1645 results about "Piperidine" patented technology

The present disclosure relates to a pharmaceutically acceptable salt of a G12D inhibitor compound and a crystal form thereof. Specifically, provided in the present disclosure are a salt of 2-amino-4-((5S,5aS,6S,9R)-12-((1-((4-(difluoromethylene)piperidin-1-yl)methyl)cyclopropyl)methoxy)-1-fluoro-5-methyl-5a,6,7,8,9,10-hexahydro-5H-4-oxa-3,10a,11,13,14-pentaaza-6,9-methanonaphtho[1,8-ab]cyclohepten-2-yl)-7-fluorobenzo[b]thiophene-3-carbonitrile and a crystal form thereof.

Embodiments of the present invention provide methods and intermediates for the large scale preparation of 2, 4, 6-trifluoro-N-[6-(1-methylpiperidine-4-carbonyl)-2-pyridyl] benzamide hemisuccinate, as well as formulations and product forms prepared by these methods. Embodiments of the present invention further provide for the preparation of lamidetan acetate (2, 4, 6-trifluoro-N-[6-(1-methylpiperidine-4-carbonyl)-2-pyridyl] benzamide acetate) and / or a pharmaceutical composition thereof, and / or the use of lamidetan acetate and formulations thereof in subcutaneous drug delivery.

The invention belongs to the technical field of anion exchange membranes, and relates to a cross-linked polyaromatic piperidine anion exchange membrane and a preparation method thereof. The exchange membrane structure comprises a copolymer structure of the following repetitive structural units, the selected rigid main chain polyaromatic hydrocarbon can ensure the mechanical strength of the anion exchange membrane, meanwhile, the toughness of the anion exchange membrane is further enhanced by adopting a cross-linked structure, and a formed cross-linked network can reduce swelling of the anion exchange membrane, so that the anion exchange membrane is more stable in performance. The mechanical performance is improved; according to the invention, ether-free skeleton polyaromatic hydrocarbon is selected as a main chain and has the characteristic of strong alkali-resistant stability, six-membered nitrogen heterocyclic ions are adopted as functional groups, and a large steric hindrance structure can hinder nucleophilic substitution and elimination reaction, so that the alkali-resistant stability of the anion exchange membrane is improved, and the service life of the anion exchange membrane is prolonged. And in the # imgabs0 #, X is equal to 0.05 to 0.15.

The invention discloses a preparation method of a GLP-1R agonist Orforglipron, which comprises the following reaction steps: carrying out four-step reaction on an oxopiperidine compound (1) and (4-fluoro-3, 5-dimethylphenyl) hydrazine (2) to obtain a compound 8, and carrying out seven-step reaction on 5-bromo-indolecarboxylic acid (9) to obtain a compound 17. Then, the compound 8 and a compound 17 are subjected to an acid amine condensation reaction, and Orforglipron (LY3502970) is obtained. The preparation method is relatively low in cost, easy to operate, relatively short in synthetic route and suitable for industrial production and application, and the total yield can reach 32%.

The invention relates to an anion exchange membrane based on isopropyl piperidone and biphenyl and a preparation method of a membrane electrode, the preparation method comprises the following steps: respectively dissolving an aromatic monomer and IPD in a first solvent, and mixing to obtain a mixed solution, the aromatic monomer being BP or TP; dropwise adding an acidic initiator into the mixed solution for reaction at the reaction temperature of-5 DEG C to 0 DEG C to obtain a nitrogen heterocyclic ring polymer intermediate; adding a quaternization reagent into the nitrogen-containing heterocyclic ring polymer intermediate to realize quaternization modification of nitrogen atoms to obtain a quaternization ionomer; and forming a film to obtain the AEM film. The preparation method of the membrane electrode comprises the following steps: respectively forming a cathode catalyst layer and an anode catalyst layer on two opposite sides of an AEM membrane through ultrasonic spraying to obtain the MEA. The AEM membrane and the MEA obtained according to the invention have the characteristics of excellent stability and high water electrolysis performance, can significantly improve the efficiency and durability of AEMWE, and are suitable for the fields of hydrogen production by water electrolysis and the like.

Compounds of formula (II) and formula (I) which are inhibitors of QPCTL and QPCT: (II) and (I) are provided herein. Also provided are pharmaceutical compositions containing this compound, as well as compounds for use in methods of treating cancer, neurodegenerative, inflammatory or autoimmune diseases. Exemplary compounds are, for example, 3-(6-fluoropyridin-3-yl)-2-[4-(4-methyl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]benzonitrile (Example 1): (1), and pharmacological data are provided. TIFF2025524039000368.tif70128

Provided is an anthraquinone derivative represented by formula (9-1). In formula (9-1), R1 and R2 are each independently an amino group or a hydroxyl group and Y1, Y2, and Z are each independently a hydrogen atom, a C1-C10 alkyl group, a C1-C10 alkoxy group, a cyano group, a nitro group, a halogen atom, a C1-C10 halogenated alkyl group, an amino group, an alkylamino group, a piperidyl group, an aryl group, or a cyclohexyl group, the aryl and cyclohexyl groups being optionally substituted.　

The invention relates to a high-efficiency preparation method of a Ritlecitinib key intermediate, which comprises the following steps: reacting (2S)-1-substituent-2-methylpiperidine-5-ketone with 4-amino-7H-pyrrolo [2, 3, d] pyrimidine to form imine, and carrying out chiral induction on the imine in the presence of a reducing agent to obtain a single chiral 4-(N-((3R, 3R)-4-(4-((3R, 3R)-4-(4-amino-7H-pyrrolo [2, 3, d] pyrimidine-5-ketone)-4-amino-7H-pyrrolo [2, 3, d] pyrimidine-5-ketone)-4-amino-7H-pyrrolo [2, the preparation method comprises the following steps: adding 2-(2, 6, 6, 6, 6-tetramethylpiperidine-3-yl)) amino-7H-pyrrolo [2, 3, d] pyrimidine into a reaction kettle, and carrying out deprotection to obtain a target product. Compared with the existing method, the method has the characteristics of short synthetic route, good selectivity, easiness in industrialization and the like.

The invention relates to the technical field of fluorescent probes, and provides a low-concentration ratio type high-concentration enhanced fluorescent probe as well as a preparation method and application thereof in order to solve the problems that a traditional fluorescent probe depends on a high-concentration use condition and is often faced with fast probe consumption, increased biotoxicity, non-specific target binding and the like in a biological sample. The preparation method of the fluorescent probe comprises the following steps: step 1, preparing phenothiazine dialdehyde; and 2, mixing phenothiazine dialdehyde, malononitrile, ethanol, acetonitrile, DMF and piperidine, and carrying out a reflux reaction to obtain the low-concentration ratio-type high-concentration enhanced fluorescent probe. The probe provided by the invention realizes quantitative detection of HClO through synchronous change of two emission channels, and the detection sensitivity and reliability are remarkably improved; when the concentration is high, an enhanced single-channel fluorescence amplification effect is shown, and strong signal identification and macroscopic visual imaging in specific application are facilitated, so that the dual requirements of trace monitoring and high-throughput screening are met.

The invention belongs to the technical field of bioengineering, and relates to a transaminase mutant, a recombinant genetically engineered bacterium and application of the transaminase mutant in catalytic synthesis of (R)-1-Boc-3-aminopiperidine.The transaminase mutant is obtained by conducting single-point or combined mutation on the 131 site and / or the 197 site of an amino acid sequence shown in SEQ ID NO.2; the mutation sites comprise that the 131 phenylalanine is mutated into aspartic acid, threonine or tyrosine, and / or the 197 lysine is mutated into arginine or leucine. Experimental results show that compared with wild type transaminase, the catalytic activity, the thermal stability and the organic solvent tolerance of the obtained mutants, especially single-point mutants MyTA1-F131Y and MyTA1-K197R and a combined mutant MyTA1-F131Y-K197R, are all remarkably improved, and compared with the wild type transaminase, the catalytic activity, the thermal stability and the organic solvent tolerance of the obtained mutants are all remarkably improved. The mutant MyTA1-F131Y-K197R can be used for efficiently catalyzing asymmetric amination of N-Boc-3-piperidone to synthesize (R)-1-Boc-3-aminopiperidine, the conversion rate of the (R)-1-Boc-3-aminopiperidine after the (R)-1-Boc-3-aminopiperidine reacts for 24 hours under the condition that the substrate concentration is 100 g / L can reach 90% or above, and the mutant MyTA1-F131Y-K197R has a good industrial application prospect.

The invention discloses an aldehyde reductase mutant and application thereof in synthesis of a dexmethylphenidate hydrochloride intermediate, and belongs to the field of molecular biology and enzyme engineering. The aldehyde reductase mutant, polynucleotide for coding the mutant, and the recombinant expression vector can express the aldehyde reductase mutant and are used for constructing a recombinant cell or a recombinant strain for expressing the aldehyde reductase mutant. The provided aldehyde reductase mutant can catalyze 2-phenyl-2-((R)-piperidine-2)-acetaldehyde into (R)-2-phenyl-2-((R)-piperidine-2)-1-ethanol, especially improves the stereoselectivity of (R)-2-phenyl-2-((R)-piperidine-2)-1-ethanol, solves the problems of strict conditions, complex reaction and high cost in the existing synthesis method, and has a wide application prospect in the field of synthesis of (R)-2-phenyl-2-((R)-piperidine-2)-1-ethanol. Wide application prospects are realized.

The present invention discloses a naphthalimide guanidine derivative, a preparation method thereof and an application thereof. The structural formula of the naphthalimide acyl guanidine compound is shown as formula (I), denoted as CAUZL-C; in formula (I), R is halogen, hydrogen, piperidyl or dimethylamino; n is 1, 2, 3 or 4. The naphthalimide guanidine derivative or a pharmaceutically acceptable salt thereof according to the present invention has good target enzyme inhibitory activity and insecticidal activity.

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.

Methods for treating immune thrombocytopenia 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.

The invention provides a preparation method of a block poly (biphenyl-trifluoroacetophenone-piperidone) bicontinuous hollow fiber loose nanofiltration membrane, which comprises the following steps: adding acid into biphenyl and N-methyl-4-piperidone to react to obtain a first product; adding acid into biphenyl and 2, 2, 2-trifluoroacetophenone to react, so as to obtain a second product; adding the second product into the first product, and carrying out condensation polymerization to obtain a PBTbBP block polymer; dissolving the PBTbBP block polymer in a solvent, and defoaming to obtain a membrane casting solution; spinning the membrane casting solution and the core solution to obtain membrane filaments; and immersing the membrane filaments in a coagulating bath, and carrying out phase separation. According to the preparation method, biphenyl, a hydrophobic trifluoroacetophenone monomer and a hydrophilic N-methyl piperidone monomer are subjected to superacid catalysis Friedel-Crafts reaction and are subjected to step-by-step copolymerization to obtain the amphiphilic block polymer PBTbBP. The membrane has efficient mass transfer channels and excellent membrane surface hydrophilicity, and the separation capacity of dye molecules and salt ions and the water permeability are improved.

The metabolic marker can be used for early diagnosis of heart failure, has the advantages of high sensitivity, rapidness, convenience and accurate and reliable result, provides a basis for clinical decision, provides a certain basis for subsequent fundamental research and clinical research, and has potential application and research values. The metabolic marker comprises one or more of 1-(4-nitrophenyl) piperidine, sphingolipid d19: 3 / 23: 0, phosphatidyl ethanolamine 16: 1e / 22: 5, phosphatidyl ethanolamine 16: 1e / 22: 6, sphingolipid d14: 0 / 22: 1, 3-phosphoglyceric acid, phosphatidylcholine 15: 0 / 20: 4, phosphatidylcholine o-16: 1 / 18: 0, phosphatidylcholine 14: 0e / 20: 1, phosphatidylcholine 17: 0 / 18: 5, betaine, phosphatidylcholine 15: 0 / 18: 2 and phosphatidylcholine 18: 5e / 20: 4.

The invention provides a novel hindered amine light stabilizer as well as a preparation method and application thereof, and relates to the field of light stabilizers. According to the preparation method of the novel hindered amine light stabilizer, specific dibasic acid dimethyl ester and 2, 2, 6, 6-tetramethylpiperidinol are used as raw materials, an alkane solvent or a benzene solvent is used as a solvent, and a catalytic reaction solution is obtained through a heating reaction under the condition of a catalyst; and neutralizing and washing the catalytic reaction liquid to obtain the novel hindered amine light stabilizer. According to the preparation method, ideal preparation effects (such as purity, yield and the like) can be achieved, meanwhile, the chroma of the product is effectively reduced, the problem that the product is prone to yellowing due to the fact that the hindered amine light stabilizer absorbs visible light is solved, and the compatibility and stability of the hindered amine light stabilizer and a high polymer material are further improved.

The invention relates to a thermoplastic molding composition (P) comprising: (A) thermoplastic polymer composition (A) comprising: (A-1) 10 to 50 wt.-% of graft copolymer (A-1), (A-2) 1 to 50 wt.-%, of thermoplastic polymer matrix (A-2) based on one or more vinylaromatic copolymers, (A-3) 20 to 50 wt.-%, of polymerized alkyl methacrylate component (A-3), and (A-4) 0 to 45 wt.-% of comonomer which is copolymerized with the at least one polymerized alkyl methacrylate component (A-3), where the sum of (A-1), (A-2), (A-3) and optional comonomers (A-4) is 83.2 to 99.8 wt.-%; (B) a hindered amine light stabilizer composition (B), comprising at least two of substances (B-1) to (B-3): (B-1) 0 to 0.9 wt.-%, of at least one hindered amine light stabilizer having a dipiperidine structure with at least one alkyl group at each of the 2 and 6 positions of the dipiperidine structure (B-2) 0 to 0.9 wt.-%, of a hindered amine light stabilizer mixture having a monopiperidine structure with at least one alkyl group at each of the 2 and 6 positions of the monopiperidine structure, and (B-3) 0 to 2 wt.-%, of at least one hindered amine light stabilizer having a polymeric structure comprising piperidine groups with at least one alkyl group at each of the 2 and 6 positions of the piperidine groups (C) 0 to 5 wt.-%, of one or more further additives (C), different from (B); and (D) 0 to 10 wt.-%, of colorants, dyes and / or pigments (D), different from (C); wherein the constituents (A) to (D) sum up to 100 wt.-% of the molding composition (P).

The invention provides a transaminase mutant and application of the transaminase mutant in chiral amine synthesis. According to the transaminase derived from Mycobacterium sp. Provided by the invention, in a 1 mL reaction system for catalyzing N-Boc-3-piperidone to generate N-Boc-3-aminopiperidine, the 24-hour conversion rate is 95%, and the e.e. Value of the product is greater than 99%. On the basis, the invention further provides a series of mutants of the transaminase, the relative enzyme activity of the mutants reaches 153%-293%, and the catalytic activity of the transaminase is further improved. Wherein the 34-hour conversion rate of the optimal transaminase mutant is increased to 90% or above under the condition of 120g / L substrate concentration in a 10mL reaction system, and the e.e. Value of the product is greater than 99%. The production technology has the advantages of high catalytic activity, easiness in fermentation, environment friendliness and the like, and has good development and application values.

The invention relates to the field of pipeline materials, and discloses a halogen-free flame-retardant MPP power pipeline material and a preparation method thereof.The pipeline material comprises polypropylene, modified multi-walled carbon nanotubes, a coating filler, a compatilizer and a lubricant; the modified multi-walled carbon nanotube is prepared by carrying out acylating chlorination on an oxidized multi-walled carbon nanotube by using thionyl chloride and then reacting with an aminated cyclotriphosphazene derivative; according to the aminated cyclotriphosphazene derivative, phosphonitrilic chloride trimer and 3, 5-di-tert-butyl-4-hydroxybenzylamine react to prepare a cyclotriphosphazene intermediate, the cyclotriphosphazene intermediate and N, N '-bis-(2, 2, 6, 6-tetramethyl-4-piperidyl)-1, 6-hexamethylenediamine are subjected to substitution to prepare a cyclotriphosphazene derivative, and then the cyclotriphosphazene derivative and 1, 6-hexamethylenediamine are subjected to substitution to obtain the aminated cyclotriphosphazene derivative. The coating filler is prepared by preparing modified lignin by combining 2, 2, 6, 6-tetramethyl-4-piperidinol and lignin and then preparing silicon dioxide-coated modified lignin by adopting a sol-gel method, and the pipe prepared by the invention has excellent mechanical properties, flame retardance, thermo-oxidative aging resistance and ultraviolet aging resistance.

Disclosed herein are dosage forms comprising a VAV1 degrader. More specifically, disclosed herein are dosage forms comprising 3-(2-chloro-4'-(2-oxopyridin-1(2H)-yl)-[1,1'- biphenyl]-3-yl)piperidine-2,6-dione or a pharmaceutically acceptable salt thereof. These dosage forms are useful, e.g., for treating a subject (e.g., a human subject) having a disorder or disease that can be treated by reducing the level of VAV1, for example an inflammatory or autoimmune disorder, a transplantation setting disorder, or a cancer.

The invention discloses a synthesis process of chiral cyclic ether indole. The synthesis process comprises the following steps: reacting 4-bromobenzaldehyde with malonic acid under the catalysis of piperidine to generate olefin carboxylic acid CHP-1; carrying out condensation reaction to prepare CHP-2; under the catalysis of a copper reagent, carrying out Michael addition reaction to obtain CHP-3; preparing a chiral alcohol intermediate CHP-4 through a reduction reaction; trifluoromethanesulfonic acid is used, and a chiral ether intermediate CHP-5 is prepared through ring closing; reacting with protected hydrazine by using a copper ion catalyst to obtain an intermediate CHP-6; the method comprises the following steps: by taking alcohol as a solvent, adding strong acid, and removing a protecting group of hydrazine to obtain an intermediate CHP-7; and carrying out ring closing by taking lewis acid as a catalyst to obtain an indole product CHP-8. The use of a noble metal catalyst palladium is avoided, and the cost is greatly reduced. The chiral center is directly constructed through a chemical method, and SFC is not needed for resolution, so that the cost is remarkably reduced, and industrial production is successfully realized.

The application provides a low-cost flow battery and application thereof, and the low-cost flow battery contains a hydroxylamine cyclic structure group with a hindered amine in a redox active material of a positive electrolyte of the low-cost flow battery, the hydroxylamine cyclic structure group with the hindered amine is preferably one or more of a 1-hydroxyl-2,2,6,6-tetrasubstituted piperidine group, a 1-oxygen radical-2,2,6,6-tetrasubstituted piperidine group and a 1-oxo-2,2,6,6-tetrasubstituted piperidinium group; and the redox active material of a negative electrolyte of the low-cost flow battery contains one or more of titanium elements, vanadium elements, chromium elements, iron elements and zinc elements. The low-cost flow battery has the advantages of high output voltage, high energy density, environmental friendliness and low cost, and has good application prospect and large-scale promotion potential in the field of energy storage.

The invention belongs to the technical field of water electrolysis hydrogen production, and discloses a branched polyaromatic piperidine anion exchange membrane, a preparation method and application. The preparation method comprises the following steps: preparing a branched polymer precursor, preparing a quaternized branched polymer, and preparing the branched anion exchange membrane: dissolving the quaternized branched polymer in a third solvent, and drying in a vacuum drying oven to obtain the branched anion exchange membrane in the form of iodide ions, and soaking the branched anion-exchange membrane in the form of iodide ions in a NaOH solution for ion exchange, so that the branched anion-exchange membrane in the form of iodide ions is completely converted into a form of hydroxyl ions. According to the invention, ether-free skeleton polyaromatic hydrocarbon is selected as a main chain and has the characteristic of strong alkali-resistant stability, six-membered nitrogen heterocyclic ions are adopted as functional groups, and a large steric hindrance structure can hinder nucleophilic substitution and elimination reaction, so that the alkali-resistant stability of the anion exchange membrane is improved, and the service life of the anion exchange membrane is prolonged.

The invention relates to a polycarboxylic acid water reducer and a preparation method thereof, and the water reducer is prepared from the following raw materials: 45 to 55 percent of isopentenyl polyoxyethylene ether, 28 to 35 percent of acrylic acid, 1.5 to 2.5 percent of modifier, 0.3 to 0.5 percent of ammonium persulfate, 0.03 to 0.06 percent of ascorbic acid, 5 to 8 percent of hydroxyethyl methylacrylate, 0.15 to 0.25 percent of 2, 4-diphenyl-4-methyl-1-pentene and the balance of water. The modifier is prepared from the following raw materials: 1, 5-dichloronaphthalene, p-nitrostyrene, dimethyl sulfate, ceric ammonium nitrate and tetramethylpiperidine oxide. The polycarboxylate superplasticizer has excellent neat paste fluidity and fluidity retention capability, has low 1h time-dependent variable slump which is below 18mm and optimally 10mm when applied to concrete, has a water-reducing rate of more than 40% and a gas content of less than 3.8%, and also has more advantages in compressive strength ratio.

The application provides a hindered amine light stabilizer and a preparation method thereof, and the preparation method comprises the following steps: putting N, N-bis(2, 2, 6, 6-tetramethyl-4-piperidyl) 1, 6-hexanediamine and an organic solvent into a reaction bottle, heating to 50-80 DEG C, adding methyl acrylate into the system dropwise, obtaining an intermediate I through an addition reaction, and then obtaining a crude product through an ester exchange reaction of the intermediate I and tetramethylpiperidinol in the presence of a catalyst and an organic solvent, washing with water, decoloring, filtering, cooling and crystallizing, filtering and drying to obtain the product; the light stabilizer obtained by the application has multiple hindered amine functional groups, has good heat resistance and extraction resistance, and has good compatibility with resin.

Described herein are pharmaceutical formulations of Bruton's tyrosine kinase (Btk) inhibitor 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo [3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one. Also disclosed are methods of using the Btk inhibitor, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

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.