56 results about "Combretastatin" patented technology

A novel derivative of combretastatins which has water solubility and is capable of releasing the drug independent of biological enzymes likely to cause individual differences and whose effective therapeutic effect can be expected has been demanded. A high-molecular weight conjugate of combretastatins, characterized by having a structure in which a hydroxyl group of a combretastatin is linked via an ester bond to a carboxylic acid group of the polymer moiety in a block copolymer of a polyethylene glycol moiety with the polymer moiety having two or more carboxylic acid groups such as polyaspartic acid or polyglutamic acid is provided.

The invention discloses a combretastatin compound and a preparation method. The preparation method of the combretastatin compound of the invention comprises the following steps: dissolving 3'-amino combretastatin and N-(1-oxyl-2,2,6,6,-tetramethyl-oxygen-carbonyl)-L-amino acid in dried dichloromethane, uniformly stirring under argon protection, adding dicyclohexylcarbodiimide and 1-hydroxybenzotriazole, stirring and reacting under argon protection, filtering and removing white precipitates after the reaction, removing the solvent by distillation to obtain a crude product, purifying the crude product by column chromatography, and eluting the product by petroleum ether and ethyl acetate liquid with a volume ratio of 10:1-5:1 to obtain the target product. The combretastatin compound of the invention is applicable to the preparation of anticancer medicaments, and is especially applicable to the preparation of medicaments for treating leukemia, liver cancer, gastric cancer, and cervical cancer.

The present invention discloses a kind of polyglycol modified antitumor compound and its preparation process. The polyglycol modified antitumor compound has Combretastatin and its derivative as matrix and linear chain polyglycol and dendritic polyglycol for modifying to improve water solubility. It has water solubility 200-2500 times that of Combretastatin and its derivative before modification. The present invention solves the difficult problem of applying Combretastatin and its derivative clinically.

The invention discloses a compound which is shown as a formula (I) and used for inhibiting generation of tumour neovascularization as well as officinal salt or a configurational isomer thereof, wherein substituent groups R1, R2 and R3 are defined in the specification. The invention also discloses a preparation method of the compound in the formula (I), a pharmaceutical composition and an application of the compound as a microtubulin inhibitor in the aspect of inhibiting the tumour neovascularization, especially an application as an oral preparation.

Methods and diagnostic kits for monitoring combretastatin resistance are provided.

Compounds are disclosed that are designed to mimic the activity of combretastatin A-4 based on chalcone, aurone, or indanone structures, or involving benzoquinone or quinone rings. The anti-cancer activity of exemplified compounds is demonstrated in a range of in vitro and in vivo assays.

The invention discloses a combretastatin derivative and an antibody drug conjugate thereof, and a preparation method and application thereof. The combretastatin derivative and the antibody drug conjugate thereof comprise a compound shown in a formula I or a pharmaceutically acceptable salt or solvate thereof, wherein in the formula I, Ab represents a targeting ligand; L represents a linker for connecting an antibody with CA4 or a derivative thereof; n represents a ratio of a drug to the targeting ligand; and X is NR, wherein R is an alkane chain or a PEG chain. The invention provides preparation of the antibody drug conjugate by taking CA4 as a drug molecule and the derivative thereof, and application of the antibody drug conjugate in treatment of high-proliferative diseases or lesions. The diseases are characterized in that cells generate an antigen or target, and the antigen can be specifically combined with the antibody.

The invention relates to a method for synthesizing and preparing antineoplastic Combretastatin A-1 phosphate ester tetrasodium salt, comprising the steps: under the anhydrous condition, Combretastatin A-1 is dissolved in aprotic polar solvent, and dialkyl oxyl phosphoryl chloride/bromine (chloride/bromine phosphoric acid when R1 and R2 are hydrogen atoms) is dipped into the solution when acid-binding agent exists for reaction, and water is added into the reaction solution for stopping the reaction when the reaction is finished; products are extracted by the aprotic polar solvent, and then is decompressed and concentrated until being dried, so that the Combretastatin A-1 phosphate ester is obtained; (2) the obtained Combretastatin A-1 phosphate ester is dissolved into polar organic solvent to remove R1 and R2 radicals, and then obtained product is salified with sodium methoxide, finally, the Combretastatin A-1 phosphate ester tetrasodium salt is obtained. The method has simple and convenient technique, high yield coefficient and utilization rate of the Combretastatin A-1, and low production cost.

This invention relates to methods for treating a hematopoietic neoplasm comprising administering a therapeutically effective amount of a combretastatin compound, or a pharmaceutically acceptable salt thereof, to a subject having a hematological malignancy, wherein the combretastatin compound comprises a catechol or quinone moiety and is capable of forming a reactive oxygen species (ROS) in vivo. The method may further comprise co-administering a second chemotherapeutic agent.

The invention discloses water-solubility derivate of the antineoplastic medicine Combretastatin and the corresponding preparing method, and belongs to the technical field of medical and chemical industry. The compound of the invention takes substituted phenylacetic acid and isovanillin or the substitutional isovanillin as the initial material, and by condensation obtains (E)-substituted styrene acid; after that decorates a target group by amphotericity multi-polymer micromolecule with ether linkage, and finally, obtains water-solubility antineoplastic medicine Combretastatin derivate decorated by amphotericity multi-polymer micromolecule through decarboxylation or further decorating alkene linkage. The water-solubility is remarkably improved compared with the Combretastatin and the derivates before decoration, and basically maintains the intrinsic lipid solubility. Apart from easy material obtaining, the invention has the advantages of short synthesis line, simple operation and high yield as well as possessing strong selectivity to the cis-product with activity.

The invention discloses the application of a compound shown as a formula I or a formula II. The application is characterized in that the compound is used for preparing medicine for destroying tumor vessels.

The invention provides a preparation method of combretastatin furan type analogues. The preparation method of the combretastatin furan type analogues (A and C) comprises the following steps of adding a solvent 1, a compound P1 and 3,4,5-triethoxy benzaldehyde into a reaction flask; adding alkali while stirring; reacting for 10 minutes at room temperature; adding diluted acid to regulate pH (Potential of Hydrogen) to be neutral; obtaining the combretastatin furan type analogue C through separation and purification; obtaining a compound A by reducing the C in a solvent 2 by using Raney Ni. The preparation method of combretastatin furan type analogues (B and D) comprises the following steps of adding the solvent 1, a compound P2 and 3-trimethylsilyl ether-4-methoxybenzaldehyde into the reaction flask; adding alkali while stirring; reacting for 10 minutes at the room temperature; adding the diluted acid to regulate pH (Potential of Hydrogen) to be neutral; obtaining the combretastatin furan type analogue D through separation and purification; obtaining a compound B by reducing the D in the solvent 2 by using the Raney Ni. The preparation method of the combretastatin furan type analogues, provided by the invention, has the advantages that the yield is high, the operation is simple, the reaction conditions are moderate, the used solvents are cheap and easy to get, industrial production is easy to realize, and the like.

Combretastatin derivatives of formula (I), preparation and use thereof are disclosed, wherein: R_f is alkyl with 1-8 carbon atoms and 1-17 fluorine atoms, R is amino, substituted amino, hydroxyl, nitro, halo, alkyloxy, phosphate or amino acid side chain. Said derivatives have a capability to inhibit the polymerization of microtubules and are useful in treatment against tumor and neovascularization.

An antitumor combination comprising a stilbene derivative and an anticancer compound selected from the group consisting of taxanes, alkylating agents, antimetabolites, vinca alkaloids, platinum compounds, epidophylloptoxins, and antibiotics as the active ingredients is provided. Methods of using these pharmaceutical preparations for the treatment of solid carcinomas and the like are also provided.