23 results about "Pyrimidifen" patented technology

The invention relates to a pyrrolo [2, 3-d] pyrimidine-4-amine derivative and application thereof in medicine, in particular to a compound shown in a formula (I) or a stereoisomer, a tautomer, a deuterated compound, a solvate, a prodrug, a metabolite, pharmaceutically acceptable salt or eutectic of the compound, and application of the compound in preparation of medicines for treating sGC-related diseases.

The present invention relates to the crystalline form of bipyrimidine compounds, as well as methods for preparing the same and their use. In particular, the present invention relates to crystalline form I of 4'-cyclopropyl-5,6'-dimethoxy-N-((4-(1-methyl-4-(trifluoromethyl)-1H-imidazole-2-yl)bicyclo[2.2.2]octan-1-yl)methyl)-[2,5'-bipyrimidine]-4-amine, wherein the X-ray powder diffraction pattern of crystalline form I includes characteristic peaks at diffraction angles (2θ) of 6.378±0.2°, 9.521±0.2°, 15.721±0.2°, 16.379±0.2°, 16.981±0.2°, 17.560±0.2°, 19.080±0.2° and 22.200±0.2°. Crystal form I possesses high stability, high solubility, high plasma concentration, high bioavailability, and excellent pharmacological activity, making it suitable for pharmaceutical preparations.

The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of a pyrrolopyrimidine-4-amine derivative, which selects methanol, ammonium formate and formic acid as a reaction system to carry out directional reaction, avoids the use of high-pressure hydrogen and a high-pressure kettle, avoids the safety risk caused by high-pressure operation, and improves the yield of the pyrrolopyrimidine-4-amine derivative. And the alcoholic solution solves the problems of low solubility and obvious amplification effect of a starting material when water is used as a solvent in the prior art, and realizes homogeneous reaction. By adopting the fixed bed reaction unit, the problem of pipeline blockage caused by sublimation of ammonium formate is solved, the potential safety hazard in large-scale production is eliminated, the fixed bed reaction unit is used for continuous catalytic reaction to replace the traditional staged reaction, the production period is remarkably shortened, the production efficiency is improved, and the method is suitable for large-scale industrial production.

The application discloses a ceramic paint for metal doors and a preparation method thereof, and relates to the technical field of paints. The ceramic paint prepared by the application contains sodium silicate, methyltrimethoxysilane, modified polyacrylate emulsion, modified silicon dioxide, glass powder, sodium fluorosilicate, dispersant, leveling agent and pure water. The modified polyacrylate emulsion is obtained by polymerizing phosphorus-containing monomers and vinyl monomers to generate polyacrylate, reacting the polyacrylate with 5-chloromethyl-2-pyrimidine amine after sulfonyl chlorination, and then emulsifying. The silicon dioxide is obtained by polymerizing aniline on the surface of pretreated silicon dioxide, reacting with 1-benzothiophene-5-carbonyl chloride, then salifying with diphenyl iodonium triflate and copper acetate, and then reacting with bis(2-ethynylphenyl) sulfane. The ceramic paint prepared by the application has good corrosion resistance, antibacterial property and anti-aging property, and greatly improves the performance of the metal door.

The present application relates to a kind of porous coordination polymers with interpenetrating framework, preparation method and application in ethane / ethylene high temperature separation, belong to coordination chemistry material technical field.Porous coordination polymers are Cu-based coordination polymers, its chemical formula is [Cu2 (BDC) 2L2] n (solvent) x , belong to C2 / c space group, L2 is 4,6-di (1H-1,2,4-triazole-1-yl) pyrimidine-2-amine, NH2 Group is again with adjacent framework forms single hydrogen bond;It is obtained by adding regulating ligand during solvothermal reaction of ligand and metal salt.The present application proposes a new method to regulate temperature-dependent dynamic characteristics in hydrogen-bonded interpenetrating framework, with the weakening of hydrogen bond, porous coordination polymers with one-dimensional narrow-neck channel exhibit promising structural response to ethane / ethylene at high temperature, so that it shows significant ability to directly obtain polymerization grade ethylene.

The invention relates to a crystal form of a bipyrimidine compound as well as a preparation method and application thereof. In particular, the present invention relates to a crystalline form I of 4 '-cyclopropyl-5, 6'-dimethoxy-N-((4-(1-methyl-4-(trifluoromethyl)-1H-imidazol-2-yl) bicyclo [2.2. 2] oct-1-yl) methyl)-[2, 5 '-bipyrimidinyl]-4-amine, a crystalline form II of 4'-cyclopropyl-5, 6 '-dimethoxy-N-((4-(1-methyl-4-(trifluoromethyl)-1H-imidazol-2-yl) bicyclo [2.2. 2] oct-1-yl) methyl)-[2 An X-ray powder diffraction pattern of the compound comprises characteristic peaks at diffraction angles (2 theta) of 6.378 + / -0.2 degrees, 9.521 + / -0.2 degrees, 15.721 + / -0.2 degrees, 16.379 + / -0.2 degrees, 16.981 + / -0.2 degrees, 17.560 + / -0.2 degrees, 19.080 + / -0.2 degrees and 22.200 + / -0.2 degrees. The crystal form I is high in stability, high in solubility, high in blood concentration, high in bioavailability and excellent in pharmacological action, so that the crystal form I is suitable for pharmaceutical preparations.

The present application provides imidazolyl pyrimidinylamine inhibitors of cyclin-dependent kinase 2 (CDK2), as well as pharmaceutical compositions thereof, and methods of treating cancer using the same.

Disclosed in the present invention are 6-arylquinazolin-4-amine and 6-arylpyridopyrimidin-4-amine derivatives, and the use thereof as PI3Kδ covalent inhibitors. Said derivatives disclosed by the present invention are compounds capable of being used as PI3Kδ inhibitors. PI3Kδ kinase activity and PI3K selectivity tests verify that the compounds disclosed in the present invention exhibit an obvious inhibition effect on PI3Kδ kinase activity and have obvious selectivity on the activity of PI3Kδ. In-vitro cell anti-proliferative activity tests by means of using various blood tumor cell lines exhibit that the compounds disclosed in the present invention have different inhibition effects on various blood tumor cells.

The invention belongs to the technical field of medicine detection, and particularly relates to a method for detecting related impurities of an imatinib mesylate intermediate. In particular to a method for detecting related substances in N-(2-methyl-5-nitrophenyl)-4-(pyridine-3-yl) pyrimidine-2-amine. The related substances in N-(2-methyl-5-nitrophenyl)-4-(pyridine-3-yl) pyrimidine-2-amine are detected by high performance liquid chromatography, and the content of each impurity in N-(2-methyl-5-nitrophenyl)-4-(pyridine-3-yl) pyrimidine-2-amine is calculated by a main component external standard method with correction factors. The methodology verification shows that the detection method provided by the invention is good in specificity and high in accuracy and sensitivity, and can be used for quality control of related substances in N-(2-methyl-5-nitrophenyl)-4-(pyridine-3-yl) pyrimidine-2-amine, so that the product quality is effectively controlled, and the medication safety of imatinib mesylate is improved.

Crystalline and amorphous forms of N-(5-((4-ethylpiperazin-1-yl)methyl)pyridin-2-yl-5-fluoro-4-(3-iso-propyl-2-methyl-2H-indazol-5-yl)pyrimidin-2-amine (Compound 1) and various salts thereof, preparation methods of these crystalline and amorphous forms, pharmaceutical compositions containing these crystalline or amorphous forms, and use of these crystalline and amorphous forms, or pharmaceutical compositions thereof, for treatment of diseases or disorders associated with cyclin-dependent kinase (CDK), especially CDK4 and CDK6, activities, such as various cancers, are disclosed.

Provided herein are solid dispersions of 5-chloro-N-(3-cyclopropyl-5-{[(3R, 5S)-dimethylpiperazine-1-yl] methyl} phenyl)-4-(6-methyl-1H-indol-3-yl) pyrimidine-2-amine and methods for preparing the solid dispersions. The solid dispersions of 5-chloro-N-(3-cyclopropyl-5-{[(3R, 5S)-dimethylpiperazine-1-yl] methyl} phenyl)-4-(6-methyl-1H-indol-3-yl) pyrimidine-2 Also provided herein is a pharmaceutical composition comprising a solid dispersion of 5-chloro-N-(3-cyclopropyl-5-{[(3R, 5S)-dimethylpiperazin-1-yl] methyl} phenyl)-4-(6-methyl-1H-indol-3-yl) pyrimidine-2-amine, and a use thereof. The invention also provides a pharmaceutical composition comprising a solid dispersion of 5-chloro-N-(3-cyclopropyl-5-{[(3R, 5S)-dimethylpiperazin-1-yl] methyl} phenyl)-4-(6-methyl-1H-indol-3-yl) pyrimidine-2-amine.

The application discloses a one-pot method for preparing a medicine building block 5-bromo-4-fluoropyrimidine-2-amine, and relates to the field of organic chemical synthesis.The specific steps of the synthesis route are as follows: step one, 2-amino-4-chloropyrimidine and a bromination reagent are added into a solvent, and stirring reaction is carried out;step two, a fluorination reagent is added into the reaction solution, and heat preservation reaction is carried out;step three, water is added to precipitate, and the filter cake is dried and filtered.The 5-bromo-4-fluoropyrimidine-2-amine is prepared by the one-pot method, and the problems of low yield, complex operation, much waste, existence of isomers, and difficult purification in the existing synthesis preparation route of the 5-bromo-4-fluoropyrimidine-2-amine are solved successfully, and the method does not cause environmental pollution, and is beneficial to the green and environment-friendly industrial production of the 5-bromo-4-fluoropyrimidine-2-amine.

The present application relates to a synergistic composition containing a biologically effective amount of compound A and component B, wherein the component B is one of thiazide ketone, avermectin, spirotetramat, pyridalyl, emamectin benzoate, azamethiphos, azocyclotin, pyridaben, quimacryd thiocyl, pyrimidifen, tebufenpyrad, flufenoxuron, chlorfenapyr, cyromazine, and halofenozide, and a method thereof for controlling pests in agronomic and non-agronomic environments. The compound A has a synergistic effect with the component B, which can improve the pest control effect, reduce the application amount, reduce the use frequency, and reduce the use cost.

The invention relates to pyrazolopyrimidine-5-amine compounds as well as a preparation method and application thereof, and belongs to the technical field of compounds and medicines. The preparation method comprises the following steps: protecting 5 # amino of pyrazolo [1, 5-a] pyrimidine-5-amine by adopting butyric acid methyl ester amide with large steric hindrance, enabling an electrophilic reagent (such as a halogenating agent) to highly selectively attack a 7 # site with small steric hindrance by utilizing a space shielding effect so as to obtain a key 7 # halogenated intermediate, and modifying the 5 # amino by virtue of a hydrolysis reaction, so that the pyrazolo [1, 5-a] pyrimidine-5-amine is obtained. According to the pyrazolo [1, 5-a] pyrimidine compound, the 5 # site and the 7 # site of the pyrazolo [1, 5-a] pyrimidine are accurately substituted, the 5 # site amino substituted pyrazolo [1, 5-a] pyrimidine compound is obtained, and the compound has better anti-tumor activity, provides a new drug choice for tumor treatment and enriches an anti-tumor drug library.

The invention belongs to the field of medical chemistry, and particularly relates to a phenyl ether linked cyclohexylpyrimidinamine CDK12 / 13 inhibitor as shown in a formula I or an isomer, a pharmaceutically acceptable salt and a preparation method thereof, and a pharmaceutical composition containing the phenyl ether linked cyclohexylpyrimidinamine CDK12 / 13 inhibitor or the isomer and the pharmaceutically acceptable salt of the phenyl ether linked cyclohexylpyrimidinamine CDK12 / 13 inhibitor. According to the present invention, the compound of the formula I has the ether cyclohexyl amine linking chain group, such that the affinity of the compound with the CDK12 / 13 protein is increased, the selectivity on the CDK12 / 13 kinase is improved, the synthesis difficulty is reduced, the druggability is substantially improved, and the application prospect is broad.

Disclosed are compounds that bind to embryonic ectoderm development (EED) protein and proteolysis-targeting chimeric (PROTAC) derivatives thereof that induce degradation of EED. The disclosed compounds may be characterized as substituted [1,2,4]triazolo[4,3-c]pyrimidin-5-amine compounds having the Formula I:where R1 is as disclosed herein. The disclosed PROTAC derivatives thereof typically include a first targeting moiety that binds to BED (MEED) which may be derived from the disclosed [1,2,4]triazolo[4,3-c]pyrimidin-5-amine compounds having the Formula I that bind to EED. The first targeting moiety typically is linked via a bond or a linker (L) to a second targeting moiety that binds to an E3 ubiquitin ligase (ME3). As such, the disclosed PROTACS may be described as having a formula MEED-L-ME3 or ME3-L-MEED.

To provide an inhibitor of complement system.SOLUTION: Compounds of Formula (I), and pharmaceutically acceptable salts thereof, are disclosed. Also provided are pharmaceutical compositions comprising such compounds, and methods of using the compounds and compositions in the treatment or prevention of diseases or conditions characterized by aberrant complement system activity.SELECTED DRAWING: None

This invention discloses a D-A type pyrimidine-based covalent organic framework material of Formula I, its preparation method, and its applications. The material is obtained by a Schiff base condensation reaction of an electron-rich monomer 1,3,5-trimethoxy-2,4,6-tricarboxyphenyl and an electron-deficient monomer 5,5',5''-(1,3,5-phenyltriyl)tris(2-pyrimidineamine). This invention synthesizes a covalent organic framework rich in pyrimidine groups linked by imine bonds through a Schiff base reaction between electron-rich and electron-deficient monomers. This enhances the light absorption capacity of the COF material, effectively modulates the band structure, reduces carrier migration resistance, and improves photocatalytic activity, significantly increasing the efficiency of photocatalytic hydrogen peroxide production in a short time. In oxygen-saturated deionized water, the photocatalytic hydrogen peroxide production rate of the COF material of this invention is 5287 µmol / h. ‑1 g ‑1 I

The present invention relates to a crystalline form of N-(4-(4-amino-6-ethynyl-5-(quinolin-3-yl)-7H-pyrrolo [2, 3-d] pyrimidin-7-yl) bicyclo [2.2. 1] heptane-1-yl)-5-methylpyrazine-2-carboxamide (TAS3351), a compound having an EGFR inhibitory effect, and an acid. The crystalline form has superior physical properties, including stability, hygroscopicity, and oral absorbability. The crystal form has a peak at a specific diffraction angle (2 [theta] + / -0.2 DEG) in a powder X-ray diffraction spectrum.

The invention discloses a 4-(2-(methylamino) thiazole-5-yl) pyrimidine-2-amine derivative and application thereof, the structural formula of the 4-(2-(methylamino) thiazole-5-yl) pyrimidine-2-amine derivative is shown in the specification, in the formula, R1 is hydrogen or methyl; r2 is a substituted benzoyl group, a substituted phenylacetyl group, and a substituted or unsubstituted benzene propionyl group; and R3 is a substituted phenyl group, a 5-nitrofuran-2-yl group or a 1H-imidazole-2-yl group. As a novel CDK9 inhibitor, the ESCC inhibitor fills the blank of special medicines for ESCC; pharmaceutical salts and compositions can be prepared, and development of oral or injection preparations is facilitated; the compound is suitable for esophageal cancer single-drug treatment or is combined with other targeting / immune / chemotherapeutic drugs to improve the curative effect and reduce the drug resistance risk; meanwhile, other CDK9 related tumors such as lung cancer and breast cancer can be expanded.

The invention belongs to the technical field of medicine synthesis, and particularly relates to a synthesis method of a tofacitinib key intermediate. According to the method, N-((3R, 4R)-1-benzyl-4-methylpiperidine-3-yl)-N-methyl-7H-pyrrolo [2, 3-d] pyrimidine-4-amine is taken as a starting material, under the action of N, N-diisopropylethylamine and 1-chloroethyl chloroformate, debenzylation is carried out through a one-pot method, conditions are mild, aftertreatment purification is simple and easy to operate, energy consumption is low, working hours are short, and the method is suitable for large-scale production.

Disclosed in the present invention are a thiazole substituted pyrimidinamine compound, a pharmaceutical composition thereof and the use thereof. Provided in the present invention is a compound as shown in formula (I), a pharmaceutically acceptable salt thereof or a stereoisomer thereof. The compound has relatively high CDK1 / CDK2 selectivity, and has good application prospects in the prevention and / or treatment of CDK2-related diseases.

The present invention relates to a substituted benzo or pyridopyrimidine amine inhibitor and its preparation method and use. Specifically, the compound of the present invention has the structure shown in formula (I). The present invention further discloses a preparation method of the compound and its use as an SOS1 inhibitor. The compound of the present invention has an excellent selective inhibitory effect on SOS1, and has better pharmacodynamic and pharmacokinetic properties, and lower toxicity and side effects. [Formula 1] JPEG2023546248000353.jpg3364