1769 results about "Pyridyne" patented technology

The present disclosure relates generally to methods for treating or preventing central nervous system (CNS) metastases with a KRAS inhibitor, and more specifically to treating CNS metastases with a pyridopyrimidine derivative.

The present disclosure relates generally to methods for treating cancer with a KRAS inhibitor in combination with an immune checkpoint inhibitor, and more specifically to treating cancer with a pyridopyrimidine derivative in combination with a PD-1 or PD-L1 inhibitor.

The invention provides a salt-responsive temperature-resistant salt-resistant water-based drilling fluid tackifying filtrate reducer as well as a preparation method and application thereof, and belongs to the technical field of drilling. The tackifying filtrate reducer is prepared from the following raw materials in parts by mass: 30 to 50 parts of 1-(2-carboxyethyl)-2-vinylpyridine, 20 to 40 parts of (3-(methacrylamido) propyl) dimethyl (3-thiopropyl) ammonium hydroxide inner salt, 35 to 55 parts of N, N-dimethylacrylamide, 10 to 25 parts of 4-vinylpyridine, 300 to 500 parts of water and 1 to 5 parts of an initiator. According to the filtrate reducer, cations and anions are concentrated on one monomer molecule, so that the synthesized product contains the cations and the anions with the same charge number, has good adsorption capacity and salt response characteristics, is compatible with salt essentially, can effectively resist high temperature and high salt, and can be recycled. And the viscosity-increasing and filtrate-reducing agent has good viscosity-increasing and filtrate-reducing effects on the drilling fluid.

The present disclosure relates generally to polymorphic forms of a KRAS inhibitor, and more specifically to polymorphic forms of a pyridopyrimidine derivative, and uses thereof.

The present disclosure relates generally to polymorphic forms of a KRAS inhibitor, and more specifically to polymorphic forms of a pyridopyrimidine derivative, and uses thereof.

Provided herein is a process for preparing compound A comprising (a) admixing 2-isopropyl-4-methylpyridin-3-amine (Compound B), or a salt thereof, a first base, and a reactive compound comprising phosgene or a phosgene equivalent in an organic solvent to form 3-isocyanato-2-isopropyl-4-methylpyridine (Compound C); (b) admixing Compound C and 2,6-dichloro-5-fluoronicotinamide (Compound D) to form 2,6-dichloro-5-fluoro-N-((2-isopropyl-4-methylpyridin-3-yl)carbamoyl)nicotinamide (Compound E); and (c) admixing Compound E and a second base to form a product mixture comprising Compound A and the second base. Also provided herein is a process for synthesizing AMG 510 comprising using Compound A prepared according to the disclosed processes

The invention belongs to the technical field of organic synthesis, and particularly discloses an ammonia aromatic alkene modified near-infrared BODIPY fluorescent probe as well as a preparation method and application thereof.The near-infrared BODIPY fluorescent probe is obtained by adopting 6-(dimethylamino) nicotinic aldehyde to directionally modify the alpha position of BODIPY and constructing an expanded conjugated system through Knoevenagel condensation. Wherein dimethylamino provides a strong electron donating effect, a molecular structure is twisted into a non-planar configuration due to steric hindrance of a pyridine ring, pi-pi accumulation is reduced, and an ACQ effect is inhibited. According to the structural modification strategy, significant red shift of absorption / emission wavelength is realized by expanding a molecular pi-conjugated skeleton, and meanwhile, the stability of the BODIPY core and the quantum yield are effectively enhanced. The probe molecule can specifically recognize the diphenylalanine dipeptide structural unit by utilizing the synergistic coordination effect of the 2-aminopyridine derivative and the BODIPY mother nucleus, so that the selective detection of the Alzheimer's disease biomarker Abeta42 is realized, and a novel optical detection tool is provided for the early molecular diagnosis and targeted therapy of AD (Alzheimer's disease).

The invention relates to the technical field of marine antifouling materials, in particular to a modified polyurethane marine antifouling coating based on a metal pyridine structure and a preparation method. According to the modified polyurethane marine antifouling paint based on the metal pyridine structure, polyhydric alcohols and diisocyanate monomers with different molecular weights are subjected to condensation polymerization to obtain a polyurethane prepolymer; then reacting a diaminopyridine monomer or a dihydroxypyridine monomer with a metal ion compound to obtain a chain extender with a metal pyridine structure; finally, the marine antifouling paint is prepared through the reaction between the terminal amino or hydroxyl of the metal pyridine structure chain extender and the terminal isocyanate group of the polyurethane prepolymer, the metal pyridine structure is introduced into polyurethane, the mechanical performance of the marine antifouling paint is enhanced, the marine antifouling paint is endowed with the antibacterial effect through metal ion release, and the service life of the marine antifouling paint is prolonged. Adhesion and growth of marine fouling organisms can be effectively inhibited, and an efficient and durable solution is provided for development of a polyurethane marine antifouling coating.

The invention discloses a yellow reduction dyeing agent, a dyeing solution and a preparation method and application thereof, and relates to the technical field of dyeing and finishing. According to the yellow reduction dyeing agent provided by the invention, the 5-hydroxy-3-aminopyridine-2, 6-(1H, 3H)-diketone is adopted as a reduction dye, and the sodium sulfite is independently used as a reducing agent for reduction dyeing, so that the obtained dye leuco body is proper in dyeing capacity, and a dyed fabric can show excellent light brittle damage resistance. The fabric dyed by the dyeing agent has similar breaking strength before and after dyeing and even is slightly improved after dyeing and illumination, meanwhile, the color depth K / S of the fabric dyed by the dyeing agent reaches 3.2 or above, the dry and wet rubbing color fastness can reach level 4 or above, and the color fastness to illumination reaches level 6 or above.

The invention discloses an antibacterial material rich in a bismuth metal organic framework and a preparation method thereof, the method comprises the following steps: adding an indole monomer and an alcohol monomer into a solvent, and then adding nitrosalicylaldehyde into the solvent to obtain a spiropyran compound; the preparation method comprises the following steps: adding humic acid into a binary solvent consisting of dioxane and butanol to obtain a mixed solution; the ratio of the mass of the humic acid to the volume of the binary solvent is (2-3): (20-40) g / ml; sequentially adding a bismuth source, 2-bromo-5-(trifluoromethyl) pyridine and 4-(trifluoromethyl) phenylboronic acid into the mixed solution to obtain a bismuth metal organic framework; and adding the spiropyran compound into the bismuth metal organic framework to obtain the antibacterial material rich in the bismuth metal organic framework. The antibacterial capability of the antibacterial material is improved.

The invention relates to a green preparation method of fluopyram intermediate 3-chloro-5-(trifluoromethyl)-2-ethylaminopyridine, which comprises the following steps: step 1, Ullmann reaction: coupling 3-chloro-2-methyl-5-trifluoromethylpyridine (C1) and N-bromomethyl phthalimide (C2) in the presence of a copper catalyst and potassium tert-butoxide to generate an intermediate (C3); and step 2, hydrolysis reaction: hydrolyzing the intermediate (C3) in the presence of hydrazine sulfate and an alkaline condition to generate the fluopyram intermediate 3-chloro-5-(trifluoromethyl)-2-ethylamino pyridine. The method has the advantages of short synthesis steps, easily available raw materials, no use of high-toxicity cyanogen compounds, low catalyst cost, difficult poisoning, recycling, simple post-treatment process, and less waste liquid generation, greatly reduces the production cost, improves the production safety, reduces the waste liquid discharge amount, and accords with the idea of green synthesis.

The present application relates to a crystal form of 4-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenethyl]pyridine-2(1H)-one, a preparation method therefor, a composition containing the crystal form and the use thereof in the treatment of phosphodiesterase-related diseases.

The invention relates to a preparation method of 3-[(1S, 2S)-1-[5-[(4S)-2, 2-dimethyl oxacyclohexane-4-yl]-2-[(4S)-2-(4-fluoro-3, 5-dimethyl phenyl)-3-[3-(4-fluoro-1-methylindazol-5-yl)-2-oxoimidazol-1-yl]-4-methyl-6, 7-dihydro-4H-pyrazolo [4, 3-c] pyridine-5-carbonyl] indol-1-yl]-2-methylcyclopropyl]-4H-1, 2, 3-triazolo [4, 3-c] pyridine-5-carbonyl] indol-1-yl]-2-methylcyclopropyl]-1, 2, 4-triazolo [4, 3-c] pyridine-5- The invention relates to synthesis of 1, 2, 4-oxadiazole-5-one or a salt thereof, and related synthesis intermediate compounds.

Disclosed in the present application are a pyridopyrimidinone compound, and a preparation method therefor and the use thereof, wherein the pyridopyrimidinone compound, or a racemate, R-isomer, S-isomer, pharmaceutically acceptable salt thereof or a mixture thereof has a structure as shown in formula (I). The pyridopyrimidinone compound provided by the present application has an agonistic effect on an HsClpP protease, and can be used for treating diseases related to HsClpP receptor activation.

The invention belongs to the technical field of medicinal chemistry, and discloses a preparation method and application of a benzofuran [2, 3-b] pyridine derivative of a targeted nuclear receptor co-activator 4 (NCOA4). The derivative has a structural general formula as shown in the following formula (I), wherein R1, R2 and R3 substituent groups can be combined at will. The compounds are combined with NCOA4 to interfere the cell iron autophagy process and effectively inhibit the ferroptosis of various cells induced by RSL3 or Erastin. Particularly, the binding affinity of the compound 4k and NCOA4 is optimal (Kd is equal to 0.78 mu M), and the compound 4k has remarkable ferroptosis inhibition activity and can be used for research and development of medicines for ferroptosis-related diseases. # imgabs0 #

The invention relates to a method for preparing a nerofloxacin chiral piperidylamine intermediate, which comprises the following steps of: carrying out condensation reaction on 5-hydroxy nicotinic acid which is simple and easy to obtain and is used as a raw material and different alcohols, screening through a series of asymmetric catalytic hydrogenation conditions to obtain optimal reaction conditions, and under the conditions, carrying out reaction on various 3, 3 '-dihydroxy nicotinic acid and 3, 3'-dihydroxy nicotinic acid to obtain the nerofloxacin chiral piperidylamine intermediate. The 2, 5-disubstituted pyridine quaternary ammonium salt is reduced into a tetrahydropyridine product, and the C5 site enantioselectivity of the product is excellent. The preparation method comprises the following steps: selecting methyl (R)-1-benzyl-5-hydroxy-1, 4, 5, 6-tetrahydropyridine-3-carboxylic acid methyl ester as a substrate, completely hydrogenating by using platinum dioxide hydrogen, and then carrying out methyl ester reduction, dehydroxylation, Mitsunobu reaction and protecting group removal to obtain a key chiral intermediate for industrial synthesis of a quinolone antibacterial drug nemonofloxacin with high enantioselectivity and high yield.

Provided herein are inhibitors of KRAS, pharmaceutical compositions comprising the inhibitory compounds, and methods for using the KRAS inhibitory compounds for the treatment of diseases or disorders.

To provide compounds as new proline derivatives, and to provide a pharmaceutical composition comprising the compounds for the treatment of diseases such as systemic lupus erythematosus, systemic sclerosis, non-alcoholic steatohepatitis, interstitial lung disease and idiopathic pulmonary fibrosis.SOLUTION: There are provided new proline derivatives of formula (I) as cGAS inhibitors, or pharmaceutical compositions comprising a prodrug, a pharmaceutically acceptable salt, or a stereoisomer of the compound.SELECTED DRAWING: None

The invention relates to the technical field of organic synthesis, and particularly discloses a synthesis process of 2-chloronicotinic acid. The synthesis process of the 2-chloronicotinic acid comprises the following steps: S1, mixing water, concentrated sulfuric acid, 3-cyanopyridine and a composite catalyst, performing pre-reaction, adding hydrogen peroxide, performing oxidation reaction, adjusting pH, performing solid-liquid separation, and washing to obtain an oxide intermediate; s2, in an inert atmosphere, adding phosphorus oxychloride into a reactor, adding the oxide intermediate and triethylamine for a chlorination reaction, recovering phosphorus oxychloride after the reaction is finished, hydrolyzing remaining materials, and performing solid-liquid separation and washing to obtain chloride; and S3, carrying out alkali dissolution, neutralization, decoloration and acidification on the chloride, carrying out solid-liquid separation, washing, carrying out secondary alkali dissolution, neutralization and secondary decoloration, adding a complexing agent, carrying out secondary acidification, carrying out solid-liquid separation, washing, drying and crushing to obtain the 2-chloronicotinic acid. The 2-chloronicotinic acid prepared by the method disclosed by the invention has relatively high purity and yield.

The invention provides an imidazo [1, 2-alpha] pyridine stimuli-responsive molecule with a D-A twisted structure as well as a preparation method and application of the imidazo [1, 2-alpha] pyridine stimuli-responsive molecule, belongs to the technical field of intelligent materials, and is used for solving the technical problem that intelligent materials for developing stimuli-responsive molecules for data encryption and information anti-counterfeiting are insufficient. The preparation method of the compounds N1 and N3 comprises the following steps: 2-aminopyridine and 2, 4 '-dibromoacetophenone are subjected to an amphiphilic reaction to obtain a compound a; the compound a and POCl3 are subjected to a Vilsmeier-Haack reaction, and a compound b is obtained; carrying out Suzuki coupling reaction on the compound a or the compound b and triphenylamine boric acid to obtain a compound N1 or N2; the compound N2 and malononitrile are subjected to a Knovenagel condensation reaction, and a compound N3 is obtained. The compound prepared in the invention has good fluorescence emission capability in a solution and a solid state and a grinding solvent acid / alkali stimulated fluorescence discoloration behavior, and can realize good data encryption and information anti-counterfeiting.

The invention is applicable to the technical field of fuel cells, and provides a blending modified polybenzimidazole proton exchange membrane and a preparation method thereof, and the preparation method comprises the following steps: S1, preparing 4-methyl-N-toluenesulfonyl benzene sulfonamide; s2, preparing 4, 4 '-[imino bis (sulfonyl)] dibenzoic acid; s3, preparation of PSI: dissolving CBSI and a proper amount of anhydrous lithium chloride in a proper amount of a mixed solution of pyridine, triphenyl phosphite and pyrrolidone, adding diamino molecules after complete dissolution, heating and stirring the solution for 12 h, pouring the solution into methanol, filtering and collecting a product, washing with water, and drying to obtain the product PSI; and S4, preparing the PSI / OPBI blended membrane. The blended membrane prepared by the invention has excellent proton conductivity and good mechanical properties, and meets the performance requirements of the proton exchange membrane of the fuel cell; moreover, the raw materials are low in cost and easy to obtain, the synthesis conditions are mature, the yield is high, the feasibility is high, and the application prospect is wide.

The invention belongs to the technical field of medicines, and provides a compound containing an oxopyridine and alicyclic ring or alicyclic ring structure as shown in a formula I. R2, R3, X1, X2, X3, X4, X5, Y1, Y2, A, o and n are defined in the specification. The compound with the novel structure provided by the invention has excellent CGRP antagonistic activity, and has potential treatment on various diseases mediated and regulated by CGRP, especially migraine or neuropathic pain.

The invention relates to a specific PET molecular probe of a targeted KRASG12D mutant as well as a preparation method and application of the specific PET molecular probe. Pyridopyrimidine compounds and R5 are subjected to cooling reaction under the action of N, N-diisopropylethylamine to generate a compound 2; the compound 2 and (2-fluorotetrahydro-1H-pyrrolizine-7A (5H)-yl) methanol are subjected to a heating reaction under the action of N, N-diisopropylethylamine, and a compound 3 is generated; carrying out heating reaction on the compound 3 and biphenyl boronic acid pinacol ester under the action of N, N-diisopropylethylamine and tetrakis (triphenylphosphine) palladium to generate a compound 4; carrying out heating reaction on the compound 4 and 1, 2-bis (tolyloxy) alkane under the action of potassium carbonate to generate a compound 5; the compound 5, radioisotope < 18 > F and an anion complexing agent are subjected to a heating reaction under the action of potassium carbonate to generate the trisubstituted pyridopyrimidine < 18 > F labeled PET molecular probe. Compared with the prior art, the kit has a positioning diagnosis effect on KRASG12D mutant tumors, and image typing of mutant and non-mutant tumors and pathological evaluation after tumor treatment are realized at the same time.

Disclosed are compounds of Formula (I), methods of using the compounds for inhibiting HPK1 activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with HPK1 activity such as cancer.

The invention relates to the technical field of metal powder material preparation, and particularly discloses antimony-doped cesium terbium chloride microcrystalline powder and a preparation method thereof. The chemical composition of the microcrystalline powder is Cs < 5 > Tb < 1-x > Sb < x > Cl < 8 >. 6H < 2 > O, wherein x is equal to 0.05 to 0.30. The preparation method comprises the following steps: mixing cesium chloride, terbium chloride hexahydrate and antimony trichloride according to a molar ratio of 5: 0.8: x; adding pyridine hydrochloride as a chlorine element supplement, wherein the dosage of the pyridine hydrochloride is that 0.05-0.20 mmol of Py.HCl is used for every 1 mmol of CsCl; adding stearic acid as a process dispersant; and through combined treatment of mechanical ball milling and freeze drying, antimony-doped cesium-terbium-chlorine microcrystal powder with regular morphology and good dispersibility is obtained. The method is simple in process and mild in condition, particle aggregation can be effectively inhibited, the crystallinity and dispersion uniformity of the powder are improved, and the prepared microcrystal powder shows excellent optical performance.

The invention relates to the technical field of nuclear waste treatment, in particular to a cucurbituril-based supramolecular organic framework material as well as a preparation method and application thereof. A construction unit of the supramolecular organic framework material is constructed by taking cucurbit [8] uril (CB8) as a subject and terephthalyl viologen ligand 1, 1 ''-(1, 4-phenylene) bis ([4, 4 '-bipyridyl]-1-onium) salt (PBV. 2X) as an object through the bonding effect of the subject and the object; in the molecular structure of the supramolecular organic framework material, the construction units are staggered and stacked in parallel in the space, and NO3 <-> is located at the gap of the adjacent CB8. The supramolecular organic framework material disclosed by the invention has high structural stability and cationic framework characteristics, and a rigid framework and a pyridine conjugated system of CB8 endow the material with excellent chemical / irradiation stability, so that the material shows ultrahigh removal rate on ReO4 <-> / TcO4 <-> in extreme environments (strong acid, strong alkali and high irradiation).

The invention discloses a preparation method of a hydrophobic modified copper-based monatomic catalyst. The preparation method comprises the following steps: S1, dissolving Cu (NO3) 2 and L-alanine in deionized water; dissolving trimesic acid in an ethanol solution; s2, mixing the two solutions, and stirring at regular time at normal temperature to obtain a Cu-BTC precursor; s3, grinding and uniformly mixing the Cu-BTC precursor and dicyandiamide, and then putting the mixture into a tubular furnace for high-temperature pyrolysis treatment to obtain Cu-N-C-Pre powder; s4, the Cu-N-C-Pre powder is subjected to acid leaching impurity removal treatment in an acid solution, and the copper-based monatomic catalyst is obtained; and S5, dissolving the Cu-N-C catalyst and triacetylene benzene in an organic solvent, adding pyridine, uniformly stirring, and carrying out a hydrothermal reaction to obtain the hydrophobic modified copper-based monatomic catalyst. Hydrophobic modification is performed on the surface of the Cu-N-C monatomic catalyst, so that the hydrophobicity of the surface of the catalyst is enhanced, the catalytic activity of the catalyst in a reaction for preparing phenol by activating a benzene C-H bond by taking H2O2 as an oxidizing agent is improved, and the yield of phenol is increased.

The invention relates to the technical field of synthesis of chlorine-containing pyridine intermediates, and discloses a preparation method of 3, 4, 5-trichloropyridine, which comprises the following steps: step 1, feeding: adding raw materials 2, 3, 4, 5-tetrachloropyridine, an acid-binding agent, a solvent and a catalyst into a reaction kettle; 2, reaction preparation: sealing the reaction kettle, and replacing with hydrogen to remove air; step 3, dechlorination reaction: heating to 60-150 DEG C, maintaining the pressure at 0.6-2.0 MPa, and reacting for 8-30 hours; 4, post-treatment: after the reaction is completed, cooling to room temperature, and filtering reaction liquid to recover the catalyst; and 5, purification: distilling the filtrate to remove the solvent, adding water, stirring, filtering to obtain a crude product, and recrystallizing to obtain the 3, 4, 5-trichloropyridine product. According to the invention, the dechlorination reaction is carried out in a metal catalysis manner, the reaction steps are few, the used reagent raw materials are fewer and milder, the danger in the reaction process is reduced, and the method is safer; the reaction does not generate waste salt and is more environment-friendly; the catalyst can be recycled, so that the cost is reduced.

The invention belongs to the field of medicine, health and health, and particularly relates to a preparation method for controllably synthesizing polysulfonic acid mucopolysaccharide with different molecular weights, which comprises the following steps: reaction, acid-base neutralization, formamide removal by alcohol precipitation, desalting and freeze-drying. Wherein the reaction process comprises the following steps: adding sodium chondroitin sulfate and a pyridine sulfur trioxide complex into a mixed solvent of N, N-dimethylformamide and dimethyl sulfoxide, and heating for reaction to obtain a reaction mixture; the volume fraction of the dimethyl sulfoxide in the mixed solvent is 0-80%. According to the method, the low-price pyridine sulfur trioxide complex (about 150 yuan / 500g) is used, and the ratio of N, N-dimethylformamide to dimethyl sulfoxide in the mixed solvent is adjusted, so that the solubility of the chondroitin sulfate sodium and the pyridine sulfur trioxide complex is changed, and the polysulfonic acid mucopolysaccharide with molecular weights in different ranges can be regulated and generated.

The invention discloses a preparation method and application of a catalyst based on pyridine ionic liquid, and belongs to the technical field of catalyst preparation. According to the invention, a hydrolysis reaction of a silane coupling agent is utilized to prepare a silicon oxide nanotube containing a pyridine unit, and then a quaternization reaction is carried out to obtain the catalyst based on the pyridine ionic liquid. The catalyst has a high specific surface area and a rich pore channel structure, exposure of active sites and contact of the active sites and reactants are facilitated, and the catalytic rate is increased. Meanwhile, the silicon oxide nanotube contains hydroxyl, and can cooperate with a pyridine ionic liquid site to catalyze a carbon dioxide cycloaddition reaction. The obtained catalyst can catalyze the reaction of carbon dioxide and an epoxy compound to prepare cyclic carbonate under solvent-free and metal-free conditions, and the catalyst is easy to recover and simple in product purification, and has a good application prospect.