82 results about "Pomalidomide" patented technology

The invention relates to ALK-targeted PROTAC and application thereof, and belongs to the technical field of anti-tumor drugs. The invention aims to provide an ALK-targeted PROTAC molecule. The PROTACmolecule has the structural formula which is shown in a formula I. A ligand pomalidomide of CRBN and a derivative of pomalidomide are adopted as a ligand of an E3 ligase, and coupling of an ALK inhibitor LDK378 with the E3 ligase is achieved through linkers of different types and different chain lengths so as to prepare the ALK-targeted PROTAC molecule successfully; through the ALK-targeted PROTACmolecule, target proteins can be targeted effectively, the content of ALK in cells is reduced, and meanwhile, the ALK-targeted PROTAC is characteristics of good anti-tumor activity in vitro and in vivo, low toxicity to normal cells and high efficiency and low toxicity.

The invention relates to the field of pharmaceutical chemistry, and discloses a novel pomalidomide crystal and a preparation method thereof. The novel pomalidomide crystal disclosed by the invention has the advantages of good crystal stability, high bioavailability, excellent property in the aspects of oral absorption and enhancement of immune response mediated by a T cell and a natural killer cell, weak toxicity and good storage and treatment stability and can be used for preparing pharmaceutical for treating multiple myeloma.

The invention relates to the technical field of medicines, and specifically relates to pomalidomide nanoparticle and preparation and a preparation method thereof. The pomalidomide nanoparticle comprises the following components in parts by weight: 0.5 to 1.5 parts of pomalidomide, and 10 to 100 parts of nano-carrier, wherein the nano-carrier comprises one or more of lecithin, povidone, polyalkylcyano-acrylate, acrylamide, N, N-methylene diacrylic acid amine, polysorbate, sorbitan monolaurate, lauryl alcohol polyoxyethylene, sodium dodecyl sulfate, poloxamer, polyethylene glycol, cyclodextrin and cyclodextrin derivates. The particle size of omalidomide nanoparticle is at nanometer level; on that basis, the prepared pomalidomide preparation is high in dissolution rate.

The invention relates to a method for preparing compound N-(3-nitro-ortho-formyl)-DL-glutamine in a formula (I). The compound is a key intermediate for preparing an antitumor drug pomalidomide.

Methods of treating, preventing and / or managing multiple myeloma are disclosed. Specific methods encompass the administration of an immunomodulatory compound, e.g., lenalidomide or pomalidomide with an anti-CS1 antibody, e.g., elotuzumab in patients who have received autologous stem cell transplantation.

The invention discloses a method for preparing pomalidomide [3-amino-N-(2,6-dioxo-3-piperidyl)-phthalimide], which comprises steps of condensation reaction, catalytic hydrogenation, refining, and the like. The process route is novel, short in steps, high in reaction yield, good in product purity, and has great implementation value and social economic benefits.

The invention belongs to the field of medicines, and particularly relates to a medicine composition and application thereof in preparation of medicines for treating brain glioma. The medicine composition is prepared from the following medicinal active ingredients: elemene and pomalidomide in an optimal proportion of (0.003-100):1, and a further optimal proportion of (0.01-50):1. Massive pharmacological experiments prove that elemene and pomalidomide have remarkable synthetic effects in the field of brain glioma treatment, and can be used for remarkably reducing the tumor size and weight and prolonging the surviving period. The medicine composition has the advantages of exact curative effect and small toxic and side effects when being used for treating brain glioma, and has good medical application prospects.

The present invention relates to clinically proven subcutaneous pharmaceutical compositions comprising anti-CD38 antibodies and methods of their uses in combination with pomalidomide and dexamethasone.

The invention relates to a method for preparing pomalidomide (compound I) by a one-pot process. The method comprises the following steps: reacting a raw material 3-nitrophthalic acid disclosed as Formula (II) with acetic anhydride in an acidic solvent to prepare 3-nitrophthalic anhydride disclosed as Formula (III), carrying out condensation reaction with 3-aminopiperidyl-2,6-dione hydrochloride disclosed as Formula (IV) under the action of an alkali, and finally, reducing with iron powder, thereby preparing the pomalidomide (compound I) by the one-pot process. The method has the advantages of high efficiency, high yield, low cost, high safety and environmental protection.

The invention relates to the field of medicine preparation, and particularly relates to a preparation method of pomalyst pomalidomide. The method comprises the following steps: carrying out intramolecular cyclization on N-carbobenzoxy-L-glutamine, so as to generate S-(-)-(2-formamido-phenoxy) glutarimide shown in a formula II; removing carbobenzoxy (CBZ) from the S-(-)-(2-formamido-phenoxy) glutarimide, and then carrying out a salt forming reaction on acid, so as to obtain a salt of S-(-)-2-amino glutaric imide shown in a formula III; carrying out an intermolecular condensation reaction on the salt of the S-(-)-2-amino glutaric imide and 3-nitrophthalicanhydride, so as to obtain 4-nitryl-thalidomide shown in a formula IV; and taking the 4-nitryl-thalidomide to prepare the pomalyst pomalidomide by reduction reaction. The preparation method of the pomalyst pomalidomide, which is provided by the invention, is short in cycle, high in product purity, high in yield, free of pressurized reaction, and more applicable to industrial production, and any individual impurity can be smaller than 0.1% in absence of purification.

The invention relates to a pomalidomide crystal form and a preparation method thereof. Specifically, the invention discloses a pomalidomide anhydrous crystal form and a preparation method thereof. The pomalidomide anhydrous crystal form of the invention has the advantages of good thermal stability, good light stability, strong antioxidant capacity and storage stability, and is suitable for application to pharmaceutical preparation.

The invention discloses a method for synthesizing pomalidomide. The method is a three-step synthetic method comprising the steps of step 1, performing condensation on 3-nitrophthalic acid under certain conditions to obtain 3-nitrophthalicanhydride; step 2, preparing 3-nitro-N-(2,6-dioxo-3-piperidyl)-phthalimide by virtue of 3-nitrophthalicanhydride and L-glutamine; step 3, performing reduction on 3-nitro-N-(2,6-dioxo-3-piperidyl)-phthalimide to obtain pomalidomide. The method disclosed by the invention is stable in process, simple in operation, high in yield and high in purity, and does not need harsh reaction conditions such as vacuum and the like; the required pressure and temperature are in conventional ranges; adopted reagents are low in toxicity and pollution, and a key intermediate namely 3-nitro-N-(2,6-dioxo-3-piperidyl)-phthalimide is prepared from 3-nitrophthalicanhydride and L-glutamine by virtue of a one-pot method; the method is used for economic and large-scale preparation of pomalidomide.

The invention discloses a method for preparing high-purity pomalidomide. The method comprises the following steps: by taking 3-nitrophthalicanhydride and 3-aminopiperidine-2,6-diketone hydrochloride as raw materials, methylbenzene as a solvent, triethylamine as an acid attaching agent and N,N'-carbonyldimidazole as a condensing agent, carrying out a condensation reaction, thereby obtaining 3-nitro-N-(2,6-dioxo-3-piperidyl)-phthalimide; carrying out a hydrogenation reaction under catalysis of a palladium carbon catalyst, and recrystallizing to obtain the high-purity pomalidomide. The total yield is 62%, and the materials used in the reaction are low in price, simple and easily available; the second-step catalytic hydrogenation is performed under normal pressure, simple operations such as pulping, distilling and performing suction filtration are only used in the two-step reaction, and the operations are conventional production operations; intense heat release phenomena in the reaction process and after-treatment process are avoided, the operation is simple, and the safety is high; a mother solution obtained by after-treatment in the first-step reaction can be directly recycled, the amount of three wastes generated after after-treatment is small, and the operation is suitable for industrial production.

The invention relates to a pharmaceutical composition for treating post-malignant tumor-chemotherapeutic osteoporosis and use thereof and belongs to the field of medicines. In order to overcome the technical defect that the medicine for treating post-malignant tumor-chemotherapeutic osteoporosis in the prior art is poor to control symptoms, the invention provides a pharmaceutical composition containing alendronic acid and pomalidomide. The pharmaceutical composition used for treating post-malignant tumor-chemotherapeutic osteoporosis is good to control symptoms and has a remarkable effect in increasing bone mineral density and bone weight coefficient as well as increasing content of serum inorganic phosphorus and blood calcium, so that the pharmaceutical composition is suitable for clinically treating tumor chemotherapy induced osteoporosis.

The invention discloses a method for purifying pomalidomide. The method comprises the following steps: mixing a pomalidomide crude product with high-performance liquid phase purity of 80-90% with a mixed solvent, and crystallizing, wherein the mixed solvent is a mixed solvent of an organic solvent and water; the organic solvent is an amide solvent or a ketone solvent; when the organic solvent is the amide solvent, the volume ratio of the amide solvent to water is 4:1 to 8:1; and when the organic solvent is the ketone solvent, the volume ratio of the ketone solvent to water is 3:1 to 1:3. The purification method disclosed by the invention is simple and convenient to operate, high in yield, high in purity and suitable for the requirements of industrial production regulated by good manufacturing practice.

The invention relates to a preparation method of pomalidomide. The preparation method includes a process of using 3-aminopiperidine-2, 6-dione hydrochloride (which is a compound shown in the formula I) and disodium 3-amino phthalate (which is a compound shown in the formula II) as raw materials. The method is simple and short in route, simple to operate, available in raw materials, reduced in production cost, and suitable for massive industrial production.

The present invention provides compounds represented by formula 1, or pharmaceutically acceptable salts thereof, and also provides a preparation method and a use thereof. Immunosuppressive agents suchas pomalidomide or lenalidomide, and a Menin-MLL1 protein-protein interaction inhibitor are combined by a suitable linker, so the obtained compounds have a certain Menin-MLL1 protein-protein interaction inhibition activity and a good cell proliferation inhibition activity.

A preparation method of pomalidomide represented by formula (VII) comprises the following steps: 1, reacting 3-nitrophthalic anhydride represented by formula (I) with D,L-isoglutamine represented by formula (II) or dimethyl D,L-glutamate represented by formula (III) in the presence of an alkaline reagent to obtain a corresponding compound of formula (IV) or formula (V); 2, carrying out ring closure on the compound of formula (IV) or formula (V) to obtain a compound of formula (VI); and 3, carrying out nitro group reduction on the compound of formula (VI) to obtain pomalidomide represented by formula (VII). The method has the advantages of novel technological route, reasonable technological conditions, short reaction steps, simple operation, low production cost, high reaction yield, good product quality, low three wastes, and large enforcement values and social and economic effects.

A combination of filanesib and pomalidomide for treating patients is provided.

The invention discloses a preparation method of pomalidomide. The preparation method of pomalidomide comprises the following step; in N,N-dimethylacetamide or a mixed solvent of N,N-dimethylacetamide and other solvents, carrying out reduction reaction shown in the formula (described in the specification) on hydrogen and a compound shown in a formula II in the presence of palladium on activated carbon, wherein other solvents can be alcohol solvents, ketone solvents or water. The preparation method of pomalidomide has the advantages of high yield, low solvent consumption and high purity and is also applicable to industrial large-scale production. The formula II is described in the specification.

The invention relates to a pomalidomide derivative. The chemical structure of the pomalidomide derivative is shown as the following formula (I), in the formula (I), R1 is phenyl or 1, 4-benzodioxane,R2 is chlorine or bromine, R3 is hydrogen or a 3-methylbenzonitrile group, and X is a linking group selected from ethylenediamine, propane diamine, butanediamine, pentanediamine, hexamethylenediamine,piperazine succinic acid, piperazine glutaric acid, piperazine diglycolic acid, ethylenediamine succinic acid, ethylenediamine glutaric acid, ethylenediamine diglycolic acid, propane diamine glutaricacid, butanediamine glutaric acid or pentanediamine malonic acid. The pomalidomide derivative disclosed by the invention can inhibit the mutual combination of a programmed cell death receptor 1 / a programmed cell death ligand 1 (PD-1 / PD-L1), can be used for preparing a PD-1 / PD-L1 inhibitor, and has a remarkable effect.

The invention discloses a pomalidomide compound which consists of pomalidomide, cyclodextrin and a modified substance thereof, a dispersant and a binder. The dosage of the cyclodextrin and the modified substance thereof is 2-8 times (w / w) of the pomalidomide, the dosage of the dispersant is 10-50 times (w / w) of the pomalidomide and the dosage of the binder is 1-5% of the entire compound. Solid preparations such as capsule prepared from the pomalidomide compound disclosed by the invention can be used for achieving good mixing uniformity within relatively short time; and meanwhile, even under severe conditions, the dissolution rate can be kept at good stability as well.

The invention relates to a preparation method of pomalidomide of high purity suitable for industrial production. 3-nitrophthalic anhydride and glutamic acid are reacted in order to obtain an intermediate, a reaction is carried out in the condition with acetic anhydride in order to obtain an intermediate, 3-nitro-N-(2,6-dioxo-3-piperidyl)phthalimide is obtained by an ammonification reaction in the DMSO condition, and palladium on carbon is used for hydrogenation in order to obtain pomalidomide. The process has the characteristics of high yield, simple operation, environmental friendliness, large scale production, and the like; a low toxicity solvent is used in order to solve the problem that products are not qualified due to solvent residues.

Provided herein are methods of treating, preventing, or managing one or more symptoms of a disease (e.g., cancer) in a subject with renal impairment, comprising administering to the subject pomalidomide. Also provided herein are methods of treating, preventing, or managing one or more symptoms of a disease (e.g., cancer) in a subject with renal impairment, comprising administering to the subject a therapeutically effective amount of pomalidomide and dexamethasone.

The invention provides an erlotinib-based targeted degradation EGFR (epidermal growth factor receptor) protein small molecule compound as well as a preparation method and application thereof. The compound (I) or pharmaceutically acceptable salt or hydrate thereof and a pharmaceutical composition containing the compound can be applied to preparation of medicines for preventing or / and treating cancers. Pomalidomide is selected as a part, combined with E3 ligase, in PROTACs, erlotinib is selected as a targeted EGFR small-molecule compound, the two parts are connected by a proper connecting chain to construct the PROTACs, and in-vitro antitumor activity test and in-vitro EGFR protein degradation activity show that the compound disclosed by the invention shows good antitumor activity, and can be used for preparing the targeted EGFR small-molecule compound. The small molecule compound shows an excellent EGFR protein degradation effect, can be used for preventing or / and treating various cancers, and has a huge application prospect in the field of medicines.

The invention discloses a preparation method of a midbody for preparing anti-multiple myeloma pomalidomide. The preparation method comprises the following steps: dissolving a compound as shown in a formula III in a solvent, reducing by using hydrogen in the existence of a palladium carbon catalyst, and then collecting a compound as shown in a formula IV from a reaction product, the compound as shown in the formula IV is the midbody, namely 3-amion-[(2,6-dioxo-3-piperidyl) carbamoyl group] benzoic acid and esters thereof for preparing the pomalidomide. The preparation method has the advantages that reaction steps are few, conditions are mild, the aftertreatment is simple, the yield is high, the preparation method is suitable for large-scale industrial production, and the reaction formula is as shown in descriptions.

The invention discloses a cell culture medium for improving DC cell activity and a culture method, and belongs to the technical field of biomedicine. The culture medium comprises an RPMI 1640 culture medium as well as comprises pomalidomide. According to the method, when the DC cells are cultured in vitro, a proper amount of pomalidomide is added, so that the DC cell activity and maturity in healthy subjects and multiple myeloma patients are remarkably improved, indicating a potential as a DC adjuvant. The cell culture medium of the present invention can be applied to DC-based treatment strategies such as DC vaccine and DC cell therapies.