35 results about "Lonidamine" patented technology

Novel compounds useful for inhibiting spermatogenesis and cancer treatment, and in particular as inhibitors of heat shock proteins and / or elongation factor 1 alpha.

Lonidamine or a lonidamine analog is administered with one or more additional anti-cancer agents or surgery or radiation to treat cancer or is administered alone or in combination to treat cancer, optionally in a sustained release formulation, and improve patient outcome.

Lonidamine derivatives can be useful in methods of treating, inhibiting, and / or preventing polycystic kidney disease (PKD). Accordingly, lonidamine derivatives can be administered in a therapeutically effective amount for inhibiting, and / or preventing polycystic kidney disease (PKD) in the subject. This can include administering a therapeutically effective amount of the lonidamine derivatives for inhibiting CFTR and / or Hsp90 or biological pathway thereof. Also, the method can include administering the lonidamine derivatives in a therapeutically effective amount for inhibiting ErbB2, Src, Raf-1, B-Raf, MEK, Cdk4, NKCC1, or combinations thereof. For example, the therapeutically effective amount of the lonidamine derivatives can be configured so as to provide a concentration in or adjacent to a kidney cell of about 0.25 uM or more or less.

The invention discloses a co-delivery nano-carrier of drugs and genes, a preparation method and an application thereof; and particularly relates to a co-delivery nano-carrier TCPL-siRNA-PPX which can carry a chemotherapeutic drug and a genetic drug simultaneously. The drug delivery system is composed of a polymer prodrug carrier TCPL, siRNA and a multifunctional polyanionic polyer PPX through electrostatic adsorption among the components in a self-assembly manner. The co-delivery nano-carrier can achieve targetedly delivery of the drug and the gene to the same tumor cell, release the siRNA at the cytoplasm, silence Bcl-2 protein, promote apotosis and relieve inhibition of the Bcl-2 on lonidamine, and can deliver the chemotherapeutic drug, lonidamine, which is mitochondrion-acted to mitochondria so that the chemotherapeutic drug and the gene can synergistically trigger the apotosis of a mitochondrial pathway and kill tumor cells cooperatively. Through in-vivo and in-vitro activity evaluation, the drug delivery system is proved to be better than drug delivery carriers which deliver single components respectively at the same time, can significantly improve the anti-cancer activity of the drug and the gene and has a definite synergistic treatment effect.

A method for treatment or prophylaxis of benign prostatic hyperplasia by administration of lonidamine or a lonidamine analog is provided. Also provided are unit dosage forms of lonidamine or an analog, useful for such treatment and prophylaxis.

The invention relates to a process for synthesizing 1-[(2,4-dichlorobenzene) methyl]-1H-indazole-3-carboxyl acid which consists of, using phenylhydrazine as starting raw material, producing beta-acetylphenylhydrazine through reaction with glacial acetic acid, reacting with hydrated chloral and hydroxylamine hydrochloride, obtaining N-acetamido-isonitro-acetanilide, preparing 1H-indazole-3-carboxylic acid under the condition of concentrated sulfuric acid, finally subjecting 1H-indazole-3-carboxylic acid with 2,4-dichlorin benzyl chloride.

The invention discloses a nano-carrier for drug and gene co-delivery and a preparation method and application thereof, and particularly relates to a co-delivery nano-carrier TCPL-siRNA-PPX for simultaneously carrying a chemotherapeutic drug and a gene-based drug. A polymeric prodrug carrier TCPL, siRNA and a multifunctional polyanionic polymer PPX are self-assembled by electrostatic adsorption between ingredients to form the drug delivery system; a drug and a gene can be targeted to be delivered to the same tumor cell, and moreover, siRNA is released in cytoplasm to silence the Bc1-2 protein, promoting apoptosis and releasing the inhibition of Bcl-2 on lonidamine; the chemotherapeutic drug acting on mitochondria, lonidamine, is delivered to the mitochondria; both cooperatively trigger the apoptosis of the mitochondrial pathway, jointly killing the tumor cell. By in-vitro and in-vivo activity evaluation, the invention proves that the system is better than the simultaneous delivery of each single component, can remarkably increase anti-cancer activity, and has a definite synergistic treatment effect.

The invention discloses zinc glutamate-coated Prussian blue nanoparticles with triphenylphosphine-clonidamine coated with cancer cell membrane and a preparation method thereof. The nanoparticle comprises Prussian blue nanocore, wherein a surface of the Prussian blue nanocore is coated with at least one zinc glutamate layer, and a surface of the zinc glutamate layer at the outermost layer is provided with a loading layer loaded with triphenylphosphine-clonidamine, and the loading layer is coated with a tumor cell membrane layer. The nanoparticle has an ability to target tumor cells, has a longcirculation time in a body, can gather in mitochondria and cause dysfunction, reduces synthesis of ATP, down-regulates synthesis of a variety of heat shock proteins, causes cell apoptosis, and effectively enhances efficacy of tumor low-temperature photothermal therapy.

Fertility management can include: administering to the subject one or more doses of a compound according to Formula I so as to reduce fertility in the subject. Fertility management can also include administering an effective amount of the compound to: impair Sertoli cell function in a male subject; inhibit spermatogenesis in the subject; reduce testis weight in the subject; reduce ovary weight in a female subject; reduce serum progesterone in the female subject; impair ovarian follicle function in the female subject; causing reversible fertility in the subject. In order to return fertility, the method can include ceasing administration of the compound to the subject so as to return fertility in the subject. The compound can be administered for irreversibly sterilizing the subject.

The invention belongs to the field of chemicals, and relates to a preparation method of indazole and an application of the indazole in medicine synthesis. The invention discloses a preparation method of indazole and an application of the indazole in synthesizing 1H-indazole-3-carboxylic acid, lonidamine, a compound 8, a compound 9, a compound 10, axitinib, YD-3, YC-1 and similar substances thereof.

A method for treatment or prophylaxis of benign prostatic hyperplasia by administration of lonidamine or a lonidamine analog is provided. Also provided are unit dosage forms of lonidamine or an analog, useful for such treatment and prophylaxis.

A method for treatment or prophylaxis of benign prostatic hyperplasia by administration of lonidarrine or a lonidamine analog is provided. Also provided are unit dosage forms of lonidamine or an analog, useful for such treatment and prophylaxis.

A method for treatment or prophylaxis of benign prostatic hyperplasia by administration of lonidamine or a lonidamine analog is provided. Also provided are unit dosage forms of lonidamine or an analog, useful for such treatment and prophylaxis.

A method for treatment or prophylaxis of benign prostatic hyperplasia by administration of lonidarrine or a lonidamine analog is provided. Also provided are unit dosage forms of lonidamine or an analog, useful for such treatment and prophylaxis.

The invention discloses a targeted tumor cell mitochondria peptidyl nano-drug as well as a preparation method and application thereof. The polypeptide derivative LND-GFFYK-cyclin is prepared by connecting a hydrophobic anti-cancer drug-lonidamine (LND) and a hydrophilic cycleanine (Cyclin) to a self-assembled short peptide sequence through covalent modification, and is a polypeptide derivative LND-GFFYK-cyclin. The product can be self-assembled to form a peptidyl nano-drug through intermolecular non-covalent interaction, is used for tumor specific and synergistic radiotherapy and chemotherapy, and has the characteristics of simple synthesis, high repeatability, good biocompatibility and large clinical transformation potential. Meanwhile, compared with free LND, the self-assembled peptidyl nano-drug obtained by the invention can significantly improve the selective killing effect of LND on tumor cells and the effect of radiotherapy and chemotherapy synergistic treatment by targeting mitochondria, and has good clinical transformation and application prospects.

Fertility management can include: administering to the subject one or more doses of a compound according to Formula I so as to reduce fertility in the subject. Fertility management can also include administering an effective amount of the compound to: impair Sertoli cell function in a male subject; inhibit spermatogenesis in the subject; reduce testis weight in the subject; reduce ovary weight in a female subject; reduce serum progesterone in the female subject; impair ovarian follicle function in the female subject; causing reversible fertility in the subject. In order to return fertility, the method can include ceasing administration of the compound to the subject so as to return fertility in the subject. The compound can be administered for irreversibly sterilizing the subject.

The invention relates to superparamagnetic electric conductive gamma-iron oxide / polyaniline-lonidamine (gamma-Fe2O3 / PAn-Lon) and a preparation method thereof. The method comprises the following steps of: mixing aniline and a hydrochloric acid solution to obtain a mixed solution which contains sodium dodecyl benzene sulfonate, adding gamma-Fe2O3, stirring, and adding ammonium persulfate, wherein the molar ratio of the ammonium persulfate to the aniline is 1:1; reducing by using ammonia water to obtain eigen polyaniline, washing by using water, and drying in vacuum to obtain gamma-Fe2O3 / PAn; and adding the gamma-Fe2O3 / PAn into a Lon acidic solution, stirring, performing suction filtering by using a vacuum pump, washing by using water, and drying in vacuum to obtain the gamma-Fe2O3 / PAn-Lon. The defects that the treatment effect cannot be limited in the specific cancerous cell, tissue or organ and normal tissue is damaged are overcome; and by the gamma-Fe2O3 / PAn-Lon, the treatment effect can be limited in the specific cancerous cell, tissue or organ, the normal tissue is not damaged, and the specific pathological cell is identified through electric conductivity of an organism in an organism microenvironment, so that the Lon can better enter a lesion site, and the toxic and side effects of the Lon on healthy tissue are reduced.

The invention discloses a manganoporphyrin-lonidamine combined drug for treating tumor, comprising manganoporphyrin, lonidamine and one or more optional pharmacy-acceptable vectors. The inventor of the application carries out a series of experimental researches. Proved by the experiment, after manganoporphyrin without a tumor-resistant function is combined with the lonidamine for pharmacy, the treatment effect for the tumor can be remarkably improved, the toxicity of the medicine can be reduced, the survival time of animals can be prolonged and the unexpected effects can be obtained.

The present invention discloses an application of a hexokinase inhibitor to preparation of a medicine for preventing and treating the Alzheimer disease. It is proposed that the hexokinase inhibitor, especially lonidamine and 3-bromopyruvic acid can improve the cognitive level of an Alzheimer disease model mouse, remove A beta and reduce A beta aggregation, the hexokinase inhibitor has the obviousanti-Alzheimer disease progression effect, and a basis is provided for the hexokinase inhibitor, especially the lonidamine and the 3-bromopyruvic acid to preparation of the medicine for preventing andor treating the Alzheimer disease.

The invention discloses a synthetic method of anti-tumor medicament lonidamine. The synthetic method comprises the following steps: taking 2,4-dichloromethylbenzene and phenylhydrazine as a starting raw material, performing acetylation on the phenylhydrazine, then reacting with hydroxylamine hydrochloride and chloral hydrate to generate N- acetylamino oximino acetylaniline, further performing rearrangement, cyclocondensation and hydrolysis under the catalysis of concentrated sulfuric acid to generate 1H-indazole-3-carboxylic acid; and enabling the 2,4-dichloromethylbenzene and N-bromosuccinimide (NBS) to react to generate 2,4-dichlorobenzyl bromide, and then reacting with the 1H-indazole-3-carboxylic acid to generate the lonidamine. The synthetic method disclosed by the invention has the characteristics of simple instruments and equipment required for the synthetic method, easiness in getting the raw materials, low cost, high yield and the like. During the reaction process, the industrial three wastes are simple to process, and the synthetic method is green and environment-friendly; and the obtained product has the advantages of stable quality, low content of single impurity and higher quality in comparison with the similar products in the industry, and is more suitable for large-scale industrial production.

The invention discloses a Prussian blue nano-particle coated with zinc glutamate loaded with triphenylphosphine-lonidamine and a preparation method thereof, comprising a Prussian blue nano-core whose surface is coated with at least A zinc glutamate layer, the surface of the outermost zinc glutamate layer has a load layer loaded with triphenylphosphine-lonidamine, and the load layer is covered with a tumor cell membrane layer. The present invention has the ability to target tumor cells, has a long circulation time in the body, and can gather in mitochondria and cause dysfunction, reduce the synthesis of ATP, down-regulate the synthesis of various heat shock proteins, and cause cell apoptosis at the same time, effectively enhancing the low-temperature light therapy of tumors. Efficacy of heat therapy.

The present invention discloses an application of a hexokinase inhibitor to preparation of a medicine for preventing and treating the Alzheimer disease. It is proposed that the hexokinase inhibitor, especially lonidamine and 3-bromopyruvic acid can improve the cognitive level of an Alzheimer disease model mouse, remove A beta and reduce A beta aggregation, the hexokinase inhibitor has the obviousanti-Alzheimer disease progression effect, and a basis is provided for the hexokinase inhibitor, especially the lonidamine and the 3-bromopyruvic acid to preparation of the medicine for preventing andor treating the Alzheimer disease.

The invention belongs to the technical field of photosensitizers, and particularly relates to a photosensitizer and a preparation method and application for improving the photodynamic performance of the photosensitizer. The structural general formula of the prepared photosensitizer is shown in the specification, r1 is I, Br or H; x is I, Br or Cl; and R2 is a linear chain or branched chain alkyl group of C1-C6. According to the application of the photosensitizer provided by the invention, the photosensitizer is a near-infrared photosensitizer, is high in optical performance, can specifically target tumor cells, and meanwhile, has small and even no damage to normal cells; the defect that two different medicines, namely the photosensitizer and the lonidamine, have different metabolic pathways in vivo and are difficult to reach the tumor site at the same time is overcome; the invention further provides a preparation method of the near-infrared photosensitizer, raw materials are easy to obtain, reaction conditions are mild, and purification is easier.

The invention provides a synthesis method of a novel estrogen receptor targeting inhibitor and application of the novel estrogen receptor targeting inhibitor in breast cancer treatment, and belongs to the technical field of pharmaceutical chemical application. According to the technical scheme, a series of estrogen receptor targeting inhibitors containing indazole and indole skeletons are synthesized, the inhibitory activity of the inhibitors on breast cancer cells is tested respectively, and a series of compounds with higher cancer cell inhibitory activity than lonidamine are found; wherein the compounds (21) and (23) show the best breast cancer cell inhibition activity, and the IC50 values of the compounds (21) and (23) are 45 mu M and 53 mu M respectively. The synthesis method and applicationhave the beneficial effects that a series of bilonidamine small molecule compounds with higher breast cancer cell inhibitory activity are provided, the compounds (21) and (23) show the strongest biological activity, and molecular docking experimental results prove that the compounds (21) and (23) play a role in inhibiting breast cancer cells through a targeted estrogen receptor.

The invention relates to preparation methods of a 1H-indazol-3-carboxylic acid derivative, granisetron and lonidamine. The 1H-indazol-3-carboxylic acid derivative is a compound with a structure shown in a formula (1) and a formula (2), and is mainly structurally characterized by having a 1H-indazol-3-carboxylic acid amide skeleton and a 1H-indazol-3-carboxylic ester skeleton. The 1H-indazol-3-carboxylic acid derivative can be synthesized by taking simple o-aminophenylacetic acid amide or o-aminophenylacetic acid ester as an initial raw material. The 1H-indazol-3-carboxylic acid derivative is a key intermediate for synthesizing a plurality of medicines, such as granisetron, lonidamine and the like. The synthesis method of the 1H-indazol-3-carboxylic acid derivative and the drug molecules glassetron and lonidamine is simple, the reaction condition is mild, the reaction speed is high, the yield is high, and purification is easy.