566 results about "Demethylation" patented technology

The invention discloses a method for preparing a compound of a formula (I) or pharmaceutically acceptable salts thereof. The method is characterized by comprising the following steps of: (1) using a compound of a formula (II) as a raw material and carrying out a reduction and amination reaction with an appropriate reducing agent to obtain a compound of a formula (III); (2) using 2-quinary heterocyclic substituted ethanol as a raw material and reacting to obtain a compound of a formula (IV) under the conditions of appropriate reagent, temperature and solvent; (3) after carrying out chiral separation on the compound of the formula (III), carrying out a condensation reaction with the compound of the formula (I) under an alkaline condition to obtain a compound of a formula (V); and (4) carrying out demethylation protection on the compound of the formula (V) under the condition of appropriate temperature and solvent to obtain the compound of the formula (I), wherein R1 in each formula is selected from C1-8 alkyl groups or aromatic bases which can be arbitrarily substituted, X is selected from halogen atoms or p-toluenesulfonic acid groups and methanesulfonic acid groups for protecting alcoholic extract hydroxyl groups, and Y is selected from O, S and N. A target product obtained by the method has high optical purity, convenient operation, lower cost, higher yield and less pollution and is suitable for industrialized production.

The present disclosure provides methods of modulating immunodeficiency virus transcription, involving modulating enzymatic activity and / or levels of a lysine-specific demethylase-1 (LSD1) polypeptide and / or LSD1-mediated demethylation of methylated Tat. The present disclosure also provides method of identifying agents that modulate LSD1-mediated demethylation of a human immunodeficiency virus (HIV) Tat polypeptide.

This invention is related to a method for the detection of early or pre-cancer using DNA isolated from blood and body fluids. This invention provides an improved methylation-based PCR assay, a panel of methylated-based cancer-related gene markers for the detection of general cancer and a panel of demethylation-based tissue- or cell-specific gene markers for discriminating different type of cancer detected from blood samples. This method couples a sequential cancer-related gene marker detection and tissue or cell-specific gene marker assay and is particularly useful as a simultaneous screening test for following type of cancer: lung, breast, ovarian, colon, stomach, prostatic, pancreatic and liver cancer.

Benzopyranone compounds having the following structure: wherein R1, X, Y and n are as defined here, are disclosed. The compounds of formula (I), wherein R1 is H, can be prepared by demethylation of the corresponding phenolic methyl ether. The compounds are useful for treating a bone-resorbing disease, cancer, arthritis or an estrogen-related condition such as breast cancer, osteoporosis, endometriosis, cardiovascular disease, hypercholesterolemia, prostatic hypertrophy, prostatic carcinomas, obesity, hot flashes, skin effects, mood swings, memory loss, and adverse reproductive effects associated with exposure to environmental chemicals or natural hormonal imbalances.

The present invention provides a method for the N-demethylation and N-functionalization of an N-methylated heterocycle such as a morphine alkaloid or tropane alkaloid. The method comprises reacting the heterocycle with an functionalization agent in the presence of a transition metal catalyst in air or in the presence of an oxidant.

The invention relates to a method for simultaneously detecting seven slimming chemical components which are illegally added to traditional Chinese medicine, health food or cosmetics. According to the method, an appropriate mobile phase and a reasonable elution gradient are adopted during liquid-phase separation, so that the slimming components needing to be detected are effectively separated within 12 min, the analysis time of a sample instrument is shortened by 88%, and the work efficiency is greatly increased. Additionally, the advantages of high separation ability of the HPLC (High Performance Liquid Chromatography) technology, high sensitivity and stronger qualitative ability of the mass spectrum and the like are combined, so screening and confirmation can be simultaneously completed during one operation. By using the method disclosed by the invention, the seven chemical components including sibutramine, fenfluramine, phenolphthalein, ephedrine, caffeine, N,N-bi-demethylation sibutramine and furosemide can be effectively separated, the inspection time can be shortened, and the slimming chemical components which are illegally added to the traditional Chinese medicine, the health food or the cosmetics can be accurately and effectively distinguished.

Alkoxy aromatic compounds are conveniently dealkylated to the corresponding phenolic compounds by treatment with aluminum chloride / N,N-dimethyl aniline complex. Aromatic poly O-demethylation is a unique feature of this invention. This process is applicable to the manufacture of polyphenols such as Resveratrol, Oxyresveratrol, Gnetol.

The invention discloses a benzothiazole derivative containing a triphenylethylene or tetraphenylethylene structure and having aggregation-induced emission property and a preparation method and application thereof. The preparation method comprises the following steps: with 2-amino-6-methoxybenzothiazole as a start raw material, performing a ring-opening reaction under an alkaline condition to generate 2-amino-5-methoxythiophenol; performing a ring-closing reaction with an aromatic aldehyde compound containing a triphenylethylene or tetraphenylethylene structure to obtain a methoxy-containing benzothiazole derivative, or performing demethylation to obtain a hydroxyl-containing benzothiazole derivative, wherein the compound also can be modified through a group substitution reaction to generate a benzothiazole derivative containing other functional groups. The benzothiazole derivative disclosed by the invention has relatively low luminous intensity in a solution, emits strong fluorescence in an aggregation state or solid state, and belongs to good aggregation-induced emission materials; the synthesis is relatively simple, and the cost of the raw materials is low, so that large-scale commercial production is easy to realize; the benzothiazole derivative plays an important role in the fields of electroluminescent devices, fluorescent probes, fluorescent switches, organism imaging and the like.

The invention discloses macrocyclic and cage-like molecules based on biphenylarene and derivatives of the macrocyclic and cage-like molecules as well as synthetic methods and applications of the macrocyclic and cage-like molecules and the derivatives. A series of novel macrocycles are obtained mainly by performing a reaction on bis(2,4-dialkoxyphenyl)arenes (naphthalene, anthracene, pyrene, porphyrin and the like) or tris(2,4-dialkoxyphenyl)arenes (benzene, sym-tribenzobenzene) and paraformaldehyde under the catalysis of a Lewis acid in high yield. In addition, perhydroxybiphenylarenes (quaterphenyl trimer, naphthalene dimer and the like) can be obtained by performing demethylation, a plurality of water-soluble derivatives can be obtained by performing further modification, and the derivatives show good bonding ability to guest molecules (viologen and the like); and moreover, functional groups introduced into the framework make the biphenylarene have excellent adsorption and separationability and photophysical properties. The compounds, derivatives and methods provided by the invention have the following advantages: raw materials of the biphenylarene are commercially available, the synthesis is simple and convenient, the yield is high, and the modification is convenient, so that the compounds and the derivatives have broad application prospects in gas adsorption and separation, performance improvement of light-emitting materials, and adsorption of water-soluble toxic substances.

The present invention provides a synthetic process for the N-demethylation of N-methyl morphinans. In particular, the invention provides improved synthetic methods for the preparation of N-demethylated morphinan compounds that may be employed as starting materials, for example, commonly available N-methyl opiates such as oripavine and thebaine, and C(3)-protected hydroxy derivatives of oripavine.

The invention provides a method for preparing induced pluripotent stem cells. A combination of 4 small molecule compounds (HDAC inhibitor, GSK3-beta inhibitor, TGF-beta inhibitor and H3K4 demethylation inhibitor) or at least two of them (such as GSK3 -beta inhibitor and TGF-beta inhibitor), can induce induced pluripotent stem cells (iPS cells) under the condition of introducing only one transcription factor (Oct4).

The invention relates to a preparation method of benzbromarone applied to the field of pharmaceutical synthesis, which comprises the following steps: taking 2-ethylbenzofuran and p-anisoyl chloride as starting raw materials, carrying out friedel-crafts acylation under the participation action of a catalyst and prepare 2-ethyl-3-p-methoxyphenyl formyl-benzofuran; carrying out demethylation reaction on the obtained 2-ethyl-3-p-methoxyphenyl formyl-benzofuran and pyridine hydrochloride, removing moisture in a reaction system by using a method that water is contained in toluene and preparing 2-ethyl-3-p-hydroxybenzene formyl-benzofuran; carrying out bromination reaction on the prepared 2-ethyl-3-p-hydroxybenzene formyl-benzofuran and bromide to prepare benzbromarone; and carrying out acidolysis with hydrochloric acid after the 2-ethylbenzofuran is fully reacted with the p-anisoyl chloride and extracting to obtain the 2-ethyl-3-p-methoxyphenyl formyl-benzofuran. The preparation method has the advantages that in the friedel-crafts acylation, methylene dichloride, trichloromethane and other halohydrocarbon are used for replacing carbon disulfide, and the post-processing process is simplified; and in the bromination reaction, bromine which is strong in corrosivity, generates great harm to human bodies and pollutes the environment is changed into the bromide.

The present application discloses a method for discovering a methylation marker gene for the conversion of a cell comprising: (i) comparing converted and unconverted cell gene expression content to identify a gene that is present in greater abundance in the unconverted cell; (ii) treating a converted cell with a demethylating agent and comparing its gene expression content with gene expression content of an untreated converted cell to identify a gene that is present in greater abundance in the cell treated with the demethylating agent; and (iii) identifying a gene that is common to the identified genes in steps (i) and (ii), wherein the common identified gene is the methylation marker gene.

The invention relates to a modification method of lignin. The modification method comprises: adding and dissolving lignin in an organic solvent in which a thiol and a basic catalyst are dissolved, carrying out a demethylation reaction, centrifuging, washing and drying to obtain pure demethylated lignin, wherein the mass ratio of lignin to the catalyst to the thiol to dimethyl formamide is 1: (0.2-0.6): (0.5-2): (5-10). The lignin provided by the invention has the advantages that the free radicals are not polymerized in the modification process, the molecular weight of the lignin is reduced and the polarity is simultaneously improved, the reaction activity with formaldehyde is improved, and the lignin can replace phenol at a high ratio. The lignin modified by the modification method is in a shape of powder, can be used for preparing thermoplastic phenolic resins and thermosetting phenolic resins, and can also be used for adhesives, phenolic foam plastics, polyurethane foam plastics, phenolic molding materials, carbonization functional materials, polyurethane films and other multiple novel polymer materials.

There is provided a method for the synthesis of norbuprenorphine, and ultimately buprenorphine, utilizing oripavine as the starting material. Conventional methods of producing buprenorphine utilize thebaine as the starting material, requiring an O-demethylation step, typically a low to moderate yield transformation. The present use of oripavine as a starting material does not require an O-demethylation step, since the oripavine molecule lacks an O-3 methyl group.

The invention belongs to the field of medicine, and especially relates to an amiodarone hydrochloride preparation method. The method takes 2-hydroxybenzaldehyde and 2-alkyl halohexoic acid ester as the raw materials to prepare 2-butylbenzofuran, 2-butylbenzofuran is taken as the raw material, and is subjected to the steps of friedel-crafts acylation, demethylation, iodination, etherification and salt forming to obtain the amiodarone hydrochloride. By employing the method, the raw materials have the advantages of low cost and easy acquisition, the process is simple, and 2-butylbenzofuran and amiodarone hydrochloride with high purity and high yield can be obtained, the cost is low, the waste water is little, and the method is suitable for industrial production.

The invention discloses a synthesis method of oxymorphone hydrochloride. The synthesis method mainly comprises the following steps of: 1) alkalifying to obtain free alkali by taking oxycodone hydrochloride as an initial a raw material; 2) carrying out a demethylation reaction to obtain oxymorphone; 3) carrying out a hydrogenation reaction on the oxymorphone under acidic condition; and 4) salifying the hydrogenated product with hydrochloric acid to obtain the target product oxymorphone hydrochloride. The synthesis method disclosed by the invention has the advantages of available raw materials, high product purity and is easy to operate and is applicable to industrial production.

The purpose of the present invention is to develop and provide a less expensive and novel oxidizing agent for 5-hydroxymethylcytosine, which can selectively oxidize 5-hydroxymethylcytosine on DNA into 5-formylcytosine while preventing the DNA structure from destabilization and suppressing side reactions, and a method for detecting a demethylation site at a high accuracy in demethylation of DNA with the use of the aforesaid oxidizing agent.Provided is an oxidizing agent for 5-hydroxymethylcytosine that comprises a nitroxyl radical molecule and a copper salt or a copper complex, and / or a nitroxyl radical molecule-copper complex.

The present invention provides a method for the N-demethylation and / or N-acylation of an N-methylated heterocycle such as morphine alkaloids or tropane alkaloids. The method comprises reacting the heterocycle with an acylating agent in the presence of a metal catalyst.

The invention relates to a preparation method of duloxetine, which takes 2-acetyl phenol, paraformaldehyde and dimethylamine hydrochloride as raw materials to obtain the target product by five steps of Mannich reaction, reduction, resolution, etherification and demethylation, and optimizes the reaction conditions of resolution and etherification, wherein, the resolution reaction comprises the steps of one-time resolution, racemization-resolution and secondary racemization-resolution. The invention can improve the yield of the duloxetine and reduce the production cost, and is easy for industrial production.

LSD1, a homolog of nuclear amine oxidases, functions as a histone demethylase and transcriptional co-repressor. LSD1 specifically demethylates histone H3 lysine 4, which is linked to active transcription. Lysine demethylation occurs via an oxidation reaction that generates formaldehyde. Importantly, RNAi inhibition of LSD1 causes an increase in H3 lysine 4 methylation and concomitant de-repression of target genes, suggesting that LSD1 represses transcription via histone demethylation. The results thus identify a histone demethylase conserved from S. pombe to human and reveal dynamic regulation of histone methylation by both histone methylases and demethylases.

A 4'-demethylepipodophyllotoxin derivative IIIa-n is prepared by taking etoposide as raw material, reacting with sodium iodide to generate 4-bit iodine substitute and obtain intermediate II, agitating while adding into barium carbonate, regulating reactive system pH 7-8, adding into amino-compound, and reacting to room temperature for 8-10 hrs to obtain final product. It's simple and efficient, it can avoid 4-bit surface isomerization and 4-bit demethylation, it has strong inhibiting function of multiple tumor cell strain and non-toxic.

The invention discloses a process for synthesis of asenapine. The asenapine is prepared through adopting a compound (18) as a key intermediate and carrying out the following steps that: 1.1, the compound 18 is subjected to a Ullmann reaction under a alkaline condition through adopting copper powder as a catalyst to generate a ether (19); 1.2, the ether (19) is subjected to a carbonyl reduction to obtain the target compound of the asenapine (1). The process has the following advantages that: cheap and available 2-bromobenzaldehyde is adopted as an initial raw material and is subjected to acondensation, a addition, a reductive amination and a intramolecular cyclization reaction, a aminomethylation, a open loop transposition and then loop closing, a demethylation and a Ullmann loop closing reaction to synthesize of the asenapine (1); cis-trans-isomer is subjected to a delicate transposition to obtain a trans-product, such that the process is simplified and easy to be operated; the raw material is easy to be obtained and has cheap price; each reaction is a normal reaction, and reaction conditions are mild; a total yield is substantially improved; production cost is reduced; a purity of the product is more than 99% through a detection by HPLC.

The present invention provides a method of generating definitive endoderm, mesoderm, or ectoderm cells. The method includes culturing embryonic stem cells, parthenogenetic cells, or induced pluripotent stem cells in the presence of a demethylation agent, a histone deacetylase inhibitor, or a combination thereof, and thereafter, culturing the stem cells in the absence of the agent or combination of agents, to produce definitive endoderm cells, mesoderm, or ectoderm cells.

The invention discloses a method for preparing Roflumilast. The method comprises the following steps of: performing cyclopropyl methylation on isovanillin to obtain 3-cyclopropylmethoxy-4-methoxybenzaldehyde; performing demethylation to synthesize an important intermediate of the Roflumilast, namely 3-cyclopropylmethoxy-4hydroxyl-benzaldehyde; and further synthesizing a key intermediate in a formula (5) according to American patent US5712298 and finally synthesizing the Roflumilast in a formula (7). A crude product of the Roflumilast is treated by isopropanol and water, and is recrystallized by ethyl acetate and petroleum ether. The preparation method has a few steps, raw materials are readily available and cheap, the reaction selectivity is high, the yield is high and the post treatment is simple.

The invention discloses nitrogen substitution podophyllum type derivatives with antitumor activity and a preparation method and application thereof. The nitrogen substitution podophyllum type derivatives (as formula V) with fine antitumor activity are prepared by introducing 1-(3-amino propyl) imidazole, benzimidazole, 2-thienylmethylamine or trihydroxymethyl aminomethane to C ring 4-position activated by 4-demethylation surface podophyllotoxin. The nitrogen substitution podophyllum type derivatives can act on tumor cells with multiple paths and multiple target points, and accordingly better antitumor curative effect is achieved. Antitumor activity of the derivatives is evidently increased compared with that of the 4-demethylation surface podophyllotoxin. The derivatives can be prepared into antitumor drugs to apply to antitumor therapies.

The invention relates to a synthesis method of 6,7-substituted-4-aniline quinazoline. In the method, substances such as 3,4-substituted benzoic acid, and the like are used as starting materials, and the 6,7-substituted-4-aniline quinazoline is prepared through a reaction path of esterification reaction, oxygen-alkylation reaction, nitration reaction, nitro reduction reaction, ring closing reaction and two-in-one reaction or a reaction path of esterification reaction, oxygen-alkylation reaction or nitration reaction, hydrolysis-demethylation reaction after the nitration reaction, esterification reaction, oxygen-alkylation reaction, nitro reduction reaction, ring closing reaction, two-in-one reaction, and the like. The invention also provides a preparation method of a 4-aniline quinazoline derivative with lower starting material cost and higher productivity, which can effectively reduce the production cost so as to improve the competitiveness of a 4-aniline quinazoline derivative product.

The present invention provides a synthetic process for the N-demethylation of N-methyl morphinans. In particular, the invention provides improved synthetic methods for the preparation of N-demethylated morphinan compounds that may be employed as starting materials, for example, commonly available N-methyl opiates such as oripavine and thebaine, and C(3)-protected hydroxy derivatives of oripavine.

The present invention relates to a method, in particular an in vitro method, for pan-cancer diagnostics, comprising identifying the amount and / or proportion of stable regulatory T cells in a patient suspected of having cancer through analyzing the methylation status of at least one CpG position in the gene foxp3 and / or the gene camta1 or orthologous or paralogous genes thereof, wherein an increased amount and / or proportion of stable regulatory T cells in said patient is indicative for an unspecific cancerous disease. In a second aspect thereof, the present invention relates to a method for diagnosing the survival of a cancer patient, comprising identifying the amount and / or proportion of stable regulatory T cells in said cancer patient through analyzing the methylation status of at least one CpG position in the gene foxp3 and / or the gene camta1 or orthologous or paralogous genes thereof, wherein a demethylation in the gene foxp3 and / or the gene camta1 or orthologous or paralogous genes thereof, is indicative of a stable regulatory T cell, and wherein an increased amount and / or proportion of stable regulatory T cells in said cancer patient is indicative for a shorter survival for said cancer patient. Furthermore, the present invention relates to an improved treatment of cancers based on the inventive methods, and a kit for performing the above methods as well as respective uses.