- Compound for targeted degradation of BTK protein
-
The invention provides a compound with the capability of degrading Bruton's tyrosine protein kinase (Btk) protein in a targeted manner, and particularly provides a compound as shown in the following formula I0, wherein the definition of each group is described in the specification. The compound provided by the invention can well degrade Btk protein in a targeted manner, so that the compound can be used for treating diseases related to Btk activity or expression quantity, such as tumors.
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- Influence of Linker Attachment Points on the Stability and Neosubstrate Degradation of Cereblon Ligands
-
Proteolysis targeting chimeras (PROTACs) hijacking the cereblon (CRBN) E3 ubiquitin ligase have emerged as a novel paradigm in drug development. Herein we found that linker attachment points of CRBN ligands highly affect their aqueous stability and neosubstrate degradation features. This work provides a blueprint for the assembly of future heterodimeric CRBN-based degraders with tailored properties.
- Bricelj, Ale?a,Dora Ng, Yuen Lam,Ferber, Dominic,Gütschow, Michael,Kr?nke, Jan,Kuchta, Robert,Müller, Sina,Monschke, Marius,Sosi?, Izidor,Steinebach, Christian,Wagner, Karl G.
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p. 1733 - 1738
(2021/11/16)
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- Method for synthesizing lenalidomide
-
The invention belongs to the field of chemical synthesis, and particularly relates to a method for synthesizing lenalidomide. The method adopts three-step polymerization, and specifically comprises: (1) carrying out a bromination reaction on 2-methyl-3-nitromethyl benzoate as a starting raw material and a bromination reagent to generate a compound 1 2-bromomethyl-3-nitromethyl benzoate; (2) performing cyclization on the compound 1 and 3-aminopiperidine-2,6-dione hydrochloride under a solvent-free condition to generate a compound 2 3-(4-nitro-1-oxo-1,3-dihydroisoindole-2-yl)piperidine-2,6-dione; and (3) reducing the compound 2 with a reducing agent to obtain lenalidomide. According to the invention, the method is a novel preparation process method of lenalidomide, and has advantages of easily available process raw materials, short steps, simple and convenient operation, environmental friendliness, implementation value of industrial production, and social and economic benefits.
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-
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- Method for preparing lenalidomide
-
The invention provides a method for preparing lenalidomide. Specifically, the invention provides a method for preparing lenalidomide, which comprises a nitro-reduction step. The nitro-reduction step comprises the following steps: in a first solvent, under acidic conditions, in the presence of a reducing agent and a catalyst, a nitro-reduction reaction is carried out on a compound shown as a formula II to obtain a compound shown as a formula I; wherein the catalyst is palladium on carbon; the reducing agent is hypophosphorous acid or hypophosphite. The process is high in reaction yield, low inproduction cost and environment-friendly, and has great implementation value and social and economic benefits.
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Paragraph 0085-0090
(2020/06/09)
-
- Anhydrous preparation method of lenalidomide
-
The invention relates to an anhydrous preparation method of lenalidomide. The invention discloses a novel method for preparing a 3-(4-amino-1-oxo-1,3-dihydro-2H-isoindole-2-yl) piperidine-2,6-diketoneanhydrous compound, and belongs to the technical field of chemical synthesis. The process route is short in steps, simple and convenient to operate and mild in reaction conditions, and the finally obtained product is excellent in quality and easy for industrial production.
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Paragraph 0045-0063
(2020/07/24)
-
- Preparation method of lenalidomide B crystal form
-
The invention provides a preparation method of a lenalidomide B crystal form. Specifically the method comprises the following steps: (1) dissolving a raw material lenalidomide in alcohol to obtain a solution containing lenalidomide; and (2) adding water into the lenalidomide-containing solution obtained in the step (1), and crystallizing to obtain a lenalidomide B crystal form, wherein the alcoholis selected from 1,3-propylene glycol, 1,2-propylene glycol, and a combination of 1,3-propylene glycol and 1,2-propylene glycol. The method has high stability and high reliability.
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Paragraph 0119-0120
(2020/06/17)
-
- Preparation method of lenadomide
-
The invention discloses a preparation method of lenalidomide, and belongs to the field of organic synthesis. 2-methyl-3-methyl nitrobenzoate and 3-N-benzyloxy-carbonyl-L-glutamine serve as starting materials, and an important intermediate 2-brooethyl-3-methyl nitrobenzoate is obtained through a bromination reaction of 2-methyl-3-methyl nitrobenzoate. 3-N-benzyloxy-carbonyl-L-glutamine is cyclizedunder catalysis to produce 3-N-benzyloxy-carbonyl-2,6-dioxopiperidine, an amino group is subjected to deprotection to produce 3-amino-2,6-piperidone halide, 3-(4-nitro-1-oxo-1,3-o-xylylenimine-2-yl)piperidine-2,6-diketone is obtained through an aminolysis reaction of 3-N-benzyloxy-carbonyl-2,6-dioxopiperidine and 2-brooethyl-3-methyl nitrobenzoate, and then lenalidomide is prepared through reduction. The method has the advantages that the cost of raw materials are low, aftertreatment is simple, and the yield is high, and the production cost of the lenalidomide as a bulk drug is greatly reduced. The method is a convenient and efficient lenalidomide synthesis method suitable for industrial production.
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-
-
- PYRIDAZINE DERIVATIVES AS SMARCA2/4 DEGRADERS
-
The present invention provides pyridazine derivatives of formula (I), which are therapeutically useful as SMARCA2/4 degraders. These compounds are useful in the treatment and/or prevention of diseases or disorders dependent upon SMARCA2/4 in a mammal. The present invention also provides preparation of the compounds and pharmaceutical compositions comprising at least one of the pyridazine derivatives of formula (I) or a pharmaceutically acceptable salt, or a stereoisomer thereof.
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- Preparation method of lenalidomide
-
The invention provides a preparation method of lenalidomide. The preparation method of the lenalidomide comprises the steps of preparing an intermediate 2-halogen methyl-3 methyl nitrobenzoate and anintermediate 3-amino piperidine-2,6-diketone, and preparing the lenalidomide by using the two intermediates. The preparation method of the lenalidomide is simple in steps, high in yield, low in cost,and beneficial to industrial production.
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- Green production method of low-cost lenalidomide
-
The invention relates to a green production method of low-cost lenalidomide. According to the method, in presence of a solvent and an alkali, 3-aminopiperidine-2,6-dione and 1-halo-acetoacetate are subjected to dehydrogenation halogen acid condensation, dealcoholizing amidation, 2-halo-4-nitrobutanal dehydration and dehydrochlorination or dehydrobromination, 3-(7-nitro-3-oxo-1H-isoindol-2-yl)piperidine-2,6-dione is obtained, the process is completed with a one-pot method, nitro is reduced into amino by catalytic hydrogenation of 3-(7-nitro-3-oxo-1H-isoindol-2-yl)piperidine-2,6-dione, and lenalidomide is prepared. The method has the advantages of cheap and easily available raw materials, short technological process, simple operation and environmental protection and is a production method beneficial to industrialization.
- -
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Paragraph 0063; 0064; 0065; 0066
(2019/03/25)
-
- 3 - (4 - Amino - 1, 3 - dihydro -1 - oxo - 2H - isoindol -2 - yl) piperidine - 2, 6 - dione
-
The present invention relates to 3-(4-amino-1, 3-dihydro-1-oxo-2 H-isoindole-2-yl)-2, 6-piperidinedione preparation method. The method is as follows: in the presence of reducing system, a target product is prepared by reaction of formula (II) compound in an organic solvent. The method provided by the present invention has no need to use hydrogen as a reducing agent, and is safe, low in cost, high in yield, easy in purification and easy in industrialization.
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Paragraph 0021-0029
(2019/03/21)
-
- Preparation method of lenalidomide (by machine translation)
-
The preparation method disclosed by the invention is simple and safe to operate. after the preparation method disclosed by the invention is I simple and safe, to operate after the: preparation method of, the present invention, is operated by a II reduction reaction with a metal in the presence of an organic I; acid in a solvent . 99.90%, 0.10%, 10ppm. (by machine translation)
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Paragraph 0040-0061
(2019/12/25)
-
- Preparation method of lenalidomide
-
The invention discloses a synthesizing method of lenalidomide. The method comprises the steps that the compound shown in the formula 1 is reacted with thionyl chloride and an alcohol solvent to obtainthe compound shown in the formula 2; the compound shown in the formula 2 is reacted with chloroformate to obtain anhydride, the anhydride is reduced to obtain the compound shown in the formula 3; thecompound shown in the formula 3 is reacted with a chloride agent to obtain the compound shown in the formula 4; the compound shown in the formula 4 and the compound shown in the formula 5 are subjected to a condensation reaction, and the compound shown in the formula 6 is obtained; the compound shown in the formula 6 is reduced in the presence of hydrogen to obtain the lenalidomide shown in the formula 7. The initial raw materials used in the method are low in cost and easy to obtain, the synthesizing steps are simple, the operation is simple, the yield is high, the production cost is low, and industrial production is facilitated.
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-
Paragraph 0067; 0068; 0069; 0070; 0071; 0072-0088
(2019/04/26)
-
- CRYSTALLINE FORMS OF LENALIDOMIDE
-
The present invention provides for novel co-crystals of lenalidomide. The present invention particularly provides for novel cocrystals of lenalidomide with Resorcinol, Methyl paraben and Saccharin. The present invention also provides for the processes for the production of cocrystals of lenalidomide with Resorcinol, Methyl paraben and Saccharin. The present invention further provides for processes for the preparation of crystalline anhydrous lenalidomide Form IV.
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Page/Page column 22; 23; 25; 26
(2019/04/26)
-
- Preparation method of substituted dioxopiperidine derivative
-
The invention discloses a preparation method of a substituted dioxopiperidine derivative. The preparation method comprises the following steps that a compound shown in the formula (II) and formamide react in the presence of C1-C4 alkanol alkali metal salt or alkaline earth metal salt, and a compound shown in the formula (I) is obtained; substituent groups in the compound shown in the formula (I) and the compound shown in the formula (II) are defined in the description. The product obtained through method is high in yield and purity, and the method is easy and convenient to operate. The formulas are shown in the description.
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Paragraph 0122-0128
(2019/04/30)
-
- A method for the preparation of amine to that (by machine translation)
-
The invention discloses a method for the preparation of amine to that, the specific step includes: to 2 - methyl - 3 - nitro benzoic acid as the raw material, to obtain 2 - bromomethyl - 3 - nitro-benzoic acid methyl ester; L - glutamic acid as the raw material to make the N - CBZ - L - glutamic acid; to N - CBZ - L - glutamic acid as the raw material to make the 3 - amino - 2, 6 - piperidine dione hydrochloride; to 2 - methyl - 3 - nitro-benzoic acid methyl ester with 3 - amino - 2, 6 - piperidine dione hydrochloride as the raw material to make the 3 - (4 - nitro - 1, 3 dihydro - 1 - oxo - 2 hydrogen - isoindol - 2 - yl) piperidine - 2, 6 - dione; to 3 - (4 - nitro - 1, 3 dihydro - 1 - oxo - 2 hydrogen - isoindol - 2 - yl) piperidine - 2, 6 - dione as raw materials to that amine. The method of the invention has simple technological process, raw material economic, few by-products, and purification is simple, high yield, environment-friendly and the like, after treatment is simple, has better practicability and application value, has great industrial prospects. (by machine translation)
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- MODULATORS OF ESTROGEN RECEPTOR PROTEOLYSIS AND ASSOCIATED METHODS OF USE
-
The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a cereblon, Von Hippel-Lindau ligase-binding moiety, Inhibitors of Apotosis Proteins, or mouse double-minute homolog 2 ligand, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
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-
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- AN IMPROVED PROCESS FOR SYNTHESIS OF LENALIDOMIDE
-
Disclosed herein is an improved process for preparation of Lenalidomide and crystalline polymorphic forms thereof.
- -
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-
- Antitumor regulator lenalidomide preparation method and antitumor regulator lenalidomide crystal form preparation method
-
The invention discloses an antitumor regulator lenalidomide preparation method and an antitumor regulator lenalidomide crystal form preparation method. According to the present invention, an antitumorregulator lenalidomide 3-(4-amino-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione (V) is prepared, and then antitumor regulator lenalidomide crystal form is prepared by using 3-(4-amino-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione (V); and the prepared antitumor regulator lenalidomide crystal form has high stability, such that the bioavailability can be improved, the applications in pharmaceutical processing and pharmaceutical combinations are easily achieved, and the method is suitable for large-scale production.
- -
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Paragraph 0025; 0026
(2018/11/22)
-
- Design, synthesis and biological evaluation of Lenalidomide derivatives as tumor angiogenesis inhibitor
-
Lenalidomide is a type of immunomodulatory agent with anti-tumor activity by mainly expressed in the anti-angiogenesis. In order to enhance the pharmacological activity of Lenalidomide, a series of Lenalidomide derivatives were designed as tumor angiogenesis inhibitors. The potential anti-angiogenesis targets of Lenalidomide derivatives were virtual screened on Auto-Dock 4.0 by using reverse docking method. The six target proteins, such as vascular endothelial growth factor receptor, epidermal growth factor receptor, fibroblast growth factor receptor, BCR-ABL tyrosine kinase, p38 mitogen activated protein kinase and metal protein kinase, were chosen as the targets. The Lenalidomide derivatives were synthesized by alkylated, acylated or sulfonylated Lenalidomide and verified by the 1H NMR, 13C NMR and LC–MS. Their anti-cancer activities were detected by using CCK-8 in the esophageal carcinoma cell line EC9706. The results indicate that the inhibitory activities of Lenalidomide derivatives were higher than that of Lenalidomide.
- Hu, Shengquan,Yuan, Libin,Yan, Hong,Li, Zhigang
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p. 4075 - 4081
(2017/08/23)
-
- Preparation method of lenalidomide for treating multiple myeloma
-
The invention relates to a drug synthesis technology and discloses a preparation method of lenalidomide for treating multiple myeloma. The preparation method comprises the following steps: firstly, carrying out hybrid reaction on 2-methyl-3-methyl 3-nitrobenzoate and 3-amino-2,6-dioxopiperidine in an organic solvent in the presence of tetramethylethylenediamine and zinc bromide, so as to obtain 3-(7-nitro-3-oxo-1H-isoindol-1-yl) piperidine-2,6-dione; secondly, carrying out catalytic hydrogenation reduction on 3-(7-nitro-3-oxo-1H-isoindol-1-yl) piperidine-2,6-dione, so as to obtain the lenalidomide. The preparation method of the lenalidomide, disclosed by the invention, has the advantages of mild conditions, simple reaction steps and environment friendliness, so that the preparation method is more suitable for industrial production.
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Paragraph 0025; 0030; 0033-0034; 0037-0038; 0041-0042; 0045
(2017/12/06)
-
- Method for synthesizing lenalidomide
-
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.
- -
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Paragraph 0058-0059
(2017/09/01)
-
- Preparation method of lenalidomide
-
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.
- -
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Paragraph 0014
(2017/08/31)
-
- BROMODOMAIN TARGETING DEGRONIMERS FOR TARGET PROTEIN DEGRADATION
-
This invention provides a Degronimer that has an E3 Ubiquitin Ligase targeting moiety (Degron) that can be linked to a Targeting Ligand for a bromodomain protein selected for in vivo degradation to achieve a therapeutic effect, and methods of use and compositions thereof as well as methods for their preparation.
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Page/Page column 251
(2017/12/05)
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- CRYSTALLINE LENALIDOMIDE PROCESS
-
The present invention relates to process for the preparation of highly pure Lenalidomide (I). The invention also relates to crystalline Form-SL obtained by the process of the present invention., the said Form-SL being substantially pure and characterized by X-ray powder diffraction pattern comprising of at least seven peaks selected from 7.061, 12.860, 16.531, 18.698, 27.925, 33.212, 34.187, 35.253, 35.921 and 38.765±0.1°2θ; a single un-split °2θ peak at 7.813±-.1°2θ; and a three-way split °2θ peak at 20.467±0.1°2θ. The invention further relates to pharmaceutical compositions comprising crystalline Form-SL of Lenalidomide, which may be useful for the treatment of cancer.
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Page/Page column 0086; 0089-0091; 0096
(2017/08/01)
-
- Preparation technology of lenalidomide for treating multiple myeloma
-
The invention discloses a preparation technology of lenalidomide for treating multiple myeloma. The preparation technology comprises the following steps: firstly, adding amino-protected 2-methyl-3-methyl anthranilate shown as a formula I, 3-amino-2,6-dioxopiperidine, tetramethylethylenediamine and zinc bromide into a reactor containing an organic solvent, and then carrying out hybrid reaction to obtain amino-protected 3-(7-amino-3-oxo-1H-isoindol-1-yl) piperidine-2,6-dione shown as a formula II; secondly, carrying out deprotection on the amino-protected 3-(7-amino-3-oxo-1H-isoindol-1-yl) piperidine-2,6-dione shown as the formula II and obtained in the first step, so as to obtain the lenalidomide (the formula is shown in the description). The preparation technology of the lenalidomide, disclosed by the invention, has the advantages of few steps, higher simplicity, mild conditions and no use of halogenating agents polluting the environment; in addition, a target product is high in yield; the preparation method is environment-friendly, and is more suitable for industrial production.
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- METHODS FOR THE TREATMENT OF NON-HODGKIN'S LYMPHOMAS USING LENALIDOMIDE, AND GENE AND PROTEIN BIOMARKERS AS A PREDICTOR
-
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.
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-
-
- Preparation method of lenalidomide
-
A preparation method of lenalidomide comprises the following steps: 1, reacting a raw material methyl 2-methyl-3-nitro-benzoate with a halogenating reagent to obtain methyl 2-halomethyl-3-nitro-benzoate represented by formula (I); 2, reacting the methyl 2-halomethyl-3-nitro-benzoate with dimethyl D,L-glutamate hydrochloride in the presence of an alkaline compound to obtain dimethyl 3-(7-nitro-1-oxo-1,3-dihydroisoindole-2-yl)glutarate represented by formula (II); 3, hydrolyzing the above compound of formula (II) to obtain 3-(7-nitro-1-oxo-1,3-dihydroisoindole-2-yl)glutaric acid represented by formula (III); 4, reducing the above compound of formula (III) to obtain 3-(7-amino-1-oxo-1,3-dihydroisoindole-2-yl)glutaric acid represented by formula (IV); and 5, carrying out ring closure on the above compound of formula (IV) to obtain lenalidomide represented by formula (V). The method has the advantages of simple process, high safety, cheap and easily available raw materials, good quality of the above product, and suitableness for industrial production.
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- Methods for the treatment of cancer and inflammatory diseases using cereblon as a predictor
-
Uses of the protein cereblon as a predictor of clinical sensitivity to cancer, inflammatory diseases, and patient response to drug treatment.
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- Lenalidomide and lenalidomide intermediate preparation method
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A lenalidomide and lenalidomide intermediate preparation method includes the following four steps: (1) intramolecular ring-closure of N-Boc-glutamine methyl ester (I) in the presence of a condensing agent and a catalyst to obtain 3-Boc-imino-piperidine-2,6-dione (II); (2) deprotection reaction of the compound (II) obtained by the step (1) to obtain 3-(N-Boc-imino) - piperidine-2,6-dione (III); (3) condensation reaction of the compound (III) obtained by the step (2) and 2-bromomethyl-3-nitrobenzoate (IV) to obtain 3-( 7-nitro-3-oxo-1H-isoindole-2-yl)-piperidine-2,6-dione (V); and (4) nitro group reduction reaction of the compound (V) obtained by the step (3) to obtain lenalidomide (VI); and a synthetic route is shown in the specification.
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Paragraph 0023; 0033; 0034; 0035; 0036
(2016/10/31)
-
- PROCESS FOR MAKING CRYSTALLINE FORM A OF LENALIDOMIDE
-
The present invention relates to a process for making crystalline lenalidomide form A of formula (1), characterized by a XRPD powder diffraction pattern comprising the peaks at about 7.89, 4.35, 14.83, 15.81, 16.23, 20.12, 23.78, 24.09, 25.96 degrees 2 theta, when measured with CuKα1 radiation (λ = 1.54060 ?), the process comprising: 1. Reduction of 3-(4-nitro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)-2,6-piperidinedione of formula (2) with a reducing agent in a mixed solvent comprising a mixture of C1-C3 aliphatic alcohol and N,N-dimethylformamide or N,N-dimethylacetamide, wherein the content of N,N-dimethylformamide or N,N-dimethylacetamide in the mixed solvent is between 20-40% (v/v), 2. Isolation of lenalidomide form.
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Page/Page column 8
(2016/03/13)
-
- Preparation method for medicinal lenalidomide semihydrate crystal
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The invention relates to a recrystallization method for preparing a medicinal lenalidomide semihydrate crystal from a lenalidomide crude product. A mixed solvent and water are adopted for carrying out recrystallization, and a semihydrate crystallized product for meeting the preparation requirement can be well obtained by controlling the rate of temperature fall and the amount of water; and the mixed solvent system is the mixed solvent of two or more compounds including methyl alcohol, 1,4-dioxane, N,N-dimethyl formamide, acetonitrile, ethyl alcohol, n-methyl pyrrolidone, isopropanol, acetone, diethyl ether, dichloromethane and the like.
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Paragraph 0054
(2016/10/09)
-
- Scalable and green process for the synthesis of anticancer drug lenalidomide
-
A new process for the synthesis of anticancer drug lenalidomide was developed, using platinum group metal-free and efficient reduction of nitro group with the iron powder and ammonium chloride. It was found that the bromination of the key raw material, methyl 2-methyl-3-nitrobenzoate, could be carried out in chlorine-free solvent methyl acetate without forming significant amounts of hazardous by-products. We also have compared the known synthetic methods for cyclization of methyl 2-(bromomethyl)-3-nitrobenzoate and 3-aminopiperidinedione to form lenalidomide nitro precursor.
- Ponomaryov, Yuri,Krasikova, Valeria,Lebedev, Anton,Chernyak, Dmitri,Varacheva, Larisa,Chernobroviy, Alexandr
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p. 133 - 138
(2016/01/15)
-
- A PROCESS FOR THE PREPARATION OF LENALIDOMIDE
-
Improvements in the preparation process of 3-(4-amino-1-oxo-1,3-dihydro-2H- isoindol-2-yl)piperidine-2,6-dione (Ienalidomide), wherein the intermediate 2-methyl- 3-nitrobenzoic acid methyl ester is brominatcd with N-bromosuccinimide in methyl acetate and the end product is obtained from 3-(4-nitro-l-oxo-l,3-dihydro- 2H-isoindol-2-yl)piperidine-2,6-dione by reducing with iron and ammonium chloride reducing system.
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Paragraph 0018
(2015/05/05)
-
- METHODS FOR THE TREATMENT OF LOCALLY ADVANCED BREAST CANCER
-
Provided herein are methods of treating, preventing and/or managing locally advanced breast cancer, including inflammatory breast cancer, which comprise administering to a patient one or more immunomodulatory compounds or enantiomers or mixtures of enantiomers thereof, or pharmaceutically acceptable salts, solvates, hydrates, co-crystals, clathrates, or polymorphs thereof.
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- Improving the solubility of lenalidomide via cocrystals
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An anticancer drug, lenalidomide, has low oral bioavailability (below 33%) due to its poor solubility in water. To improve its solubility, three cocrystals of lenalidomide with urea (1) and 3,5-dihydroxybenzoic acid (2, 3) were prepared. The structures of
- Song, Jia-Xi,Yan, Yan,Yao, Jia,Chen, Jia-Mei,Lu, Tong-Bu
-
p. 3069 - 3077
(2014/06/23)
-
- PROCESS FOR LENALIDOMIDE
-
The present invention provides an improved process for the preparation of 3-(benzyloxycarbonylamino)piperidine-2,6-dione. The present invention also provides an improved process for the preparation of 3-(4-nitro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione. The present invention further provides a process for the preparation of lenalidomide crystalline Form H1.
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- PROCESS
-
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.
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Page/Page column 8
(2012/04/04)
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- ACID ADDITION SALTS OF LENALIDOMIDE
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The invention relates to acid addition salts of lenalidomide as well as to desirable polymorphic forms of lenalidomide hydrogen sulfate. Furthermore, the invention provides a process for producing acid addition salts of lenalidomide, which optionally can comprise a further step producing lenalidomide in form of the free base.
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-
- METHODS FOR THE TREATMENT OF NON-HODGKIN'S LYMPHOMAS USING LENALIDOMIDE, AND GENE AND PROTEIN BIOMARKERS AS A PREDICTOR
-
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.
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- ANHYDROUS LENALIDOMIDE FORM-I
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Anhydrous polymorphic form-I of anti cancer drug, Lenalidomide whose chemical name is 3-(4-amino-1-oxo-1, 3-dihydro-isoindole-2-yl)-piperidine-2, 6-dione, is disclosed. Alternate methods for making anhydrous polymorphic form-I of Lenalidomide are also disclosed.
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- PROCESS FOR THE PREPARATION OF LENALIDOMIDE
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The present invention relates to a process for the preparation of lenalidomide, wherein the process comprises: reducing 3- (4 -nitro- loxo-1, 3-dihydro- 2H-isoindol - 2 -yl) piperidine- 2, 6-dione to obtain lenalidomide.
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Page/Page column 12
(2011/04/14)
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- PROCESS FOR THE PREPARATION OF A CRYSTALLINE FORM OF LENALIDOMID
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The present invention relates to an in-situ process for the preparation of polymorphic Form A of lenalidomide.
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Page/Page column 4
(2011/04/19)
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- PROCESS FOR THE PREPARATION OF FORM B OF LENALIDOMIDE
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The present invention relates to process for preparation of polymorphic Form B of lenalidomide.
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Page/Page column 4
(2011/06/19)
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- CRYSTALLINE FORM OF LENALIDOMIDE AND A PROCESS FOR ITS PREPARATION
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The present invention relates to a novel crystalline form of lenalidomide having formula (I) and chemically known as 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione. The present invention further relates to a process for the preparation of said novel form and its use in pharmaceutical preparations for the treatment of autoimmune disease, inflammation, inflammatory disease and diseases such as cancer, in particular the management of multiple myeloma.
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Page/Page column 6
(2011/11/06)
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- LENALIDOMIDE SOLVATES AND PROCESSES
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The present application relates to lenalidomide salts and solvates, and processes for the preparation thereof.
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Page/Page column 7-8
(2011/10/12)
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- Methods and Compositions Using Immunomodulatory Compounds for the Treatment and Management of Spirochete and Other Obligate Intracellular Bacterial Diseases
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Methods of treating, preventing and/or managing a spirochete and/or other obligate intracellular bacterial disease or disorder are disclosed. Specific methods encompass the administration of an immunomodulatory compound alone or in combination with a second active agent.
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- METHODS FOR SYNTHESIZING 3-(SUBSTITUTED DIHYDROISOINDOLINONE-2-YL)-2,6-DIOXOPIPERIDINE, AND INTERMEDIATES THEREOF
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The present invention discloses methods for synthesizing 3-(substituted dihydroisoindolinone-2-yl)-2,6-dioxopiperidine and intermediates thereof, namely, the synthesis of compounds of the Formula (I), with each substitutional group defined in the patent specification. Owing to the advantages of high productivity, little influence to the environment and material accessibility, the methods of the present invention is suitable for industrial production.
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Page/Page column 56-57
(2010/12/29)
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- IMPROVED PROCESS
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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.
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Page/Page column 23-24
(2010/09/18)
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- LENALIDOMIDE SOLVATES AND PROCESSES
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The present application relates to lenalidomide salts and solvates, and processes for the preparation thereof.
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Page/Page column 19
(2010/06/15)
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