39 results about "Desmethyl" patented technology

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.

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 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 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.

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.

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.

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.

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.

The invention provides a sulfuryl quaterphenyl [3] arene sulfate macrocyclic compound as shown in a formula IV as well as a preparation method and an application of the sulfuryl quaterphenyl [3] arene sulfate macrocyclic compound. The preparation method of the compound comprises four steps of reaction: Suzuki coupling, cyclization, demethylation and sulfation, the process is simple, the total yield is high, and the yield of each step of reaction is superior to 70%. The compound has excellent water solubility and biocompatibility and can form a stable host-guest inclusion complex with an anti-cancer drug terpyridyl ruthenium through hydrogen bonds, pi-pi accumulation and other supramolecular acting forces, and the binding constant of the compound is as high as (3.59 + / -1.48) * 10 < 6 > M <-1 >. A cytotoxicity experiment shows that the half inhibitory concentration (IC50) of the inclusion complex to human colon cancer cells HCT116 is 2.95 mu M, and compared with a free terpyridyl ruthenium drug (IC50 = 64.93 mu M), the anticancer activity of the inclusion complex is improved by about 22 times. The invention provides an efficient and convenient new strategy for drug delivery, the bioavailability and the treatment effect of the drug can be remarkably improved without covalent modification of drug molecules, and the drug delivery system has a good industrialization prospect.

The application provides a high-efficiency polymerization inhibitor and a preparation method and application thereof, and the method comprises the following steps: dispersing demethylated lignin, a mercapto carboxylic acid compound, a phenothiazine carboxylic acid derivative, a carbodiimide coupling agent and a carboxyl activating agent in anhydrous aprotic solvent, and performing esterification reaction between alcohol hydroxyl groups of the demethylated lignin and carboxyl groups of the mercapto carboxylic acid compound and the phenothiazine carboxylic acid derivative to obtain the high-efficiency polymerization inhibitor. The polymerization inhibitor is suitable for storage and transportation of acrylate monomers, and can significantly improve the storage stability and heat resistance of polymers.

The invention provides a method for determining the content of demethylated curcumin and trace components in a turmeric extract, and belongs to the technical field of medicine detection.The method comprises the steps that the turmeric extract is taken to be prepared into a test solution, gradient elution is conducted through acetonitrile (A) and a 0.08-0.12 wt% phosphoric acid aqueous solution (B), and the content of demethylated curcumin and trace components in the turmeric extract is determined through an external standard method or a standard curve method. And calculating the contents of ferulic acid, dehydrozingerone, bisabolol and demethylated curcumin in the turmeric extract. The method for determining the content of demethylated curcumin and trace components in the turmeric extract is established, and the quality of the turmeric extract can be more comprehensively controlled.

The invention relates to the technical field of medicine preparation, in particular to a synthesis method of dalbavancin demethylated B2 nitrosamine. The synthesis method comprises the following steps: S1, taking a dalbavancin precursor A-40926-B0 as a raw material, and carrying out methylation reaction to obtain an intermediate I; s2, performing esterification protection on the intermediate I to obtain an intermediate II; s3, carrying out condensation reaction on the intermediate II and 3-methylaminopropylamine to obtain an intermediate III, and carrying out alkaline hydrolysis to obtain an intermediate IV; s4, carrying out nitrosation on the intermediate IV through a nitrosation reagent to obtain dalbavancin demethylated B2 nitrosamine; the synthesis method is high in reaction yield, the purity of the demethylated B2 nitrosamine compound of the dalbavancin can be as high as that of the dalbavancin, and a reference substance is provided for quality control of the dalbavancin.

The invention discloses a targeted protein degradation agent utilizing an autophagy-lysosome pathway as well as a preparation method and application of the targeted protein degradation agent, and belongs to the technical field of degradation agent preparation. The preparation method comprises the following steps: carrying out nucleophilic substitution reaction on a GW5074 derivative and a linker arm precursor to obtain a GW5074 derivative-linker arm intermediate, and coupling the GW5074 derivative-linker arm intermediate with demethylated imatinib to obtain the targeted protein degradation agent utilizing the autophagy-lysosome pathway. The protein degradation agent disclosed by the invention is relatively few in preparation steps, easy to synthesize and relatively high in yield, and can be used for preparing medicines for treating cancers, particularly antitumor medicines for treating chronic granulocytic leukemia.

The invention discloses application of a cinnabar tobacco glandular hair specific gene in acylated demethylated nicotine synthesis and aroma improvement and a method, and belongs to the fields of biochemistry, molecular biology and agricultural application. The specific gene is NtNAT1-NtNAT4, the nucleotide sequences of the specific gene are respectively shown as SEQ ID NO.1-4, the gene is highly expressed in glandular hair, prokaryotic expression and enzymatic activity analysis verify that the gene has acyltransferase activity, and jasmonic acid methyl ester can efficiently induce the expression of the gene. The gene participates in tobacco nicotine metabolism, and the encoded protein of the gene can catalyze acylation of demethylated nicotine, increase the accumulation amount of acylated demethylated nicotine and improve the tobacco fragrance. The invention provides a method for improving the tobacco aroma, and the method has important application value in tobacco modification and breeding.

The invention relates to the technical field of medicine preparation, in particular to a method for preparing a nitrosamine compound. The method comprises the following steps: S1, carrying out esterification protection by taking a dalbavancin precursor A-40926-B0 as a raw material to obtain an intermediate I; s2, carrying out condensation reaction on the intermediate I and 3-methylaminopropylamine to obtain an intermediate II, and carrying out alkaline hydrolysis to obtain an intermediate III; s3, protecting secondary amine on a parent nucleus of the intermediate III through a protective reagent to obtain an intermediate IV; s4, carrying out nitrosation on the intermediate IV through a nitrosation reagent to obtain an intermediate V; s5, after the intermediate V is subjected to deprotection, dalbavancin demethylated B0 nitrosamine is obtained; the product prepared by the method is high in purity, a reference substance can be provided for quality control of dalbavancin, and important guiding significance is provided for safe medication.

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.

Provided are methods for determining the amount of tamoxifen and its metabolites in a sample by mass spectrometry. In some aspects, the methods provided herein determine the amount of N-Desmethyl Tamoxifen. In some aspects, the methods provided herein determine the amount of N-Desmethyl Tamoxifen and other tamoxifen metabolites. In some aspects, the methods provided herein determine the amount of tamoxifen, N-Desmethyl Tamoxifen, and other tamoxifen metabolites.

The application discloses a doxorubicin-quadruple platinum drug-norcantharidin three-drug combination nano drug and a preparation method and application thereof, and belongs to the technical field of medical materials. 2+ The application constructs a novel nano drug through coordination of doxorubicin and a quadruple platinum drug modified by norcantharidin, and then polymerizes polydopamine with a mild photothermal effect to prepare a nano drug for the three-drug combination of doxorubicin, the quadruple platinum drug and norcantharidin. The nano drug has the ability of controlled release of drugs under acidity and reduction, can realize photothermal conversion to generate a mild photothermal effect under laser irradiation, has a better tumor cell killing effect, has the ability of consumption of glutathione and generation of hydroxyl radicals, can enter cancer cells through an endocytosis mode and release DOX, and provides a new idea for multi-drug combination, chemotherapy-chemical kinetics treatment-photothermal treatment multi-mode combined treatment.

Aspects of this invention are related to the use of N-desmethyl ruboxistaurin and pharmaceutically acceptable formulations thereof to modulate CDK4 / 6 signaling. The invention encompasses methods for administering N-desmethyl ruboxistaurin to subjects in need, particularly those with a history of cancer or currently experiencing breast cancer, liposarcoma, lung cancer, glioblastoma, melanoma, pancreatic cancer, prostate cancer, colon cancer, ovarian cancer, colorectal cancer, bladder cancer, hepatocellular carcinoma, osteosarcoma, germ cell tumors, advanced solid tumors, lymphoma, leukemia and other hematologic malignancies. 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, is effective in modulating CDK4 / 6 signaling while mitigating toxicity associated with other treatments.

The present invention provides a method for synthesizing 5-hydroxy-4,6-dimethylbenzocyclopentanone, which relates to the field of organic chemical synthesis technology and includes a two-step reaction. Specifically, using 2-methoxy-1,3-dimethylbenzene as a starting material, it first reacts with 3-chloropropionyl chloride to obtain 4-methoxy-3,5-dimethyl-1-(3-chloropropionyl)benzene. Then, the 4-methoxy-3,5-dimethyl-1-(3-chloropropionyl)benzene undergoes intramolecular cyclization and demethylation to obtain 5-hydroxy-4,6-dimethylbenzocyclopentanone. The synthetic route of the present invention is short and feasible, the starting materials and excipients are inexpensive and readily available, the reaction is highly reactive, the operation is simple and easy to control, and the yield of the target product is high.

This invention proposes a photo-triggered pyroptosis nanomedicine composition, its preparation method, and its application, belonging to the field of pharmaceutical technology. The nanomedicine composition consists of spherical nanoparticles with a core-shell structure: an outer carrier (bovine serum albumin); a middle photothermal agent (poly(dithiophene-pyrrolopyrroledione); and a core demethylating agent (lipophilic demethylating agent RG108). This invention achieves successful triggering of pyroptosis and a sustained anti-tumor immune cycle with only a single dose and minimal light exposure, significantly improving the response rate of immunotherapy and providing a novel and highly innovative strategy for photo-immunotherapy of tumors.