79 results about "Osimertinib" patented technology

The invention relates to the field of drug-resistance cell systems, and particularly relates to a drug-resistance cell system and a preparation method thereof. The method comprises the following steps: inoculating the lung cancer cells to a culture medium containing a 21-93nM lung cancer targeted drug; culturing until cells can normally live and multiply under the same concentration; improving andculturing at 50nM concentration difference; improving and culturing at concentration difference of every 100nM when the cell multiplying inhibiting concentration is 4 times of IC50; improving and culturing at concentration difference of every 1 microns when the drug sieving concentration is 8 times of IC50; and obtaining the drug-resistance cell systems for the lung cancer when the lung cancer cells can live and multiply in a cell culture system of 10 microns osimertinib. According to the method, the drug-resistance cell system is prepared on the basis of gradually increasing the concentration of drugs in the culture medium; the foundation is provided for later simulation of clinical drug resistance, researching of drug resistance mechanism of lung cancer targeted drugs, and developing ofeffective drug resisting drugs.

The present invention relates to an osimertinib preparation method, which comprises: (1) carrying out a nucleophilic substitution reaction on 3-(2-chloro-4-pyrimidinyl)-1-methyl-1H-indole and 4-fluoro-2-methoxy-5-nitroaniline to prepare a compound 1; (2) carrying out a substitution reaction on the compound 1 and N,N,N-trimethylethylenediamine in the presence of an organic alkali to prepare a compound 2; (3) reducing the compound 2 in the presence of a reducing agent to prepare a compound 3; (4) carrying out condensation on the compound 3 and 3-chloropropionyl chloride in the presence of an alkali to obtain a compound 4; (5) carrying out a heat elimination reaction on the compound 4 through heating in the presence of an alkali to prepare a compound 5; and (6) carrying out salification on the compound 5 and methanesulfonic acid under a heating condition to obtain osimertinib. According to the present invention, the osimertinib synthesis process has characteristics of stability, controllability, no high-toxicity solvent is used, energy saving and environmental protection.

A drug containing, as an active ingredient, a compound represented by ALK inhibitors such as brigatinib, AP26113-analog, and AZD3463 has been found to be effective against a non-small cell lung cancer having a point mutation at C797S in EGFR which has acquired a resistance to chemotherapy agents. Further, the drug used in combination with an anti-EGFR antibody demonstrates a notable suppression effect on the tumor growth. The drug has a potential to be a therapeutic agent effective against a non-small cell lung cancer which is resistant to gefitinib, a first generation therapeutic agent and osimertinib, a third generation therapeutic agent.

The invention discloses a synthesis method of Osimertinib. The method comprises the following steps that (1) 4-fluoro-2-methoxyl-5-nitroaniline is subjected to formylation to obtain N-(4-fluoro-2-methoxyl-5-nitrophenyl) methanamide; (2) N-methylindole is subjected to acylation reaction to prepare 3-(1-methyl-1H-indole-3-yl)prop-2-en-1-one; (3) products generated in the former two-step reactions are subjected to one-step cyclization to obtain 2-(4-fluoro-2- methoxyl-5- nitroanilino)-4-(1-methyl-1H-indole-3-yl) pyrimidine; (4) the product generated in the step (3) is sequentially subjected to nucleophilic substitution reaction, reduction reaction and condensation amidation reaction to obtain the Osimertinib. The method provided by the invention has the advantages that the raw materials can be easily obtained; the steps are simple; the yield is high; the reaction conditions are mild; the synthesis method is suitable for industrial production.

The invention belongs to the field of biomedicine and gene detection, and particularly relates to a human EGFR gene missense mutation molecular marker and application thereof in predicting drug resistance of a targeted inhibitor. The molecular marker provided by the invention comprises 242 types of EGFR missense mutants related to the drug resistance of erlotinib, gefitinib and icotinib, and other 15 types of EGFR missense mutants related to the drug resistance of afatinib and osimertinib, and the mutants can be used for predicting the drug resistance of non-small cell lung cancer patients to targeted inhibitor treatment. According to the invention, a mutant library of EGFR gene tyrosine kinase functional regions is constructed by using a synthetic biology method, and the EGFR mutants are highly enriched in drug screening; the molecular marker can be clinically used as a potential molecular marker for predicting drug resistance of a lung cancer patient after the lung cancer patient is treated by a targeted inhibitor.

A drug containing, as an active ingredient, a compound represented by ALK inhibitors such as brigatinib, AP26113-analog, and AZD3463 has been found to be effective against a non-small cell lung cancer having a point mutation at C797S in EGFR which has acquired a resistance to chemotherapy agents. Further, the drug used in combination with an anti-EGFR antibody demonstrates a notable suppression effect on the tumor growth. The drug has a potential to be a therapeutic agent effective against a non-small cell lung cancer which is resistant to gefitinib, a first generation therapeutic agent and osimertinib, a third generation therapeutic agent.

The invention discloses a novel anti-lung cancer medicine, particularly relates to a 2-(2,4,5-substituted phenylamino)pyrimidine derivative I and a crystal form B thereof, and belongs to the field ofmedicinal chemistry. The 2-(2,4,5-substituted phenylamino)pyrimidine derivative adopts a structure as follows: FORMUAL. According to pharmacokinetic and pharmacodynamic studies, compared with osimertinib, dositinib significantly reduces production of an N-Me metabolite with relatively toxicity and maintains or improves the medicinal efficacy. The dositinib can be expected to be developed into a novel medicine which can treat the non-small cell lung cancer with EGFR mutation more safely and more effectively than the osimertinib.

The invention relates to a preparation method of a biomass derived palladium catalyst and application to synthesis of an anti-tumor drug osimertinib. The preparation method comprises the following process: enabling chitosan and palladium salt to react in the presence of a solvent to form a complex; then cooling to room temperature; drying a solid in vacuum to remove a solvent; under the protectionof argon gas, carbonizing at high temperature to obtain the catalyst; dissolving a raw material N-(2-dimethylamino-ethyl-2-methoxy-N-methyl-N-[4-(1-methyl-1H-indole-3-yl-pyrimidine-2-yl)-5-nitryl-benzene-1,4-diamine and adding the catalyst; stirring at temperature of 0 to 120 DEG C for 5 to 12h; dropwise adding hydrazine hydrate; after completely reacting, cooling to room temperature and filtering; spinning and drying the solvent to obtain a faint yellow solid. The preparation method provided by the invention has the advantages of wide raw material source, relatively low price, moderate reaction conditions and high yield; the catalyst has high activity, high stability, high dispersity of active components and long service life; the catalyst can be repeatedly used for a plurality of timesand the preparation method also has the advantages of short flow, easiness for controlling reaction and simple equipment requirements; complicated post-treatment is avoided and environment pollution is avoided.