38 results about "Tubulin Polymerization Inhibitors" patented technology

A novel series of BPU analogues were synthesized and evaluated for antitumor activity. In particular, BPU sulfur analogues 6n and 7d were shown to possess up to 10-fold increased potency, when compared to compound 1, against cancer cell lines. 6n was more effective than compound 1 in causing apoptosis of MCF-7 cells. When compared to other drugs with a similar mechanism of action, 6n retained significant ability to inhibit tubulin assembly, with an IC50 of 2.1 μM.

The present invention relates to methods for the synthesis of chemical compounds for screening as potential tubulin polymerization inhibitors. The invention also provides chemical compounds with tubulin polymerization inhibitor activity.

The present invention relates generally to substituted isoquinolines and their use as tubulin polymerization inhibitors. In particular, the invention relates to substituted isoquinolines which possess useful therapeutic activity, use of these compounds in methods of therapy and the manufacture of medicaments as well as compositions containing these compounds.

Substituted 4-amino-5-benzoyl-2-(phenylamino)thiophene-3-carbonitriles and substituted 4-amino-5-benzoyl-2-(phenylamino)thiophene-3-carboxamides and their salts are tubulin polymerization inhibitors, useful in the treatment of cancer.

The invention discloses 1,2,3-triazole compounds, preparation methods thereof and application thereof in tubulin polymerization inhibition, and belongs to the field of antitumor medicinal chemistry. The preparation methods are simple and efficient, and are environmentally friendly in the synthesis of the 1,2,3-triazole compounds. The compounds have the following structural formula: as shown in thespecification. An anti-cancer activity test of the compounds shows that the compounds have certain inhibition effect on various tumor cells PC3, HepG2 and MGC803 and also has a significant inhibitionaction on tubulin polymerization. The compound (6c) has the activity, superior to that of an antitumor drug colchicine and an antitumor drug 5-fluorouracil, to three cancer cells, and the compounds (6a, 6b, 6c, 6g, 6j) have the activity, superior to the antitumor drug 5-fluorouracil, to three cancer cells. The compounds can be used as candidate or pilot compounds for further development and are applied to preparation of antitumor drugs.

A pharmaceutical composition of a tubulin polymerisation inhibitor and an mTOR inhibitor and a method of treating proliferative disease with a combination of a tubulin polymerisation inhibitor and an mTOR inhibitor.

The invention discloses a pyridine-2-aryl-3-sulfonamide compound as well as a synthesis method and application thereof in preparation of an antitumor drug or tubulin polymerization inhibitor. The pyridine-2-aryl-3-sulfonamide compound has a structural general formula (I), X, Y and Z are selected from C or N atoms, and R1 represents a monosubstituted or polysubstituted group; r2 represents a monosubstituted or polysubstituted group; and R3 represents hydrogen or a different C1-5 alkoxy-substituted benzenesulfonyl group. The invention discloses application of pyridine-2-aryl-3-sulfonamide compounds in preparation of medicines. The pyridine-2-aryl-3-sulfonamide compounds are used as active ingredients for preparing antitumor medicines or tubulin polymerization inhibitors. The antitumor drugsare drugs for resisting colon cancer, breast cancer, liver cancer, lung cancer, stomach cancer or pancreatic cancer.

The invention discloses novel three-stage amide microtubulin polymerization inhibitors, a preparation method of the novel three-stage amide microtubulin polymerization inhibitors and application thereof to medicine for treating gastric cancer, prostatic cancer, breast cancer and the like, and belongs to the field of anti-tumor medicine chemistry. A kind of novel microtubulin polymerization inhibitors are synthesized in an efficient green and environment-friendly way. The inhibitors have the following structure general formula shown in the description. The in vitro anticancer activity experiments prove that the inhibitors have certain inhibition effects on various tumor cells PC3, MCF7 and MGC803; meanwhile, the obvious inhibition effects are achieved on microtubulin. The activity of compounds (IId, IIe, IIg, IIi, IIm, IIo, IIp, IIq and IIr) on three kinds of cancer cells is better than that of anti-tumor medicine 5-fluorouracil. The inhibitors can be applied to anti-tumor medicine preparation through being used as candidate or lead compounds for further development.

A novel series of BPU analogues were synthesized and evaluated for antitumor activity. In particular, BPU sulfur analogues 6n and 7d were shown to possess up to 10-fold increased potency, when compared to compound 1, against cancer cell lines. 6n was more effective than compound 1 in causing apoptosis of MCF-7 cells. When compared to other drugs with a similar mechanism of action, 6n retained significant ability to inhibit tubulin assembly, with an IC50 of 2.1 μM.

A pharmaceutical composition of a tubulin polymerisation inhibitor and an mTOR inhibitor and a method of treating proliferative disease with a combination of a tubulin polymerisation inhibitor and an mTOR inhibitor.

The present invention relates to application of IMB5046 compound in the preparation of antineoplastic drugs. The antineoplastic drug is composed of, by weight, 0.1-99.9% of a compounds shown as a formula I and 0.1-99.9% of pharmaceutically acceptable excipients. The compound shown as formula I can inhibit the polymerization of tubulin and destroy microtubules within cells, has strong cytotoxic activity on tumor cells, especially drug-resistant cells, and can inhibit the growth of xenograft tumor in nude mice. The compound is a tubulin polymerization inhibitor with a novel structure, and has good prospects in developing into antineoplastic drug.

The present invention relates to application of IMB5046 compound in the preparation of antineoplastic drugs. The antineoplastic drug is composed of, by weight, 0.1-99.9% of a compounds shown as a formula I and 0.1-99.9% of pharmaceutically acceptable excipients. The compound shown as formula I can inhibit the polymerization of tubulin and destroy microtubules within cells, has strong cytotoxic activity on tumor cells, especially drug-resistant cells, and can inhibit the growth of xenograft tumor in nude mice. The compound is a tubulin polymerization inhibitor with a novel structure, and has good prospects in developing into antineoplastic drug.

The present invention relates to compounds of general formula (I) as tublin polymerization inhibitors and methods for preparing such compounds.

The present invention relates to (E)-ethyl 2-(2-methyl-3-((2-(naphtho[2,1-b]furan-2-carbonyl)hydrazono)methyl)-1H-indol-1-yl)acetate as a novel tubulin polymerization inhibitor and a method for synthesizing the same. The compound of the present invention can inhibit mitosis and induce apoptosis and thus be used as an anticancer agent, by binding to tubulin to inhibit microtube polymerization. According to the synthesis method of the present invention, the reaction is simplified and the efficiency is 60%, or higher, leading to a very high yield, thereby providing an effective synthesis method.

The invention discloses a class of sulfonamide-1,2,3-triazole-containing compounds, their preparation method and their application in Tubulin polymerization inhibitors, belonging to the field of antitumor pharmaceutical chemistry. The present invention uses classic click chemistry to combine the sulfa-1,2,3-triazole active unit with the sulfa-1,2,3-triazole active unit, thereby synthesizing the sulfa-1,2,3-triazole compounds in a simple, efficient, and environmentally friendly manner. It has the following general structural formula: the in vitro anticancer activity test of this type of compound shows that it has a certain inhibitory effect on a variety of tumor cells PC-3, MCF-7, MGC-803, and has a significant inhibitory effect on the polymerization of Tubuli , which can be used as a candidate or lead compound for further development in the preparation of antitumor drugs.

The invention is directed to compounds having the following structures:N-(3-ethoxyphenyl)-1,4-dihydro-6-ethoxy-7-(3-hydroxypropoxy)-1-methylindeno[1,2-c]pyrazole-3-amine;3-[3-(3-Bromo-phenylamino)-6-ethoxy-1-methyl-1,4-dihydro-indeno[1,2-c]pyrazol-7-yloxy]-propan-1-ol; or3-[3-(2-Chloro-pyridin-4-ylamino)-6-ethoxy-1-methyl-1,4-dihydro-indeno[1,2-c]pyrazol-7-yloxy]-propan-1-ol, and N-oxides, pharmaceutically acceptable salts, solvates, tautomers and stereochemical isomers thereof and the uses of such compounds as inhibitors of tubulin polymerization and for the treatment of solid tumors. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.

The invention discloses a pyridine-2-aryl-3-sulfonamide compound, its synthesis method and its application in the preparation of antitumor drugs or tubulin polymerization inhibitors. The pyridine-2-aryl-3-sulfonamide compound of the present invention has the general structural formula (I), X, Y, Z are taken from C or N atom, R 1 Represents a monosubstituted or polysubstituted group; R 2 Represents a monosubstituted or polysubstituted group; R 3 Represents hydrogen or benzenesulfonyl substituted by different C1-5 alkoxy groups. The application of pyridine-2-aryl-3-sulfonamide compounds in the preparation of medicines is used as an active ingredient for the preparation of antitumor medicines or tubulin polymerization inhibitors. The antitumor drugs are anti-colon cancer, anti-breast cancer, anti-liver cancer, anti-lung cancer, anti-gastric cancer or anti-pancreatic cancer drugs.

The invention discloses novel three-stage amide microtubulin polymerization inhibitors, a preparation method of the novel three-stage amide microtubulin polymerization inhibitors and application thereof to medicine for treating gastric cancer, prostatic cancer, breast cancer and the like, and belongs to the field of anti-tumor medicine chemistry. A kind of novel microtubulin polymerization inhibitors are synthesized in an efficient green and environment-friendly way. The inhibitors have the following structure general formula shown in the description. The in vitro anticancer activity experiments prove that the inhibitors have certain inhibition effects on various tumor cells PC3, MCF7 and MGC803; meanwhile, the obvious inhibition effects are achieved on microtubulin. The activity of compounds (IId, IIe, IIg, IIi, IIm, IIo, IIp, IIq and IIr) on three kinds of cancer cells is better than that of anti-tumor medicine 5-fluorouracil. The inhibitors can be applied to anti-tumor medicine preparation through being used as candidate or lead compounds for further development.

The invention relates to the field of medicine and specifically relates to application of a microtubule polymerization inhibitor (which is shown in a formula I) containing a pyrazoline structure in preparing drugs for treating and resisting tumor.

The invention relates to the field of medicine, in particular to the use of a novel tubulin polymerization inhibitor (general formula I) containing a pyrazoline structure in the preparation of antitumor drugs.

Substituted 4-amino-5-benzoyl-2-(phenylamino)thiophene-3-carbonitriles and substituted 4-amino-5-benzoyl-2-(phenylamino)thiophene-3-carboxamides and their salts are tubulin polymerization inhibitors, useful in the treatment of cancer.

The invention discloses an application of a compound in improving the transplantation efficiency of human hematopoietic stem cells. The compound is selected from one or more than two of a microtubulin polymerization inhibitor, LND-212854, AZD0364, SCH772984, Pimsertib, Trametinib, IWR-1-endo, TTNPB, JNK-inhibitor IX and CHIR99021. The invention further discloses an application of the compound in improving the transplantation efficiency of the human hematopoietic stem cells. The compound provided by the invention can improve the expression of the hematopoietic stem cell surface protein CD184 through in-vitro short-time treatment without influencing the phenotype, motility rate and various characteristics of cells. Through the combination of the chemokine receptor CD184 expressed by the HSC and the chemokine ligand SDF1 in the bone marrow microenvironment, the migration ability of the HSC and the homing ability of the HSC in the bone marrow are improved, and the transplantation efficiency and the treatment effect of the HSC are enhanced.

Substituted 4-amino-5-benzoyl-2-(phenylamino)thiophene-3-carbonitriles and substituted 4-amino-5-benzoyl-2-(phenylamino)thiophene-3-carboxamides and their salts are tubulin polymerization inhibitors, useful in the treatment of cancer.

The invention discloses a synthesis method of Combretastatin A-4 derivatives. Aiming at double targets of BFGF and tubulin, a tubulin polymerization inhibitor CA-4 and its analogues are respectively coupled with aminosugar having BFGF inhibition effects so that eight novel compounds are designed and synthesized. A preliminary pharmacological test result shows that the desired compounds have human umbilical vein endothelial cell proliferation inhibition effects superior to that of a positive drug CA-4.

An aspect described herein includes a method for treating acute myeloid leukemia (AML) in a subject in need thereof comprising, administering to the subject an effective amount of a small molecule tubulin polymerization inhibitor compound. More particularly, another aspect described herein includes a method for treating acute myeloid leukemia in a subject in need thereof comprising, administering to the subject an effective amount of the small molecule tubulin polymerization inhibitor compound described herein in combination with a chemotherapeutic agent.

Methods and combination therapies for treating, preventing, and / or delaying the onset and / or development of cancer using a tubulin polymerization inhibitor such as a compound of formula I, or a pharmaceutically acceptable salt thereof, and a poly (ADP-ribose) polymerase (PARP) inhibitor,or a pharmaceutically acceptable salt thereof, are provided.

The invention is directed to compounds having the following structures:N-(3-ethoxyphenyl)-1,4-dihydro-6-ethoxy-7-(3-hydroxypropoxy)-1-methylindeno[1,2-c]pyrazole-3-amine;3-[3-(3-Bromo-phenylamino)-6-ethoxy-1-methyl-1,4-dihydro-indeno[1,2-c]pyrazol-7-yloxy]-propan-1-ol;or3-[3-(2-Chloro-pyridin-4-ylamino)-6-ethoxy-1-methyl-1,4-dihydro-indeno[1,2-c]pyrazol-7-yloxy]-propan-1-ol, and N-oxides, pharmaceutically acceptable salts, solvates, tautomers and stereochemical isomers thereof and the uses of such compounds as inhibitors of tubulin polymerization and for the treatment of solid tumors. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.