- One-pot method to construct isoindolinones and its application to the synthesis of DWP205109 and intermediate of Lenalidomide
-
Herein a practical and efficient system for concise synthesis of isoindolinones is described by using substituted methyl 2-(halomethyl)benzoates and substituted amines. Structurally various methyl 2-(halomethyl)benzoates and amines were transformed into isoindolinones 80–99% yield and purity in catalyst-free and solvent-free conditions. The method has a wide substrate scope. The synthetic utility of the one-pot reaction was demonstrated by the concise syntheses of Lenalidomide intermediate and DWP205190.
- Liu, Jinbiao,Lu, Bowei,Lu, Junrui,Wang, Hongbo,Xie, Zhiqiang,Zhong, Kaikai
-
supporting information
(2021/06/07)
-
- 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.
- -
-
Paragraph 0458; 0465-0467
(2021/06/22)
-
- 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.
-
supporting information
p. 1733 - 1738
(2021/11/16)
-
- 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.
- -
-
Paragraph 0024-0025; 0027-0028; 0030-0031
(2020/01/12)
-
- 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.
- -
-
Paragraph 0035-0044
(2020/07/24)
-
- 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.
- -
-
Paragraph 0083; 0084
(2020/06/09)
-
- DIMERIC IMMUNO-MODULATORY COMPOUNDS AGAINST CEREBLON-BASED MECHANISMS
-
Disclosed are small molecules against cereblon to enhance effector T cell function. Methods of making these molecules and methods of using them to treat various disease states are also disclosed.
- -
-
Page/Page column 112
(2020/02/06)
-
- Chemical synthesis method of lenalidomide key intermediate
-
The invention relates to a chemical synthesis method of a lenalidomide key intermediate, i.e., 3-(4-nitro-1-oxo-1,3-dihydro-2H-isoindole-2-yl)piperidine-2,6-dione. The target compound 3-(4-nitro-1-oxo-1,3-dihydro-2H-isoindole-2-yl)piperidine-2,6-dione is prepared by taking a compound 3-nitrophthalic acid as a raw material through cyclization ammoniation, carbonyl reduction, condensation and selective oxidation. The synthesis method has the advantages of few reaction steps, easily available raw materials, mild reaction conditions, low equipment requirements, simple product separation and purification, environmental friendliness, simple operation, good safety, realization of another selection of a lenalidomide synthesis scheme, and good industrial application prospect.
- -
-
-
- 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)
- -
-
Paragraph 0038; 0039
(2019/12/25)
-
- 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.
- -
-
Page/Page column 120
(2019/11/12)
-
- 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.
- -
-
Paragraph 0059; 0060
(2019/03/25)
-
- 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.
- -
-
-
- 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.
- -
-
-
- 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.
- -
-
-
- AN IMPROVED PROCESS FOR SYNTHESIS OF LENALIDOMIDE
-
Disclosed herein is an improved process for preparation of Lenalidomide and crystalline polymorphic forms thereof.
- -
-
Paragraph 0060; 0061; 0062
(2018/12/04)
-
- 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)
- -
-
Paragraph 0045; 0046; 0049; 0059; 0060; 0073; 0074
(2018/07/30)
-
- 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.
- -
-
Paragraph 00392
(2018/08/20)
-
- 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.
- -
-
Paragraph 0025; 0026
(2018/11/22)
-
- 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.
- -
-
Paragraph 0013
(2017/08/31)
-
- Antitumor drug lenalidomide intermediate preparation method
-
The invention discloses an antitumor drug lenalidomide intermediate preparation method. The preparation method comprises the following steps: 1) under existence of cuprous iodide and organic alkali, performing contact reaction between 4-nitro indoline and 3-bromine-2,6-piperidine to obtain 3-(4-nitro-1,3-xylylenimine-2-yl)piperidine-2,6-diketone; 2) performing oxidizing reaction on the 3-(4-nitro-1,3-xylylenimine-2-yl)piperidine-2,6-diketone obtained in the step 1) to obtain lenalidomide intermediate of 3-(4-nitro-1-oxo-1,3-xylylenimine-2-yl)piperidine-2,6-diketone. The method disclosed by the invention has obviously smaller steps, the raw materials are easy to obtain, a yield is also improved, and the method is more suitable for industrial production.
- -
-
-
- 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.
- -
-
Paragraph 0025; 0030-0032; 0034-0036; 0038-0040; 0042-0044
(2017/12/06)
-
- 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
-
p. 4075 - 4081
(2017/08/23)
-
- 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.
- -
-
Page/Page column 250
(2017/12/05)
-
- Lenalidomide and lenalidomide intermediate preparation method
-
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.
- -
-
-
- 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
-
p. 133 - 138
(2016/01/15)
-
- Solid form of 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione having specified X-ray diffraction pattern
-
The invention relates to a packaging comprising one or more administration units comprising a solid form of 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione.
- -
-
Paragraph 0124
(2015/01/18)
-
- THIO COMPOUNDS
-
A compound, or a pharmaceutically acceptable salt or ester thereof, having a structure of: wherein A, B and D are each oxygen or sulfur, provided that least one of A, B and D is sulfur; and R1-R8 are each independently hydrogen, hydroxyl, acyl, substituted acyl, acyloxy, substituted acyloxy, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkoxy, aryl, substituted aryl, amino, substituted amino, halogen, heterocycloalkyl, substituted heterocycloalkyl, heteroaryl, substituted heteroaryl, or a thio-containing group
- -
-
Paragraph 0085; 0086
(2013/06/26)
-
- 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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-
Page/Page column 8
(2013/03/26)
-
- SOLID FORMS OF 3-(4-NITRO-1-OXOISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE
-
Solid forms comprising crystalline 3-(4-nitro-1-oxoisoindolin-2-yl)piperidine-2,6-dione are disclosed. Compositions comprising the solid forms, methods of making the solid forms and methods of their use are also disclosed.
- -
-
Paragraph 00123-00125
(2013/09/12)
-
- 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.
- -
-
Page/Page column 7-8
(2012/04/04)
-
- PROCESS FOR THE PREPARATION OF LENALIDOMIDE
-
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 11
(2011/04/14)
-
- ACID ADDITION SALTS OF LENALIDOMIDE
-
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.
- -
-
Page/Page column 31
(2011/05/11)
-
- ANHYDROUS LENALIDOMIDE FORM-I
-
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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-
Page/Page column 16
(2011/10/05)
-
- IMPROVED 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 22-23
(2010/09/18)
-
- METHODS FOR SYNTHESIZING 3-(SUBSTITUTED DIHYDROISOINDOLINONE-2-YL)-2,6-DIOXOPIPERIDINE, AND INTERMEDIATES THEREOF
-
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 55
(2010/12/29)
-
- PREPARATION OF LENALIDOMIDE
-
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.
- -
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Page/Page column 19-20
(2009/10/22)
-
- METHOD FOR THE PRODUCTION OF SUBSTITUTED 2,6-DIOXOPIPERIDINE-3-YL COMPOUNDS
-
Disclosed is a method for producing compounds of general formula (I), wherein one of the substituents R1, R2, R3, and R4 represents nitro, amino, -NHR5, or -N(R5)R6 while the remaining three substituents among R1, R2, R3, and R4 independently represent hydrogen, (C1-4) alkyl or (C1-4) alkoxy, and R5 as well as R6 independently represent (C1-4) alkyl or a protective group. According to the inventive method, a compound of general formula (II), wherein one of the substituents R'1, R'2, R'3, R'4 represents nitro, -NHR5, or -N(R5)R6 while the remaining substituents have the meaning indicated above and R7 respectively represents amino, -O-(NH4+), -OH, -O-alkyl, or linear or branched (C1-12) alkyl, is reacted so as to separate NH3 and/or water or alkyl-OH (if R7 = -O-alkyl), and optionally provided protective groups are separated.
- -
-
Page/Page column 7
(2008/06/13)
-
- Substituted 2(2,6-dioxopiperidin-3-yl)isoindolines
-
Substituted 1,3-dioxo-2-(2,6-dioxopiperidin-3-yl)isoindolines and 1-oxo-2-(2,6-dioxo-piperidin-3-yl)isoindolines reduce the levels of TNFα in a mammal and are useful in treating oncogenic conditions, inflammation, and autoimmune diseases. Typical embodiments are 1-oxo-2-(2,6-dioxo-3-methylpiperidin-3-yl)-4,5,6,7-tetrafluoroiso-indoline and 1,3-dioxo-2-(2,6-dioxo-3-methylpiperidin-3-yl)-4-aminoisoindoline.
- -
-
-
- Amino-substituted thalidomide analogs: Potent inhibitors of TNF-α production
-
Thalidomide, (1), is a known inhibitor of TNF-α release in LPS stimulated human PBMC. Herein we describe the TNF-α inhibitory activity of amino substituted analogs of thalidomide (1) and its isoindolin-1-one analog, EM-12 (2). The 4-amino substituted analogs were found to be potent inhibitors of TNF-α release in LPS stimulated human PBMC.
- Muller, George W.,Chen, Roger,Huang, Shaei-Yun,Corral, Laura G.,Wong, Lu Min,Patterson, Rebecca T.,Chen, Yuxi,Kaplan, Gilla,Stirling, David I.
-
p. 1625 - 1630
(2007/10/03)
-