100 results about "Desmethyl" patented technology

The invention relates to the field of biological engineering and technology, in particular to an enzyme for synthesizing glabridin, a biological synthesis method of glabridin and an engineering-modified biological host. The invention discloses a series of glabridin synthesizing enzymes (4 '-O-methyltransferase, isoflavone 2'-hydrogenase, isoflavone reductase, Vissisoketoreductase, isoprenyltransferase, pterocarpin reductase, oxidative cyclase and demethylase) from glycyrrhiza glabra for the first time, and the glabridin synthesizing enzymes have corresponding activities in various biological hosts. The heterologous biosynthesis of the glabridin is realized for the first time, and the yield of the glabridin can reach 60% or above.

The invention belongs to the field of medicine, relates to application of a combination containing a trifluoromethyl compound and a chemotherapeutic drug including a demethylated drug to treatment of hematologic tumors, and particularly relates to application of a combination of a salt shown as a formula I-1 or pharmaceutically acceptable salt thereof and a chemotherapeutic drug to treatment of hematologic tumors. # imgabs0 #

The invention discloses an adriamycin-tetravalent platinum drug-norcantharidin three-drug combined nano-drug as well as a preparation method and application thereof, and belongs to the technical field of medical materials. A tetravalent platinum drug modified by demethylated cantharidin and adriamycin are used as raw materials, a novel nano-drug is constructed through Cu < 2 + > coordination, and then the nano-drug combining adriamycin, the tetravalent platinum drug and demethylated cantharidin is prepared by polymerizing polydopamine with a mild photo-thermal effect. The polymer has the capacity of controllably releasing drugs under acidity and reduction, can realize photo-thermal conversion under laser irradiation to generate a mild photo-thermal effect, has a better tumor cell killing effect, has the capacity of consuming glutathione and generating hydroxyl radicals, can enter cancer cells in an endocytosis mode and release DOX, and can be used for killing tumor cells. And a new thought is provided for multi-drug combination and chemotherapy-chemokinetics therapy-photothermal therapy multi-mode combined therapy.

The invention discloses a demethylase ODM gene for synthesizing benzylisoquinoline alkaloids and application thereof, the demethylase ODM gene is an ODM1 gene or an ODM2 gene, the nucleotide sequence of the CDS region of the ODM1 gene is shown as SEQ ID NO: 1, and the nucleotide sequence of the CDS region of the ODM2 gene is shown as SEQ ID NO: 2. Aiming at the current situation that the research basis of a key gene for synthesizing corydalmine in rhizoma corydalis is weak, the ODM1 gene for catalyzing tetrahydropalmatine demethylation to specifically generate corydalmine and tetrahydrojatrorrhizine and the ODM2 gene for specifically generating tetrahydrojatrorrhizine are cloned from rhizoma corydalis for the first time. An important theoretical basis is provided for producing the corydalmine by utilizing a synthetic biological method in the future, and the corydalmine mutant has a wide application prospect and a great economic value.

The invention relates to the technical field of chemical synthesis, and discloses a preparation method and control of an abelsiril impurity A, namely 6-(4-chloro-5-fluoropyrimidine-2-yl)-4-fluoro-1-isopropyl-2-methyl-1H-benzimidazole. The preparation method comprises the following steps: S1, carrying out aromatic nucleus nucleophilic substitution reaction on a compound I and a nucleophilic reagent in an organic reagent, washing an organic phase, drying, filtering, and drying to obtain a compound II; concentrating under reduced pressure to obtain a compound II; s2, mixing the compound II, the compound III, a palladium catalyst, alkali and an organic solvent, performing heating reflux under the protection of nitrogen, performing Suzuki coupling reaction, performing vacuum concentration, and washing a filter cake with tetrahydrofuran to obtain a compound IV; s3, carrying out demethylation reaction on the compound IV to obtain a compound V; s4, the compound V reacts with a chlorination reagent, reduced pressure distillation is conducted, separation and purification are conducted, and the abelsilib impurity A is obtained. The design route provided by the invention is reasonable, the reaction site selectivity is good, and the impurity A with relatively high purity can be obtained.

The present disclosure is concerned with substituted cyclopropyl carbamate and cyclopropyl sulfonamide compounds, pharmaceutical compositions comprising the compounds, and methods of using the compounds in the treatment of various cancers such as, for example, cancers comprising cells that express at least one Sox 2 stem cell marker. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

The present application relates to a kind of from androsta 1, 4-diene-3, 17-dione starting synthesis of estren and the method of a kind of compound thereof.Especially, the present application provides a kind of preparation method of estren shown in formula I, comprising the following steps: in inert solvent, androsta-1, 4-diene-3, 17-dione (II) with reagent R4VX carries out demethylation aromatization reaction step directly to obtain estren (I);Wherein, the definition of reaction substrate, reagent and reaction condition is as claimed in claim or specification.The method is simple in operation, and good in selectivity, and product purity is high, suitable for industrial production.

Aspects of this invention are related to the use of N-desmethyl ruboxistaurin and pharmaceutically acceptable formulations thereof to modulate RSK signaling. Some aspects of the invention relate to the use of N-desmethyl ruboxistaurin to inhibit RSK. Some aspects of the invention provide methods of using N-desmethyl ruboxistaurin in the treatment of subjects with cancer, including breast cancer, ovarian cancer, prostate cancer, lung cancer, hepatocellular carcinoma, colorectal cancer, melanoma, osteosarcoma, myeloproliferative neoplasms, leukemia, and bladder cancer. The disclosed methods extend beyond disease treatment, including supportive care during radiation chemotherapy and prevention of cancer relapse. N-desmethyl ruboxistaurin administration, alone or in combination with other cancer therapies, inhibits RSK and shows a safety profile that supports its long-term use.

Provided herein are compositions including a CRISPR / dCas9-based demethylation cocktail targeting a methylated endothelial PLCγ2 promoter and methods of treating wounds using the same.

The present invention relates to the field of microbial technology, and specifically discloses an oxygen-resistant Blautia sp. and its application in the aerobic synthesis of 3'-demethyl arctiin. The oxygen-resistant Blautia sp. (Blautia sp.) Aeroto-AUH-df6 has a deposit number of CGMCC NO.30297. The oxygen-resistant Blautia sp. Aeroto-AUH-df6 provided by the present invention can efficiently transform arctiin under the condition of air oxygen, and the transformation performance is stable, which solves the problem that 3'-demethyl arctiin cannot be biosynthesized on a large scale under the condition of air oxygen, and the problem that 3'-demethyl arctiin resources are scarce, and 3'-demethyl arctiin is the only product of the transformation of the substrate arctiin by the strain Aeroto-AUH-df6, which greatly simplifies the subsequent separation and purification steps, and is of great significance for studying the pharmacological activity of 3'-demethyl arctiin and the development of new drugs.

The invention relates to a sterol compound, a preparation method and a medicine for treating pulmonary fibrosis, and belongs to the technical field of medicines. The demethylated cryptosterol separated from the fungus coniothyrium minitans has good anti-pulmonary fibrosis activity, and can be used as a lead compound for developing drugs for treating idiopathic pulmonary fibrosis. The invention provides an alternative compound for developing a new medicine for treating idiopathic pulmonary fibrosis, and has very important significance for development and utilization of natural product resources.

The invention relates to a metabolite marker for early diagnosis of colorectal cancer as well as application and a device of the metabolite marker. The marker comprises sulfate, ubiquinone-1, a deoxycholic acid glycine conjugate, demethylchlorophyllin, 3-(3, 5-diiodine-4-hydroxyphenyl) lactate, vitamin K1, O-decanoyl-L-carnitine, sedoheptulose 1, 7-diphosphoric acid, cholesterol-docosahexaenoic acid ester and acyl AMP (adenosine monophosphate). The marker combination has excellent performance in colorectal cancer detection, AUROC can reach 0.97, and noninvasive screening and early diagnosis of colorectal cancer can be accurately, quickly and simply realized.

The invention discloses a series of colchicine deuterated derivatives for resisting multiple myeloma, which can effectively inhibit proliferation of multiple myeloma cells by improving the metabolic effect of colchicine in the multiple myeloma cells and overcome the defect of large toxic and side effects of metabolism of original drugs. According to the series of colchicine deuterated derivatives capable of resisting multiple myeloma, colchicine is used as a raw material, two reactions of demethylation and deuterated methyl are sequentially performed to obtain a target compound, the reaction steps are few, the reaction conditions are mild, the operability is high, and the efficiency is high.

The invention relates to the technical field of drug monitoring, and mainly relates to a method for detecting multiple antitumor drugs and metabolites in human plasma through liquid chromatography-tandem mass spectrometry and application of the method. The medicine to be detected is prepared from cevaltinib, loratinib, vomitinib, amitinib, sovantinib, anlotinib, glutamitinib, emtricitinib, N-demethylated vomitinib and N-demethylated emtricitinib; s2, preparing a calibration product and a quality control product, and preparing a working curve concentration table; s3, carrying out pretreatment on the calibration product and the quality control product obtained in the step S2; s4, carrying out liquid chromatography-tandem mass spectrometry detection on the pretreated liquid; and S5, performing methodological verification on the detection method. The detection method has the advantages of high sensitivity, good detection result accuracy, simple and rapid detection process, short analysis time and the like, and is suitable for detection of large-flux samples.

The invention provides a bidentate cobalt complex containing an imidazo [1, 2-alpha] pyridine group as well as a preparation method and application of the bidentate cobalt complex, and belongs to the technical field of organic chemical synthesis. The structural formula of the bidentate cobalt complex is shown in the specification, and the preparation method comprises the following steps: carrying out bromination reaction and cyclization reaction on 2-methoxy-6-acetylpyridine to obtain a bidentate ligand with methoxy and imidazo [1, 2-alpha] pyridyl, and carrying out demethylation reaction on the ligand to obtain another bidentate cobalt complex with hydroxyl and imidazo [1, 2-alpha] pyridyl. The imidazo [1, 2-alpha] pyridyl-containing bidentate cobalt complexes are prepared from imidazo [1, 2-alpha] pyridyl-containing bidentate ligands, and the two ligands react with anhydrous cobalt chloride respectively to obtain various imidazo [1, 2-alpha] pyridyl-containing bidentate cobalt complexes. The electron effect of the complex is adjusted by changing substituent groups on imidazo [1, 2-a] pyridine groups, then the activity of the complex in catalytic reaction is adjusted, and the complex can be further applied to hydrosilylation reaction of styrene and has very important application prospects.

The invention provides an application of O-demethylangorapin in preparation of a medicine for relieving renal toxicity and myotoxicity of cis-platinum and cachexia manifestation caused by the renal toxicity and the myotoxicity of the cis-platinum. The active ingredient of the medicine is one or more of O-demethylated angorapin, a hydrate of the O-demethylated angorapin, a pharmaceutically acceptable salt of the O-demethylated angorapin, a tautomer of the O-demethylated angorapin, a stereoisomer of the O-demethylated angorapin and a precursor compound of the O-demethylated angorapin. The O-demethylangiecarpin has the potential to be developed into a drug for relieving the toxicity of cis-platinum.

The application provides a preparation method of a 6-position or 10-position oxidatively modified steroid drug, and the method comprises the following steps: S1: irradiating a solution of 19-methyl steroid drug Ia or 19-demethyl steroid drug Ib and a catalyst with a light source under an oxygen or air atmosphere, and removing the solvent after the irradiation is completed; S2: treating the reaction product after the solvent removal in S1 with a reducing agent, so that 6-position oxidatively modified steroid drug IIa and IIIa or 10-position oxidatively modified steroid drug IIb is obtained. In the preparation method, no reagent with high danger and environmental pollution, such as metal, strong base or peroxide, is used, the yield is high, the method is green, environmentally friendly, simple and easy to implement, and the production applicability is strong.

The invention belongs to the field of medicine synthesis, and particularly discloses a preparation method of 7-demethylated amazonicycline. The preparation method comprises the following steps: by taking 7-aminosancycline as an initial raw material, adding N-benzyl and N-methyl, then carrying out substitution reaction by using N-hydroxymethyl phthalimide, then removing phthaloyl by using methylamine, carrying out amination reduction reaction by using sodium borohydride and pivalaldehyde, and finally, carrying out hydrogenation by using pd / C to remove benzyl, thereby obtaining the 7-methyl oxalicycline. According to the route, the target product can be prepared with the total yield of 55%. According to the method, the impurity reference substance of the high-purity 7-methyl omalonin can be prepared, the accuracy of qualitative and quantitative analysis of the impurity is improved, the control on the impurity is enhanced, and the quality of an omalonin finished product is further improved.

The invention relates to a compound, which has good H3K27me3 demethylation inhibition activity at a cellular level, can effectively inhibit KDM6A / B activity, and can effectively treat inflammation and tumor diseases. The compound is shown in the formula.

Novel compositions of N-desmethyl ruboxistaurin L-lactate salt and L-lactate salt polymorphs. The use of compositions of N-desmethyl ruboxistaurin L-lactate salt and polymorphs to modulate GSK-3 signaling is disclosed, as is the use of compositions of N-desmethyl ruboxistaurin L-lactate salt and polymorphs to inhibit protein kinase C. Methods are also disclosed of using compositions of N-desmethyl ruboxistaurin L-lactate salt and polymorphs in the treatment of subjects having a neurological disease and / or psychiatric disorder, including Alzheimer's disease, bipolar disorder, depression, schizophrenia, Parkinson's disease, or neuroinflammation, as well as methods of using compositions of N-desmethyl ruboxistaurin L-lactate salt and polymorphs in treating conditions associated with diabetes mellitus or its complications, or ischemia, inflammation, pulmonary hypertension, congestive heart failure, cardiovascular disease, dermatological disease, or cancer. In addition, compositions of N-desmethyl ruboxistaurin L-lactate salt and polymorphs administered in combination with lithium or other treatments for bipolar disorder are also disclosed.

A method of preparing MEP including the steps of: (a) adding N-methylpyrrolidine to an excess amount of ethyl bromide located in a reactor, wherein the N-methylpyrrolidine will react with the ethyl bromide forming MEP, wherein the reaction will have a reaction temperature that can varies over time; (b) stopping addition of N-methylpyrrolidine when the excess of ethyl bromide to the N-methylpyrrolidine falls within a range of 3:1 to 1.5:1; (c) adding water to the reactor creating a two phase system to develop which includes: (i) a top layer containing aqueous MEP and (ii) a bottom layer containing ethyl bromide; (d) separating the top layer from the bottom layer yielding a first aqueous solution of MEP and a second solution of ethyl bromide; and (e) removing N-methylpyrrolidine and ethyl bromide from the first aqueous solution of MEP.

This invention discloses a compound of formula I and a method for preparing minocycline hydrochloride. The method for preparing compound I involves dissolving 6-demethyltetracycline in acidic water, adding a chlorination reagent for chlorination, then adding p-aminobenzenesulfonic acid diazonium hydrochloride and alkaline solution for coupling reaction, followed by post-treatment. The method for preparing minocycline hydrochloride uses 6-demethyltetracycline as a starting material, proceeding through the intermediate of compound I, and removing the C7 chlorine, p-aminobenzenesulfonic acid group, and C6 hydroxyl group via catalytic hydrogenation, followed by reductive amination and post-treatment. This invention achieves low-pressure palladium-carbon catalytic removal of the C6 hydroxyl group by introducing an electron-donating amino group at the C7 position, eliminating the need for expensive rhodium-carbon catalysts. The reaction conditions are mild, column chromatography purification is unnecessary, the overall yield is ≥85%, and the product purity is ≥96%, making it suitable for industrial production.

Aspects of this invention are related to the use of N-desmethyl ruboxistaurin and pharmaceutically acceptable formulations thereof to modulate GSK3|3 signaling. Some aspects of the invention relate to the use of N-desmethyl ruboxistaurin to inhibit protein kinase C. Some aspects of the invention provide methods of using N-desmethyl ruboxistaurin in the treatment of subjects having a neurological disease and / or psychiatric disorder, including Alzheimer's disease, frontotemporal dementia, behavioral complications of dementia, bipolar disorder, depression, schizophrenia, Parkinson's disease, or neuroinflammation. Some aspects of this invention provide methods of using N-desmethyl ruboxistaurin in treating conditions associated with diabetes mellitus or its complications, or ischemia, inflammation, pulmonary hypertension, congestive heart failure, cardiovascular disease, dermatological disease, or cancer. Some aspects of the invention relate to the use of N-desmethyl ruboxistaurin as an alternative to ruboxistaurin, with a better pharmacokinetic profile, lower potential for prolongation of the electrocardiogram QT interval, and / or a lower potential for adverse drug interactions. In some embodiments, N-desmethyl ruboxistaurin is administered in combination with lithium or other treatments for bipolar disorder.

To provide a production method of lysine-specific demethylase (LSD1) inhibitors that is easier to implement and has higher yields.SOLUTION: A method for producing a compound represented by formula (I) or a pharmaceutically acceptable salt thereof comprises the step of converting a compound C to a compound D in a solvent under the action of an oxidizing agent.SELECTED DRAWING: None

The invention relates to the technical field of medicine analysis, in particular to a method for detecting the content of N-nitroso-demethylated olopatadine in an olopatadine hydrochloride raw material medicine. The analysis method comprises the following steps: preparing a blank solution, a system applicability solution and an olopatadine hydrochloride bulk drug test solution; sequentially injecting the blank solution, the system applicability solution and the olopatadine hydrochloride raw material medicine test solution, injecting into a high performance liquid chromatography-tandem mass spectrometer, and detecting the content of N-nitroso-demethylated olopatadine according to an external standard method; the invention discloses a method for detecting the content of N-nitroso-demethylated olopatadine in an olopatadine hydrochloride bulk drug, which has the advantages of high sensitivity, simplicity, rapidness, strong specificity, good accuracy, high precision, good stability and good linear relationship, and can be used for detecting the content of N-nitroso-demethylated olopatadine in the olopatadine hydrochloride bulk drug.

The present invention relates to novel compounds which can be used as the main component of a composition for stimulating hair growth, and also to their use in stimulating hair growth, wherein the novel compounds are 9-deoxy-31-O-demethyl-proline-FK506, 9-deoxy-36,37-dihydro-FK506, 31-O-demethyl-36,37-dihydro-FK506, 9-deoxy-31-O-demethyl-36,37-dihydro-FK506, 9-deoxy-FK520, 31-O-demethyl-FK520, 9-deoxy-31-O-demethyl-FK520, 9-deoxy-FK523 and 9-deoxy-31-O-demethyl-FK523.

The invention relates to a photo-enzyme catalytic reaction for producing methane through oxygen demethylation of aryl methyl ether and application of the photo-enzyme catalytic reaction. According to the method, demethylase MTase I and cobalamine binding protein CP which are purified by a nickel column are utilized, the demethylase MTase I, the cobalamine binding protein CP and 5-denitrified riboflavin react with different aryl methyl ether substrates respectively in a buffer solution with the pH value of 6.5 under the conditions of purple light irradiation and anaerobic conditions, O-demethylation of aryl methyl ether is catalyzed, and the 5-denitrified riboflavin is obtained. Demethylation products of methane and phenols are generated; according to the method disclosed by the invention, demethylation methane production reaction is completed, and meanwhile, the reaction efficiency and the substrate spectrum of oxygen demethylation of aryl methyl ether are improved. In-vitro catalysis of the demethylation methane production reaction of flavone aryl ether and natural biomass lignin alkaline hydrolysate is realized for the first time, and compared with the current demethylation reaction, the method has the advantages of mild reaction conditions, environmental protection and the like, and meanwhile, the removed methyl is converted into methane, so that the method is suitable for industrial production. The addition of additional methyl acceptors and the generation of byproducts are effectively avoided, and the atom economy is improved.

This invention discloses a desmethylmenoprenone methyltransferase mutant, its construction method, and its applications, belonging to the field of biotechnology. Desmethylmenoprenone methyltransferase is a key enzyme in the MK-7 biosynthetic pathway, responsible for catalyzing the methylation reaction of desmethylmenoprenone to generate a series of methylnaphthoquinone (MK) products, ultimately forming MK-7. This invention, through metabolic network regulation and rational design, successfully obtained 19 single-point mutants, among which 5 mutants showed significantly higher catalytic efficiency than the wild-type enzyme. Experimental results show that the recombinant engineered bacteria constructed based on these mutants exhibit significant advantages in the whole-cell catalytic production of vitamin K2 (MK-7), with MK-7 yield increased by more than 20% compared to the wild-type strain. The excellent catalytic performance of the menG mutant provided by this invention provides strong technical support for the industrial production of vitamin K2, and has broad application prospects and market value.

The invention relates to a method for preparing a bathroom mat from a nano antibacterial and mildew-proof environment-friendly material, and belongs to the technical field of bathroom mats. Polyvinyl chloride, an antioxidant, a stabilizer, trioctyl trimellitate, a filler, polyester, a lubricant, a plasticizer and a mildew-proof antibacterial agent are put into a mixing machine to be stirred, extruded in a double-screw extruder, mixed on a double-roller open mill and tableted on a flat vulcanizing machine, and the nano antibacterial mildew-proof environment-friendly material bathroom mat is obtained. The mildew-proof antibacterial agent is prepared by the following steps: stirring 3-mercaptoquinoline, methyl pyrrolidone, O-allyl-2-bromophenol ether and triethanolamine to react; adding tributyl isopropenyl tin, stirring to react, and distilling to remove the methyl pyrrolidone, thereby obtaining the product. The prepared bathroom mat has excellent mildew resistance and good bacteria resistance, has lasting mildew-proof and antibacterial effects, and is an ideal bathroom mat manufacturing material.

The invention belongs to the technical field of bioactive components, and particularly relates to a screening method of a deep-eutectic solvent and application of the deep-eutectic solvent in selective demethylation of polymethoxylated flavonoids. According to the method, the five eutectic solvents are screened on the basis of physicochemical properties and thermodynamic properties, the eutectic solvent capable of being efficiently demethylated is obtained, and the requirement for obtaining hydroxylated PMFs is met; meanwhile, the concentration, the reaction temperature and the reaction time of the demethylation reagent are optimized, and the optimal reaction condition is obtained, so that the technical problem that a high-performance demethylation special reagent is lacked in the prior art is solved.