38 results about "Diphenylmethylpiperazine" patented technology

The present invention is directed to compositions of taste-masked microparticles comprising a substituted benzhydrylpiperazine coated and a taste-masking layer comprising a water-insoluble polymer and a gastrosoluble polymer, and methods of making such taste-masked microparticles. The present invention is also directed to stable orally disintegrating compositions comprising taste-masked microparticles of a substituted benzhydrylpiperazine and rapidly dispersing granules, and methods of making such orally disintegrating compositions.

Synthesis of levo-citilitrin chloride is carried out by taking mono-p-chlorophenacyl ketone as raw material, synthesizing mixed active mono-p-chlorobenzhydrylamine, resoluting to obtain levo-mono-p-chlorobenzhydrylamine by levo-o-chloromandelic acid, synthesizing levo-1-N-mono-p-chlorodiphenyl-methyl-4-N-toluene-p-sulfonyl-piperazine, removing protection to obtain levo-N-mono-p-chlorodiphenyl-methyl-piperazine, reacting with ethylene chlohydrin to synthesize levo-1-N-mono-p-diphenyl-methyl-4-N-piperaethanol, reacting with sodium acetate chloride, and adding into hydrochloride to obtain final product. It costs low and is simple and can be used for industrial production.

The invention relates to a substituted benzhydryl piperazine derivative and a preparation method and an application of the substituted benzhydryl piperazine derivative. The substituted benzhydryl piperazine derivative has a compound in structural formula (I): FORMULA. A part of compound provided by the invention is administrated preventively to prolong the survival time of mice suffering from acute cerebral ischemia so that the derivative has a certain neuroprotective effect of preventing cerebral ischemia. Thus, the compound provided by the invention can be used to prepare medicines for treating cerebral arterial thrombosis.

The present invention relates to the preparation process of diphenyl ofloxacin and its application in preparing medicine for treating cardiac and cerebral vascular diseases. The preparation process includes the following steps: A) preparing gamma-chloro-4-fluorobenzene-1-butanone through the reaction between gamma-butyrolactone and sulfoxide chloride to obtain gamma-butyryl chloride and the subsequent reaction in mixed solvent with catalyst; B) preparing benzhydryl piperazine through the reaction between diphenylcaabinol and concentrated hydrochloric acid to obtain diphenyl chloromethane, the subsequent reaction in mixed solvent with catalyst and filtering; and C) preparing the product diphenyl ofloxacin with proper amount of benzhydryl piperazine, gamma-chloro-4-fluorobenzene-1-butanone, solvent methyl isobutyl ketone and catalyst potassium iodide and potassium carbonate, and through mixing and reaction.

The invention relates to a restrainer non-peptide SARS corona-virus 3CL prolease, wherein said restrainer is cyclizine derivant functioning at volume occupation and dewatering function with 3CL prolease. The invention uses the enzyme active system of reverse-phase high-pressure liquid spectrum method and substrate pNA mark to test its effect on the activity of SARS corona-virus 3CL prolease. Said test can prove that it has restrain effect on 3CL prolease, and its cell test can restrain SARS coron-avirus of cell cultivation. The invention can treat and prevent SARS virus affection.

The invention relates to Benzhydryl piperazine salts of [R-(E)]-1-[[[1-[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropaneacetic acid represented by the formula (III). Furthermore, the invention relates to the use of Benzhydryl piperazine salts of [R-(E)]-1-[[[1-[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropaneacetic acid represented by the formula (III) for the preparation of substantially pure [R-(E)]-1-[[[1-[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropane acetic acid or its alkali salts and pharmaceutical composition comprising the same.

A method of increasing the bioavailability of a compound of formula 1 by orally administering to a patient a compound of formula 1, or a pharmaceutically acceptable salt thereof, with food:

The invention relates to a class of inhibitors of non-peptidic SARS coronavirus 3CL protease and uses thereof. The inhibitor is a benzhydryl piperazine derivative, and its inhibition mechanism lies in the volume occupation and the hydrophobic interaction with 3CL protease. Utilize reversed-phase high-pressure liquid chromatography method and substrate pNA-labeled enzyme activity system to test the influence of the inhibitor on SARS coronavirus 3CL protease activity, confirm that it has inhibitory effect on 3CL protease, and cell experiments also confirm its effect on cell culture SARS coronavirus has inhibitory effect and can be used for treating and preventing SARS virus infection.

The present invention provides a calcium ion channel antagonist manidipine preparation method, which comprises that: methyl 2-(3-nitrobenzylidene)acetoacetate 2 and beta-amino crotonic acid diphenylmethyl piperazine ethyl ester 3 are subjected to a cyclization reaction in an alcohol solvent to obtain a manidipine 1 crude product, and re-crystallization is performed to obtain the manidipine 1. The preparation method has advantages of short reaction period, simple synthesis route, less impurities in a reaction process, simple post-treatment, mild process conditions and the like, and is suitable for industrial production, wherein a yield is more than 68%.

The present invention relates to a liquid composition containing an active substance belonging to the family of substituted benzhydryl piperazines with reduced amounts of preservatives.

The invention discloses a preparation method of a manidipine intermediate 2-(4-diphenylmethyl piperazinyl)ethyl acetoacetate. According to the invention, alkali is adopted as a catalyst. In an organic solvent, 1-diphenylmethyl-4-(2-hydroxyethyl)piperazine is adopted as a raw material, and is subjected to trans-esterification by using ethyl acetoacetate. Through reduced-pressure concentration extraction, the material is purified with a salt-forming and freeing method, such that the 2-(4-diphenylmethyl piperazinyl)ethyl acetoacetate is obtained. According to the method provided by the invention, the application of diketene with defects of high tearing property, high toxicity, low flash point, and easy explosion is avoided. The reaction is mild, safety is high, and yield is high. The method is more suitable for industrialized productions.

The invention belongs to the technical field of energy harvesting, in particular to a preparation method of a composite thermoelectric thin film. The method proposed by the present invention is to successively vacuum-plate silver on polyester non-woven fabrics, and heat emboss 1,3-dibenzyl-4,5-cis-bis(p-toluenesulfonyloxymethyl)-2-imidazolidinone , 1,3‑dibenzyl‑tetrahydro‑1H‑thieno[3,4‑d]imidazol‑2(3H)‑one, vacuum aluminized, hot embossed bis(4‑diphenylmethylpiperazine ‑1‑base) methane, screen printing conductive silver glue and polymethyl methacrylate, a multi-layer sandwich structure film; and then annealing the multi-layer sandwich structure film in a hot embossing machine to obtain a composite thermoelectric film. The power factor of the composite thermoelectric thin film measured by a pyroelectric coefficient measuring instrument is 4.8~5.5 mW.m ‑1 .K ‑2 , the thermoelectric figure of merit is 3.6~4.1.

The invention discloses a preparation process of optically pure manidipine hydrochloride for treating hypertension. The preparation process comprises the following steps: a) preparing 2-(4-benzhydryl-1-piperazinyl) ethyl acetoacetate Ester, m-nitrobenzaldehyde, 3-aminocrotonate methyl ester, (S)-BINAP, ferric iron compound and reaction solvent are added in reaction vessel and react to obtain (S)-manidipine; b) gaining (S) )-manidipine and hydrogen chloride solution are added in the reactor to react, and the reaction is completed, concentrated under reduced pressure, recrystallized, and dried to obtain optically pure (S)-manidipine hydrochloride. The target product (S)-manidipine of the preparation process provided by the present invention has higher yield and ee value, and the method of the present invention is simple to operate, has short reaction time, and is suitable for industrial production.

The present invention is directed to a composition comprising a modulator of the Wnt / β-catenin pathway or a pharmaceutically acceptable salt thereof and an N-cinnamyl-N′-benzhydryl piperazine or a pharmaceutically acceptable salt thereof. The present invention is also directed to a method of treating a neoplastic condition in a subject by administering the modulator of the Wnt / βcatenin pathway or a pharmaceutically acceptable salt thereof and an N-cinnamyl-N′-benzhydryl piperazine or a pharmaceutically acceptable salt thereof to the subject under conditions effective to treat a neoplastic disorder.

Synthesis of levo-citilitrin chloride is carried out by taking mono-p-chlorophenacyl ketone as raw material, synthesizing mixed active mono-p-chlorobenzhydrylamine, resoluting to obtain levo-mono-p-chlorobenzhydrylamine by levo-o-chloromandelic acid, synthesizing levo-1-N-mono-p-chlorodiphenyl-methyl-4-N-toluene-p-sulfonyl-piperazine, removing protection to obtain levo-N-mono-p-chlorodiphenyl-methyl-piperazine, reacting with ethylene chlohydrin to synthesize levo-1-N-mono-p-diphenyl-methyl-4-N-piperaethanol, reacting with sodium acetate chloride, and adding into hydrochloride to obtain final product. It costs low and is simple and can be used for industrial production.

The present invention is directed to compositions of taste-masked microparticles comprising a substituted benzhydrylpiperazine coated and a taste-masking layer comprising a water-insoluble polymer and a gastrosoluble polymer, and methods of making such taste-masked microparticles. The present invention is also directed to stable orally disintegrating compositions comprising taste-masked microparticles of a substituted benzhydrylpiperazine and rapidly dispersing granules, and methods of making such orally disintegrating compositions.

The invention relates to a synthesis method of oxatomide, and belongs to the technical field of medicine synthesis. According to the preparation method, 2-ethoxy-1H-benzimidazole and 1-(3-chloropropyl)-4-diphenylmethyl piperazine dihydrochloride are taken as initial raw materials, 1-[3-(4-diphenylmethyl-1-piperazinyl) propyl]-2-ethoxy-1H-benzimidazole is obtained through a condensation substitution reaction, and then acidolysis deprotection is carried out to obtain oxatomide. The method has the advantages of few synthesis steps, simple operation, low cost, economy and environmental protection, and is suitable for industrial production.

The invention discloses a preparation method for a manidipine intermediate 2-(4-diphenylmethyl piperazine)ethyl acetoacetate, wherein the method comprises the following specific processes: adding an alkali catalyst into a reaction vessel containing an organic solvent, heating to make the temperature rise to 60-90 DEG C, then dissolving 1-diphenylmethyl-4-(2-hydroxyethyl)piperazine with trichloromethane, dropwise adding the dissolved 1-diphenylmethyl-4-(2-hydroxyethyl)piperazine into the reaction vessel, dropwise adding ethyl acetoacetate while stirring, carrying out heat preservation reaction until the reaction is completed, and carrying out reduced pressure concentration, extraction and purification of the reaction solution to obtain 2-(4-diphenylmethyl piperazine)ethyl acetoacetate. The method has the advantages of mild and safe whole reaction process and less impurity, the purity of the obtained product is as high as 99.5% or more, the yield is 99% or more, and the method is suitable for industrialized production.

The embodiment of the invention discloses a benzhydryl piperazine compound containing straight-chain olefin and a preparation method of the benzhydryl piperazine compound. The benzhydryl piperazine compound is expected to directly act on a focus or be used as a molecular building block to participate in new drug research and development. According to the preparation method of the new benzhydryl piperazine compound containing straight-chain olefin, 1-bromo-2-(bromo(phenyl)methyl)benzene is taken as a raw material, and a target compound is obtained through two-step reaction of nucleophilic substitution and carbon-carbon coupling. In the carbon-carbon coupling reaction, a catalytic system consisting of Pd2(dba)3 and 1,3-bis(dicyclohexylphosphino)propane is preferably selected to catalyze the reaction, the reaction activity is remarkably improved, the reaction is realized at high yield, particularly, a NiCl2(PCy3)2 and tricyclohexylphosphine catalytic system is adopted to carry out the reaction, the reaction result is relatively ideal, and a reference is provided for catalyzing the carbon-carbon coupling of the compound by a nickel catalyst. The whole preparation route is stable in reaction, mild in used condition, simple and convenient to operate and high in reaction yield.

The invention discloses a novel flame retardant for polyolefin and a preparation method, and belongs to the field of flame retardants. The preparation method of the flame retardant comprises the following steps: 1, adding phytic acid and water into a reactor, conducting stirring, respectively heating and melting diphenylmethylpiperazine and 2,6-diaminopyridine, simultaneously dropwise adding the diphenylmethylpiperazine and 2,6-diaminopyridine into the reactor for reaction, separating out reactants, conducting filtering to obtain a crude product, and conducting drying to obtain an intermediate; and 2, carrying out dehydration condensation reaction on the intermediate under an inert gas condition to obtain a final product. The synthesized novel flame retardant has good stability and hydrolysis resistance, and can be used for improving the flame retardant property of polyolefin resin.

The present invention provides: a novel compound which has a useful pharmacological action for treating heart failure or shock without increasing heart rate; and a pharmaceutical composition using the same. The present invention relates to a diphenylmethyl piperazine derivative represented by general formula (I)(In the formula, R1 is a hydrogen atom or a hydroxy group. R2 is a hydrogen atom, a halogen atom, a hydroxy group, an alkyl group having one to five carbon atoms, or an alkoxyl group having one to five carbon atoms, excluding the case where R1 is a hydroxy group and R2 is a chlorine atom.) or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition containing the same.

The invention discloses a preparation process of optically-pure manidipine hydrochloride for treating high blood pressure. The preparation process comprises the following steps: a) adding 2-(4-benzhydryl-1-piperazinyl)ethyl acetoacetate, m-nitrobenzaldehyde, methyl 3-aminocrotonate, (S)-BINAP, a ferric compound and a reaction solvent into a reaction vessel, and performing a reaction to obtain (S)-manidipine; and b) adding the obtained (S)-manidipine and a hydrogen chloride solution into a reactor for a reaction, after the reaction is completed, performing reduced-pressure concentration, performing recrystallization, and performing drying to obtain the optically-pure (S)-manidipine hydrochloride. According to the preparation process provided by the invention, the target product (S)-manidipine has a higher yield and ee value, and the method provided by the invention has simple operation and short reaction time, and is suitable for industrialized production.

The present invention provides: a novel compound which has a useful pharmacological action for treating heart failure or shock without increasing heart rate; and a pharmaceutical composition using the same. The present invention relates to a diphenylmethyl piperazine derivative represented by general formula (I)(In the formula, R1 is a hydrogen atom or a hydroxy group. R2 is a hydrogen atom, a halogen atom, a hydroxy group, an alkyl group having one to five carbon atoms, or an alkoxyl group having one to five carbon atoms, excluding the case where R1 is a hydroxy group and R2 is a chlorine atom.) or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition containing the same.

The invention relates to a substituted benzhydryl piperazine derivative and a preparation method and an application of the substituted benzhydryl piperazine derivative. The substituted benzhydryl piperazine derivative has a compound in structural formula (I): FORMULA. A part of compound provided by the invention is administrated preventively to prolong the survival time of mice suffering from acute cerebral ischemia so that the derivative has a certain neuroprotective effect of preventing cerebral ischemia. Thus, the compound provided by the invention can be used to prepare medicines for treating cerebral arterial thrombosis.

The invention belongs to the technical field of medicine, and relates to 2-[(pyridyl-2-yl methyl)thio]-1H-benzimidazole compounds, a preparation method thereof and application of the compounds in preparation of drugs for antitumor diseases. The structural general formula of the 2-[(pyridyl-2-yl methyl)thio]-1H-benzimidazole compounds and prodrugs, pharmaceutically active metabolites and pharmaceutically acceptable salts of the 2-[(pyridyl-2-yl methyl)thio]-1H-benzimidazole compounds are shown in the description, wherein R1 and R2 are the same or different, and are selected from hydrogen, C3-C6cycloalkyl groups, phenyl groups, halogen-substituted phenyl groups, C1-C4 alkoxy-substituted phenyl groups, phenyl groups with simultaneous substitution of halogen and C1-C4 alkoxy groups and benzylgroups, or substituted or unsubstituted phenylpiperazinyl, benzylpiperazinyl or diphenylmethylpiperazinyl groups are formed by R1, R2 and nitrogen atoms attached to R1 and R2; and the substituent groups comprise C1-C4 alkyl groups, C1-C4 alkoxy groups and halogen, and R3 and R5 can be selected from H and C1-C4 alkyl groups. The synthesis method of the compounds is simple and convenient, and is suitable for industrial production, and it is shown by biological activity tests that the compounds have antitumor activity, and are novel antitumor drugs.

The invention belongs to the technical field of medicine, and relates to 2-[(pyridin-2-ylmethyl)thio]-1H-benzimidazole compounds and their preparation methods and applications. The general formula of described 2-[(pyridin-2-ylmethyl)thio]-1H-benzimidazoles and pharmaceutically acceptable salts is as follows: R 1 , R 2 Same or different, selected from hydrogen, C1‑C8 alkyl, C3‑C6 cycloalkyl, phenyl, halogen substituted phenyl, C1‑C4 alkyl substituted phenyl, C1‑C4 alkoxy substituted phenyl , phenyl substituted with halogen and C1‑C4 alkoxy, phenyl substituted with halogen and C1‑C4 alkoxy, phenyl substituted with halogen substituted C1‑C4 alkyl, benzyl, 4‑benzyloxy Phenyl; or R 1 , R 2 Together with the nitrogen atoms connected to them, they form substituted or unsubstituted morpholinyl, phenylpiperazine or benzhydrylpiperazine; the substituents are C1-C4 alkoxy, C1-C4 alkyl, halogen; R 3 , R 5 Can be selected from H, C1-C4 alkyl. The synthesis method of the compound of the invention is simple and convenient, suitable for industrial production, and has obvious antitumor activity.

The invention discloses a preparation method of a cinnarizine impurity. The preparation method comprises the following steps: (1) reacting cinnamyl alcohol with a halogenating reagent in a solvent at -10 to 30 DEG C; (2) reacting the reaction product in the step (1) with metal in a solvent under the catalysis of iodine to form an organic metal reagent intermediate, and reacting with cinnamyl aldehyde; (3) reacting a reaction product in the step (2) with a halogenating reagent in a solvent at -10 DEG C to 30 DEG C; and (4) reacting the reaction product in the step (3) with benzhydryl piperazine under the action of the halogenating reagent to obtain a crude product. The invention further provides the cinnarizine impurity prepared by the method, and the cinnarizine impurity prepared by the method is high in yield and good in purity.