133 results about "Lenalidomide" patented technology

Methods of treating, preventing or managing leukemias are disclosed. The methods encompass the administration of an immunomodulatory compound of the invention known as Revlimid® or lenalidomide. The invention further relates to methods of treatment using this compound with chemotherapy, radiation therapy, hormonal therapy, biological therapy or immunotherapy. Pharmaceutical compositions and single unit dosage forms suitable for use in the methods of the invention are also disclosed.

Disclosed herein are compositions and kits which comprise anti-CD38 antibodies and lenalidomide compounds. Also disclosed are methods for treating cancers, such as multiple myeloma, in subjects with the compositions and kits.

Methods of treating or managing specific cancers, including non-Hodgkin's lymphoma, by the administration of 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione are disclosed. Methods of using gene and protein biomarkers as a predictor of non-Hodgkin's lymphoma response to treatment with 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione are also disclosed.

The invention relates to the field of pharmaceutical chemistry, and in particular to a lenalidomide derivative (I). G and n are defined in a direction book. Pharmacological tests show that the lenalidomide derivative plays an inhibiting role in vascular endothelial cell proliferation and can be used for clinical treatment of tumors or chronic inflammations.

The present invention relates to improved processes for preparing 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione (I) (lenalidomide) and its intermediate 3-(1-oxo-4-nitro-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione. The present invention further relates to improved processes for preparing lenalidomide crystalline form A, use of said crystalline form A as an active pharmaceutical ingredient or as an intermediate in the preparation of further crystalline or amorphous forms of lenalidomide, compositions comprising lenalidomide crystalline form A and their use in the treatment of disease.

The invention relates to an anticancer slow-release gel injection which contains slow-release microspheres containing an angiogenesis inhibitor, an amphiphilic block polymer, a solvent and a slow-release agent, wherein the composition of the amphiphilic block polymer and the non-organic solvent exhibit the property of temperature-sensitive gelation. After the in vivo injection, the injection turns into a stagnant and biodegradable water-insoluble gel and the gel slowly releases the drug contained therein for a plurality of weeks to a plurality of months. After the intratumoral or peritumoral injection, the anticancer slow-release gel injection can significantly reduce the general drug reactions and is used for treating tumors of different stages. The angiogenesis inhibitor is selected from SU5416, SU6668, bosutinib, sprycel, erlotinib, vandetanib, gefitnib, canertinib, lapatinib, lestaurtinib, masitinib, vatalanib, mubritinib, tandutinib, nilotinib, marimastat, nilotinib, pelitinib, telatinib, sunitinib, sorafenib, zarnestra, sirolimus, imatinfb, lenalidomide and thalidomide.

Processes for the preparation of substantially pure lenalidomide. The application also relates to an enriched, substantially pure, and pure amorphous form of lenalidomide and solid dispersions containing amorphous lenalidomide.

The invention relates to a lenalidomide derivative and a use thereof as a medicine, and in particular relates to a compound shown as a formula (I), a solvate, a hydrate, a stereoisomer or pharmaceutically acceptable salt thereof. The invention further relates to a pharmaceutical composition comprising the compound, and the use of the compound in preparing medicines for preventing or treating malignant tumors, in particular malignant tumors in the blood-lymphatic system. Compared with lenalidomide, the compound provided by the invention has a longer half-life period and can be used for preparing long-acting preparations.

The invention discloses a composite for treating myelodysplastic syndrome. The composite comprises the following components: lenalidomide, a carrier, a solubilizing agent, a disintegrating agent, a lubricating agent, a flow aid and an adhesive, wherein the carrier is a mixture of any one or several of a high-molecular water-soluble polymer, a water-soluble small molecule compound, a hydrophilic auxiliary material and an inorganic carrier; the solubilizing agent is a mixture of one or several of lauryl sodium sulfate, poloxamer, beta. cyclodextrin and a derivative thereof, polysorbate and polyoxyethylene alkyl ether. The invention also provides a preparation method of the composite, and the preparation method comprises the steps of grinding, mixing, dry granulation, total mixing and tabletting or capsule filling. The preparation method disclosed by the invention effectively enhances the water solubility and bioavailability of the lenalidomide; the dry granulation preparation process simplifies the preparation steps, reduces the cost, saves the energy resources, reduces the labor expenditure and realizes the energy conservation and environment protection in production.

The invention discloses a method for preparing lenalidomide. The method comprises the following steps: firstly, etherifying 2-methyl-3-nitrobenzoic acid to obtain 2-methyl-3-nitrobenzoic acid methyl ester, brominating to obtain 2-brooethyl-3-nitrobenzoic acid methyl ester, reacting L-glutamine and tert-butyl dicarbonate to obtain N-Boc glutamic acid, acquiring 3-amino-2,6-piperidine diketone protected by Boc from N-Boc-glutamic acid in the presence of a condensing agent and a catalyst, further reacting with acid to prepare 3-amino-2,6-piperidine diketone hydrochloride, reacting 3-amino-2,6-piperidine diketone with 2-brooethyl-3-nitrobenzoic acid methyl ester so as to obtain 3-(4-nitryl-1,3 dihydro-1-oxo-2 hydrogen-isobenzazole-2-yl) piperidine-2,6-diketone, and finally reducing, thereby obtaining lenalidomide. The method disclosed by the invention is high in product yield.

The invention discloses a method for simultaneously detecting multiple anti-tumor drugs in a blood sample. A pretreated sample to be detected is detected by adopting ultra-high performance liquid chromatography-tandem mass spectrometry (HPLC-MS / MS). The pretreatment process comprises the following steps: adding serum into a mixed solution of methanol and acetonitrile, oscillating and centrifuging,taking out the centrifuged supernatant, drying, dissolving the dried powder into a methanol aqueous solution, and filtering to obtain a sample to be detected. The method can be used for simultaneously detecting 13 kinds of anti-tumor drugs such as methotrexate, 5-fluorouracil, apatinib, busulfan, carboplatin, cyclophosphamide, docetaxel, gemcitabine, imatinib, illinotecan, lenalidomide, oxaliplatin, paclitaxel and the like in blood.

The invention discloses an immunomodulator slow-release preparation and a preparation method thereof. A lenalidomide slow-release tablet is composed of a slow-release layer and an optional quick-release layer, wherein the slow-release layer contains active ingredients of lenalidomide and a slow-release framework material simultaneously; the quick-release layer does not contain the slow-release framework material. The lenalidomide slow-release tablet disclosed by the invention is capable of slowly and uniformly releasing medicines by virtue of the slow-release framework material, so as to reduce the release speed, delay the time to peak, prolong the action time of lenalidomide, and provide a uniform and constant blood concentration. Moreover, The lenalidomide slow-release tablet disclosed by the invention is simple in prescription and excellent in quality stability; the preparation process is simple to operate, free from special treatment and production equipment, low in production cost, and beneficial to batch-enlarged industrial production for the product; the preparation method is high in yield, the granulation and crushing procedures are simple and practicable to operate, the intermediate material is good in stability, flowability, compressibility and content uniformity, and completely meets the requirements of tabletting, and the surface of the prepared tablet is smooth and beautiful.

The invention discloses a method for preparing lenalidomide. The method comprises the step of synthesizing lenalidomide by taking 3-amino-2-methylbenzoic acid as an initial raw material. By utilizing the method for preparing lenalidomide, lenalidomide can be effectively prepared, the method is simple in technology, and high in synthesis efficiency, and the purity of prepared lenalidomide is higher. In addition, the preparation method has the advantages of being easily available for the initial raw material, simple for technological operation and mild in reaction conditions, dispensing with special reaction equipment, and having no difficultly separable compounds in the preparation process and the like, thus being more suitable for producing lenalidomide industrially on a large scale.

The invention provides novel anti-cancer precursor medicaments using NGR(NO2) as a targeting carrier. The novel anti-cancer precursor medicaments are prepared by designing and synthesizing a 5-fluorouracil precursor medicament, a lenalidomide precursor medicament, a cytarabine precursor medicament, an epirubicin precursor medicament and a dasatinib precursor medicament. According to the initial research on the anti-tumor activity of the 5-fluorouracil precursor medicament, the 5-fluorouracil precursor medicament can inhibit the invasion and metastasis of tumor cells and the growth of solid tumors. The 5-fluorouracil precursor medicament is modified in both effectiveness and preparation compared with the 5-fluorouracil serving as a parent medicament and is widely applicable. Concretely, the invention mainly relates to three aspects: (1) design and antiangiogenic effect of a novel tumor-targeted tripeptide NGR(NO2); (2) preparation of anti-cancer precursor medicaments by coupling the tumor-targeted tripeptide NGR(NO2) and 5 anti-cancer medicaments through covalent bonds; and (3) antitumor and antiangiogenic medical use of the novel 5-fluorouracil precursor medicament.

The invention discloses a novel preparation method of lenalidomide. Glutarimide and 4-nitro-isoindolin-1-one are used as raw materials of the lenalidomide. The lenalidomide is prepared by (1) performing bromination in the alpha position of the carbonyl of the glutarimide to obtain 3; (2) condensing 4-nitro-isoindolin-1-one and the 3 to obtain 4; and (3) subjecting the 4 to reduction to obtain 5, namely the lenalidomide. The preparation method has easily available raw materials, short steps, simple operation, high reaction yield and low production cost, and is environmental friendly. The preparation method has large implement value and social and economic benefit.

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

Provided herein are methods for the treatment of multiple myeloma, wherein the methods comprise administration of lenalidomide and administration of a second active agent such as a CDK inhibitor.

The invention relates to a pharmaceutical composition containing lenalidomide, and a preparation method thereof. The pharmaceutical composition is prepared from the lenalidomide, a thinning agent, a disintegrating agent, a lubricating agent and an optional pharmaceutically acceptable carrier. The pharmaceutical composition containing the lenalidomide provided by the invention has favorable stability and drug dissolution rate, the product quality can be controlled, and the preparation method is simple in process, high in operability and suitable for industrialized mass production.

The invention relates to fatty acid lenalidomide derivatives; compositions comprising an effective amount of a fatty acid lenalidomide derivative; and methods for treating or preventing a metabolic disease comprising the administration of an effective amount of a fatty acid lenalidomide derivative.

A method of identifying a subject having chronic lymphocytic leukemia (CLL) who is likely to be responsive to a treatment compound, comprising obtaining a first sample and a second sample from the subject having CLL; administering 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione (Compound A) to the first sample and administering lenalidomide to the second sample; determining the level of a biomarker in the first sample and determining the level of the biomarker in the second sample; and diagnosing the subject as being likely to be responsive to the treatment compound if the level of the biomarker in the first sample is different from the level of the biomarker in the second sample.

The invention relates to the field of drug synthesis, and particularly relates to a preparation method of a lenalidomide intermediate and lenalidomide. The compound is a drug for treating multiple myeloma. The method comprises the steps of adopting 2-bromomethyl-3-nitrobenzoate and 3-amino-2,6-piperidione hydrochloride as reaction substrates and an inorganic base as an acid-binding agent and obtaining a white to almost white key intermediate 3-(4-nitro-1-oxo-1,3-dihydro-2H-isoindole-2-yl) piperidine-2,6-diketone of the lenalidomide through simple post-treatment; and adopting a mixed solvent of an organic solvent and water as a reaction solvent and carrying out catalytic hydrogenation in the presence of palladium on carbon to prepare the lenalidomide (II). The process route is low in production cost, and a product is high in purity and friendly to environment, and has relatively great implement value and social and economical benefits.

The invention provides a method for synthesizing lenalidomide, belongs to the field of anti-tumor and anti-leukemia medicines in organic synthesis, and particularly relates to the method for synthesizing lenalidomide. To solve the problems of low yield, low purity, environmental pollution caused by massive harmful waste, excessive cost for environment-friendly treatment, easily occurred risk of violent explosive, degradation caused by long reacting time at high temperature and low catalyst recycling frequency in a traditional lenalidomide synthesis reaction, the method comprises the following steps: 1, adding a lenalidomide precursor nitro compound into an organic solvent, adding an activated carbon catalyst having a Pd loading capacity of 10 percent, then leading the mixture serving as a material I into a pre-heating module of a microchannel reactor; and 2, respectively pumping preheated material I and a material II hydrogen into a reaction module of the microchannel reactor into a reactor, collecting outflowing reaction liquid, and treating to obtain the lenalidomide. The method is environment-friendly, and has the advantages of high reaction yield, high purity and good economical efficiency.

The present invention relates to improved processes for preparing 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione (I) (lenalidomide) and its intermediate 3-(1-oxo-4-nitro-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione. The present invention further relates to improved processes for preparing lenalidomide crystalline form A, use of said crystalline form A as an active pharmaceutical ingredient or as an intermediate in the preparation of further crystalline or amorphous forms of lenalidomide, compositions comprising lenalidomide crystalline form A and their use in the treatment of disease.

The invention relates to a lenalidomide-based small-molecular compound targeting to EGFR protein degradation, and preparation and application thereof, and provides a compound targeting to ubiquitination induced EGFR protein degradation and shown as a formula (I) which is described in the specification, and a preparation method and application thereof. Based on lenalidomide, chimeric small molecules capable of targeting to EGFR protein degradation are designed; in-vitro anti-tumor activity tests and in-vitro EGFR protein degradation activity show that the compound has good anti-tumor activity and EGFR protein degradation level, can be used for preventing or / and treating various cancers, and has good application prospects in the field of medicine.

The invention discloses a method for refining a crude lenalidomide product. The method comprises the following steps of: (1) adding the crude lenalidomide product to a mixed solution of isopropanol and water; (2) heating, after the crude lenalidomide product is completely dissolved, adding activated carbon and nanometer ceramic powder and carrying out heat preservation for the first time; (3) filtering when the solution is hot, and cooling filtrate till crystals precipitate; and (4) carrying out heat preservation for the second time, carrying out suction filtering after the crystal precipitation is finished, and finally drying. Due to adoption of the technical scheme, the method for refining the crude lenalidomide product has the beneficial effects of low isopropanol toxicity, high safety, simpleness in process, no need of special equipment and environment requirements, suitability for industrial production, high product content and high refining yield; and the purify of the lenalidomide is remarkably improved.

Disclosed herein are methods of treating multiple myeloma using an antibody that specifically binds CD38 in combination with lenalidomide and dexamethasone.

The invention relates to the field of chemical synthesis, and discloses a method for preparing lenalidomide, which comprises the following steps: condensing 3-aminopiperidyl-2,6-diketohydrochloride with 2-halomethyl-3-nitro-methyl benzoate under weakly alkaline conditions, cooling the reaction solution to room temperature, adding into water, stirring, filtering to obtain a filter cake, sequentially washing with water and alcohol reagents, and drying to obtain 3-(7-nitro-3-oxo-1H-isoindazolyl-2-yl)piperidyl-2,6-dione; and carrying out nitro-amino reduction reaction, filtering the reaction solution, concentrating, crystallizing at -20 DEG C to room temperature, filtering, washing the filter cake with alcohol reagents, drying to obtain a lenalidomide crude product, and recrystallizing to obtain the lenalidomide finished product. By adjusting the after-treatment technique, the invention enhances the total yield of lenalidomide, and ensures the high purity; and the whole method has the advantages of mild reaction conditions and no high temperature or high pressure, and can be used for preparing lenalidomide in a simple and efficient way. 2-halomethyl-3-nitro-methyl benzoate.

The present invention relates to a lenalidomide enantiomer supercritical fluid chromatographic separation method, which comprises: dissolving a lenalidomide sample in a lower alcohol, and carrying outchiral analysis separation at a chiral stationary phase by using a supercritical fluid chromatography method, wherein the mobile phase is the mixture of supercritical carbon dioxide and a lower alcohol, the lower alcohol is methanol or ethanol, a volume ratio of the supercritical carbon dioxide to the lower alcohol in the mobile phase is 60-75:40-25, and the chiral stationary phase is one selected from a silica gel surface coated or bonded tris(3,5-dimethylphenylcarbamylated)amylose chiral stationary phase, a silica gel surface bonded 4-chlorophenylcarbamylated-beta-cyclodextrin chiral stationary phase, and a silica gel surface bonded 3,5-dimethylphenylcarbamylated-beta-cyclodextrin chiral stationary phase. According to the present invention, with the supercritical fluid chromatographic separation method, the chiral chromatographic separation of the lenalidomide enantiomer can be well achieved, and under the preferred condition, the resolution of the lenalidomide enantiomer is 5.05.