WO2017149550A1 - Forme amorphe du 4-méthyl-n-[3-(4-méthyl-1h-imidazol-1-yl)-5-(trifluorométhyl)phényl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzamide - Google Patents

Forme amorphe du 4-méthyl-n-[3-(4-méthyl-1h-imidazol-1-yl)-5-(trifluorométhyl)phényl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzamide Download PDF

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WO2017149550A1
WO2017149550A1 PCT/IN2017/000053 IN2017000053W WO2017149550A1 WO 2017149550 A1 WO2017149550 A1 WO 2017149550A1 IN 2017000053 W IN2017000053 W IN 2017000053W WO 2017149550 A1 WO2017149550 A1 WO 2017149550A1
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methyl
pyridinyl
phenyl
pyrimidinyl
trifluoromethyl
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Srinivasan Thirumalai Rajan
Sajja Eswaraiah
Gogulapati Venkata Panakala Rao
Boge RAJESHAM
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MSN Laboratories Pvt Ltd
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MSN Laboratories Pvt Ltd
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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
    • A61K31/495—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
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • 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

Definitions

  • the present invention relates to amorphous form of 4-methyl-N-[3-(4-methyl-lH- imidazol-l-yl)-5-(trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]- benzamide compound of fo structural formula:
  • Nilotinib hydrochloride is a kinase inhibitor, approved as Nilotinib hydrochloride monohydrate, sold using the trade name Tasigna®, in the form of capsule for the treatment of chronic phase and accelerated phase Philadelphia chromosome positive chronic myelogenous leukemia (CML) in adult patients resistant to or intolerant to prior therapy that included imatinib.
  • Nilotinib hydrochloride designated as forms Tl, T2, T3, T4, T5, T6, T7, T8, T9, T10, Ti l , T12, T13, T14, T15 T16, T17, T18, and T19. Further, it also describes solid dispersion of Nilotinib hydrochloride in combination with a pharmaceutically suitable excipient.
  • International publication No. WO201 1/163222 describes polymorphic forms of
  • Nilotinib hydrochloride designated as forms T20, T27, T28 and T29.
  • Nilotinib hydrochloride crystalline form HI characterized by peaks in the powder x-ray diffraction spectrum having 2-theta angle positions at about 8.6, 1 1 .4, 13.2, 14.3, 15.5, 1 7.3, 19.2 and 25.3 ⁇ 0.2 degrees and process for its preparation.
  • IP.com Journal (2010), 10(3B), 1 1 describes the crystalline forms T24, T25, and T26 of Nilotinib hydrochloride and process for their preparation.
  • Nilotinib hydrochloride designated as Forms T19 and T20 and process for their preparation.
  • IP.com Journal (2009), 9( 12B), 14 describes the Nilotinib hydrochloride crystalline forms T2-T6, T9 and Tl 1 -T13 and process for their preparation.
  • IP.com Journal (2010), 10(5A), 25 describes the Nilotinib hydrochloride crystall ine form T5 and process for its preparation.
  • IP.com Journal (2010), 10(7B), 3 describes a method for the preparation of the of 4- methyl-N-[3-(4-methyl- l H-imidazol- l -yl)-5-(trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2- pyrimidinyl]amino]-benzamide salts in amorphous form.
  • Polymorphism is the occurrence of different crystall ine forms of a single compound and it is a property of some compounds and complexes. Thus, polymorphs are distinct solids sharing the same molecular formula, yet each polymorph may have distinct physical properties.
  • a single compound may give rise to a variety of polymorphic forms where each form has different and distinct physical properties, such as different solubil ity profiles, different melting point temperatures and/or different x-ray diffraction peaks. Since the solubility of each polymorph may vary, identifying the existence of pharmaceutical polymorphs is essential for providing pharmaceuticals with predicable solubil ity profiles. It is desirable to investigate all solid state forms of a drug, including all polymorphic forms, and to determine the stability, dissolution and flow properties of each polymorphic form.
  • Polymorphic forms of a compound can be distinguished in a laboratory by X-ray diffraction spectroscopy and by other methods such as, infrared spectrometry.
  • polymorphic forms of the same drug substance or active pharmaceutical ingredient can be administered by itself or formulated as a drug product (also known as the final or finished dosage form), and are well known in the pharmaceutical art to affect, for example, the solubility, stability, flowability, tractability and compressibility of drug substances and the safety and efficacy of drug products.
  • amorphous form of some of the drugs exhibit much higher bioavailability than the crystalline forms, which leads to the selection of the amorphous form as the final drug substance for pharmaceutical dosage from development.
  • the aqueous solubility of crystalline form is lower than its amorphous form in some of the drugs, which may resu lt in the difference in their in vivo bioavailability. Therefore, it is desirable to have amorphous forms of drugs with high purity to meet the needs of regulatory agencies and also highly reproducible processes for their preparation. Accordingly, there remains a need to reproducibly obtain amorphous nilotinib free base of similar quality for use in a pharmaceutical preparation.
  • the first aspect of the present invention is to provide an amorphous form of 4-methyl- N-[3-(4-methyl- l H-imidazol- l -yl)-5-(trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2- pyrimidinyl]amino]-benzamide compound of formula- 1.
  • the second aspect of the present invention is to provide a process for the preparation of amorphous form of 4-methyl-N-[3-(4-methyl- l H-imidazol- ] -yl)-5-(trifluoromethyl) phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzamide compound of formula- 1.
  • the third aspect of the present invention is to provide a process for the preparation of amorphous sol id dispersion of 4-methyl-N-[3-(4-methyl- l H-im idazoI- l -yl)-5-(trifluoro methyl)phenyl]-3-[[4-(3-pyrid inyl)-2-pyrimidinyl]am ino]-benzamide compound of formula- 1 in combination with one or more pharmaceutical acceptable carrier.
  • Figure 1 Illustrates the PXRD pattern of amorphous 4-methyl-N-[3-(4-methyl- l H-im idazol- l -yl)-5-(trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzamide.
  • Figure 2 Illustrates the PXRD pattern of amorphous solid dispersion of 4-methyl-N-[3-(4- methyl- l H-imidazol- l -yl)-5-(trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl] amino]-benzamide in combination with HPC.
  • Figure 3 Illustrates the PXRD pattern of amorphous solid dispersion of 4-methyl-N-[3-(4- methyl- l H-imidazol- l -yl)-5-(trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl] amino]-benzamide in combination with PVP K-30.
  • Figure 4 Illustrates the PXRD pattern of amorphous solid dispersion of 4-methyl-N-[3-(4- methyl- l H-imidazol- l -yl)-5-(trifluoromethyl)phenyI]-3-[[4-(3-pyridinyl)-2-pyrimidinyl] amino]-benzamide in combination with HPMC.
  • suitable solvent refers to "hydrocarbon solvents” such as n-hexane, n-heptane, cyclohexane, pet ether, toluene, pentane, cycloheptane, methylcyclohexane, m-, o-, or p-xylene, and the like; "ether solvents” such as dimethoxy methane, tetrahydrofuran, 1 ,3-dioxane, 1 ,4-dioxane, furan, diethyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, triethylene glycol dimethyl ether, anisole, t-butyl methyl ether, 1 ,2-dimethoxy ethane and the like; "ester solvents” such as methyl acetate,
  • the first aspect of the present invention provides an amorphous form of 4-methyl-N- [3-(4-methyl- l H-imidazol- l -yl)-5-(trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2- pyrimidinyl]amino]-benzamide compound of formula- 1 .
  • the amorphous form of 4-methyl-N-[3-(4-methyl- l H-im idazol- l -yl)-5-(trifluoro methyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzamide compound of formula- 1 is further characterized by powder x-ray diffraction pattern as depicted in figure 1 .
  • the second aspect of the present invention provides a process for the preparation of amorphous form of 4-methyI-N-[3-(4-methyl- l H-imidazol- l -yl)-5-(trifluoromethyl)phenyl]- 3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzamide compound of formula- 1 , comprising of the following steps:
  • step-b) removing the solvent from the filtrate obtained in step-b) or step-c) to provide amorphous form of 4-methyl-N-[3-(4-methyl- l H-imidazol- l -yl)-5-(trifluoiOmethyl) phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]am ino]-benzamide compound of formula- 1.
  • the suitable solvent is selected from alcohol solvents, chloro solvents, ester solvents, polar aprotic solvents, nitrile solvents, ketone solvents, hydrocarbon solvents and polar solvent like water or mixture thereof;
  • step-d) removal of solvent may be carried out by filtration, solvent dry distillation, spray drying, agitated thin film drying ("ATFD”), freeze drying (lyophilization), and the like or any other suitable technique or by adding suitable anti-solvent.
  • solvent dry distillation solvent dry distillation
  • spray drying agitated thin film drying
  • freeze drying lyophilization
  • the preferred embodiment of the present invention provides a process for the preparation of amorphous form of 4-methyl-N-[3-(4-methyl- l H-imidazol- l -yl)-5-(trifluoro methyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzamide compound of formula- 1 , comprising of the following steps:
  • step-c) spray drying the filtrate obtained in step-c) to provide amorphous form of 4-methyl- N-[3-(4-methyl- l H-imidazol- l -yl)-5-(trifluoiOmethyl)phenyl]-3-[[4-(3-pyridinyl)-2- pyrimidinyl]amino]-benzamide compound of formula- 1 .
  • the preferred embodiment of the present invention provides a process for the preparation of amorphous form of 4-methyl-N-[3-(4-methyl- l H-im idazol- l -yl)-5-(trifluoro methyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrim idinyl]amino]-benzamide compound of formu la- 1 , comprising of the following steps:
  • a preferred method to remove the solvent involves spray-drying, in which a solution of Nilotinib free base is sprayed with spray drier at the flow rate ranging from about 1 to about 30 ml/min, and preferably about 5 to about 20 ml/min.
  • the air inlet temperature to the spray drier used may range from about 25°C to about 150°C, and preferably from about 60°C to about 65°C and the outlet air temperature used may range from about 30° C. to about 90°C.
  • spray drying broadly refers to processes involving breaking up l iquid mixtures into small droplets (atomization) and rapidly removing solvent from the mixture.
  • spray drying apparatus there is a strong driving force for evaporation of solvent from the droplets, which may be provided by providing a drying gas.
  • Spray drying processes and equipment are described, for example, in Perry's Chemical Engineer's Handbook, pages. 20-54 to 20-57 (Sixth Edition 1984).
  • the solid residue obtained after the solvent removal is isolated and, if desired, can be dried further using conventional methods.
  • the advantages of the process include simplicity, eco-friendliness and suitability for commercial use.
  • the substantially pure amorphous Nilotinib free base obtained according to the present invention may be further drying by utilizing Vacuum Tray Dryer, Rotocon Vacuum Dryer, Vacuum Paddle Dryer or pi lot plant Rotavapor, to further lower residual solvents.
  • a typical spray drying apparatus comprises a drying chamber, atomizing means for atomizing a solvent-containing feed into the drying chamber, a source of drying gas that flows into the drying chamber to remove solvent from the atomized-solvent-containing feed, an outlet for the products of drying, and product collection means located downstream of the drying chamber.
  • atomizing means for atomizing a solvent-containing feed into the drying chamber
  • source of drying gas that flows into the drying chamber to remove solvent from the atomized-solvent-containing feed
  • an outlet for the products of drying and product collection means located downstream of the drying chamber.
  • Examples of such apparatuses include Niro Models PSD-I, PSD-2 and PSD-4 (Niro AJS, Soeborg, Denmark).
  • the product collection means collecting the product utilizing a cyclone connected to the drying apparatus.
  • the particles produced during spray drying are separated from the drying gas and evaporated solvent, allowing the particles to be collected.
  • a filter may also be used to separate and col lect the particles produced by spray drying.
  • Amorphous 4-methyl-N-[3-(4-methyl- l H-imidazol- l -yl)-5-(trifluoromethyl)phenyl]- 3-[[4-(3-pyridinyl)-2-pyrim idinyl]amino]-benzamide compound of formula- 1 obtained according to the present invention is substantially free of crystalline forms.
  • Amorphous 4-methyl-N-[3-(4-methyl- l H-imidazol- l -yl)-5-(trifluoromethyl)phenyl]- 3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzamide compound of formula- 1 obtained according to the present invention is substantially free from residual solvents.
  • the third aspect of the present invention provides a process for the preparation of amorphous solid dispersion of 4-methyl-N-[3-(4-methyl- l H-imidazol- l -yl)-5-(trifluoro methyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzamide compound of formula- 1 in combination with one or more pharmaceutical acceptable carrier, comprising of:
  • the suitable solvent is selected from alcohol solvents, ketone solvents, ester solvents, hydrocarbon solvents, ether solvents, chloro solvents, polar aprotic solvents, nitrile solvents and polar solvents like water or mixture thereof;
  • the suitable pharmaceutical acceptable carrier is selected from starches, modified starches, cellulose, methyl cellulose (MC), Microcrystalline cel lulose (MCC), ethyl cellulose (EC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), hydroxypropylmethyl cellulose (HPMC), hydroxypropyl methylcellulose acetate succinate (HPMC AS), polycarbophil, polyethylene glycol (PEG), polyethylene oxides, polyoxyalkylene derivatives, polymethacrylates, polyvinyl pyrrolidone (PVP), PVP K-30, polyvinyl acetate (PVAc), PVP vinylacetate-copolymer (PVP-VA), Kollidon VA 64 (vinylpyrrolidone-vinyl acetate copolymer), lactose, sorbitol, mannitol, maltitol, saccharose, isomalt, cyclodextrins such as cc-
  • propyl-cyclodextrin sodium carboxymethyl cellulose cross linked polyacrylic acid (carbipol), or a mixture thereof; in step-e)
  • the isolation can be carried out using a rotational distillation device such as a Buchi Rotavapor, vacuum drying, spray drying, spray granulating, freeze drying and spray- freeze drying, agitated thin film drying (ATFD) or melt extrusion or freeze drying (lyophilization) or by any other suitable techniques.
  • a rotational distillation device such as a Buchi Rotavapor, vacuum drying, spray drying, spray granulating, freeze drying and spray- freeze drying, agitated thin film drying (ATFD) or melt extrusion or freeze drying (lyophilization) or by any other suitable techniques.
  • the preferred embodiment of the present invention provides a process for the preparation of amorphous solid dispersion of 4-methyl-N-[3-(4-methyl- l H-imidazol- l -yl)-5- (trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzamide compound of formula- 1 in combination with HPC, comprising of:
  • the preferred embodiment of the present invention provides a process for the preparation of amorphous solid dispersion of 4-methyl-N-[3-(4-methyl- l H-im tdazol- l -yl)-5- (trifliioromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]am ino]-benzamide compound of formula- 1 in combination with PVP -30, comprising of:
  • the preferred embodiment of the present invention provides a process for the preparation of amorphous solid dispersion of 4-methyl-N-[3-(4-methyl- 1 H-imidazol- 1 -yl)-5- (trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]am ino]-benzami compound of formula- 1 in combination with HPMC, comprising of:
  • Amorphous form of 4-methyl-N-[3-(4-methyl- l H-imidazol- l -yl)-5-(trifluoromethyl) phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzamide is useful in the preparation of pharmaceutical composition.
  • Amorphous 4-methyl-N-[3-(4-methyl-l H-imidazol- l -yl)-5-(trifluoromethyl)phenyl]- 3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzamide compound of formula- 1 obtained according to the present invention is having particle size distribution D90 less than 1 50 ⁇ , preferably less than 100 ⁇ , more preferably less than 50 ⁇ .
  • the invention also encompasses pharmaceutical compositions comprising compound of formula- 1 or salts thereof of the present invention.
  • pharmaceutical compositions or “pharmaceutical formulations” include tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, suppositories, or injection preparations.
  • P-XRD Method of Analysis PXRD analysis of compounds produced by the present invention were carried out using BRUKER D8 ADVANCE/AXS X-Ray diffractometer using Cu a radiation of wavelength 1.5406 A 0 and continuous scan speed of 0.03 min.
  • PSD method of Analysis Particle size distribution (PSD) analysis was performed using Malvern Mastersizer 2000 instrument.
  • Example-1 Preparation of Amorphous 4-methyl-N-[3-(4-methyI-lH-imidazol-l-yl)-5-
  • Inlet temperature 55°C to 60°C
  • Example-2 Preparation of Amorphous 4-methyl-N-[3-(4-methyl-lH-imidazol-l-yl)-5- (trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzamide:
  • the obtained filtrate was spray dried at below mentioned parameters to obtain amorphous 4-methyl-N-[3-(4-methyl- l H-imidazol- l - yl)-5-(trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzamide.
  • Inlet temperature 55°C to 60°C
  • Particle Size Distribution D(0. 1 ) is 2.26 ⁇ ; D(0.5) is 5.58 ⁇ ; D(0.9) is 1 1 .0 ⁇ ; D[4.3] is 6.20 um.
  • the P-XRD pattern of the obtained compound was shown in figure- 1 .
  • Example-3 Preparation of Amorphous 4-methyl-N-[3-(4-methyl-lH-imidazol-l-yl)-5- (trifluoromethyl)phenyl]-3-
  • the obtained filtrate was spray dried at below mentioned parameters to obtain amorphous 4-methyl-N-[3-(4-methyl- l H-imidazol- l -yl)-5-(trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]- benzamide.
  • Inlet temperature 55°C to 60°C
  • the P-XRD pattern of the obtained compound was shown in figure- 1 .
  • Exaniple-4 Preparation of Amorphous solid dispersion of 4-methyl-N-[3-(4-methyl-lH- imidazol-l-yl)-5-(trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]- benzamide in combination with HPC: (1 : 1)
  • the obtained filtrate was spray dried at below mentioned parameters to obtain amorphous sol id d ispersion of 4-methyl-N-[3-(4-methyl- l H-imidazol- l -yI)-5-(trifluoromethyl)phenyl]-3-[[4-(3- pyridinyl)-2-pyrimidinyl] amino]-benzamide in combination with HPC.
  • Inlet temperature 55°C to 60°C
  • ExampIe-5 Preparation of Amorphous solid dispersion of 4-methyl-N-[3-(4-methyl-lH- imidazol-l-yl)-5-(trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]- benzamide in combination with PVP K-30: (1 : 1 )
  • the obtained filtrate was spray dried at below mentioned parameters to obtain amorphous sol id dispersion of 4-methyl-N-[3- (4-methyl- l H-imidazol- l -yl)-5-(trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimid inyl] amino]-benzamide in combination with PVP K-30.
  • Inlet temperature 55°C to 60°C
  • ExampIe-6 Preparation of Amorphous solid dispersion of 4-methyl-N-[3-(4-methyl- l H- imidazol-l-yl)-5-(trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]- benzamide in combination with HPMC: (1 : 1)
  • the obtained filtrate was spray dried at below mentioned parameters to obtain amorphous solid dispersion of 4-methyl-N-[3-(4-methyl- l H-imidazol- l -yl)-5-(trifluoromethyl)phenyl]-3-[[4- (3-pyridinyl)-2-pyrimidinyl]amino]-benzamide in combination with HPMC.
  • Inlet temperature 55°C to 60°C

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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Abstract

La présente invention concerne une forme amorphe du 4-méthyl-N- [3-(4-méthyl-1H-imidazol-1-yl)-5-(trifluorométhyl)phényl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl] amino]-benzamide de formule 1 et son procédé de synthèse, représenté par la formule structurale suivante.
PCT/IN2017/000053 2016-03-02 2017-02-28 Forme amorphe du 4-méthyl-n-[3-(4-méthyl-1h-imidazol-1-yl)-5-(trifluorométhyl)phényl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzamide Ceased WO2017149550A1 (fr)

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IN201641007312 2016-03-02

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Cited By (4)

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WO2020172120A1 (fr) * 2019-02-18 2020-08-27 Slayback Pharma Llc Composition pharmaceutique du nilotinib
JP2022524424A (ja) * 2019-03-11 2022-05-02 ピーティーシー セラピューティクス， インコーポレイテッド 向上したバイオアベイラビリティを有する化合物形態及びその製剤
JP2023543815A (ja) * 2020-09-29 2023-10-18 シェンチェン ファーマシン シーオー．，エルティーディー． 医薬組成物
US12023335B2 (en) 2018-08-17 2024-07-02 Ptc Therapeutics, Inc. Method for treating pancreatic cancer

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WO2007015871A1 (fr) * 2005-07-20 2007-02-08 Novartis Ag Sels de 4-methyl-n-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide
WO2007015870A2 (fr) * 2005-07-20 2007-02-08 Novartis Ag Formes cristallines de 4-methyl-n-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide

Patent Citations (2)

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Publication number Priority date Publication date Assignee Title
WO2007015871A1 (fr) * 2005-07-20 2007-02-08 Novartis Ag Sels de 4-methyl-n-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide
WO2007015870A2 (fr) * 2005-07-20 2007-02-08 Novartis Ag Formes cristallines de 4-methyl-n-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12023335B2 (en) 2018-08-17 2024-07-02 Ptc Therapeutics, Inc. Method for treating pancreatic cancer
US11793809B2 (en) 2019-02-18 2023-10-24 Slayback Pharma Llc Pharmaceutical compositions of nilotinib
CN113573712A (zh) * 2019-02-18 2021-10-29 斯莱班克制药有限责任公司 尼洛替尼的药物组合物
EP3914252A4 (fr) * 2019-02-18 2022-03-30 Slayback Pharma LLC Composition pharmaceutique du nilotinib
WO2020172120A1 (fr) * 2019-02-18 2020-08-27 Slayback Pharma Llc Composition pharmaceutique du nilotinib
US10874671B2 (en) 2019-02-18 2020-12-29 Slayback Pharma Llc Pharmaceutical compositions of nilotinib
EP4509123A3 (fr) * 2019-02-18 2025-05-07 Slayback Pharma LLC Composition pharmaceutique du nilotinib
US12403140B2 (en) 2019-02-18 2025-09-02 Azurity Pharmaceuticals, Inc. Pharmaceutical compositions of nilotinib
JP2022524424A (ja) * 2019-03-11 2022-05-02 ピーティーシー セラピューティクス， インコーポレイテッド 向上したバイオアベイラビリティを有する化合物形態及びその製剤
JP2023543815A (ja) * 2020-09-29 2023-10-18 シェンチェン ファーマシン シーオー．，エルティーディー． 医薬組成物
EP4221690A4 (fr) * 2020-09-29 2024-10-30 Shenzhen Pharmacin Co., Ltd. Compositions pharmaceutiques
US12186316B2 (en) 2020-09-29 2025-01-07 Shenzhen Pharmacin Co., Ltd. Pharmaceutical compositions
US12527793B2 (en) 2020-09-29 2026-01-20 Shenzhen Pharmacin Co., Ltd. Pharmaceutical compositions

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