44 results about "Angiogenic inhibitors" patented technology

Disclosed herein are angiogenesis inhibitors represented by formula (I) or formula (II): The variables for formulas (I) and (II) are defined herein.

The problems of the present invention are to find a pharmaceutical composition and a method for treating cancer that exhibit excellent anti-tumor effect. Excellent anti-tumor effect is achieved when 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, an analogous compound thereof, a pharmacologically acceptable salt thereof or a solvate thereof is used in combination with taxane.

The present invention relates to novel angiogenic-inhibitory compounds of formula (I) 1 and pharmaceutically acceptable salts thereof, wherein: Y is a direct bond or a linker group selected from a group of CH.sub.2, NH, NR.sub.1, S, SO, SO.sub.2, or O; Z is CO, CS, SO, SO.sub.2, or C.dbd.NH; R.sup.1 is H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, acyl, alkoxyacyl, aryloxyacyl, or aminoacyl groups; R.sup.2 is O, S, or NH; A is one to three cycloalkyl or aryl ring groups, in which any of these ring groups may be connected with other ring through a single bond or fused with at least one other ring, and these ring groups are optionally substituted at one or more positions with alkyl, alkoxy, aryl, aryloxy, arylalkyl, arylalkyloxy, hydroxyl, halogen, trihalomethyl, S(O)R, SO.sub.2NRR', SO.sub.3R, SR, B(OR).sub.2, PR.sub.3, P(O)(OR).sub.2, OP(O)(OR).sub.2, NO.sub.2, NRR', OR, CN, C(O)R, NHC(O)R, (CH.sub.2).sub.nCO.sub.2R, or CONRR', wherein R and R' are each independently selected from the group consisting of H, alkyl, alkoxy, aryl, aryloxy, arylalkyl, and arylalkyloxy and n is 0-11; and B is alkyl, arylalkyl, or one to three cycloalkyl or aryl ring groups, in which any of ring groups may be connected with other ring through a single bond or fused with at least one other ring; and these alkyl, arylalkyl or ring groups are optionally substituted at one or more positions with alkyl, alkoxy, aryl, aryloxy, arylalkyl, arylalkyloxy, hydroxyl, halogen, trihalomethyl, S(O)R, SO.sub.2NRR', SO.sub.3R, SR, B(OR).sub.2, PR.sub.3, P(O)(OR).sub.2, OP(O)(OR).sub.2, NO.sub.2, NRR', OR, CN, C(O)R, NHC(O)R, (CH.sub.2).sub.nCO.sub.2R, or CONRR', wherein R and R' are each independently selected from the group consisting of H, alkyl, alkoxy, aryl, aryloxy, arylalkyl, and arylalkyloxy and n is 0-11, pharmaceutical composition comprising them and their use.

A Tie2 activator containing, as an active ingredient, a hawthorn extract, a starfruit extract, a shellflower extract, a lotus extract, a rooibos extract, an Indian date extract, a Chinese quince extract, a Psidium guava extract, a long pepper extract, a Quillaja extract, a Kouki extract, a ginkgo extract, an oyster extract, a turmeric extract, a chrysanthemum extract, a jujube extract, a Chinese wolfberry extract, a chamomile extract, or a Butcher's Broom extract, or any combination thereof.

The invention belongs to the technical field of organic synthetic medicines, and particularly relates to a substituted 1-(isoxazol-3-yl)-3-(3-fluoro-4-phenyl) urea derivative, and a preparation methodand use thereof. The substituted 1-(isoxazol-3-yl)-3-(3-fluoro-4-phenyl) urea derivative has a structural formula shown in Formula I. The invention also provides the preparation method of the substituted 1-(isoxazol-3-yl)-3-(3-fluoro-4-phenyl) urea derivative and use of the substituted 1-(isoxazol-3-yl)-3-(3-fluoro-4-phenyl) urea derivative in preparation of FMS-tyrosine kinase 3 inhibitors. A new and effective choice is provided for the preparation of the kinase inhibitors, the preparation of drugs for anti-autoimmune diseases, the preparation of neovascularization inhibitors and anti-tumordrugs in the field, and the substituted 1-(isoxazol-3-yl)-3-(3-fluoro-4-phenyl) urea derivative has a good application prospect.

The present invention relates to a pharmaceutical composition, a kit and a method for treating cancer and / or a method for inhibiting angiogenesis, comprising a sulfonamide compound in combination with Bevacizumab.

The invention provides application of echinacoside or acteoside in preparation of angiogenesis inhibitor medicines. Tests prove that angiogenesis echinacoside and acteoside can be used for effectively inhibiting reproduction of vascular endothelial cells, can be used as angiogenesis inhibitors for treating tumors, diabetic retinopathy, rheumatoid arthritis, prostatic hyperplasia or psoriasis and other angiogenesis dependent diseases and have a wide market prospect.

The present invention describes stem cells and progenitor cells derived from hemangiomas, including testing of angiogenic inhibitors using these cells. The invention as described is useful in providing a process to culture and propagate hemangioma stem cells and generate xenograft models to develop treatments for infantile hemangiomas and other types of vascular lesions.

Compounds of Structural Formula I or pharmaceutically acceptable salts thereof, are effective inhibitors of angiogenesis:

The object is to discover a pharmaceutical composition having an excellent anti-tumor effect and a therapeutic method for cancer. 4-(3-Chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7- methoxy-6-quinolinecarboxamide, an analogous compound or pharmacologically acceptable salt thereof, or a solvate of the compound or the analogous compound or pharmacologically acceptable salt can exhibit an excellent anti-tumor effect when used in combination with a taxane.

The invention relates to a temperature-controlled sustained-release injection containing an alkylating agent and a preparation method thereof, the temperature-controlled sustained-release injection comprises effective anti-cancer amount of the alkylating agent, an amphiphilic block copolymer, a solvent and a certain amount of drug release regulator, wherein, the mixture of the amphiphilic block copolymer and a solvent without organic solvent has the temperature-sensitive gelatinization feature, which is flowable liquid in the environment that is lower than the body temperature and can be automatically converted to the water-insoluble gel that can not flow and be biodegradable for absorption in an endotherm, and the water-insoluble gel can allow the contained angiogenesis inhibitor to have the local sustained release in a tumor and maintain the effective drug concentration for a plurality of weeks to a plurality of months. The sustained-release gel injection can be injected in the tumor or the tumor periphery or be arranged in the postoperative tumor cavity, thus significantly reducing the systemic reaction of the drug and being used for the treatment of the tumors in different stages. The alkylating agent is selected from cyclophosphamide, melphalan, leukeran, 4H-cyclophosphamide peroxide, norcantharidin, mannosulfan, treosulfan, ritrosulfan, ethoglucid, pipobroman, piposulfan, pumitepa, uredepa, azatepa and so on.

The invention relates to a preparation method of an oyster shell extract. The method comprises the following steps of: adding water-containing solution of alcohol into oyster shell powder in a material to liquid ratio of 1g:2-20mL, performing reflux extraction and filtering or centrifugally separating liquid out; and concentrating the obtained liquid under reduced pressure, extracting with an organic solvent, separating an organic solvent layer out, concentrating under reduced pressure and drying to obtain the oyster shell extract. Tests by a lissamine rhodamine B method indicate that the prepared oyster shell extract has the function of inhibiting cell proliferation of a plurality of tumor cell strains; and tests by a methyl thiazolyl tetrazolium method indicate that the oyster shell extract has the function of inhibiting cell proliferation of human umbilical vein endothelial cells. Experiments indicate that the oyster shell extract can play a role in resisting tumors by inhibiting tumor cell proliferation and angiogenesis. Therefore, the oyster shell extract of the invention can be taken as a cell proliferation inhibitor, an angiogenesis inhibitor and an anti-tumor agent.

Compounds having the formula are angiogenesis inhibitors. Also disclosed are compositions containing the compounds, methods of making the compounds, and methods of treatment using the compounds.

The invention relates to a sustained release injection which comprises agiogenesis inhibitor and anticarcinogen sustained release preparation of synergistic agent thereof. The sustained release injection comprises sustained release microspheres and menstruum; wherein, the sustained release microspheres comprise anticancer active principles and sustained release auxiliary material.The menstruum is a special menstruum that contains suspending agent. The anticancer active principles are agiogenesis inhibitor and / or synergistic agent of the agiogenesis inhibitor selected from hormone anticarcinogens and / or platinum compounds; the sustained release auxiliary material is one or the compositions of poly-dl-lactide and copolymer thereof, monomethyl polyethylene glycol and polylactictide copolymer, polyethylene glycol and polylactictide copolymer, terminal carboxyl group polylactic acid and glycolic acid copolymer, di-fatty acid and decanedioic acid copolymer, poly (erucic acid dipolymer decanedioic acid), poly (fumaric acid decanedioic acid), polifeprosan and copolymer of ethylene-vinyl acetate; the viscosity of the suspending agent is 80cp-3,000cp. The sustained release microspheres, which can also be made into sustained release implant to be injected or placed in or around tumor, with the release lasting as long as about 40 days, can be used solely or in combination with chemotherapeutics and / or with non-operative treatments, such as radiotherapy, etc.

The invention provides a medicine composition, which comprises a vascular disrupting agent and an angiogenesis inhibitor. The medicine composition provided by the invention comprises an effective amount of the vascular disrupting agent and an effective amount of the angiogenesis inhibitor. The inventor discovers that the vascular disrupting agent can destroy the internal blood vessels of a tumor and give rise to tumor hypoxia, and the vascular disrupting agent and the angiogenesis inhibitor can have a synergistic effect and further enhance inhibition to the tumor when the vascular disrupting agent is in combined medication with the angiogenesis inhibitor. The combination of the vascular disrupting agent and the angiogenesis inhibitor provided by the invention can synergistically enhance aninhibiting effect on the tumor, and has a broad application prospect in the cancer treatment field.

Disclosed is an anticancer slow release injection carrying both anti-angiogenesis agent and cytotoxic drugs, which comprises slow release micro-balloons and dissolvent, wherein the slow release microballoons comprise anti-cancer active constituents and slow release auxiliary materials, the dissolvent being specific dissolvent containing suspension adjuvant. The anticancer active constituents being the combination of anti-angiogenesis agent selected from Marimastat, SU5416, SU6688, Fumagillin or TNP-470, with cytotoxic drugs selected from Eptaplatin, Nedaplatin, Melphalan, 4-hydroperoxycyclophosphamide, hydroxyl radical Paclitaxel, 10-desacetyltaxuyunnanin, 7-epi-taxol, Vinorelbine, Tamoxifen, Amethopterin, Adriamycin, pidorubicin, actinomycin D, Tallimustine, Atrimustine, Semustine or Ranimustine, the slow release auxiliary materials are selected from di-aliphatic acid and sebacylic acid copolymer, ethylene-vinylacetate copolymer or lactic acid polymer, the viscosity of the suspension adjuvant is 100-3000cp and is selected from sodium carboxymethylcellulose.

An anticarcinogenic slow release injection carrying an angiogenesis inhibitor and a synergist thereof is made from slow release microspheres and a dissolvant. The slow release microspheres comprise anticancer active components and a slow release adjuvant, and the dissolvant is a special dissolvant containing a suspending agent. The anticancer active components are angiogenesis inhibitors such as gefitinib, erlotinib, lapatinib, vatalanib, pelitinib, thalidomide, ranolamine, angiostatin, endostatin, imatinib, thalidomide, ranolamine, simatinib, dasatinib, avastin, kanatini, sorafenib, sunitinib, telstar or panitoma, and the like, and / or cytotoxic drugs selected from a phosphoinositide-3-kinase inhibitor, pyrimidine analogue and / or a DNA repair enzyme inhibitor; the slow release adjuvant is biocompatible macromolecule; the viscosity of the suspending agent is 100cp-3,000cp (at the temperature of 20-30 DEG C), and the suspending agent is selected from sodium carboxymethyl cellulose, and the like. The slow release microspheres can be also made into a slow release implant, and the curative effects of non-operative therapies such as radiotherapy, chemotherapy, and the like, can be improved when the slow release injection is injected or placed in tumors or around the tumors.

Novel derivatives of fumagalone have the general formula (I): and are useful angiogenes is inhibitors; these can be formulated into pharmaceutical compositions suited for human or veterinary medicine, or can be formulated into cosmetic compositions.

The present invention relates to pharmaceutical compositions comprising a sulfonamide-including compound in combination with an angiogenesis inhibitor.

Compounds represented by formula (I) below; a process for producing the compounds by culturing a microorganism belonging to the genus Aspergillus and isolating the above-mentioned compounds from the culture; an angiogenesis inhibitory agent containing as an active ingredient the compounds; and an Aspergillus sp. F-1491 (FERM BP-8288) strain capable of producing the compounds. In formula (I), R represents a methyl group or an ethyl group, R1 represents a hydrogen atom, a chlorine atom, a hydroxyl group or a methoxy group, R2 represents a hydroxyl group, or R1 and R2 taken together form an epoxy ring structure.

The invention provides a composition which comprises a component A and a component B. The component A comprises hyaluronidase, and the component B comprises quercetin, volatile oil of ligusticum wallichii and recombinant angiogenesis inhibitors. The invention further provides application of the composition and a preparation. The composition can be applied to preparing cosmetics, medicine and / or healthcare products for preventing and / or repairing scar. The preparation comprises a first preparation and a second preparation. The first preparation comprises hyaluronidase and medically acceptable solvents, and the second preparation comprises volatile oil of ligusticum wallichii, quercetin recombinant angiogenesis inhibitors and medically acceptable solvents. The composition, the application and the preparation have the advantages that the components are added into the preparation, so that scar preventing effects can be realized by the preparation, and the formed scar can be treated.

The present invention relates to a novel selenophenochromene hydroxamic acids as angiogenesis inhibitors, as well as methods of their manufacturing and use in different pharmaceutical compositions for the treatment or prevention of various diseases and disorders by administration of such substances.

A compound sustained-released injection containing an angiogenesis inhibitor marimastat comprises sustained-released microspheres and a solvent. The sustained-released microspheres comprise a sustained-released adjuvant, an angiogenesis inhibitor selected from marimastat and fumagillin, and a cell toxicant selected from hydroxycamptothecin, mitozolomide, 4-carboxy temozolomide, docetaxel, oxaliplatin, sunplatinum, iphosphamide, lomustine, estramustine, fotemustine, semustine, etoposide, teniposide, vinblastine, anastrozole, fluorouracil and mitomycin c; and the solvent is a common solvent or a special solvent containing a suspending agent. The sustained-released adjuvant is selected from polifeprosan, poly(lactic acid), sebacic acid polymer such as poly(erucic acid dimmer-sebacic acid) and poly(fumaric acid-sebacic acid), EVAc, etc.; and the suspending agent has a viscosity of 100-3,000cp (20-30 DEG C) and is selected from sodium carboxymethyl cellulose, etc. The sustained-released microspheres can also be made into a sustained-released implant, which can enhance the curative effect of non-operative treatments such as chemotherapy and radiotherapy by intratumoral or peritumoral injection or placement.

The invention discloses itraconazole isomer oral liquid, which comprises itraconazole, cyclodextrin or derivative of cyclodextrin and other auxiliary materials, wherein itraconazole is 2S4R itraconazole. The solubility of the 2S4R itraconazole in an aqueous medium containing hydroxypropyl-beta-cyclodextrin is much higher than that of the racemic mixture of four isomers of itraconazole, namely under the condition of medicines at the same concentration, only a small amount of hydroxypropyl-beta-cyclodextrin is required as a solubilizer, so the consumption of hydroxypropyl-beta-cyclodextrin is reduced; thus, the clinic dose and administration period of the medicine are reduced, the clinic treatment effect is enhanced, and adverse reactions are reduced. In addition, because hydroxypropyl-beta-cyclodextrin is very expensive, the reduction of dose can reduce the production cost of the preparation. In the invention, the preparation which is prepared by using 2S4R itraconazole as the active ingredient requires much less hydroxypropyl-beta-cyclodextrin than the conventional itraconazole oral liquid and is suitable to be used as an angiogenesis inhibitor to treat various tumor diseases in clinic.

Compounds of formula I as defined herein, or pharmaceutically acceptable salts, solvates or derivatives thereof, are potent inhibitors of angiogenesis and accordingly are of use in the treatment and prevention of various angiogenesis-related disorders such as cancer.