- SUBSTITUTED BORIC ACID COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, AND APPLICATION THEREOF
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A substituted boric acid compound, a pharmaceutical composition comprising same, and an application thereof. The substituted boric acid compound is a compound represented by formula (I), or a crystal form, a pharmaceutically acceptable salt, a prodrug, a stereoisomer, a hydrate, or a solvent compound thereof. The boric acid compound has proteasome inhibitory activity, good pharmacodynamic/pharmacokinetic performance, good applicability, and high safety, and can be used for preparing drugs for treating diseases related to proteasomes.
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Paragraph 0048; 0049
(2019/05/10)
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- p53 DEGRADATION INDUCING MOLECULE AND PHARMACEUTICAL COMPOSITION
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A p53 degradation inducing molecule which can induce degradation of p53 proteins or p53 composites, and a pharmaceutical composition containing said p53 degradation inducing molecule are provided. This p53 degradation inducing molecule is a conjugate of a p53 affinity molecule which has affinity for p53 proteins or p53 composites, and a proteolysis induction tag which has affinity for protease and which does not inhibit proteolysis of proteins by protease.
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Paragraph 0088; 0090; 0094; 0096
(2019/10/10)
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- Ras PROTEIN DEGRADATION INDUCING MOLECULE AND PHARMACEUTICAL COMPOSITION
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A Ras protein degradation inducing molecule that can induce degradation of Ras proteins, and a pharmaceutical composition that contains this Ras protein degradation inducing molecule are provided. The Ras protein degradation inducing molecule is a conjugate of a Ras protein affinity molecule which has affinity to Ras proteins, and a proteolysis-inducing tag which has affinity to protease and does not inhibit proteolysis of proteins by the protease.
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Paragraph 0080; 0082
(2019/10/10)
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- PROCESS FOR MAKING IXAZOMIB OR INTERMEDIATES THEREFOR
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This invention relates to a process for preparing Ixazomib 1, its trimer 1.trimer, its citrate ester 2 or an intermediate for their synthesis. The process comprising at least one amide coupling reaction in the presence of a cyclic alkyl triphosphonic anhy
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- Virtues of Volatility: A Facile Transesterification Approach to Boronic Acids
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Boronic acids are an increasingly important compound class for many applications, including C-C bond formation reactions, medicinal chemistry, and diagnostics. The deprotection of boronic ester intermediates is frequently a problematic and inefficient step in boronic acid syntheses. We describe an approach that highly facilitates this transformation by leveraging the volatility of methylboronic acid and its diol esters. The method is performed under mild conditions, provides high yields, and eliminates cumbersome and problematic purification steps.
- Hinkes, Stefan P.A.,Klein, Christian D.P.
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p. 3048 - 3052
(2019/05/10)
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- Synthetic process research of ixazomib
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The invention discloses a synthesis method of ixazomib. The yield and the purity of a target product can be greatly increased with the method.
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- Synthesis and application of peptide borate compounds
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The invention belongs to the field of drug synthesis, and specifically relates to a series of novel peptide borate compounds or pharmaceutical salts thereof, and a preparation method and pharmaceutical application thereof. The structure of the peptide borate compounds or the pharmaceutical salts thereof is as shown in a formula I which is described in the specification. The compounds of the invention can be used for preparing proteasome inhibitors, and thus can be further used for treating solid tumors and blood tumors.
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Paragraph 0163; 0188-0190; 0191-0194
(2019/12/25)
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- A PROCESS FOR THE PREPARATION OF IXAZOMIB CITRATE
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The present invention relates to a process for the preparation of compound of formula (I), wherein, R1 and R2 are each independently hydroxy, alkoxy, aryloxy, or aralkoxy; or R1 and R2 together form a moiety derived from an alpha-hydroxy carboxylic acid compound or a beta-hydroxy carboxylic acid compound, wherein the atom attached to boron in each case is an oxygen atom; or R1 and R2 together form the boronate esters of boronic acid.
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Page/Page column 24; 25
(2018/09/21)
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- NOVEL CRYSTALLINE FORMS OF IXAZOMIB CITRATE AND ITS PROCESS FOR PREPARATION THEREOF
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The present invention related to novel crystalline forms of Ixazomib citrate of formula-I and its process for preparation thereof. The chemical structure of said compound represented by the following formula-I. This invention also provides a process for the preparation of Ixazomib citrate of formula-I and also its solid dispersions.
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Page/Page column 16
(2018/10/19)
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- PROTEIN DEGRADATION INDUCING TAG AND USAGE THEREOF
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Provided are: a protein degradation inducing tag which is a molecule that has affinity with proteases and does not inhibit degradation of a protein by proteases; a protein degradation inducing molecule that is a conjugate of at least one protein degradation inducing tag and at least one protein binding molecule that binds to a protein; and a usage of those.
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Paragraph 0151; 0154
(2018/05/03)
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- Synthesizing method of boric acid citric acid ester compounds including ixazomib
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The invention relates to a method for synthesizing ixazomib. The method includes the steps of firstly, using 2,5-dichlorobenzoyl chloride or 2,5-dichlorobenzoic acid as the initial raw material, subjecting the 2,5-dichlorobenzoyl chloride or 2,5-dichlorobenzoic acid and glycine ester to condensation reaction to prepare N-(2,5-dichlorobenzoyl) glycine ester, and performing de-protection reaction toobtain N-(2,5-dichlorobenzoyl) glycine; secondly, subjecting the N-(2,5-dichlorobenzoyl) glycine obtained in the first step and (R)-leucine boric acid pinacol ester to condensation reaction to prepare (R)-[N-(2,5-dichlorobenzoyl) glycyl] leucine boric acid pinacol ester; thirdly, allowing the(R)-[N-(2,5-dichlorobenzoyl) glycyl] leucine boric acid pinacol ester obtained in the second step to haveone-step reaction with citric acid to generate the ixazomib. The invention further relates to a method for synthesizing boric acid citric acid ester compounds, and the method includes allowing boric acid pinacol ester to have one-step reaction with citric acid to generate the boric acid citric acid ester compounds. By the methods, the boric acid citric acid ester compounds including the ixazomib can be conveniently synthesized.
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- Preparation process method for boron-containing compound
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The invention discloses a preparation method for a boron-containing compound MLN2238. The method for preparing the MLN2238, disclosed by the invention, comprises the steps of adopting a solid compound intermediate II, which is stable in properties and can be subjected to recrystallization and purification, as an intermediate node for quality control, carrying out recrystallization or pulping purification on the intermediate, and then, carrying out a next-step reaction, thereby obtaining the boron-containing compound MLN2238 with relatively high purity. The synthesis process route is free of special requirements on production equipment, the reaction conditions are mild, and all the raw materials are all marketable products, so that the process route is very applicable to industrial production.
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- Synthetic method of proteasome inhibitor MLN9708
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The invention provides a synthetic method of a proteasome inhibitor MLN9708. The method comprises: taking 2,5-dichloro benzoic acid as an initial raw material, and performing condensation and saponification to prepare N-(2,5-dichlorobenzoyl) glycine; joining N-(2,5-dichlorobenzoyl) glycine to L-leucine boronic acid pinacol ester hydrochloride; purifying the obtained product through forming a complex with diethanolamine and performing hydrolysis for deprotection to obtain corresponding free boric acid; and reacting the obtained product with citric acid to obtain MLN9708. The method is cheap and available in raw materials, simple and convenient to operate, mild in reaction conditions and easy for industrial production.
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- Deuterated dipeptide boric acids or esters thereof, and synthetic methods and uses of the compounds
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Deuterated dipeptide boric acids or esters thereof, or crystal forms thereof, or pharmaceutically acceptable hydrates or solvates thereof are disclosed. The general structure of the compounds is shown as a formula (a) in the specification, wherein R1, R2, R3, R4, R5 and R6 are independently selected from hydrogen, deuterium or halogens, or C1-C4 alkyl one or a plurality of or all hydrogen atoms of which are deuterated; and at least one of the R1, the R2, the R3, the R4, the R5 and the R6 is deuterated or deuterium. The compounds can effectively inhibit proteasomes and effectively treat or prevent cancer, cardiovascular disease, inflammation, immune disease, nephropathy, vasculogenesis or prostate disease.
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- Boron-containing intermediate and application of same to medical industry
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The invention discloses a preparation method for novel boron-containing intermediate I and a boron-containing drug MLN9708. The novel boron-containing intermediate I prepared by using a fluorination reagent is applied to preparation of the antitumor drug MLN9708; the intermediate has stable chemical properties in normal-temperature air, is easy to recrystallize and purify; and the intermediate and citric acid undergo a one-step reaction under the action of an alkaline reagent and a silicon reagent so as to prepare the antitumor drug MLN9708. The preparation method provided by the invention has no special requirements on production equipment, is mild in reaction conditions, uses commercially available raw materials and is suitable for industrial production.
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- High-efficiency preparation method for high-purity boron-containing compound
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The invention discloses a simple high-efficiency preparation method for a high-purity boron-containing compound MLN9708. According to the preparation method for MLN9708, a simple and easily available raw material (II) and citric acid are subjected to a borate exchange reaction, so the boron-containing compound MLN9708 is prepared in one step. The preparation method is short in route, mild in reaction conditions, simple to operate, high in product yield and purity and suitable for industrial production.
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- Preparation method of boron-containing compound
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The invention discloses a preparation method of boron-containing compound MLN9708. The preparation method of the MLN9708 includes use of a raw material IV convenient and easy to obtain for synthesis of an intermediate II capable of purification by recrystallization and then use of citric acid for boric acid ester exchange reaction to obtain the boron-containing compound MLN9708. The synthetic process route has no special requirement on production equipment, the reaction condition is mild, all the raw materials are commercially available products, and the process route is very suitable for industrial production.
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- A PROCESS OF PREPARING IXAZOMIB CITRATE
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A novel production process of Ixazomib citrate of formula I, wherein the boroester of formula VII is hydrolyzed with boric acid, followed by esterification with citric acid. The hydrolysis with boric acid and esterification with citric acid are performed in a single step. The usual amount of boric acid varies between 1 to 3-fold the amount of the compound of formula VII (molar ratio). In a preferred embodiment the acid is used in a slight excess, i.e. 1.05 to 1.3-fold, optimally 1.1 -fold the molar amount of the compound of formula VII.
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Page/Page column 2
(2016/10/27)
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- Dipeptide boric acid composed of carboxylic acid and alpha-amino acid as well as ester compound thereof, and preparation method and application of dipeptide boric acid and ester compound thereof
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The invention belongs to the field of drug synthesis and in particular relates to a series of novel peptide boric acids as well as an ester compound or pharmaceutical salt thereof, and a preparation method and application of the peptide boric acids as well as the ester compound or pharmaceutical salt thereof in pharmacodynamics. A structure of the peptide boric acid and the ester compound or pharmaceutical salt thereof is shown in a formula I (described in the specification). The compound provided by the invention can be used for preparing a proteasome inhibitor and can further be used for treating solid tumours and blood tumours, wherein the solid tumours are selected from non-small cell lung cancer, small cell lung cancer, lung adenocarcinoma, lung squamous carcinoma, pancreatic cancer, breast cancer, prostate cancer, liver cancer, skin cancer, epithelial cell cancer, gastrointestinal stromal tumor, nasopharynx cancer and leukemia; and the blood tumours are selected from multiple myeloma, mantle cell lymphoma and histiocytic lymphoma.
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Paragraph 0166; 0167; 0168; 0169; 0170
(2016/12/01)
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- BORONATE ESTER COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF
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The present invention provides novel compounds useful as proteasome inhibitors. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various diseases.
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Page/Page column 61
(2010/01/12)
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