of treating cancer which comprises the steps of administering to a person in need thereof of a therapeutically effective amount of Compound (I) in crystalline form as defined hereinbefore.
  • a method of treating breast cancer including oestrogen receptor positive breast cancer, prostate cancer including castrate resistant prostate cancer and metastatic castrate resistant prostate cancer and gastric cancer which comprises the steps of administering to a person in need thereof of a therapeutically effective amount of Compound (I) in crystalline form as defined hereinbefore.
  • the cancer may be breast cancer. In any embodiment, aspect or claim where "cancer” is mentioned, the cancer may be oestrogen receptor positive breast cancer.
  • the cancer may be prostate cancer.
  • the cancer may be castrate resistant prostate cancer.
  • the cancer may be gastric cancer.
  • the cancer treatment defined hereinbefore may be applied as a sole therapy or may involve, in addition to the compound of the invention, conventional surgery or
  • abiraterone or an ester prodrug thereof ((3P)-17-(pyridin-3-yl)androsta-5, 16-dien- 3-ol "abiraterone", or "abiraterone acetate”); and
  • MDV-3100 is alternatively known as "enzalutamide”.
  • Such chemotherapy may also include a combination comprising Compound (I) in crystalline form and a taxane, particularly a taxane selected from docetaxel and paclitaxel.
  • a method of treating prostate cancer including castrate resistant prostate cancer and metastatic castrate resistant prostate cancer which comprises the steps of administering to a person in need thereof of a therapeutically effective amount of Compound (I) in crystalline form as defined
  • abiraterone or an ester prodrug thereof ((3P)-17-(pyridin-3-yl)androsta-5, 16-dien- 3-ol "abiraterone", or "abiraterone acetate”); and
  • abiraterone or an ester prodrug thereof ((3P)-17-(pyridin-3-yl)androsta-5, 16-dien- 3-ol "abiraterone", or "abiraterone acetate”); and
  • abiraterone or an ester prodrug thereof ((3P)-17-(pyridin-3-yl)androsta-5, 16-dien- 3-ol "abiraterone", or "abiraterone acetate”); and
  • prostate cancer including castrate resistant prostate cancer and metastatic castrate resistant prostate cancer.
  • the collimated X-ray source was passed through a fixed divergence slit.
  • the sample was exposed for 0.2 seconds per 0.014° 2-theta increment (continuous scan mode) over the range 2 degrees to 40 degrees 2-theta in theta-theta mode.
  • the running time was approximately 9 minutes and 3 seconds.
  • the instrument was equipped with a Position sensitive detector. Control and data capture was by means of a Dell Optiplex 686 NT 4.0 Workstation operating with Diffrac+ software.
  • a 'TA Instruments Q1000' Differential Scanning Calorimeter was used to analyse Forms A, B and C of Compound (I). Typically less than 5mg of material (contained in a standard aluminium pan fitted with a lid) was heated from 25-300°C at a constant heating rate of 10°C/minute. A purge gas using nitrogen was used - flow rate 50mL per minute.
  • One skilled in the art will have the ability to determine substantial identities of diffractograms, spectra and thermograms.
  • WO 2009/047563 discloses three processes for the preparation of Compound (I) - Example 9 and alternative routes 1 and 2.
  • “Example 9 alternative route 1" includes a slurry of Compound (I) in ethyl acetate, the other two processes isolate Compound (I) as a solid by evaporating fractions of a column.
  • Three historical batches of Compound (I) from our compound collection synthesised using a procedure identical to, or substantially similar to, one of these three processes were analysed by XRD and all three identified as being a semi-crystalline form, designated as Form A, that had a melting point of 155.2°C (onset).
  • Example 1 Preparation of Form B
  • Form A was placed in a vial with a magnetic flea, and approximately 2mL of methanol added, the vial was then sealed tightly with a cap and left to stir on a magnetic stirrer plate. After 3 days, the sample was removed from the plate, the cap taken off and the slurry left to dry under ambient conditions before it was analysed by XRPD and DSC.
  • This form (Form C) was determined to be semi- crystalline by XRPD. This material had a melting point of 142.7°C (onset) and a peak at about 149.2°C, followed by a further melting endotherm with an onset of 161.6°C and a peak at 164.5°C.
  • the initially produced Form A of Compound (I) may be converted to Form B using the following process: Compound (I) is mixed with 7-8 relative volumes of absolute ethanol and the mixture is then heated to 70-75°C under reflux. The mixture is then filtered to remove undissolved particulate matter and the filtrate is cooled to 60-65°C. A small amount of previously prepared seed (e.g. 0.5wt% of Form B of Compound (I)) is then added to the mixture. The fluid surrounding the reaction vessel is then cooled to -10°C at a cooling rate of 0.3°C/minute and then the mixture is stirred for a further 8-12 hours before the resulting solid is isolated by filtration.
  • a small amount of previously prepared seed e.g. 0.5wt% of Form B of Compound (I)

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
PCT/GB2013/050973 2012-04-17 2013-04-16 Crystalline forms of (s) -4-amino-n- (1- (4 - chlorophenyl) - 3 - hydroxypropyl) -1- (7h - pyrrolo [2, 3-d] pyrimidi n-4-yl) piperidine-4-carboxamide Ceased WO2013156772A1 (en)

Priority Applications (14)

Application Number Priority Date Filing Date Title
ES13718618.5T ES2650797T3 (es) 2012-04-17 2013-04-16 Formas cristalinas de (S)-4-amino-N- (1-(4-clorofenil)-3-hidroxipropil)-1-(7H-pirrolo [2,3-d] pirimidin-4-il) piperidina-4-carboxamida
JP2015506302A JP2015514741A (ja) 2012-04-17 2013-04-16 結晶形態の（Ｓ）−４−アミノ−Ｎ−（１−（４−クロロフェニル）−３−ヒドロキシプロピル）−１−（７Ｈ−ピロロ［２，３−ｄ］−ピリミジン−４−イル）ピペリジン−４−カルボキサミド
CN201380020297.1A CN104203953B (zh) 2012-04-17 2013-04-16 (s)‑4‑氨基‑n‑(1‑(4‑氯苯基)‑3‑羟丙基)‑1‑(7h‑吡咯并[2,3‑d]嘧啶‑4‑基)哌啶‑4‑甲酰胺的晶型
HK15106857.2A HK1206337B (en) 2012-04-17 2013-04-16 Crystalline forms of (s)-4-amino-n-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide
BR112014025586-5A BR112014025586B1 (pt) 2012-04-17 2013-04-16 Forma cristalina de (s)-4-amino-n-(1-(4-clorofenil)-3-hidroxipropil)-1-(7h-pirrolo[2,3-d] pirimidin4-il)piperidina-4-carboxamida, composições farmacêuticas compreendendo a mesma, seu uso e comprimido farmacêutico compreendendo a mesma
RU2014143529A RU2652377C3 (ru) 2013-04-16 Кристаллические формы (S)-4-амино-N-(1-(4-хлорфенил)-3-гидроксипропил)-1-(7Н-пирроло[2,3-d]пиримидин-4-ил)пиперидин-4-карбоксамида
KR1020147031099A KR20150002767A (ko) 2012-04-17 2013-04-16 결정질 형태의 (S)-4-아미노-N-(1-(4-클로로페닐)-3-히드록시프로필)-1-(7H-피롤로[2,3-ｄ]-피리미딘-4-일)피페리딘-4-카르복사미드
CA2869936A CA2869936C (en) 2012-04-17 2013-04-16 Crystalline forms of (s)-4-amino-n-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(7h-pyrrolo [2, 3-d] pyrimidi n-4-yl) piperidine-4-carboxamide
MX2014012642A MX2014012642A (es) 2012-04-17 2013-04-16 Formas cristalinas de (s) -4-amino-n- (1- (4-clorofenil) -3-hidroxipropil) -1- (7h-pirrolo [2,3-d] pirimidin-4-il) piperidina-4-carboxamida.
EP13718618.5A EP2847194B1 (en) 2012-04-17 2013-04-16 Crystalline forms of (s)-4-amino-n-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide
US14/394,918 US9487525B2 (en) 2012-04-17 2013-04-16 Crystalline forms of (s)-4-amino-n-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(7h-pyrrolo[2,3-d]pyrimidin-4-yl) piperidine-4-carboxamide
SG11201405963YA SG11201405963YA (en) 2012-04-17 2013-04-16 Crystalline forms of (s) -4-amino-n- (1- (4 - chlorophenyl) - 3 - hydroxypropyl) -1- (7h - pyrrolo [2, 3-d] pyrimidi n-4-yl) piperidine-4-carboxamide
IL234966A IL234966A0 (en) 2012-04-17 2014-10-02 Crystal forms of (4-(s-amino-4)-1)-n-chlorophenyl)-3-hydroxypropyl)-1-(7h-pyrrolo [3,2-d]pyrimidin-4-yl)piperidine-4-carboxamide
US15/291,370 US10039766B2 (en) 2012-04-17 2016-10-12 Crystalline forms of (s)-4-amino-n-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(7h-pyrrolo[2,3-d] pyrimidin-4-y1) piperidine-4-carboxamide

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201261625312P 2012-04-17 2012-04-17
US61/625,312 2012-04-17

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US14/394,918 A-371-Of-International US9487525B2 (en) 2012-04-17 2013-04-16 Crystalline forms of (s)-4-amino-n-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(7h-pyrrolo[2,3-d]pyrimidin-4-yl) piperidine-4-carboxamide
US15/291,370 Division US10039766B2 (en) 2012-04-17 2016-10-12 Crystalline forms of (s)-4-amino-n-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(7h-pyrrolo[2,3-d] pyrimidin-4-y1) piperidine-4-carboxamide

Publications (1)

Publication Number Publication Date
WO2013156772A1 true WO2013156772A1 (en) 2013-10-24

Family

ID=48184235

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2013/050973 Ceased WO2013156772A1 (en) 2012-04-17 2013-04-16 Crystalline forms of (s) -4-amino-n- (1- (4 - chlorophenyl) - 3 - hydroxypropyl) -1- (7h - pyrrolo [2, 3-d] pyrimidi n-4-yl) piperidine-4-carboxamide

Country Status (15)

Country Link
US (2) US9487525B2 (cg-RX-API-DMAC7.html)
EP (1) EP2847194B1 (cg-RX-API-DMAC7.html)
JP (2) JP2015514741A (cg-RX-API-DMAC7.html)
KR (1) KR20150002767A (cg-RX-API-DMAC7.html)
CN (1) CN104203953B (cg-RX-API-DMAC7.html)
AU (1) AU2013204533B2 (cg-RX-API-DMAC7.html)
BR (1) BR112014025586B1 (cg-RX-API-DMAC7.html)
CA (1) CA2869936C (cg-RX-API-DMAC7.html)
ES (1) ES2650797T3 (cg-RX-API-DMAC7.html)
IL (1) IL234966A0 (cg-RX-API-DMAC7.html)
MX (1) MX2014012642A (cg-RX-API-DMAC7.html)
MY (1) MY175052A (cg-RX-API-DMAC7.html)
SG (1) SG11201405963YA (cg-RX-API-DMAC7.html)
TW (1) TWI605046B (cg-RX-API-DMAC7.html)
WO (1) WO2013156772A1 (cg-RX-API-DMAC7.html)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2815749A1 (en) 2013-06-20 2014-12-24 IP Gesellschaft für Management mbH Solid form of 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione having specified X-ray diffraction pattern
RU2674027C2 (ru) * 2014-05-28 2018-12-04 Астразенека Аб Способ получения AZD5363 (варианты) и применяемое в нем новое промежуточное соединение
WO2022147519A1 (en) * 2021-01-04 2022-07-07 Teva Pharmaceuticals International Gmbh Solid state forms of capivasertib and process for preparation thereof
WO2024245953A1 (en) 2023-05-26 2024-12-05 Astrazeneca Ab Pharmaceutical compositions

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017078752A1 (en) * 2015-11-06 2017-05-11 The Penn State Research Foundation Compositions and methods relating to cancer
CN119789849A (zh) * 2022-08-31 2025-04-08 阿斯利康(瑞典)有限公司 药物制剂
WO2025238662A1 (en) * 2024-05-15 2025-11-20 Msn Laboratories Private Limited, R&D Center Improved process for the preparation of 4-amino-n-[(1s)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidinecarboxamide and its salts
CN122234059A (zh) * 2024-12-12 2026-06-19 安礼特（上海）医药科技有限公司 卡匹色替盐型及其制备方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009047563A1 (en) 2007-10-11 2009-04-16 Astrazeneca Ab Pyrrolo [2, 3 -d] pyrimidin derivatives as protein kinase b inhibitors

Family Cites Families (65)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL297170A (cg-RX-API-DMAC7.html) 1963-04-04 1900-01-01
DE3372965D1 (en) 1982-07-23 1987-09-17 Ici Plc Amide derivatives
ES2138618T3 (es) 1992-03-31 2000-01-16 Btg Int Ltd Esteroides 17-sustituidos utiles en el tratamiento del cancer.
US5439686A (en) 1993-02-22 1995-08-08 Vivorx Pharmaceuticals, Inc. Methods for in vivo delivery of substantially water insoluble pharmacologically active agents and compositions useful therefor
US6749868B1 (en) 1993-02-22 2004-06-15 American Bioscience, Inc. Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof
WO1999000113A1 (en) 1997-06-27 1999-01-07 Vivorx Pharmaceuticals, Inc. Novel formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof
GB9312853D0 (en) 1993-06-22 1993-08-04 Euro Celtique Sa Chemical compounds
EP0944388A4 (en) 1996-04-03 2001-08-16 Merck & Co Inc INHIBITORS OF FARNESYL PROTEIN TRANSFERASE
US6432947B1 (en) 1997-02-19 2002-08-13 Berlex Laboratories, Inc. N-heterocyclic derivatives as NOS inhibitors
WO1999007703A1 (en) 1997-08-05 1999-02-18 Pfizer Products Inc. 4-AMINOPYRROLE(3,2-d) PYRIMIDINES AS NEUROPEPTIDE Y RECEPTOR ANTAGONISTS
US6162804A (en) 1997-09-26 2000-12-19 Merck & Co., Inc. Tyrosine kinase inhibitors
AU4231299A (en) 1998-06-04 1999-12-20 Abbott Laboratories Cell adhesion-inhibiting antinflammatory compounds
PA8474101A1 (es) 1998-06-19 2000-09-29 Pfizer Prod Inc Compuestos de pirrolo [2,3-d] pirimidina
US6262066B1 (en) 1998-07-27 2001-07-17 Schering Corporation High affinity ligands for nociceptin receptor ORL-1
HK1045306A1 (zh) 1999-06-03 2002-11-22 Abbott Laboratories 抑制细胞黏附的抗炎化合物
US7160890B2 (en) 1999-12-02 2007-01-09 Osi Pharmaceuticals, Inc. Compounds specific to adenosine A3 receptor and uses thereof
OA12292A (en) 2000-06-26 2003-11-11 Pfizer Prod Inc PyrroloÄ2,3-dÜpyrimidine compounds as immunosuppressive agents.
KR100602929B1 (ko) 2000-08-31 2006-07-20 에프. 호프만-라 로슈 아게 알파-1 아드레날린성 길항제로서 퀴나졸린 유도체
BR0115847A (pt) 2000-12-01 2004-02-25 Osi Pharm Inc Compostos especìficos para receptor para adenosina a1, a2a, e a3 e usos dos mesmos
US6680324B2 (en) 2000-12-01 2004-01-20 Osi Pharmaceuticals, Inc. Compounds specific to adenosine A1 receptors and uses thereof
US6673802B2 (en) 2000-12-01 2004-01-06 Osi Pharmaceuticals, Inc. Compounds specific to adenosine A3 receptor and uses thereof
UY27220A1 (es) 2001-03-23 2002-09-30 Aventis Pharma Sa Combinación de un taxano con una quinasa ciclina-dependiente
DE60305446T4 (de) 2002-01-07 2009-07-09 Eisai R&D Management Co., Ltd. Desazapurine und deren verwendung
TW200403058A (en) 2002-04-19 2004-03-01 Bristol Myers Squibb Co Heterocyclo inhibitors of potassium channel function
NZ535992A (en) 2002-05-17 2008-11-28 Aventis Pharma Sa Use of docetaxel/doxorubicin/cyclophosphamide in adjuvant therapy of breast and ovarian cancer
DK1522314T3 (da) 2002-06-26 2014-05-26 Ono Pharmaceutical Co Midler for sygdomme forårsaget af vaskulær sammentrækning eller udvidelse
US20040138238A1 (en) 2002-08-08 2004-07-15 Dhanoa Dale S. Substituted aminopyrimidine compounds as neurokinin antagonists
US20030139427A1 (en) 2002-08-23 2003-07-24 Osi Pharmaceuticals Inc. Bicyclic pyrimidinyl derivatives and methods of use thereof
WO2004021979A2 (en) 2002-09-06 2004-03-18 Smithkline Beecham Corporation PYRROLO[2, 3-d]PYRIMIDINE-4-YL AND PURIN-6-YL UREA COMPOUNDS
US20060159617A1 (en) 2002-11-08 2006-07-20 Ashfaq Mahmood Small technetium-99m and rhenium labeled agents and methods for imaging tissues, organs and tumors
AU2003302657B8 (en) 2002-12-04 2009-12-03 Eisai R&D Management Co., Ltd. Fused 1,3-dihydroimidazole ring compounds
EP1444982A1 (de) 2003-02-06 2004-08-11 Merckle Gmbh Verwendung von Purinderivaten als selektive Kinase-Inhibitoren
MXPA05009722A (es) 2003-03-10 2006-03-09 Schering Corp Inhibidores heterociclicos de cinasa: metodos de uso y sintesis.
AU2004232392A1 (en) 2003-04-21 2004-11-04 Ustav Organicke Chemie A Biochemie Akademie Ved Ceske Republiky (Purin-6-yl) amino acid and production method thereof
FR2856685B1 (fr) 2003-06-25 2005-09-23 Merck Sante Sas Derives de thiazolylpiperidine, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent
WO2005020921A2 (en) 2003-08-29 2005-03-10 Exelixis, Inc. C-kit modulators and methods of use
CN100457108C (zh) * 2003-09-02 2009-02-04 默克公司 一种二肽基肽酶iv抑制剂的磷酸盐新晶体
WO2005044181A2 (en) 2003-09-09 2005-05-19 Temple University-Of The Commonwealth System Of Higher Education Protection of tissues and cells from cytotoxic effects of ionizing radiation by abl inhibitors
TW200526626A (en) 2003-09-13 2005-08-16 Astrazeneca Ab Chemical compounds
AU2004293026B2 (en) 2003-11-21 2012-01-19 Array Biopharma Inc. AKT protein kinase inhibitors
WO2005063704A1 (ja) 2003-12-25 2005-07-14 Ono Pharmaceutical Co., Ltd. アゼチジン環化合物およびその医薬
WO2005117909A2 (en) 2004-04-23 2005-12-15 Exelixis, Inc. Kinase modulators and methods of use
MY179032A (en) 2004-10-25 2020-10-26 Cancer Research Tech Ltd Ortho-condensed pyridine and pyrimidine derivatives (e.g.purines) as protein kinase inhibitors
UY29177A1 (es) 2004-10-25 2006-05-31 Astex Therapeutics Ltd Derivados sustituidos de purina, purinona y deazapurina, composiciones que los contienen métodos para su preparación y sus usos
AU2005322085B2 (en) 2004-12-28 2012-07-19 Exelixis, Inc. [1H-pyrazolo[3, 4-d]pyrimidin-4-yl]-piperidine or -piperazine compounds as serine-threonine kinase modulators (p70S6K, Atk1 and Atk2) for the treatment of immunological, inflammatory and proliferative diseases
FR2880626B1 (fr) 2005-01-13 2008-04-18 Aventis Pharma Sa Derives de la purine, compositions les contenant et utilisation
FR2880540B1 (fr) 2005-01-13 2008-07-11 Aventis Pharma Sa Utilisation de derives de la purine comme inhibiteurs de la proteine hsp90
US7423043B2 (en) 2005-02-18 2008-09-09 Lexicon Pharmaceuticals, Inc. 4-Piperidin-1-yl-7H-pyrrolo[2,3-d]pyrimidine compounds
NZ564223A (en) 2005-05-13 2011-03-31 Univ California Diarylhydantoin compounds for treating hormone refractory prostate cancer
US20060281768A1 (en) 2005-06-10 2006-12-14 Gaul Michael D Thienopyrimidine and thienopyridine kinase modulators
JP5071374B2 (ja) 2005-07-14 2012-11-14 アステラス製薬株式会社 ヘテロ環ヤヌスキナーゼ３阻害剤
US20070049591A1 (en) 2005-08-25 2007-03-01 Kalypsys, Inc. Inhibitors of MAPK/Erk Kinase
CN101291658B (zh) 2005-08-31 2014-04-16 阿布拉科斯生物科学有限公司 用于制备稳定性增加的水难溶性药物的组合物和方法
US7771751B2 (en) 2005-08-31 2010-08-10 Abraxis Bioscience, Llc Compositions comprising poorly water soluble pharmaceutical agents and antimicrobial agents
WO2007084667A2 (en) 2006-01-19 2007-07-26 Osi Pharmaceutical, Inc. Fused heterobicyclic kinase inhibitors
WO2007125321A2 (en) 2006-04-25 2007-11-08 Astex Therapeutics Limited Purine and deazapurine derivatives as pharmaceutical compounds
EP2037931A2 (en) 2006-04-25 2009-03-25 Astex Therapeutics Limited Pharmaceutical combinations of pk inhibitors and other active agents
JP2009534456A (ja) 2006-04-25 2009-09-24 アステックス、セラピューティックス、リミテッド 医薬化合物
JP2009534454A (ja) 2006-04-25 2009-09-24 アステックス、セラピューティックス、リミテッド 医薬化合物
US20090253718A1 (en) 2006-04-25 2009-10-08 Astex Therapeutics Limited Pharmaceutical Compounds
AR064416A1 (es) 2006-12-21 2009-04-01 Cancer Rec Tech Ltd Derivados de purina, piridina y pirimidina condensadas con heterociclos, moduladores de pka y/o pkb, composiciones farmaceuticas que los contienen, y usos para el tratamiento de enfermedades hiperproliferativas.
AR064415A1 (es) 2006-12-21 2009-04-01 Cancer Rec Tech Ltd Derivados de pirrolo-piperidinas y purinas,composiciones farmaceuticas que los contienen y usos en trastornos y/o enfermedades mediadas por pka y pkb.
WO2008079346A1 (en) 2006-12-21 2008-07-03 Vertex Pharmaceuticals Incorporated 5-cyan0-4- (pyrrolo [2, 3b] pyridine-3-yl) -pyrimidine derivatives useful as protein kinase inhibitors
WO2010092371A1 (en) 2009-02-10 2010-08-19 Astrazeneca Ab Triazolo [4,3-b] pyridazine derivatives and their uses for prostate cancer
MX367640B (es) * 2011-11-30 2019-08-29 Astrazeneca Ab Tratamiento combinado del cáncer.

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009047563A1 (en) 2007-10-11 2009-04-16 Astrazeneca Ab Pyrrolo [2, 3 -d] pyrimidin derivatives as protein kinase b inhibitors

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BUNN, C.W.: "Chemical Crystallography", 1948, CLARENDON PRESS
JENKINS, R; SNYDER, R.L: "Introduction to X-Ray Powder Diffractometry", 1996, JOHN WILEY & SONS
KLUG, H. P.; ALEXANDER, L. E., X-RAY DIFFRACTION PROCEDURES, 1974

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2815749A1 (en) 2013-06-20 2014-12-24 IP Gesellschaft für Management mbH Solid form of 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione having specified X-ray diffraction pattern
RU2674027C2 (ru) * 2014-05-28 2018-12-04 Астразенека Аб Способ получения AZD5363 (варианты) и применяемое в нем новое промежуточное соединение
WO2022147519A1 (en) * 2021-01-04 2022-07-07 Teva Pharmaceuticals International Gmbh Solid state forms of capivasertib and process for preparation thereof
US20240051964A1 (en) * 2021-01-04 2024-02-15 Teva Pharmaceuticals International Gmbh Solid state forms of capivasertib and process for preparation thereof
WO2024245953A1 (en) 2023-05-26 2024-12-05 Astrazeneca Ab Pharmaceutical compositions

Also Published As

Publication number Publication date
MX2014012642A (es) 2014-11-25
CA2869936A1 (en) 2013-10-24
CN104203953A (zh) 2014-12-10
ES2650797T3 (es) 2018-01-22
TW201345913A (zh) 2013-11-16
BR112014025586A2 (cg-RX-API-DMAC7.html) 2017-06-20
SG11201405963YA (en) 2014-11-27
RU2652377C2 (ru) 2018-04-26
AU2013204533B2 (en) 2017-02-02
EP2847194A1 (en) 2015-03-18
EP2847194B1 (en) 2017-10-04
HK1206337A1 (en) 2016-01-08
BR112014025586B1 (pt) 2022-02-22
KR20150002767A (ko) 2015-01-07
RU2014143529A (ru) 2016-06-10
CN104203953B (zh) 2016-11-16
JP2018039807A (ja) 2018-03-15
US20170027943A1 (en) 2017-02-02
US20150087661A1 (en) 2015-03-26
MY175052A (en) 2020-06-03
TWI605046B (zh) 2017-11-11
US10039766B2 (en) 2018-08-07
CA2869936C (en) 2020-07-28
AU2013204533A1 (en) 2013-10-31
JP2015514741A (ja) 2015-05-21
IL234966A0 (en) 2014-12-31
US9487525B2 (en) 2016-11-08

Similar Documents

Publication Publication Date Title
US10039766B2 (en) Crystalline forms of (s)-4-amino-n-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(7h-pyrrolo[2,3-d] pyrimidin-4-y1) piperidine-4-carboxamide
HK1248217A1 (zh) 选择性cdk4/6抑制剂的固态形式
JP4456079B2 (ja) ｛６，７−ビス（２−メトキシ−エトキシ）−キナゾリン−４−イル｝−（３ｅ）の多形体
WO2020079637A1 (en) Pharmaceutical composition for oral administration comprising aminopyrimidine derivative or its salt
US20100249063A1 (en) Amorphous body composed of heterocyclic compound, solid dispersion and pharmaceutical preparation each comprising the same, and process for production of the same
EP3808742A1 (en) Polymorph of selinexor
JP2023025000A (ja) （ｓ）－［３，４－ジフルオロ－２－（２－フルオロ－４－ヨードフェニルアミノ）フェニル］［３－ヒドロキシ－３－（ピペリジン－２－イル）アゼチジン－１－イル］－メタノンの結晶性フマル酸塩
US7932383B2 (en) Crystalline forms of [(1R), 2S]-2-aminopropionic acid 2-[4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy]-1-methylethyl ester
HK1206337B (en) Crystalline forms of (s)-4-amino-n-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide
RU2828311C1 (ru) Фармацевтическая композиция, способ ее получения и ее применение
JP7671362B2 (ja) 医薬組成物、その製造方法及び使用
CN120383595A (zh) 抑制cdk4/6活性化合物的半l-酒石酸盐一水合物
EA046959B1 (ru) Фармацевтическая композиция для перорального введения, содержащая производное аминопиримидина или его соль
HK40023529A (en) Solid forms of a selective cdk4/6 inhibitor
HK40058521A (en) Pharmaceutical composition for oral administration comprising aminopyrimidine derivative or its salt
HK40058521B (en) Pharmaceutical composition for oral administration comprising aminopyrimidine derivative or its salt
EP4100125A1 (en) Polymorph of rucaparib mesylate

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: 13718618

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2869936

Country of ref document: CA

ENP Entry into the national phase

Ref document number: 2015506302

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 14394918

Country of ref document: US

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: MX/A/2014/012642

Country of ref document: MX

REEP Request for entry into the european phase

Ref document number: 2013718618

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2013718618

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 20147031099

Country of ref document: KR

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 2014143529

Country of ref document: RU

Kind code of ref document: A

REG Reference to national code

Ref country code: BR

Ref legal event code: B01A

Ref document number: 112014025586

Country of ref document: BR

ENP Entry into the national phase

Ref document number: 112014025586

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20141014