64 results about "Vilazodone" patented technology

The invention provides a method for preparing an anti-depression medicine vilazodone, which comprises the following steps of: performing nitro reduction on 5-nitrobenzofuran-2-ethyl carboxylate serving as a raw material, conjugating with chlorohydrin, chlorinating by using phosphorus trichloride, cyclizing with 4-aminobutyric acid to generate a piperazine ring, performing acylchlorination, condensing with halogenated indole, performing carbonyl reduction, cyaniding, performing amidation, and the like to obtain the vilazodone. The method overcomes the defects in the prior art, is suitable for industrial production and has high application value, the used raw material is readily available, operating cost is low, and reaction yield is high.

The invention provides a preparation method of vilazodone, which comprises the following steps: reacting 5-cyanoindole, which is used as the initial raw material, with substituted phenylsulfonyl chloride under alkaline conditions, carrying out Friedel-Crafts reaction under the catalytic action of Lewis acid, reducing the product, and carrying out substitution reaction with 5-(1-piperazino)-benzofuryl-2-formamide to obtain the vilazodone. The invention also provides three intermediate compounds related to the vilazodone preparation method. The preparation method provided by the invention has the advantages of low cost, high yield and simple after-treatment, and is easy to operate and convenient for industrial production; and all the reagents are conventional reagents.

The invention discloses a new method for preparing 3-(4- chlorobutyl)-1H-5-cyanoindole as a vilazodone intermediate, comprising the following steps: step (1), a compound of formula II is reacted with a compound of formula III in the presence of an acylation catalyst in an organic solvent to form a compound of formula IV, step (2), the compound of formula IV formed in step (1) is subjected to carbonyl reduction reaction in the presence of a reducing catalyst in the organic solvent. The preparation method for 3-(4- chlorobutyl)-1H-5-cyanoindole as the vilazodone intermediate has cheap and easily-available raw materials, mild reaction condition, simple operation, high synthesis efficiency and is suitable for industrial production, thereby providing a new way for preparing vilazodone.

The invention relates to the field of drug synthesis, and in particular relates to a preparation method of an antidepressant drug-vilazodone. The preparation method is characterized by comprising the following steps of: protecting a 1-location nitrogen atom of 5-cyano benzopyrrole used as an initial raw material through utilizing toluenesulfonyl, carrying out 3-location Friedel-Carfts acylation, and selectively reducing carbonyl into methylidyne so as to obtain 1-tosyl-3-(4-chlorobutyl)-5-cyano benzopyrrole; reacting the 1-tosyl-3-(4-chlorobutyl)-5-cyano benzopyrrole with 5-(piperazine-1-radical) benzofuran-2-nonanoic acid-ethyl ester hydrochloride, hydrolyzing through one step, and removing tosyl and ethyl at the same time so as to obtain 5-(4-(4-(5-cyan-1H-benzopyrrole-3-radical) butyl) piperazine-1-radical) benzofuran-2-carboxylic acid; finally, amidating so as to obtain vilazodone, and salifying vilazodone with hydrogen chloride so as to obtain hydrochloric acid vilazodone. The method can be used for overcoming a plurality of defects of a conventional synthetic method, and has the advantages of easiness in raw material acquisition, high yield, good selectivity, convenience in operation, suitability for industrial production and high application value.

The invention belongs to the technical field of medicines, and in particular relates to a medical composition which is high in stability, digestion and absorption and a preparation method thereof. The medical composition contains vilazodone or officinal salt of vilazodone and a solid matrix.

The invention provides a method for preparing vilazodone and an intermediate thereof. According to the method, an intermediate shown in formula (V) can be obtained by virtue of a coupling reaction, and vilazodone can be obtained from the intermediate shown in formula (V) by virtue of olefinic bond reduction and N protecting group removal; or vilazodone can be obtained by virtue of further transformation. The method provided by the invention overcomes defects in the existing preparation method for vilazodone and an intermediate thereof, as well as is easy to get raw materials, high in reaction yield, suitable for industrialized production, and high in application value.

The invention discloses a new method of preparing vilazodone intermediate 5-piperazin-2-acyl substituted benzofuran. The method comprises a coupling reaction of 5-halogen substituted 2-acyl substituted benzofuran (III) and piperazine compound (IV) in the presence of a metal palladium catalyst, a ligand, a solvent and a base to obtain the 5-piperazin-2-acyl substituted benzofuran. The method has advantages of short route, convenient synthesis and high yield, and is suitable for industrial production.

The invention provides a method of preparing vilazodone and an intermediate thereof. The method comprises the following steps: obtaining the intermediate shown as a formula (V) through a coupling reaction; and obtaining vilazodone by reducing an acetylenic bond and removing an N protective radical for the intermediate shown as the formula (V); or further converting to obtain vilazodone. The method provided by the invention overcomes the deficiencies in existing preparation of vilazodone and the intermediate thereof. The raw material is easy to obtain, the reaction yield is high, and the method is suitable for industrialized production and has a greater application value.

The invention relates to a synthesis method of a vilazodone intermediate 5-(4-[4-(5-cyano-3-indyl)-butyl]-1-piperazinyl)benzofuran-2-carboxylic acid ethyl ester and a salt thereof, belonging to the technical field of drug synthesis. The synthesis method comprises the following steps of: dissolving 3-(4-chlorobutyl)-5-cyanoindole and a catalyst into an inorganic water solution under the protection of nitrogen gas, carrying out heating reflux, stirring, then, adding 5-(piperazinyl-1-yl)benzofuran-2-carboxylic acid ethyl ester and alkaline, reacting at the temperature of 80-110 DEG C for 4-6h, slowly pouring an aqueous alkaline solution while stirring at room temperature until a solid is separated out, and then, carrying out after-treatment to obtain the 5-(4-[4-(5-cyano-3-indyl)-butyl]-1-piperazinyl)benzofuran-2-carboxylic acid ethyl ester. The synthesis method is low in production cost, environment-friendly, high in operation safety, high in product yield and purity, good in quality and suitable for large-scale industrial production.

The invention discloses a new synthetic process of a vilazodone intermediate 5-cyano-3(4-chlorobutyl)-indole. The synthetic process comprises the steps of enabling 5-amino-formyl-indole and 4-chlorobutyryl chloride undergo a 3-bit acylation reaction and a dehydration reaction of an amido bond in the presence of a catalyst to produce 5-bit cyan, then performing a decarbonylation reaction in the presence of a reducing agent to generate a product, and finally refining by the product by use of methanol to obtain high-purity high-content 5-cyano-3(4-chlorobutyl)-indole. The process is concise, simple to operate and applicable to large-scale industrial production.

The invention discloses a method for preparing an antidepressant medicine vilazodone (I). The method comprises the steps of (1) enabling 5-nitrosalicylaldehyde (II) to react with 2-bromomalonic acid diester under an alkali effect to generate 5-nitrobenzopropylfurazan-2-formate (III); then generating 5-aminobenzopropylfuran-2-formate (IV) under the effect of a reducing agent from the (III); enabling the (IV) to react with bi(2-chloroethyl)amine to generate 5-piperazinobenzopropylfuran-2-formate (V); enabling the obtained (V) to react with ammonia gas or an ammonia gas solution to generate 5-piperazinobenzopropylfuran-2-formamide (VI); finally, performing a coupling reaction between the (VI) and 3-(4-chlorobutyl)-5-cyanoindole under an alkaline condition to obtain the vilazodone (I).

The present invention provides a synthesis method for an antidepressant drug vilazodone, belonging to the technical field of drug synthesis, and the method comprises the steps of: reacting 5-nitrosalicylaldehyde as a raw material with ethyl bromoacetate under the action of potassium carbonate by heating, to obtain a compound 5-nitrobenzofuran-2-carboxylic acid via hydrolysis; adding in aqueous ammonia after the reaction between 5-nitro-benzofuran-2-carboxylic acid and isobutyl chloroformate is completed, to give 5-nitrobenzofuran-2-carboxamide; reducing the 5-nitrobenzofuran-2-carboxamide by using sodium hydrosulfite to give an intermediate 5-aminobenzofuran-2-carboxamide; cyclizing the 5-aminobenzofuran-2-carboxamide with bis(2-chloroethyl)amine in the action of an alkaline to give 5-piperazinyl-benzofuran-2-carboxamide; and subjecting the 5-piperazinyl-benzofuran-2-carboxamide and 3-(4-chloro-butyl)-5-cyano indole to a substitution reaction to obtain the vilazodone. According to the synthesis method of the invention, the raw materials are cheap, and the reaction process is simple.

The present invention provides an immediate release oral dosage form comprising therapeutically effective amount of vilazodone or a salt thereof and at least one excipient. The dosage form includes 10 to 40 mg of vilazodone or a salt thereof, and is compressed in a tablet formulation. The tablet comprising 40 mg vilazodone or a salt thereof has a hardness of more than 9 kp and less than or equal to 14 kp. The tablet comprising 20 mg vilazodone or a salt thereof has a hardness of more than 8 kp and less than or equal to 12 kp, and the tablet comprising 10 mg vilazodone or a salt thereof has a hardness of more than 6 kp and less than or equal to 9 kp.

The invention discloses a hydrochloric acid vilazodone quick-release tablet and a preparation method thereof. The hydrochloric acid vilazodone quick-release tablet comprises the follow components by mass: 2-12% of hydrochloric acid vilazodone, 28-45% of lactose, 40-60% of microcrystalline cellulose, 0.5-3% of lubricants and 1-5% of coating materials. The lubricants include magnesium stearate and colloidal condition silica or one of the magnesium stearate and the colloidal condition silica. The hydrochloric acid vilazodone quick-release tablet is prepared through the following steps: evenly mixing the hydrochloric acid vilazodone, the lactose, the microcrystalline cellulose and the lubricants according to proportion of a formula, detecting whether content uniformity is qualified, and pressing the mixture into tablets when the content uniformity is qualified. The hydrochloric acid vilazodone quick-release tablet has special requirements for grain size of the hydrochloric acid vilazodone, and the preparation process saves time and labor, reduces energy consumption and improves production efficiency. Disintegration speed of medicines is fastened, the dissolving-out time is obviously less than that of a prescription which has no limitation on the grain size of the hydrochloric acid vilazodone, and simultaneously the process which directly performs mixing tabletting greatly improves stability of the medicines in preparations.

The invention relates to a preparation method of 5-(piperazine-1-group) benzofuran-2-carboxylic acid ethyl ester. 5-(piperazine-1-group) benzofuran-2-carboxylic acid ethyl ester is an important intermediate for synthetizing hydrochloric vilazodone. Under the existence of alkali and phase transfer catalyst, 5-amino-benzofuran-2-carboxylic acid ethyl ester and N, N-di (2-chlorine ethyl) amine hydrochloride are reacted in solvent, reaction time is 2-6 hours, and reaction temperature ranges from room temperature to backflow temperature of the solvent. By the preparation method, reaction time is shortened, and yield rate and purity of products are improved. The preparation method is simple, reliable and low in production cost and has higher implement value and social and economic benefits.

The invention discloses a preparation method of a vilazodone intermediate 5-nitrobenzofuran-2-formate, which comprises the following steps: (1) heating a compound II and triethyl phosphite to react, thereby obtaining a compound III; and (2) reacting the compound III with a compound IV in an organic solvent under the action of alkali, thereby obtaining a compound I, wherein X is a halogen or hydroxyl group, and R is a C1-C6 straight-chain alkyl group or alkyl group with branched chains. The invention is simple to operate, has the advantages of mild reaction conditions, stable quality and simple after-treatment, and is suitable for industrial production. Step (1) Step (2).

The invention discloses a method for preparing a vilazodone intermediate 5-piperazinyl-2-acyl substituted benzofuran. By the method, a corresponding vilazodone intermediate 5-piperazinyl-2-acyl substituted benzofuran is obtained by performing a coupling reaction on 5-halogen-substituted-2-acyl substituted benzofuran and piperazine under the actions of copper serving as a catalyst and a suitable solvent. The invention provides a new method for preparing the vilazodone intermediate 5-piperazinyl-2-acyl substituted benzofuran, has the advantages of short course, conveniences in synthesis, high yield, low cost and the like, and is suitable for industrial production.

The invention discloses a sustained release tablet containing an effective component hydrochloric acid vilazodone. The sustained release tablet is prepared from the effective component hydrochloric acid vilazodone and sustained release materials; the weight ratio of effective component hydrochloric acid vilazodone to sustained release materials is (1: 0.2)-(1: 20), preferably (1:0.5)-(1:10); and the sustained release material used by the sustained release tablet is one or a combination of several of guar gum, xanthan gum, acrylic resin and cellulose. The hydrochloric acid vilazodone has the characteristics of lasting functions, low toxic and side effects and less medicine-taking times; the release degree in vitro of the sustained release tablet is 8-24 hours; the blood medicine concentration is stable; the occurrence ratio of poor reaction is reduced; the curative effect of the medicines is improved; and the pain of patients is relieved.

The invention discloses a vilazodone dropping pill for treating adult moderate and major depressive disorders and a preparation method of the vilazodone dropping pill. The preparation method comprises the steps of with vilazodone as a raw material, adding a matrix according to a prescription, and uniformly mixing to obtain a mixed material; heating the mixed material to be molten, and uniformly stirring to obtain a mixture; placing the mixture into a special pill dropping machine; and dropping pills into a condensing agent at a proper speed to condense to form the vilazodone dropping pill. The vilazodone dropping pill is high in bioavailability, capable of rapidly releasing drugs, high in effect taking speed and drug stability and convenient to take; in addition, the consumption of auxiliary materials is reduced, the production process is simple, the preparation method is easy to operate, the weight difference is small, and the production cost is reduced; and no dust is generated, and labor protection can be favorably realized.

The invention discloses a vilazodone orally disintegrating tablet which has good taste, does not need water for administration, is capable of quickly disintegrating after entering the mouth, suitable for patients, having trouble in swallowing, like old people and psychiatric patients to take and also suitable for administration under conditions that water is difficult to get during travelling and wartime. an indication of the vilazodone orally disintegrating tablet is major depression disorder of adults, and administration compliance of the patients can be improved due to good taste and a simple and quick administration mode. In addition, the invention further discloses a preparation method of the vilazodone orally disintegrating tablet. The preparation method is simple in process and low in cost. The orally disintegrating tablet prepared by the method is quick to disintegrate and act, so that administration discomfort of the patients is reduced.

Disclosed herein are inclusion complexes comprising vilazodone or a pharmaceutically acceptable salt thereof and an inclusion material, compositions and pharmaceutical formulations comprising the inclusion complexes, and methods for preparing the inclusion complexes, compositions or pharmaceutical formulations.

Provided herein are novel, commercially viable and industrially advantageous processes for the preparation of benzofuran-2-carboxamide derivatives and their intermediates, or a pharmaceutically acceptable salt thereof, in high yield and purity. Provided particularly herein are novel, commercially viable and industrially advantageous processes for the preparation of vilazodone or a pharmaceutically acceptable salt thereof in high yield and purity. Provided also herein is an improved and commercially viable process for the preparation of 3-(4-hydroxybutyl)-1H-indole-5-carbonitrile, in high yield and purity, using novel intermediate compound 3-(4-hydroxybutyryl)-1H-indole-5-carbonitrile.

The invention discloses a method for preparing a vilazodone intermediate 3-(4-chlorobutyl)-1H-indol-5-cyano. By the method, 3-(4-chlorobutyryl)-1H-indol-5-cyano is reduced into the 3-(4-chlorobutyl)-1H-indol-5-cyano by potassium borohydride serving as a reducing agent under the catalysis of lewis acid at the reaction temperature of 0 to 10 DEG C. The method has the advantages of short course, conveniences in synthesis, high yield, low cost and the like, and is suitable for industrial production.

The invention belongs to the technical field of medicine and relates to a substituted piperazine compound and a preparation method for an intermediate of vilazodone. Substituted piperazine phenol is employed as a raw material and is subjected to a hydroformylation reaction, a cyclization reaction and a formylation reaction to obtain 5-(1-piperazine)-benzofuran-2-methanamide of a salt thereof. Finally vilazodone is prepared. The preparation method overcomes defects in a preparation method in the prior art, is simple in operation, is environment-friendly in processes and is free of any expensive catalysts. The intermediate is convenient to separate, is outstanding in yield, is low in cost and is suitable for industrial production.

The invention relates to the field of chemical synthesis of medicines, particularly a 3-(4-(4-substituted-piperazino)-1-butyryl)indolyl-5-formonitrile and a preparation method thereof, and application of the compound for preparing an intermediate 3-(4-piperazino-1-yl-butyl)indolyl-5-formonitrile for synthesizing vilazodone.

The invention belongs to the field of medicinal chemistry and relates to a compound for preparing vilazodone as well as an intermediate and an application thereof. The compound for preparing vilazodone is shown as a formula I, and the intermediate for synthesizing the compound of the formula I is shown as a formula II. The compound of the formula I can be applied to preparation of vilazodone and pharmaceutically acceptable salts thereof. The compound of the formula I serving as a novel intermediate is applied in preparation of the vilazodone, the defects in the conventional literature report are overcome, metal catalysts with high toxicity and organic phosphorus ligands thereof are avoided, the preparation cost is greatly reduced, the operation is simplified, and the compound is stable and controllable in quality and suitable for large-scale industrial preparation.

The invention provides application of vilazodone or a derivative thereof and a pharmaceutical composition containing the vilazodone or the derivative thereof in preparation of drugs for preventing and / or treating tumors. The compound has an obvious growth inhibition effect on various human tumor cells, and particularly has an obvious inhibition effect on tumor growth of nude mice inoculated with human tumor cells; the vilazodone or derivative thereof has broad-spectrum antitumor activity, and has good inhibitory activity on breast cancer, colorectal cancer, ovarian cancer, lung cancer, liver cancer, gastric cancer, leukemia, lymphoma, melanoma, pancreatic cancer, esophagus cancer, thyroid cancer, cervical cancer, renal clear cell adenocarcinoma, glioma, nasopharynx cancer and other tumors; and experiments show that vilazodone and the derivative thereof can become antitumor drugs.

The invention discloses a Vilazodone intermediate synthesis method. According to the Vilazodone intermediate synthesis method, 6-nitrocoumarin serves as an initial raw material, through the steps of ring opening, intramolecular cyclization, esterification, reduction, piperazine-ring preparation and the like, the key Vilazodone intermediate 5-(1-piperazinyl)-2-benzofuran-2-carboxylic acid ethyl ester shown in the formula I is obtained. The Vilazodone intermediate synthesis method is simple is synthesis path, the yield of the targeted product is high, and the Vilazodone intermediate synthesis method is suitable for industrial large-scale production.

Provided are a vilazodone solid dispersion, a preparation method therefor and a use thereof, wherein the vilazodone solid dispersion contains an active ingredient' vilazodone, a water-soluble polymer carrier material and a surfactant. The water-soluble polymer carrier material is selected from at least one of polyvidone, copovidone and hydroxypropyl methylcellulose. The vilazodone is present in the solid dispersion in a non-crystalline state. The solid dispersion has good stability and significantly improves the solubility and in-vitro dissolution rate of the vilazodone, thereby significantly increasing the oral bioavailability thereof. The vilazodone solid dispersion can be used for preparing vilazodone-related preparations.

The present invention provides continuous flow processes for the preparation of the compound of Formula (1), an intermediate in the preparation of Vilazodone.