1354 results about "Pyrazole" patented technology

The invention belongs to the technical field of liquid chromatography-mass spectrometry detection pretreatment, and particularly relates to a pretreatment method for liquid chromatography-tandem mass spectrometry analysis of pesticide and veterinary drug residues in serum, which comprises the following steps: (S1) carrying out heating reaction on Sc (III) salt, Cu (II) salt and 1H-pyrazole-4-formic acid (H2PyC) in a polar aprotic solvent, and cooling to obtain a green crystal, namely MOF-919; the chemical formula of the MOF-919 is [Sc < 3 > (mu3-O) (OH) < 3 >] [Cu3 (mu3-O) (mu-PyC) < 3 > (H2O) < 6 >] < 2 >; (S2) mixing the serum sample with an acetonitrile solution containing formic acid, carrying out ultrasonic treatment, vortex oscillation and centrifugation, taking supernate, and diluting the supernate with an aqueous solution containing formic acid to obtain a to-be-purified solution; and (S3) adding MOF-919 into the to-be-purified liquid, mixing, performing ultrasonic treatment, performing vortex oscillation, centrifuging, and taking supernate, thereby completing the pretreatment of the to-be-purified liquid. According to the method, the MOF-919 is used for adsorbing chemical pollutant residues in serum, especially phospholipids, so that the purpose of removing the chemical pollutant residues in blood is achieved. The method is simple and convenient to operate, small in organic solvent consumption and good in purification effect, and can be widely applied to residue analysis of chemical pollutants in serum.

The present disclosure relates to pharmaceutically acceptable salts, cocrystals, and crystalline forms thereof, of a compound which is N—((S)-1-(3-(4-chloro-3-(methylsulfonamido)-1-(2,2,2-trifluoroethyl)-1H-indazol-7-yl)-6-(3-methyl-3-(methylsulfonyl)but-1-yn-1-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2- ((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-TH-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamide, which is useful in the treatment of a Retroviridae viral infection including an infection caused by the HIV virus.

The invention relates to substituted pyrazolo piperidine carboxylic acids, their salts and to processes for their preparation, and also to their use for preparing medicaments for the treatment and / or prophylaxis of diseases, in particular cardiovascular and cardiac diseases, preferably heart failure with reduced and preserved ejection fraction (HFrEF, HFmrEF and HFpEF), hypertension (HTN), peripheral arterial diseases (PAD, PAOD), cardio-renal and kidney diseases, preferably chronic and diabetic kidney disease (CKD and DKD), cardiopulmonary and lung diseases, preferable pulmonary hypertension (PH), and other diseases, preferably neurodegenerative diseases and different forms of dementias, fibrotic diseases, systemic sclerosis (SSc), sickle cell disease (SCD), wound healing disorders such as diabetic foot ulcer (DFU).

The invention relates to the technical field of energetic materials, in particular to a laser response type high-entropy alloy-based initiating explosive material and a preparation method thereof. The initiating explosive material is mainly formed by uniformly loading a heat-sensitive high-energy compound (such as lead stilbeneate or hexa (4-amino-3, 5-dinitropyrazole) copper) on high-entropy alloy nanoparticles containing five or more metal elements, wherein the heat-sensitive high-energy compound is such as lead stilbeneate or hexa (4-amino-3, 5-dinitropyrazole) copper. The preparation method comprises the following steps: mixing acetylacetone metal salt, a surfactant and a reducing agent in an organic solvent, and stirring and reacting at 180-220 DEG C to prepare high-entropy alloy nanoparticles; the nano particles and a high-energy compound are co-dispersed in a mixed solvent containing a dispersing agent, ultrasonic treatment is carried out to form suspension liquid, and freeze drying is carried out to obtain the nano particles. The method is characterized in that the excellent photo-thermal conversion performance of the high-entropy alloy is utilized, under low laser energy irradiation, a high-energy compound can be effectively excited, and stable detonation of secondary charge CL-20 is successfully achieved. According to the invention, the problems of high response threshold and low output energy of the existing laser initiating explosive material are solved.

The invention relates to the technical field of synthesis of pyroxasulfone intermediates, in particular to a synthesis method and application of a pyroxasulfone intermediate. Comprising the following preparation steps: (1) adding a reaction solvent into sodium formaldehyde sulfoxylate, adding 1-methyl-3-trifluoromethyl-5-hydroxy-1H-pyrazole, heating, and completely reacting to obtain sodium hydroxypyrazole methyl sulfinate; and (2) cooling the reaction liquid, adding acetonitrile and alkali liquor, introducing monochlorodifluoromethane gas, after the reaction is completed, concentrating, removing acetonitrile and water, adding methanol, stirring, filtering, and concentrating the filtrate to obtain the pyroxasulfone intermediate difluoromethoxy pyrazole methyl sodium sulfinate. The specific reaction process is as follows. According to the method, the sodium formaldehyde sulfoxylate which is low in cost and easy to obtain is used, synthesis of a 5, 5-dimethyl-4, 5-dihydroisoxazole thioether compound is avoided when pyroxasulfone is prepared from the intermediate obtained in the invention, three wastes and production cost are reduced, industrial production is easy to realize, and the method has relatively high practical value.

Described herein are pharmaceutical formulations of a farnesoid X receptor agonist, 4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl)pyridin-2-yl)((4-(4-methoxy-3-methylphenyl)bicyclo[2.2.2]octan-1-yl)methyl)carbamoyl)cyclohexyl 3-hydroxyazetidine-trans-1-carboxylate, and methods of using such pharmaceutical formulations in the treatment of conditions, diseases, or disorders associated with farnesoid X receptor activity.

The invention discloses a continuous flow production method of high-purity chlorantraniliprole, and belongs to the technical field of chemical synthesis. The method comprises the following steps: simultaneously pumping a mixed solution containing 3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-formic acid, a solvent, an acid-binding agent and 2-amino-5-chloro-N, 3-dimethylbenzamide and a catalyst solution into a mixing unit of a continuous flow reactor I to form a reaction mixture flow; the material flow enters a continuous flow reactor I for condensation reaction to obtain a chlorantraniliprole solution; simultaneously pumping the mixed solution and a quenching agent solution into a continuous flow reactor II, and quenching to separate out crystals; and continuously centrifugally separating the quenching liquid containing the crystals, washing and drying to obtain a chlorantraniliprole refined product. According to the present invention, the full continuous flow process is adopted, the reaction unit and the post-treatment unit are included, the material continuously flows, and when the process is stable, the material composition, the temperature and other parameters in the reactor are only related to the reaction position and do not change with time, such that the production process and the product quality stability are ensured.

The invention belongs to the technical field of organic synthesis, and particularly relates to a pyroxasulfone preparation method which specifically comprises the following steps: dissolving 3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5, 5-dimethyl-2-isoxazoline serving as a raw material with a solvent, then adding a boron compound, finally dropwise adding hydrogen peroxide, and reacting at room temperature to obtain the pyroxasulfone. Reacting for several hours to obtain pyroxasulfone; the adopted boron compound is cheap and easy to obtain, so that the use of a transition metal catalyst is avoided, and the raw material cost is reduced; organic acid reagents with heavy odor are not used, waste water and solid waste are less, and the method has great advantages in the aspect of environmental protection; the method is simple to operate, free of complex treatment steps and suitable for industrial production, and when the boron compound is selected from sodium metaborate, sodium perborate or a mixture of borax and sodium metaborate, the yield and purity of the process are higher, and sulfoxide impurities are fewer.

The invention provides an epoxy adhesive solution composition, a preparation method of an epoxy adhesive solution and a modified cellular board. The epoxy adhesive liquid composition comprises the following components in parts by weight: 53-58 parts of epoxy resin, 2-10 parts of a silane coupling agent, 1-10 parts of a curing agent, 1-5 parts of blocked isocyanate and 60-70 parts of water, wherein a blocking group of the blocked isocyanate is selected from hydroxyl, oximido, acylamino, amino, imidazolyl, pyrazolyl or piperazinyl. By introducing the blocked isocyanate with the specific structure, the epoxy adhesive liquid can be subjected to pre-crosslinking reaction in the early drying treatment process, the modulus and high temperature resistance of a formed dry film are improved, and the phenomenon of glue overflow in the subsequent curing stage is inhibited; therefore, the structural integrity and the bonding strength of the adhesive layer in the modified cellular board under the high-temperature condition are improved.

The present disclosure relates to pyrazoloheteroaryl derivatives, their preparation methods, and their pharmaceutical applications. Specifically, the present disclosure relates to pyrazoloheteroaryl derivatives represented by general formula (I), their preparation methods, pharmaceutical compositions containing the derivatives, and their use as therapeutic agents, particularly their use as ATR kinase inhibitors and in the preparation of medicaments for treating and / or preventing hyperproliferative diseases. The definitions of each group in general formula (I) are as described in the specification. TIFF2023502458000095.tif4136

Provided are pyrazole-containing polycyclic derivative inhibitors, preparation methods therefor, and uses thereof. In particular, provided are compounds represented by formula (I), preparation methods therefor, pharmaceutical compositions containing the compounds, and uses thereof as P2X3 inhibitors in the treatment of P2X3 receptor dysfunction, particularly in the treatment of neurological diseases, wherein the substituents in formula (I) are the same as those described in the definitions. TIFF2023506436000188.tif48169

The invention discloses a preparation method and application of a metal covalent organic framework material, and the prepared metal covalent organic framework material can be used for adsorption separation of elemental iodine pollutants and shows excellent iodine adsorption capacity and rate. According to the preparation method, 1H-pyrazole-4-formaldehyde and copper nitrate trihydrate are subjected to a solvothermal reaction to prepare a copper ion ring trinuclear metal complex with an aldehyde group, and the copper ion ring trinuclear metal complex and 1, 3, 5-tri (4-aminophenyl) benzene are further subjected to a Schiff base reaction to prepare the metal covalent organic framework material containing copper ions. According to the metal covalent organic framework material disclosed by the invention, copper ion active adsorption sites in a chemical structure are also retained while a developed microporous structure is maintained, and the interaction strength of pore channels to iodine is remarkably enhanced, so that the iodine adsorption rate and capacity are remarkably improved. The preparation method is simple, convenient, universal and high in controllability, and large-scale production and manufacturing of the metal covalent organic framework adsorption material can be achieved.

Provided herein are 19-nor C3,3-disubstituted C21-pyrazolyl steroids of Formula (I):and pharmaceutically acceptable salts thereof; wherein , R1, R2, R3a, R3b, R4a, R4b, R5, R6, and R7 are as defined herein. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, convulsive disorders, disorders of memory and / or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and / or withdrawal syndromes, and tinnitus.

Methods for treating patients with wAIHA comprising administering at least one compound chosen from (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile (rilzabrutinib) and pharmaceutically acceptable salts thereof are disclosed.

Described herein is the farnesoid X receptor agonist, 4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl)pyridin-2-yl)((4-(4-methoxy-3-methylphenyl)bicyclo[2.2.2]octan-1-yl)methyl)carbamoyl)cyclohexyl 3-hydroxyazetidine-trans-1-carboxylate, including crystalline forms and pharmaceutically acceptable salts, solvates, and formulations thereof.

The application provides an acid ester composite diesel anti-wear agent and a preparation method thereof, and belongs to the technical field of diesel additives, and comprises the following steps: S1, preparing a silanized solid acid catalyst; S2, preparing C18 polyol ester; S3, mixing an acid type anti-wear component and the C18 polyol ester, and then stirring after heating, and then adding tetrahydropyrazole pyridine derivatives and a diluent to continue stirring, and then cooling and filtering to obtain the acid ester composite diesel anti-wear agent. The application can improve the lubricity and anti-wear performance of low-sulfur diesel at a lower additive dosage, and has low corrosion and good oxidation stability.

The present invention relates to pharmaceutical compositions containing N-(1,3-dimethylpyrazol-4-yl)sulfonyl-6-[3-(3,3, 3-trifluoro-2,2-dimethyl-propoxy)pyrazol-1-yl]-2-[(4S)-2,2,4-trimethylpyrrolidin-1-yl]pyridine-3-carboxamide, a solid dispersion of (R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-7V-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-en indol-5-yl)cyclopropanecarboxamide, and a solid dispersion of N-[2,4-Bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxo-quinoline-3-carboxamide, including formulations of the solid dispersions into powders, granules and mini-tablets, methods for manufacturing and processing the powders, granules and mini-tablets, and methods for treating cystic fibrosis employing the pharmaceutical compositions.

The invention relates to the technical field of agricultural plant disease control, and particularly discloses a biological and chemical compound bactericide and application thereof. The biological and chemical compound bactericide comprises a bacterial solution of a biocontrol strain bacillus velezensis LHN1 and a chemical bactericide, the biocontrol strain bacillus velezensis LHN1 is preserved in Guangdong Microbial Culture Collection Center, and the preservation number is GDMCC No: 63550; the chemical bactericide is selected from at least one of prochloraz, pyraclostrobin or tebuconazole; in the compound bactericide, the volume ratio of the LHN1 bacterial liquid to the chemical bactericide is (1: 4)-(4: 1). Through the synergistic effect of biological prevention and control and chemical prevention and control, the problems that a single chemical bactericide pollutes the environment and the single biological prevention and control effect is unstable are solved, the prevention effect in a pot experiment reaches up to 83.99%, meanwhile, the dosage of chemical agents is reduced by 30%-50%, and the method has the advantages of being efficient, low in toxicity and low in cost and is suitable for root rot prevention and control in large-scale planting of rhizoma polygonati.

Methods for treating Sickle Cell Disease (SCD) comprising administering a BTKi, such as at least one compound chosen from (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile (rilzabrutinib) and pharmaceutically acceptable salts thereof, are disclosed.

The invention discloses a pyrazolecarboxamide compound and application of the pyrazolecarboxamide compound. Specifically, the invention discloses a compound shown as a formula I or a pharmaceutically acceptable salt thereof. The compounds of the present invention are IL-17 small molecule modulators, and can be used for the treatment or prevention of IL-17 mediated diseases, such as autoimmune diseases.

The compound cis)-N—((S)-1-(6-(4-fluoro-1H-pyrazol-1-yl)pyridin-3-yl)ethyl)-1-methoxy-4-(4 methyl-6-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)cyclohexanecarboxamide can be prepared as a free base in various crystalline solid forms, and in various salt forms each having one or more solid forms.

The invention provides a preparation method of a pyrazolopyridine derivative (formula (I)). The method has the advantages of mild reaction conditions, simple operation, high reaction yield, high product purity and convenient post-treatment, and is suitable for industrial production.

The application discloses a kind of compound fertilizer with nitrogen fertilizer slow-release and biocontrol function and preparation method, it is related to microbial compound fertilizer field, including the following components: nitrogen source carrier, physical net trapping material, 3,4-dimethyl pyrazole phosphate, biocontrol component, binder.A kind of preparation method, including the following steps: after silanization modification treatment is carried out to attapulgite, with polyglutamic acid aqueous solution mixed reaction, obtain self-assembly gel;Bacillus subtilis is embedded and handled, rhamnolipid is pre-emulsified, chitosan oligosaccharide is crosslinked with boric acid treatment, and is blended;Nitrogen source carrier is heated to melt, add self-assembly gel, mix evenly;Temperature control, add 3,4-dimethyl pyrazole phosphate, and keep warm reaction;Cooling, add the blend obtained in step S200, binder, mix evenly;Extrusion granulation, after fluidized bed drying, slow-release coating is carried out, and the target compound fertilizer is obtained.The application makes disease control efficiency to improve to 89.2%, and blocks nitrosomonas AMO enzyme activity for 120 days.

The application discloses a flexible metal organic framework material with molecular sieve-like separation performance and a preparation method and application thereof, and preparation of the flexible metal organic framework material comprises the following steps: a copper hexafluorosilicate solution is added drop by drop into a 3,5,3,5-tetramethyl-1H,1H-[4,4]bipyrazole solution in an ice water environment, after dropping, the reaction is stirred for 10-15 hours in the ice water environment, and the obtained reaction solution is subjected to post-treatment to obtain the flexible metal organic framework material [Cu(bpz)(SiF6)] with molecular sieve-like separation performance. The framework material has a great adsorption difference for C2H2 and CO2, can be used for separating C2H2 / CO2 mixed gas, has very high separation selectivity, has a large adsorption capacity for C2H2, and is a solid physical adsorbent with both characteristics.

The disclosure provides the development of enantiomer-specific 7V-arylpyrazole dipeptides as novel N0D2 agonists which are effective at promoting immune checkpoint inhibitor therapy requiring N0D2 for activity. Given the significant functions of N0D2 in innate and adaptive immunity, these novel agonists afford new therapeutic compounds for a variety of NOD2-responsive diseases.

Provided herein are crystalline salt and free base forms and amorphous forms of a compound having the following formula (I): (I) Compound 1. Also provided are pharmaceutical compositions comprising such crystalline and amorphous forms, processes for their manufacture and their use for the treatment of various conditions such as hemolytic anemia, sickle cell disease and MDS (very low risk MDS, low risk MDS, lower risk MDS and / or moderate risk MDS).

Compounds and salts thereof that are useful as JAK kinase inhibitors are described herein. Also provided are pharmaceutical compositions that include such a JAK inhibitor and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of treating or lessening the severity of a disease or condition responsive to the inhibition of a Janus kinase activity in a patient.

The application provides a synthesis process of metrafenone, in which inorganic alkali KOH is used as a catalyst, a key intermediate 4-(((5,5-dimethyl-dihydroisoxazole-4-yl)thio)methyl)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol can be obtained at low production cost and high yield, metrafenone is prepared through substitution reaction and oxidation reaction, the reaction yield is high, raw materials are simple and easy to obtain, three-waste emissions are small, and the process is beneficial to industrial mass production.

The invention belongs to the technical field of chemical synthesis, and particularly relates to a preparation method of 4, 4 '-[oxygen bis (methylene)] bis [5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole]. The invention provides a preparation method of 4, 4 '-(oxybis (methylene)) bis (5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole, which comprises the following steps: dissolving a compound shown in a formula IV and a compound shown in a formula V in a solvent, adding alkali, carrying out coupling reaction to obtain a reaction solution, and carrying out post-treatment to obtain a compound shown in a formula VI, namely 4, 4'-(oxybis (methylene)) bis (5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole. The compound is 4, 4 '-(oxybis (methylene)) bis (5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole). The preparation method disclosed by the invention is simple and easy to implement, mild in condition, high in safety, suitable for preparing reference substances in laboratories, and beneficial to product quality control and production process development.