99 results about "Tubulin Inhibitors" patented technology

The invention provides a novel tubulin inhibitor and an application thereof. The novel tubulin inhibitor is a series of substituted heterocyclic skeleton-based compounds with colchicine binding sites in tubulins as targets. The compounds have the following structure as shown in the specification, wherein the formula is as shown in the specification; n independently represents an integer of 0-5 under the condition that n is less than or equal to 5; A represents a monosubstituted or polysubstituted group; and the group is selected from H, C1-C20 acylamino, C1-C20 acyloxy, C1-C20 alkanoyl, C1-C20 alkoxycarbonyl, C1-C20 alkoxy, C1-C20 alkylamino, C1-C20 alkylcarboxy amino, aroyl, arylalkanoyl, carboxyl, cyano, halogen, hydroxyl, nitro and methylthienyl.

The present invention is directed to novel pharmaceutical compositions comprising nano- and micro-particulate formulations of poorly water soluble tubulin inhibitors of the indole chemical class, preferably N-substituted indol-3-glyoxyamides, and more preferably N-(Pyridin-4-yl)-[1-(4-chlorobenzyl)-indol-3-yl]glyoxylic acid amide (D-24851), also known as “Indibulin,” and methods of making and using such compositions for the treatment of anti-tumor agent resistant cancers and other diseases.

The present invention relates to a computer-assisted method of a designing of a tubulin inhibitor comprising: a) determining an interaction between a tubulin protein and a chemical known to bind the tubulin protein by evaluating a binding of the tubulin protein to the chemical known to bind the tubulin protein; b) based on the interaction, designing a candidate tubulin inhibitor; c) determining an interaction between the tubulin protein and the candidate tubulin inhibitor by evaluating a binding of the tubulin protein to the candidate tubulin inhibitor; and d) concluding that the candidate tubulin inhibitor inhibits the tubulin protein wherein the conclusion is based on the interaction of step c). The invention also provides compositions and methods of treatment of diseases with the candidate tubulin inhibitors.

The invention aims to provide a neural restoration material combined with the acellular nerve application. The neural restoration material is prepared from nerves of an acellular allogene or acellular heterogeneous living organism, a restoration material, a microtubulin inhibitor, neurotrophic factors and stem cells. The neural restoration material disclosed by the invention has good biocompatibility, can provide nutrition supplies needed by nerve regeneration and restoration, is capable of maintaining an optimal physicochemical and biology microenvironment for nerve regeneration for a long time and has dual functions of preventing nerve tumor formation and promoting defect nerve restoration.

The invention discloses a reagent formula for multiplying a plant chromosome by using a composite reagent without colchicines and a multiplying method. The plant chromosome is multiplied by using a composite formula prepared from multiple mitosis inhibitors and tubulin inhibitors; compared with a conventional chromosome multiplying method, the method has the characteristics of low toxicity, high efficiency and wide application range; cooperative use of three compounds such as a multiplying agent, an aid and a detoxicant with different functions is the key point of the reagent formula, and functions of improving multiplying effects and reducing medicine damage are achieved; by adopting the reagent formula, the problems that growth abnormity, malformation or even death of a treated plant material are generally caused, and the multiplication success rate is relatively low since the treated plant material is seriously damaged in conventional process that a plant chromosome is multiplied byusing colchicines, are solved; and more importantly, the problems that the colchicines are highly toxic, have potential carcinogeneses for mammals including human beings, and can cause serious harm to health of operators and environment security, can be solved.

The invention provides a new carbazole sulfonamide derivation and medicinal salt, comprising the general formula as follows (I). The compound can be small molecular microtubulin depressant which not only have the effect of antimicrocapillarity but also have the prominent antineoplastic activity, also the molecular weight is small, it is simple to synthesize and the toxic side effect is little. This invention also provides the medicinal compounds which contain the carbazole sulfonamide derivation as active constituent.

The invention discloses a sulfonamide compound and medicinal compositions thereof, and preparation methods and applications thereof. The sulfonamide compound can be used as a micro-molecular tubulin inhibitor, has an anti-microtubule effect in vitro, can induce the apoptosis of tumor cells in vitro, has an obvious inhibition effect on multidrug resistance cells in vitro, and has a substantial in-vivo oral antitumor activity. Additionally, the compound has the advantages of small molecular weight, simple synthesis, and small toxic side effects. The invention also provides medicinal compositions containing the sulfonamide compound and pharmaceutically acceptable salts thereof as an active component.

The invention discloses aryl heterocycle micromolecule compounds shown as a general structure formula I, derivatives or pharmaceutically acceptable salts and prodrugs thereof, and preparing methods and uses of the compounds, the derivatives, the pharmaceutically acceptable salts and the prodrugs of the compounds. The compounds have good physicochemical properties, and have antitumor activity. Research on mechanisms of action shows that: the compounds act on tubulin and are novel tubulin inhibitors. The general structure formula I is shown in the specification.

The invention discloses a 3-(3,4,5-trimethoxybenzoyl)-benzofuran microtubulin inhibitor as well as a preparation method and use thereof. A 3-(3,4,5-trimethoxybenzoyl)-benzofuran compound in the invention has an action mechanism similar to colchicine and is capable of inhibiting polymerization of microtubulins. The 3-(3,4,5-trimethoxybenzoyl)-benzofuran compound has very strong proliferation inhibition activity to human lung cancer cells A549, human gastric cancer cells MGC-803, human liver cancer cells HepG2, human colon cancer cells HCT-116, human cervical cancer cells HeLa and human breast cancer cells MCF-7.

A compound of general formula (I) or pharmaceutically acceptable prodrugs, salts, hydrates, solvates, crystal forms or diastereomers thereof is described. A method of treating a hyperproliferation-related disease state or disorder in a subject using a compound of formula (I) is also described.

A compound of general formula (I) or pharmaceutically acceptable prodrugs, salts, hydrates, solvates, crystal forms or diastereomers thereof is described. A method of treating a hyperproliferation-related disease state or disorder in a subject using a compound of formula (I) is also described.

The present invention provides a process for the preparation of 6-[(substituted)phenyl]-triazolopyrimidine dicarboxylic acid salt and as a hydrated salt having the structural formula (I) wherein: R1 is CF3 or C2F5; R2 is H or C1-C3 alkyl; n is an integer of 2, 3, or 4; X is Cl or Br; R3 and R4 are each independently H or C1-C3 alkyl; or R3 and R4 when optionally taken together with the nitrogen atom to which each is attached form a 4 to 6 membered saturated heterocyclic ring having 1-2 nitrogen atoms and 0-1 oxygen atoms or 0-1 sulfur atoms, and optionally substituted with R5; R5 is C1-C3 alkyl; wherein the dotted line is an optional bond.

The present invention provides one kind of new antitumor compound and its preparation process. The compound is heteroaromatic ring ketone (alcohol) or its derivative in the structure as shown. The compound of the present invention may be used in preparing tubulin inhibitor, and possesses antitumor effect. The present invention also provides antitumor medicine composition with the compound as the active component. The compound has the advantages of small molecular weight, simple synthesis process and less toxic side effect.

Implantable medical devices having anti-restenotic coatings are disclosed. Specifically, implantable medical devices having coatings of certain antiproliferative agents, particularly a certain beta-tubulin inhibitor, are disclosed. The anti-restenotic beta-tubulin inhibitor is T-900607, and pharmaceutically acceptable derivatives thereof. The anti-restenotic medical devices include stents, catheters, micro-particles, probes and vascular grafts. Intravascular stents are preferred medical devices. The medical devices can be coated using any method known in the art including compounding the beta-tubulin inhibitor with a biocompatible polymer prior to applying the coating. Moreover, medical devices composed entirely of biocompatible polymer-beta-tubulin inhibitor blends are disclosed. Additionally, medical devices having a coating comprising at least one beta-tubulin inhibitor in combination with at least one additional therapeutic agent are also disclosed. Furthermore, related methods of using and making the anti-restenotic implantable devices are also disclosed.

Compounds represented by the formula (I) or pharmaceutically acceptable salts thereof:R2—Y—Z-Q-A-R1  Formula (I)wherein R1, R2, Y, Z, Q, and A are as defined. These compounds are inhibitors of tubulin polymerization by binding at colchicines binding site and are useful in the treatment of tumors or mitotic diseases such as cancers, gout, and other conditions associated with abnormal cell proliferation.

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.

The present invention relates to pharmaceutical compositions for treating cancer comprising BRAF inhibitors, (e.g. vemurafenib) and / or MEK inhibitor, (e.g. trametinib, RO5068760), in combination with anti-tubulin compounds of the invention or other known tubulin inhibitors, and using such compositions for treating cancer such as melanoma, drug-resistant cancer, and cancer metastasis.

The invention provides a novel tubulin inhibitor and an application thereof. The novel tubulin inhibitor is a series of substituted heterocyclic skeleton-based compounds with colchicine binding sites in tubulins as targets. The compounds have the following structure as shown in the specification, wherein the formula is as shown in the specification; n independently represents an integer of 0-5 under the condition that n is less than or equal to 5; A represents a monosubstituted or polysubstituted group; and the group is selected from H, C1-C20 acylamino, C1-C20 acyloxy, C1-C20 alkanoyl, C1-C20 alkoxycarbonyl, C1-C20 alkoxy, C1-C20 alkylamino, C1-C20 alkylcarboxy amino, aroyl, arylalkanoyl, carboxyl, cyano, halogen, hydroxyl, nitro and methylthienyl.

The present invention relates to a pharmaceutical formulation for oral administration of the poorly soluble and therefore hardly bioavailable microtubule polymerization inhibitor Indibulin and a process for its manufacture. In particular, there is provided a pharmaceutical formulation of Indibulin for oral administration comprising a granulate containing micronized Indibulin having a particle size of less than 20 μm for at least 99% of the volume of particles, at least one hydrophilic surfactant, and at least one capsulation excipient. The present invention also discloses a method of treating hyperproliferative disorders, malignancies and neoplasms with Indibulin.

The invention discloses an alpha-tubulin inhibitor and application thereof. The active ingredients of the alpha-tubulin inhibitor consist of effective quantities of at least one lactone compound of alantolactone, isoalantolactone, dihydro-alantolactone, dehydrocostunolide lactone, costunolide and dihydro-costunolide. The alpha-tubulin inhibitor disclosed by the invention can obviously inhibit alpha-tubulin and the mRNA (Messenger Ribonucleic Acid) level thereof, can inhibit the forming of spindles, block the cell cycle in the G2 / M period, induce cell apoptosis and the like, can effectively inhibit the tumor growth speed, can obviously inhibit growth of various tumor cells, particularly has an obvious effect on melanoma, can be expected to be used for preparing medicament preparations for resisting tumors and has wide application prospect, wherein the tumors comprise lung cancer, pancreatic cancer, prostatic cancer, neuroblastoma, melanoma and breast cancer.

The invention relates to 7-(trimethoxyphenyl)-pyrrolo[2,3-d]pyrimidine. The chemical structure of the compound is shown in a following formula (a), wherein R<1> is selected from 3-indolyl, 4-methylphenyl, phenyl, 4-methoxyphenyl, 4-trifluoromethoxyphenyl, 4-fluorophenyl, 5-(1-methylindazolyl), 6-indolyl, 3-methylphenyl, 3,4-dimethylphenyl, 5-(1-methylindolyl), 3-(1-methylindolyl), 6-(1-methylindolyl), 4-N,N-dimethylphenyl, 4-(1-methylpyrazolyl), 4-vinylphenyl, 3-(1-hydroxymethylindolyl), 3-fluoro-4-methoxyphenyl, 3-amino-4-methoxyphenyl, 3-(1-Boc indolyl) and 4-hydroxymethylphenyl. The 7-(trimethoxyphenyl)-pyrrolo[2,3-d]pyrimidine disclosed by the invention can inhibit tumor cell proliferation and tubulin aggregation and can enable a cell cycle to be stay in a G2 / M period, so that a noveltubulin inhibitor is provided for inhibiting tumor cell proliferation.

The invention provides square acid derivate and pharmaceutical salt thereof. The square acid derivate has a structure shown as the formula (I). The square acid derivate can be taken as micro-molecular tubulin inhibitor, having the function of resisting microtubule and remarkable anti-tumor activity and the advantages of small molecular weight, simple synthesis and small toxic and side effects. The invention further provides a synthesis method of the square acid derivate and an anti-tumor medical composite taking the square acid derivate and the pharmaceutical salt thereof as active components.

The invention discloses a novel quinoline substituted chalcone compound as well as pharmaceutically acceptable salts and a preparation method thereof. The invention further discloses a pharmaceuticalcomposition which comprises a therapeutically effective amount of the novel quinoline substituted chalcone compound and / or the pharmaceutically acceptable salts and a pharmaceutically acceptable carrier. The invention further discloses a tubulin inhibitor which comprises the novel quinoline substituted chalcone compound and / or the pharmaceutically acceptable salts. The invention further disclosesapplication of the novel quinoline substituted chalcone compound and / or the pharmaceutically acceptable salts in preparing drugs for treating but not limited to colon cancer, leukemia, liver cancer, breast cancer and other diseases. The compound in the application shows excellent anti-tumor activity, and has more stable metabolic properties and better druggability prospect.

The present invention relates to pharmaceutical compositions for treating cancer comprising BRAF inhibitors, (e.g. vemurafenib) and / or MEK inhibitor, (e.g. trametinib, RO5068760), in combination with anti-tubulin compounds of the invention or other known tubulin inhibitors, and using such compositions for treating cancer such as melanoma, drug-resistant cancer, and cancer metastasis.

The invention discloses a novel indole compounds containing alpha-methylene-gamma-butyrolactone structures, a preparation method thereof and an application thereof serving as tubulin inhibitors in antitumor activity, and belongs to the field of medicinal chemistry. According to the invention, an alpha-methylene-gamma-butyrolactone structure unit is combined with different N substituted indole structures by a simple, convenient and efficient synthetic method to synthesize the indole compounds containing alpha-methylene-gamma-butyrolactone structures, the indole compounds have the following structural general formula shown in the description, in vitro antitumor activity evaluation indicates that the compounds have excellent in vitro antitumor activity in a broad spectrum, and the compounds can be further used as tubulin inhibitors to serve as antitumor candidates or develop lead compounds.

The invention provides a carbazole sulfamide derivative or pharmaceutical slat thereof as well as a preparation method and an application thereof. The carbazole sulfamide derivative or the pharmaceutical slat thereof has the general formula (I). As a small-molecular tubulin inhibitor, the carbazole sulfamide derivative or the pharmaceutical slat thereof has an anti-tubulin function and significant anti-tumor activity, and meanwhile, the carbazole sulfamide derivative or pharmaceutical slat thereof is small in molecular weight, is simple to synthesize and has small toxic and side effects.

The invention is a process for the preparation of compounds of the Formula I: where R1, R2, R3, R4 and R5 are defined in the specification, which are intermediates useful for the preparation of tubulin inhibitors which are useful in the treatment of cancer.

Compounds represented by the formula (I) or pharmaceutically acceptable salts thereof:R2—Y—Z-Q-A-R1  Formula (I)wherein R1, R2, Y, Z, Q, and A are as defined. These compounds are inhibitors of tubulin polymerization by binding at colchicines binding site and are useful in the treatment of tumors or mitotic diseases such as cancers, gout, and other conditions associated with abnormal cell proliferation.

The invention discloses a podophyllotoxin derivative with a structure as shown in a formula I or a pharmaceutically acceptable salt or solvate. The invention further discloses application of the podophyllotoxin derivative or the pharmaceutically acceptable salt or solvate in preparation of a tubulin inhibitor, proliferation of tumor cells can be inhibited on the cellular level, growth of transplanted tumors in nude mice can be inhibited on the animal level, and the podophyllotoxin derivative or the pharmaceutically acceptable salt or solvate can be used for treating various cancers. And the podophyllotoxin derivative has low toxic and side effects, almost has no obvious toxicity to normal cells, and improves the safety.

The invention discloses an indeno pyrazole micromolecular tubulin inhibitor which is characterized by comprising a structure which is shown in a general formula I, wherein R represents NH2 or NHOH. The invention further discloses a preparation method of an indeno pyrazole compound or officinal salt of the indeno pyrazole compound. The compound disclosed by the invention is the indeno pyrazole micromolecular tubulin inhibitor which is novel in structure, and has strong proliferation inhibition activity to a human liver cancer HepG2 cell, a human prostatic cancer PC3 cell, a human cervical carcinoma HeLa cell, a human breast cancer MCF-7 cell and a human leukemia K562 cell. The mechanism of action of the compound is similar to that of colchicine. Tubulin polymerization can be inhbited, and the tubulin inhibitor has important meaning for enhancing the specificity and effectiveness of the medicine, reducing the toxic and side effects, preventing drug resistance and the like.