78 results about "Desmethyl" patented technology

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 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 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 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 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 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.

The invention discloses a supramolecular compound and a preparation method and application thereof.The supramolecular compound is carrier-free nanoparticles (CDN) obtained by conducting molecular self-assembly on tripterine (CeL) and demethylwedelolactone, and experiments show that the CDN can effectively relieve clinical symptoms, inflammation infiltration and bone erosion. Besides, the CDN can be transferred to an inflammation part of rheumatoid arthritis (RA) in a targeted manner, so that bone degenerative change and joint skeleton damage can be remarkably reduced, the inflammation part is targeted, the expression of proinflammatory cytokines is reduced, the drug concentration of the affected part is improved, and the toxic and side effects of the tripterine are reduced. The research provides a new strategy for improving the curative effect and safety of the traditional Chinese medicine, and provides a brand new solution for RA treatment.

The embodiment of the present application discloses a preparation method of nor-tropine alcohol. The method comprises the following steps: performing demethylation reaction on tropinone and chloroethyl chloroformate in the presence of a solvent, performing vacuum concentration and evaporation, and obtaining demethyltropinone; performing reduction reaction on the demethyltropinone and lithium tri-t-butoxyaluminum hydride in the presence of a solvent, and obtaining the nor-tropine alcohol. The present application adopts a new type of reducing agent lithium tri-t-butoxyaluminum hydride, which is safe, not sensitive to air and water, and simple in post-treatment, thus avoiding safety hazards from the source. The present application avoids the use of dangerous Raney nickel and does not need to use an autoclave, so that the production capacity is greatly improved. The present application performs the reaction under low-temperature conditions, is low in energy consumption, can effectively reduce production cost, and is moderate in reaction conditions, safe and simple in operation, and is conducive to large-scale industrial production.

Compositions and methods for inhibiting histone lysine demethylases are provided. Several new DFP-based KDM inhibitors which alter the velocity of HP1-mediated heterochromatin gene repression are provided.

The application belongs to the technical field of polymer medical materials, and particularly relates to a four-arm PEG and a preparation method thereof. Specifically, the preparation method comprises the following steps: reacting monomethoxy PEG with bromo-pentaerythritol in an alkaline solvent to form four-arm PEG tetramethyl ether; and then removing the methyl groups from the four-arm PEG tetramethyl ether under the conditions of thiol, boron trifluoride ether and the like for a certain time to generate four-arm PEG. The application can effectively overcome the defects in the existing four-arm PEG preparation method, such as high safety risk and high cost caused by the use of ethylene oxide, and crosslinking products caused by the use of double-end PEG raw materials. The method should use safe and easily available raw materials, and the reaction conditions are mild and controllable, so that the directional high-yield synthesis of four-arm PEG is realized, and therefore the method has good practical application value.

The present application relates to a deuterium-labeled psychoactive substance, which has a chemical structural formula as shown in the description.The present application also provides a preparation method of the deuterium-labeled psychoactive substance, which comprises the following steps: (1) removing the methyl group of sufentanil under the action of a demethylating agent to generate a demethylated intermediate; (2) reacting the demethylated intermediate with a deuterated methyl reagent to generate the deuterium-labeled sufentanil.The present application also provides the use of the deuterium-labeled sufentanil in detecting the content of sufentanil in biological samples or environmental samples.

This invention discloses a berberine-dimethylaniline photosensitizer, its preparation method, and its application, belonging to the field of biomedical technology. The method involves sequentially reacting berberine with magnesium methyl bromide via Grignard addition, followed by bromomethylation with N-bromosuccinimide, and basic condensation with dimethylaminobenzaldehyde, then demethylating under high temperature and vacuum to obtain the active berberine-dimethylaniline. Finally, it undergoes weakly alkaline treatment to obtain the inactivated berberine-dimethylaniline. This invention introduces the electron-donating group dimethylaniline onto the berberine backbone, constructing an electron push-pull structure that red-shifts the absorption wavelength, facilitating deeper tissue penetration. Furthermore, this photosensitizer maintains high activity in the weakly acidic microenvironment of tumors while remaining inactive under normal physiological conditions, thereby achieving intelligent "on-off" regulation based on pH differences, improving the safety and precision of photodynamic therapy for tumors.

The invention relates to a metabolite and methylation combined marker for early diagnosis of colorectal cancer as well as application and a device of the metabolite and methylation combined marker. The marker comprises sulfate, ubiquinone-1, a deoxycholic acid and glycine conjugate, demethylchlorophyllin, 3-(3, 5-diiodine-4-hydroxyphenyl) lactate, vitamin K1, O-decanoyl-L-carnitine, sedoheptulose 1, 7-diphosphoric acid, cholesterole-docosahexaenoic acid ester, acyl AMP, cg 19669457, cg 19181811, cg 18092474, cg 05452319, cg 06270401, cg 24911721, cg 07732037, cg 21805179, cg 25288194, cg 15845821 and cg 01649837, and is characterized in that the cg 19669457, the The marker combination has excellent performance in colorectal cancer detection, AUROC can reach 0.98, and noninvasive screening and early diagnosis of colorectal cancer can be accurately, rapidly and simply realized.

The invention relates to application of 4 '-demethyl epipodophyllotoxin or a medicinal derivative thereof in depression resistance, and belongs to the technical field of biological medicines. Depression is a serious nervous and mental disease and affects millions of people in the world. Major depression is the most common mental disorder and is also one of the main causes of global disability. Depression is considered to be a complex disease caused by interaction of genetic, physiological, psychological and environmental factors. It is found that the novel antidepressant drug capable of treating depression has great significance. A per2- / -mutant zebrafish depression model is utilized to perform drug screening on traditional Chinese medicine monomers, and finally, 10 mu M of 4 '-demethylepipodophyllotoxin has an anti-depression characteristic and can effectively improve the depression-like phenotype of per2- / -mutant zebrafish. A medicinal plant podophyllotoxin from which 4 '-demethyl epipodophyllotoxin is extracted is safe and non-toxic, and no report about 4'-demethyl epipodophyllotoxin depression resistance exists at present.