WO2021069571A1 - Polymorphe de lorlatinib - Google Patents

Polymorphe de lorlatinib Download PDF

Info

Publication number
WO2021069571A1
WO2021069571A1 PCT/EP2020/078254 EP2020078254W WO2021069571A1 WO 2021069571 A1 WO2021069571 A1 WO 2021069571A1 EP 2020078254 W EP2020078254 W EP 2020078254W WO 2021069571 A1 WO2021069571 A1 WO 2021069571A1
Authority
WO
WIPO (PCT)
Prior art keywords
lorlatinib
crystalline
range
crystalline form
temperature
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/EP2020/078254
Other languages
English (en)
Inventor
Doris Braun
Ulrich Griesser
Marijan STEFINOVIC
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.)
Sandoz AG
Original Assignee
Sandoz AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sandoz AG filed Critical Sandoz AG
Priority to EP20789571.5A priority Critical patent/EP4041396A1/fr
Publication of WO2021069571A1 publication Critical patent/WO2021069571A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/18—Bridged systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • reflection with regard to powder X-ray diffraction as used herein, means peaks in an X-ray diffractogram, which are caused at certain diffraction angles (Bragg angles) by constructive interference from X-rays scattered by parallel planes of atoms in solid material, which are distributed in an ordered and repetitive pattern in a long-range positional order.
  • a solid material is classified as crystalline material, whereas amorphous material is defined as solid material, which lacks long-range order and only displays short-range order, thus resulting in broad scattering.
  • long-range order e.g.
  • polymorph refers to crystalline forms having the same chemical composition but different spatial arrangements of the molecules, atoms, and/or ions forming the crystal.
  • mother liquor refers to the solution remaining after crystallization of a solid from said solution.
  • Figure 6 illustrates a representative PXRD of crystalline Form S-DMF of lorlatinib of the present invention.
  • the x-axis shows the scattering angle in °2-Theta
  • the y-axis shows the intensity of the scattered X-ray beam in counts of detected photons.
  • Form B of the present invention combines the advantageous properties of high physical stability and high solubility and is therefore the ideal solid-state form of lorlatinib for the preparation of an improved pharmaceutical composition e.g. a pharmaceutical composition with increased bioavailability, which is safe and effective during its whole shelf-life.
  • the present invention relates to an anhydrous and non-sovated crystalline form (Form B) of lorlatinib characterized by having an FTIR spectrum comprising peaks at wavenumbers of:
  • the present invention relates to an anhydrous and non-solvated crystalline form (Form B) of lorlatinib characterized by having an FTIR spectrum essentially the same as shown in Figure 3 of the present invention, when measured at a temperature in the range of from 20 to 30 °C with a diamond ATR cell.
  • Form B anhydrous and non-solvated crystalline form of lorlatinib characterized by having an FTIR spectrum essentially the same as shown in Figure 3 of the present invention, when measured at a temperature in the range of from 20 to 30 °C with a diamond ATR cell.
  • the present invention relates to an anhydrous and non-solvated crystalline form (Form B) of lorlatinib characterized by having a DSC curve comprising an endothermic peak having an onset at a temperature of (191 ⁇ 5) °C, preferably of (191 ⁇ 3) °C, more preferably of (191 ⁇ 1) °C, when measured at a heating rate of 10 K/min.
  • Form B an anhydrous and non-solvated crystalline form of lorlatinib characterized by having a DSC curve comprising an endothermic peak having an onset at a temperature of (191 ⁇ 5) °C, preferably of (191 ⁇ 3) °C, more preferably of (191 ⁇ 1) °C, when measured at a heating rate of 10 K/min.
  • the present invention relates to an anhydrous and non-solvated crystalline form (Form B) of lorlatinib characterized by having a TGA curve showing a mass loss of not more than 2.0 w-%, preferably of not more than 1.0 w-%, more preferably of not more than 0.5 w-%, based on the weight of the crystalline form, when heated from 25 to 200 °C at a rate of 10 K/min.
  • Form B an anhydrous and non-solvated crystalline form of lorlatinib characterized by having a TGA curve showing a mass loss of not more than 2.0 w-%, preferably of not more than 1.0 w-%, more preferably of not more than 0.5 w-%, based on the weight of the crystalline form, when heated from 25 to 200 °C at a rate of 10 K/min.
  • the present invention relates to a composition
  • a composition comprising the anhydrous and non-solvated crystalline form (Form B) of lorlatinib of the present invention as defined in any one of the above described embodiments, said composition having a PXRD comprising no reflections at 2-Theta angles of (9.6 ⁇ 0.2)°, (12.6 ⁇ 0.2)° and (16.2 ⁇ 0.2)°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalphai,2 radiation having a wavelength of 0.15419 nm.
  • step (b) desolvating the solvate provided in step (a);
  • the predetermined and/or effective amount of the anhydrous and non-solvated crystalline form (Form B) of lorlatinib or the composition comprising the crystalline form B of lorlatinib as defined in any one of the above described aspects and their corresponding embodiments is selected from the group consisting of 25 mg, 50 mg, 75 mg and 100 mg calculated as anhydrous and non-solvated lorlatinib.
  • the present invention relates to the anhydrous and non-solvated crystalline form (Form B) of lorlatinib or the composition comprising the crystalline form B of lorlatinib or the pharmaceutical composition comprising the same as defined in any one of the above described aspects and their corresponding embodiments for use as a medicament.
  • the invention concerns a method of treating and/or preventing cancer, said method comprising administering an effective amount of the anhydrous and non-solvated crystalline form (Form B) of lorlatinib or the composition comprising the crystalline form B of lorlatinib or the pharmaceutical composition comprising the same as defined in any one of the above described aspects and their corresponding embodiments to a patient in need of such a treatment.
  • anhydrous and non-solvated crystalline form (Form B) of lorlatinib or the composition comprising the crystalline form B of lorlatinib or the pharmaceutical composition comprising the same as defined in any one of the above described aspects and their corresponding embodiments to a patient in need of such a treatment.
  • the invention relates to a crystalline DMF solvate (Form S-DMF) of lorlatinib characterized by having a PXRD comprising reflections at 2-Theta angles of (7.6 ⁇ 0.2)°, (10.3 ⁇ 0.2)°, (12.6 ⁇ 0.2)°, (16.8 ⁇ 0.2)°, (17.2 ⁇ 0.2)°, (20.2 ⁇ 0.2)°, (21.3 ⁇ 0.2)°, (21.9 ⁇ 0.2)°, (23.4 ⁇ 0.2)° and (23.6 ⁇ 0.2)°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalphai,2 radiation having a wavelength of 0.15419 nm.
  • the invention relates to a crystalline DMF solvate (Form S-DMF) of lorlatinib characterized by having a PXRD comprising reflections at 2-Theta angles of (7.6 ⁇ 0.1)°, (10.3 ⁇ 0.1)°, (12.6 ⁇ 0.1)°, (16.8 ⁇ 0.1)°, (17.2 ⁇ 0.1)°, (20.2 ⁇ 0.1)°, (21.3 ⁇ 0.1)°, (21.9 ⁇ 0.1)°, (23.4 ⁇ 0.1)° and (23.6 ⁇ 0.1)°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalphai,2 radiation having a wavelength of 0.15419 nm.
  • Form S-DMF Form S-DMF
  • the present invention relates to a crystalline DMF solvate (Form S- DMF) of lorlatinib characterized by having a PXRD essentially the same as shown in Figure 6 of the present invention, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalphai,2 radiation having a wavelength of 0.15419 nm.
  • the present invention relates to a process for the preparation of the crystalline DMF solvate (Form S-DMF) of lorlatinib of the present invention comprising: a) contacting solid lorlatinib with DMF; b) separating at least a part of the crystalline lorlatinib DMF solvate from DMF and c) optionally drying the crystalline lorlatinib DMF solvate.
  • a process for the preparation of the crystalline DMF solvate (Form S-DMF) of lorlatinib of the present invention comprising: a) contacting solid lorlatinib with DMF; b) separating at least a part of the crystalline lorlatinib DMF solvate from DMF and c) optionally drying the crystalline lorlatinib DMF solvate.
  • any solid form of lorlatinib can be used as starting material in step (a) of the above described process e.g. crystalline lorlatinib, amorphous lorlatinib or mixtures thereof.
  • Suitable crystalline forms may for example be selected from the group consisting of Form 1-3 of WO 2014/207606 Al, Form 24 of WO 2019/073347 A1 and Form 7 of WO 2017/021823 Al, which may be prepared according to the teachings provided in the descriptions of the respective patent applications.
  • the starting material is amorphous lorlatinib, which can be prepared according to the procedure described in Example 2 of WO 2013/132376 Al.
  • the obtained crystals may then optionally be dried. Drying is performed at a temperature in the range of from about 15 to 25 °C. Drying may be performed for a period in the range of from about 1 to 48 hours, preferably of from about 1 to 24 hours. Drying is performed at ambient pressure. For example, the Form S-DMF crystals may be air-dired for 16 to 24 hours.
  • the invention relates to the use of the crystalline lorlatinib DMF solvate (Form S-DMF) as defined in anyone of the above described embodiments for the preparation of the anhydrous and non-solvated crystalline form (Form B) of lorlatinib or the composition comprising the crystalline form B of lorlatinib as defined in any one of the above described aspects and their corresponding embodiments.
  • Form S-DMF crystalline lorlatinib DMF solvate
  • Form B anhydrous and non-solvated crystalline form
  • the invention relates to a crystalline 1,4-dioxane solvate (Form S-DX) of lorlatinib characterized by having a PXRD comprising reflections at 2-Theta angles of:
  • the invention relates to a crystalline 1,4-dioxane solvate (Form S-DX) of lorlatinib characterized by having a PXRD comprising reflections at 2-Theta angles of (5.5 ⁇ 0.2)°, (7.0 ⁇ 0.2)°, (8.6 ⁇ 0.2)°, (9.0 ⁇ 0.2)°, (10.0 ⁇ 0.2)°, (15.0 ⁇ 0.2)°, (17.1 ⁇ 0.2)°, (18.8 ⁇ 0.2)°, (21.8 ⁇ 0.2)° and (22.2 ⁇ 0.2)°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalphai,2 radiation having a wavelength of 0.15419 nm.
  • Form S-DX crystalline 1,4-dioxane solvate
  • the present invention relates to a crystalline 1,4-dioxane solvate (Form S-DX) of lorlatinib characterized by having a PXRD comprising reflections at 2-Theta angles of:
  • the present invention relates to a crystalline 1,4-dioxane solvate (Form S-DX) of lorlatinib characterized by having a PXRD essentially the same as shown in Figure 7 of the present invention, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalpha i,2 radiation having a wavelength of 0.15419 nm.
  • Form S-DX crystalline 1,4-dioxane solvate
  • the present invention relates to a process for the preparation of the crystalline 1,4-dioxane solvate (Form S-DX) of lorlatinib of the present invention comprising: a) contacting solid lorlatinib with a solvent comprising 1,4-dioxane and optionally at least one anti solvent; b) separating at least a part of the crystalline lorlatinib 1,4-dioxane solvate from the solvent and c) optionally drying the crystalline lorlatinib 1,4-dioxane solvate.
  • any solid form of lorlatinib can be used as starting material in step (a) of the above described process e.g. crystalline lorlatinib, amorphous lorlatinib or mixtures thereof.
  • Suitable crystalline forms may for example be selected from the group consisting of Form 1-3 of WO 2014/207606 Al, Form 24 of WO 2019/073347 A1 and Form 7 of WO 2017/021823 Al, which may be prepared according to the teachings provided in the descriptions of the respective patent applications.
  • the starting material is amorphous lorlatinib, which can be prepared according to the procedure described in Example 2 of WO 2013/132376 Al.
  • the 1 ,4-dioxane///-heptane ratio may range from (v/v): 1:3, 1:2, 1:1, 2:1 and 3:1, most preferably the 1 ,4-dioxane///-heptane ratio is (v/v): 1:3.
  • Separating at least a part, preferably all of the crystalline lorlatinib 1,4-dioxanes solvate crystals from the solvent mixture comprising 1,4-dioxane and optionally at least one antisolvent encompasses any conventional method such as filtration, centrifugation or decantation.
  • the invention relates to the use of the crystalline lorlatinib 1,4-dioxane solvate (Form S-DX) as defined in anyone of the above described embodiments for the preparation of the anhydrous and non-solvated crystalline form (Form B) of lorlatinib or the composition comprising the crystalline form B of lorlatinib as defined in any one of the above described aspects and their corresponding embodiments.
  • Form S-DX crystalline lorlatinib 1,4-dioxane solvate
  • Lorlatinib Form S-DMF (e.g. prepared according to one of the procedures described in Example 2 herein) was air-dried for 24 hours at RT, then ground using a mortar and pestle. The sample was then air-dried for another 24 hours at RT. The solvate (approximately 200 mg) was then heated from RT to 180 °C using a heating rate of ⁇ 10 K/min. Heating was performed using a hot-stage microscope. The resulting solid form was characterised with powder X-ray diffaction and TGA and consisted of Form B. The sample was heated a second time from RT to 180 °C, heating rate ⁇ 10 K/min (HSM) and confirmed to still be form B using powder X-ray diffaction.
  • HSM heating rate ⁇ 10 K/min
  • Lorlatinib Form S-DX (e.g. prepared according to one of the procedures described in Example 3 herein) was air-dried for 30 minutes at RT, then ground using a mortar and pestle.
  • the solvate (approximately 150 mg) was then heated from RT to 180 °C using a heating rate of ⁇ 10 K/min. Heating was performed using a hot-stage microscope.
  • the resulting solid form was characterised with powder X-ray diffaction and TGA and consisted of Form B.
  • the sample was heated a second time from RT to 180 °C, heating rate ⁇ 10 K/min (HSM) and confirmed to still be form B using powder X-ray diffaction.
  • Amorphous lorlatinib 250 mg, e.g. prepared according to the procedure described in Example 2 of WO 2013/132376 Al was placed in a round-bottom flask and dissolved in DMF (2 mL). The solvent was evaporated using a rotary evaporator (40 °C/8-10 mbar) until crystallization of a white solid had occured. The obtained solid was air-dried for 24 hours to obtain lorlatinib Form S-DMF.
  • Amorphous lorlatinib 50 mg e.g. prepared according to the procedure described in Example 2 of WO 2013/132376 Al was placed into glass vials. Up to five drops of different mixtures of 1,4-dioxane and «-heptane (v/v): 1:3, 1:2, 1:1, 2:1 and 3:1 were added and the mixtures were stirred for 12 hours at RT. After filtration all experiments produced lorlatinib Form S-DX. Method B :
  • Example 4 Characterization of the solid-state forms of the present invention (Form B, Form S-DMF and Form S-DX)
  • Powder X-ray diffraction PXRDs of Form B, S-DMF and Form S-DX were recorded (at 25 °C) with an X’Pert PRO diffractometer (PANalytical, Almelo, The Netherlands) equipped with a Theta/Theta coupled goniometer in transmission geometry, programmable XYZ stage with well plate holder, Cu- Kai,2 radiation source with a focussing mirror, a 0.5° divergence slit, a 0.02° sober slit collimator and a 1° anti -scattering slit on the incident beam side, a 2 mm anti -scattering slit, a 0.04° sober slit collimator, a Ni-fbter and a solid-state PIXcel detector on the diffracted beam side.
  • X’Pert PRO diffractometer PANalytical, Almelo, The Netherlands
  • the patterns were recorded at a tube voltage of 40 kV, tube current of 40 mA, applying a step-size of 0.013° 2-Theta with 1000 s or 2400 s per step (255 channels) in the angular range of 2° to 40° 2-Theta.
  • a representative diffractogram of crystalline form B of lorlatinib is displayed in Figure 1 herein.
  • the corresponding reflection list is provided in Table 1 below.
  • Table 1 PXRD reflection positions of crystalline Form B of lorlatinib in the range of from 2 to 30° 2- Theta; a typical precision of the 2-Theta values is in the range of ⁇ 0.2° 2-Theta, preferably of ⁇ 0.1° 2- Theta.
  • Figure 2 illustrates an overlay of the PXRDs of lorlatinib Form B of the present invention (bottom) and Form 7 of WO 2017/021823 A1 (top).
  • both forms can be readily distinguished from each other by powder X-ray diffractometry.
  • the PXRD of lorlatinib Form B possesses refelections at (8.7 ⁇ 0.2)°, (13.3 ⁇ 0.2)°, (16.7 ⁇ 0.2)° and (18.8 ⁇ 0.2)° 2-Theta, whereas no reflections are visible in the PXRD of lorlatinib Form 7 in this range.
  • the PXRD of lorlatinib Form 7 displays i.a. reflections at (9.6 ⁇ 0.2)°, (12.6 ⁇ 0.2)° and (16.2 ⁇ 0.2)° 2-Theta, whereas the PXRD of lorlatinib Form 7 shows no reflection in these ranges.
  • a representative diffractogram of the crystalline DMF solvate (Form S-DMF) of lorlatinib is displayed in Figure 6 herein.
  • the corresponding reflection list is provided in Table 2 below.
  • Table 2 PXRD reflection positions of crystalline Form S-DMF of lorlatinib in the range of from 2 to 30° 2-Theta; a typical precision of the 2-Theta values is in the range of ⁇ 0.2° 2-Theta, preferably of ⁇ 0.G 2-Theta.
  • Table 3 PXRD reflection positions of crystalline Form S-DX of lorlatinib in the range of from 2 to 30° 2-Theta; a typical precision of the 2-Theta values is in the range of ⁇ 0.2° 2-Theta, preferably of ⁇ 0.1° 2-Theta.
  • Table 4 FTIR peak list of crystalline Form B of lorlatinib according to the present invention; atypica precision of the wavenumbers is in the range of ⁇ 4 cm 1 , preferably of ⁇ 2 cm 1 .
  • Differential scanning calorimetry DSC was performed on a Mettler Polymer DSC R instrument. The sample (4.46 mg) was heated in a 40 microL aluminium pan with a pierced aluminium lid from 25 to 250 °C at a rate of 10 K/min. Nitrogen (purge rate 50 mL/min) was used as purge gas.
  • a representative DSC curve (excerpt from 25 to 220 °C) is displayed in Figure 4 hereinafter and shows an endotherm with an onset temperature of about 191 °C and a peak temperature of about 198 °C, which is due to the melting of the sample.
  • TGA was carried out with a TGA7 system (Perkin-Elmer, Norwalk, Connecticut, USA) using Pyris 2.0 software. Approximately 4 mg of sample was weighed into a platinum pan. Two-point calibration of the temperature was performed with ferromagnetic materials (Alumel and Ni, Curie-point standards, Perkin-Elmer). The sample was heated to 225 °C at a rate of 10 K/min and dry nitrogen was used as a purge gas (sample purge: 20 mL/min, balance purge: 40 mL/min).
  • Form B was stored at ambient condition and the phase consistency analysed periodically using powder X-ray diffraction. No transformation to Form 7 or any other solid form was seen within 59 days.
  • Form B was stored at 40 °C (drying oven) and the phase identity checked periodically with powder X-ray diffraction. Within 47 days no transformation to Form 7 or any other form was seen.
  • Form B was stored at 98% RH (RT) and the phase identity checked periodically with powder X-ray diffraction. Within 55 days no transformation to Form 7 or any other form was seen.
  • Stress Condition D :
  • Drop shape analysis gives information about the wetting behaviour of a compound.
  • the shadow images of the sessile water drops were captured by a Kruess DSA25E instrument ⁇ Kruess, D-Hamburg, Germany ), equipped with illumination, a manual lift table (z-axis) and a video camera.
  • the software Kruess Advance 1.6.2 was used for measuring the contact angle. The results are displayed in Table 6 below:
  • Form B shows better water wettability than Form 7.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (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

La présente invention concerne un polymorphe de lorlatinib et un procédé pour sa préparation. La présente invention concerne également des solvates de lorlatinib, qui peuvent être utilisés en tant qu'intermédiaires pour la préparation du polymorphe de la présente invention. L'invention concerne également une composition pharmaceutique comprenant le polymorphe de lorlatinib de la présente invention, de préférence dans une quantité prédéterminée et/ou efficace et au moins un excipient pharmaceutiquement acceptable. La composition pharmaceutique de la présente invention peut être utilisée en tant que médicament, en particulier dans le traitement et/ou la prophylaxie de cancers tels que le cancer du poumon non à petites cellules (NSCLC).
PCT/EP2020/078254 2019-10-10 2020-10-08 Polymorphe de lorlatinib Ceased WO2021069571A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP20789571.5A EP4041396A1 (fr) 2019-10-10 2020-10-08 Polymorphe de lorlatinib

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP19202401 2019-10-10
EP19202401.6 2019-10-10

Publications (1)

Publication Number Publication Date
WO2021069571A1 true WO2021069571A1 (fr) 2021-04-15

Family

ID=68242557

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2020/078254 Ceased WO2021069571A1 (fr) 2019-10-10 2020-10-08 Polymorphe de lorlatinib

Country Status (2)

Country Link
EP (1) EP4041396A1 (fr)
WO (1) WO2021069571A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12391708B2 (en) 2019-07-18 2025-08-19 Tapi Croatia Industries Ltd Crystalline Lorlatinib : fumaric acid and solid state form thereof

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013132376A1 (fr) 2012-03-06 2013-09-12 Pfizer Inc. Dérivés macrocycliques pour le traitement de maladies prolifératives
WO2014207606A1 (fr) 2013-06-28 2014-12-31 Pfizer Inc. Formes solides d'un inhibiteur de kinases macrocycliques
WO2017021823A1 (fr) 2015-07-31 2017-02-09 Pfizer Inc. Forme cristalline de base libre de lorlatinib
WO2019073347A1 (fr) 2017-10-10 2019-04-18 Pfizer Inc. Forme cristalline d'hydrate de base libre de lorlatinib
WO2019209633A1 (fr) * 2018-04-23 2019-10-31 Pliva Hrvatska D.O.O. Formes à l'état solide de lorlatinib et préparation associée

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013132376A1 (fr) 2012-03-06 2013-09-12 Pfizer Inc. Dérivés macrocycliques pour le traitement de maladies prolifératives
WO2014207606A1 (fr) 2013-06-28 2014-12-31 Pfizer Inc. Formes solides d'un inhibiteur de kinases macrocycliques
WO2017021823A1 (fr) 2015-07-31 2017-02-09 Pfizer Inc. Forme cristalline de base libre de lorlatinib
WO2019073347A1 (fr) 2017-10-10 2019-04-18 Pfizer Inc. Forme cristalline d'hydrate de base libre de lorlatinib
WO2019209633A1 (fr) * 2018-04-23 2019-10-31 Pliva Hrvatska D.O.O. Formes à l'état solide de lorlatinib et préparation associée

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
VITALIJ K. PECHARSKYPETER Y. ZAVALIJ: "Fundamentals of Powder Diffraction and Structural Characterization of Materials", 2003, KLUWER ACADEMIC PUBLISHERS, pages: 3

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12391708B2 (en) 2019-07-18 2025-08-19 Tapi Croatia Industries Ltd Crystalline Lorlatinib : fumaric acid and solid state form thereof

Also Published As

Publication number Publication date
EP4041396A1 (fr) 2022-08-17

Similar Documents

Publication Publication Date Title
US20250188054A1 (en) Crystalline forms of n-(3-(2-(2-hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methvlphenyl)-2 (trifluoromethyl)isonicotinamide as raf inhibitors for the treatment of cancer
EP3808742A1 (fr) Polymorphe de selinexor
HK1248217A1 (zh) 选择性cdk4/6抑制剂的固态形式
EP4359410B1 (fr) Forme cristalline de sotorasib
EP3331881B1 (fr) Nouvelle forme crystalline et adduits d'acide acétique du palbociclib
US20210206770A1 (en) Co-Crystal of an Orally Available Janus Kinase Inhibitor
WO2016079313A1 (fr) Formes cristallines de dimaléate d'afatinib
CA3088596A1 (fr) Forme cristalline de bictegravir sodique
KR20150002767A (ko) 결정질 형태의 (S)-4-아미노-N-(1-(4-클로로페닐)-3-히드록시프로필)-1-(7H-피롤로[2,3-ｄ]-피리미딘-4-일)피페리딘-4-카르복사미드
EP3997090A1 (fr) Formes cristallines d'un kit sélectif disponible par voie orale et inhibiteur de kinase pdgfr
EP4041396A1 (fr) Polymorphe de lorlatinib
WO2020108941A1 (fr) Cristaux à plusieurs composants d'un inhibiteur de hif prolyl hydroxylase disponible par voie orale
WO2022069357A1 (fr) Forme cristalline du selpercatinib
WO2022117448A1 (fr) Formes cristallines de pralsetinib
WO2021259732A1 (fr) Composés à composants multiples comprenant du zanubrutinib et un dérivé d'acide benzoïque
EP4227305A1 (fr) Forme cristalline de sotorasib
WO2021156140A1 (fr) Polymorphe de mésylate de rucaparib
CA3080657A1 (fr) Sel cristallin d'un inhibiteur de poly(adp-ribose) polymerase tricyclique
US20250179025A1 (en) Crystalline form of darolutamide
HK40127061A (en) New crystalline forms of n-(3-(2-(2-hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methvlphenyl)-2(trifluoromethyl) isonicotinamide as raf inhibitors for the treatment of cancer
TW202440585A (zh) MDM2-p53抑制劑之晶型及醫藥組合物
HK40065390A (en) New crystalline forms of n-(3-(2-(2-hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methvlphenyl)-2(trifluoromethyl)isonicotinamide as raf inhibitors for the treatment of cancer
HK40065390B (en) New crystalline forms of n-(3-(2-(2-hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methvlphenyl)-2(trifluoromethyl)isonicotinamide as raf inhibitors for the treatment of cancer
HK40023529A (en) Solid forms of a selective cdk4/6 inhibitor

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: 20789571

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2020789571

Country of ref document: EP

Effective date: 20220510

WWW Wipo information: withdrawn in national office

Ref document number: 2020789571

Country of ref document: EP