- Impurity Free and Scalable Process of Sorafenib Tosyalte: Hepatocellular Carcinoma
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An efficient, impurities free and scalable process of hepatocellular carcinoma and renal cell carcinoma of sorafenib tosylate with good quality and higher yield.
- Birudaraju, Saritha,Kasina, Krishna Chaitanya,Tirukkovalluri, Siva Rao
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p. 711 - 714
(2022/02/22)
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- Synthesis, anticancer activity, and β-lactoglobulin binding interactions of multitargeted kinase inhibitor sorafenib tosylate (SORt) using spectroscopic and molecular modelling approaches
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Sorafenib tosylate (SORt) is an oral multikinase inhibitor used for treatment of advanced renal cell, liver, and thyroid cancers. In this study, this drug was synthesized and its antiproliferative activities against HCT116 and CT26 cells were assessed. The interaction of SORt with β-lactoglobulin (BLG) was studied using different fluorescence techniques, circular dichroism (CD), zeta potential measurements, and docking simulation. The results of infrared (IR), mass, HNMR, and CNMR spectra demonstrated that the drug was produced with high quality, purity, and efficiency. SORt showed potent cytotoxicity against HCT116 and CT26 cells with IC50 of 8.12 and 5.42 μM, respectively. For BLG binding of SORt, the results showed that static quenching was the cause of the high affinity drug–protein interaction. Three-dimensional fluorescence and synchronous spectra indicated that SORt conformation was changed at different levels. CD suggested that the α-helix content remained almost constant in the BLG–SORt complex, whereas random coil content decreased. Zeta potential values of BLG were more positive after binding with SORt, due to electrostatic interactions between BLG and SORt. Thermodynamic parameters confirmed van der Waals and hydrogen bond interactions in the complex formation. Molecular modelling predicted the presence of hydrogen bonds and electrostatic forces in the BLG–SORt system, which was consistent with the experimental results.
- Tanzadehpanah, Hamid,Bahmani, Asrin,Hosseinpour Moghadam, Neda,Gholami, Hamid,Mahaki, Hanie,Farmany, Abbas,Saidijam, Massoud
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p. 117 - 128
(2020/08/19)
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- Preparation method of high-purity tosylate salt crystal III (by machine translation)
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The invention belongs to the field of pharmaceutical chemical engineering, and particularly relates to a preparation method of a high-purity tosylate salt crystal III. The method can effectively reduce the content of genotoxic impurities by controlling specific reaction conditions, and has a good technical effect. (by machine translation)
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- Sorafenib hemicamsylate and processes for preparation thereof
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The present invention relates to: novel sorafenib hemi camsylate salt for treating cancer (chemical formula III); a novel crystalline form thereof; and a method for manufacturing the same. More specifically, the present invention relates to: hemi camsylate salt having high stability, solubility, and purity; a crystalline form thereof; and a method for manufacturing the same. The problem to be solved by the present invention is to provide novel sorafenib salt which is easy to make various preparations, and the method for manufacturing novel salt.COPYRIGHT KIPO 2020
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- PROCESS FOR THE PREPARATION OF SORAFENIB TOSYLATE POLYMORPH III
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The present invention relates to a process for the preparation of sorafenib tosylate form III from sorafenib base through sorafenib tosylate methanol solvate. The present invention relates to an improved process for the preparation of Sorafenib tosylate form III with high purity and high yield. The present process controls the genotoxic impurities content in final API.
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Page/Page column 4
(2019/08/29)
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- Method for preparing sorafenib tosylate salt targeted anti-tumor drug
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The invention discloses a method for preparing a sorafenib tosylate salt targeted anti-tumor drug. The method is characterized in that a synthesis route is as followings (please see the specificationsfor the synthesis route), wherein carbonate (M2CO3) in the synthesis route is sodium carbonate, potassium carbonate or cesium carbonate, and a solvent in the synthesis route is MDF or DMA. The carbonate is adopted to replace potassium tert-butoxide, reaction operation is greatly simplified, and the cost is lowered; and through repeated testing and condition screening, the problem of excessively long reaction time is solved finally through heating reflux.
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- Variable scale method for preparing sorafenib tosylate ethanol solvate and type III sorafenib tosylate
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The present invention relates to a variable scale method for preparing a sorafenib tosylate ethanol solvate and type III sorafenib tosylate.
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Paragraph 0241-0243; 0312-0314; 0315-0322
(2018/07/30)
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- A paratoluene sulfonic acid zola non-nepal preparation method (by machine translation)
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The invention relates to a preparation method of toluene sulfonic acid zola non-nepal, in particular relates to a 3 - trifluoromethyl - 4 - chloroaniline, triphosgene, diisopropyl serotonin reuptake, 4 - (4 - aminophenoxy) - N - methyl - 2 - pyridine carboxamide, paratoluene sulfonic acid as the raw material, after [...] reaction, coupling reaction, salt forming reaction three-step reaction. Wherein the two-step reaction without the need of separation, the use of "one-pot" reaction, to obtain a simple and highly efficient zola non-nepal, the invention provides a paratoluene sulfonic acid zola non-nepal preparation method is a high-yield, low-cost, three-wastes, and easy to operate, safe, suitable for industrial preparation method. (by machine translation)
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- SORAFENIB HEMI-P-TOSYLATE MONOHYDRATE CRYSTAL AND PREPARATION PROCESS THEREOF
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The present invention relates to the field of medicinal technology, and in particular, to sorafenib hemi-p-tosylate monohydrate crystal and preparation process thereof. The crystal has diffraction peaks occurring at 2θ angle of about 5.62, 6.67, 8.05, 9.06, 9.63, 9.91, 10.95, 11.25, 13.48, 14.00, 14.60, 15.08, 15.75, 16.20, 16.62, 16.80, 17.23, 18.40, 18.97, 19.32, 19.82, 20.49, 20.74, 21.51, 22.56, 22.86, 23.37, 23.71, 24.20, 24.71, 24.97, 25.54, 25.80, 26.18, 27.14, 27.48, and 28.29 degree in a X-ray powder diffraction pattern, and some advantages, such as a high stability, a low hygroscopicity and the like.
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Page/Page column 9
(2017/07/06)
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- Preparation method for crystal form II of sorafenib tosylate
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The invention provides a preparation method for a crystal form II of sorafenib tosylate. The preparation method comprises the following steps: (1) adding sorafenib free alkali into ethanol and carrying out heating; (2) adding p-toluenesulfonic acid monohy
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Paragraph 0020; 0021; 0022; 0023; 0024; 0025; 0026; 0027
(2017/05/23)
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- Sorafenib hemi-tosylate amorphous form and preparation method thereof
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The invention relates to a sorafenib hemi-tosylate amorphous form, a preparation method thereof, a drug composition comprising the sorafenib hemi-tosylate amorphous form and an application of the sorafenib hemi-tosylate amorphous form to an anti-cancer dr
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Paragraph 0022; 0023; 0024; 0025
(2017/10/07)
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- Method for preparing a SUO draw non-Buddhist nun (by machine translation)
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This invention involves a kind of SUO draw non-Buddhist nun (structural formula as follows) and its toluene sulfonate preparation method, this method, in order to P-nitro-phenol as raw materials, by the benzyl protection, reduction, condensation, debenzylation, coupling and salt forming the several step to synthesize SUO draw non-Buddhist nun. The preparation method of fewer steps, high yield, low cost, environmental pollution is small, is suitable for industrial production. (by machine translation)
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- Preparation method of sorafenib tosylate
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The invention relates to a preparation method of sorafenib tosylate. The preparation method comprises the steps of reacting propylene chloroformate (5) with low cost and 4-chloro-3-trifluoromethyl phenylamine (2) with low cost to generate activated ester (6); reacting activated ester and 4-(4-aminophenoxy)-N-methyl-2-pyridine carboxamide (3) under the catalysis of N-methylpyrrolidine to obtain sorafenib with high yield; carrying out simple aftertreatment on the reaction to obtain sorafenib with relatively high purity; and then, reacting sorafenib and p-toluene sulphonic acid to generate the target product. The method is low in cost, simple in operation, few in reaction step, short in period, low in energy consumption, safe in process, free of high-toxicity reagents and suitable for industrial production, and the obtained product is high in yield and purity and free of potential safety problems.
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- Novel sorafenib TsOH crystal form as well as preparation method and application thereof
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The invention relates to the technical field of medicine, in particular to a novel sorafenib TsOH crystal form as well as a preparation method and an application thereof, and provides a type E crystal of a sorafenib TsOH monohydrate. In an X-ray powder diffraction pattern, the type E crystal of the sorafenib TsOH monohydrate displays characteristic diffraction peaks when 2-theta is about 8.961 degrees plus/minus 0.2 degrees,13.379 degrees plus/minus 0.2 degrees, 13.939 degrees plus/minus 0.2 degrees, 19.718 degrees plus/minus 0.2 degrees, 20.658 degrees plus/minus 0.2 degrees, 22.761 degrees plus/minus 0.2 degrees, 23.561 degrees plus/minus 0.2 degrees, 24.080 degrees plus/minus 0.2 degrees and 24.881 degrees plus/minus 0.2 degrees. A compound shown in a formula (II) of the type E crystal of the sorafenib TsOH monohydrate is high in product yield and excellent in product quality and has the advantages of good stability, high crystal purity, convenience in storage and the like.
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Paragraph 0073; 0074; 0075; 0052
(2016/12/01)
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- A process for the preparation of SUO draw non-Buddhist nun-toluene-sulfonic acid (by machine translation)
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The invention discloses a method for the preparation of SUO draw non-Buddhist nun-toluene-sulfonic acid. The method is as follows: P-amino-phenol and 4?Polybromide?2?Cyano pyridine the reaction is performed in the presence of sodium hydroxide, then is acidified to obtain 4?(4?Aminophenoxy)?2?(Formic acid) pyridine; the substitution after the reaction, thionyl chloride, in the presence of potassium carbonate, the reaction is carried out with methyl amine, to obtain the 4?(4?Aminophenoxy)?2?(Methyl carbamoyl) pyridine; then with compound 4?Chlorotrifluoromethylbenzene?3?Phenylisocyanate (trifluoromethyl) after direct condensation, with toluene-P-sulfonic acid salifying-toluene-sulfonic acid SUO draw non-Buddhist nun. The preparation method adopts a 4?Polybromide?2?Cyano pyridine as the starting raw materials for preparing the 4?(4?Aminophenoxy)?2?(Methyl carbamoyl) pyridine, the follow-up at the same time simplifying the step of reacting, simple steps of the reaction, the yield of the product is high. (by machine translation)
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- PROCESS FOR PREPARING CRYSTALLINE SORAFENIB TOSYLATE
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The present invention provides an industrially suitable process for the preparation of substantially pure 4-{4-[({[4-chloro-3-(trifluoromethyl)-phenyl]amino}carbonyl)amino]phenoxy}-N-methylpyridine-2-carboxamide or Sorafenib and its tosylate salt, with a suitable impurity profile and without requirement of any additional purification steps. The present invention also provides Sorafenib base (II) as stable crystalline Form-SSB. The present invention further relates to a process for the preparation of crystalline Sorafenib tosylate Form-I which is free from contamination of any other polymorphic form of Sorafenib tosylate, for e.g. Form II or Form III, and does not involve any seeding requirement for crystallization step.
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Paragraph 0079-0080
(2015/04/28)
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- PROCESS FOR SORAFENIB TOSYLATE POLYMORPH III
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The present invention provides a novel process for the preparation of sorafenib tosylate polymorph III.
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Paragraph 0026
(2015/05/26)
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- A NOVEL PROCESS FOR THE PREPARATION OF SORAFENIB TOSYLATE FORM III
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The present invention relates to a novel process for the preparation of Sorafenib Tosylate Form I II from Sorafenib Tosylate Ethanol Solvate.
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Page/Page column 6
(2014/08/19)
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- PROCESS FOR SORAFENIB TOSYLATE POLYMORPH III
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The present invention provides a novel process for the preparation of sorafenib tosylate polymorph III.
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Page/Page column 3; 4
(2014/01/07)
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- PROCESS FOR PREPARING CRYSTALLINE SORAFENIB TOSYLATE
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The present invention provides an industrially suitable process for the preparation of substantially pure 4-{4-[({[4-chloro-3-(trifluoromethyl)-phenyl]amino}carbonyl)amino]phenoxy}-N-methylpyridine-2-carboxamide or Sorafenib and its tosylate salt, with a suitable impurity profile and without requirement of any additional purification steps. The present invention also provides Sorafenib base (II) as stable crystalline Form-SSB. The present invention further relates to a process for the preparation of crystalline Sorafenib tosylate Form-I which is free from contamination of any other polymorphic form of Sorafenib tosylate, for e.g. Form II or Form III, and does not involve any seeding requirement for crystallization step.
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Page/Page column 18
(2014/01/07)
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- SORAFENIB DIMETHYL SULPHOXIDE SOLVATE
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The present invention provides dimethyl sulphoxide solvate of 4-(4-{3-[4-chloro-3-(trifluoromethyl)phenyl]ureido}phenoxy)-N2-methylpyridine-2-carboxamide, process for its preparation, pharmaceutical composition comprising it and its use for the treatment of cancer. The present invention also provides a novel HPLC method for the identification, quantification and isolation of related substances of sorafenib.
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Paragraph 0146; 0147
(2013/08/28)
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- SORAFENIB ETHYLSULFONATE SALT, PROCESS FOR PREPARATION AND USE
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The present invention provides sorafenib ethane sulphonate, process for its preparation, pharmaceutical composition comprising sorafenib ethane sulphonate and its use for the treatment of cancer. Formula (III).
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Page/Page column 10-11
(2011/06/16)
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- 4-(4-{3-[4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL]UREIDO}PHENOXY)-N2-METHYLPYRIDINE-2-CARBOXAMIDE DIMETHYL SULPHOXIDE SOLVATE
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The present invention provides dimethyl sulphoxide solvate of 4-(4-{3-[4-chloro- 3-(trifluoromethyl)phenyl]ureido }phenoxy)-N2 -methylpyridine-2-carboxamide, process for its preparation, pharmaceutical composition comprising it and its use for the treatment of cancer. The present invention also provides a novel HPLC method for the identification, quantification and isolation of related substances of sorafenib.
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Page/Page column 21
(2011/08/21)
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- PROCESS FOR THE PREPARATION OF SORAFENIB TOSYLATE
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The present invention provides a process for the preparation of sorafenib tosylate, comprising contacting sorafenib free base with p-toluenesulphonic acid in water.
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Page/Page column 5
(2011/04/24)
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- POLYMORPHS OF 4-[4-[[4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL]CARBAMOYLAMINO]PHENOXY]-N-METHYL-PYRIDINE-2-CARBOXAMIDE
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The present invention relates to polymorphs of 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]- carbamoylamino]phenoxy]-N-methyl-pyridine-2-carboxamide and pharmaceutical compositions comprising the same.
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Page/Page column 28-29
(2010/12/29)
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- Process for the Preparation of a RAF Kinase Inhibitor and Intermediates for Use in the Process
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There is provided a process for preparing sorafenib or a salt thereof comprising the use of a compound of formula (A) wherein R′ is selected from the group consisting of hydrogen, —C(O)OA, —C(O)CX3, —C(O)NH2, —C(O)—NHOH or There is also provided intermediate compounds of general formula (A), N-methyl-4-(4-ureidophenoxy)picolinamide, 4-(2-(methylcarbamoyl)pyridin-4-yloxy)phenylcarbamate derivative and N-methyl-4-(4-(2,2,2-trihaloacetamido)phenoxy)picolinamide, processes for their preparation and their use in the preparation of sorafenib.
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Page/Page column 21-22
(2010/12/29)
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- POLYMORPHS OF SORAFENIB TOSYLATE AND SORAFENIB HEMI-TOSYLATE, AND PROCESSES FOR PREPARATION THEREOF
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Provided are sorafenib hemi-tosylate, polymorphs thereof, polymorphs of sorafenib tosylate, preparation thereof and pharmaceutical compositions thereof.
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Page/Page column 6
(2009/08/14)
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- Process for the preparation of sorafenib and salts thereof
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Methods for the synthesis of the N-carbamoyl imidazole (I) and its 1:1 adduct with imidazole are provided. Methods for the preparation of these crystalline intermediates in a high state of purity are also provided. These intermediates react cleanly under mild conditions to produce sorafenib in high yield and purity, without generating difficult-to-remove impurities.
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Page/Page column 7
(2009/10/18)
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- PROCESS FOR THE PREPARATION OF A RAF KINASE INHIBITOR AND INTERMEDIATES FOR USE IN THE PROCESS
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There is provided a process for preparing sorafenib or a salt thereof comprising the use of a compound of formula (A), wherein R' is selected from the group consisting of hydrogen, -C(O)OA, -C(O)CX3, - OH C(O)NH2, -C(O)-NHOH or (a). There is also provided intermediate compounds of general formula (A), N-methyl-4-(4-ureidophenoxy)picolinamide, 4-(2- (methylcarbamoyl)pyridin-4-yloxy)phenylcarbamate derivative and N-methyl-4-(4-(2,2,2- trihaloacetamido)phenoxy)picolinamide, processes for their preparation and their use in the preparation of sorafenib.
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Page/Page column 50; 57-58
(2009/04/25)
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- TREATMENT OF CANCERS HAVING RESISTANCE TO CHEMOTHERAPEUTIC AGENTS
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The present invention provides compositions and methods for treating cancer with sorafenib, wherein the cancer that has acquired resistance to another therapeutic agent, such as kinase inhibitors. Sorafinb can also be used to treat cancers which have become refractory to other chemotherapeutic agents .
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Page/Page column 16
(2010/11/27)
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- TREATMENT OF CANCERS WITH ACQUIRED RESISTANCE TO KIT INHIBITORS
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The present invention provides compositions and methods for treating cancers ; which have acquired resistance to a KIT inhibitor by administering effective amounts of sorafenib.
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Page/Page column 13
(2012/04/23)
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- PROCESS FOR THE PREPARATION OF 4-{4-[({[4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL]AMINO}CARBONYL)AMINO]PHENOXY}-N-METHYLPYRIDINE-2-CARBOXAMIDE
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The present invention relates to a process for preparing 4-{4-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenoxy}-N-methylpyridine-2-carboxamide and its tosylate salt. Formula (I), which comprises, in a first step, reacting the compound of the formula (V) with 4-chloro-3-trifluoromethylphenyl isocyanate in a nonchlorinated organic solvent, inert toward isocyanates, by initially charging the compound of the formula (V) at a temperature of from 20°C to 60°C and admixing with 4-chloro-3-trifluoromethylphenyl isocyanate in such a way that the reaction temperature does not exceed 70°C to give the compound of the formula (II) and, in a second step, admixing the compound of the formula (II) with p-toluenesulfonic acid in a polar solvent at a reaction temperature of from 40°C up to the reflux temperature of the solvent used.
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Page/Page column 21
(2010/10/20)
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- THERMODYNAMICALLY STABLE FORM OF BAY 43-9006 TOSYLATE
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The present invention relates to a novel form, thermodynamically stable at room temperature, of the tosylate salt of 4-{4-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenoxy}-N-methylpyridine-2-carboxamide, to processes for its preparation
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Page/Page column 18
(2008/06/13)
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