- A solid-phase approach for the synthesis of α-Aminoboronic acid peptides
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A solid-phase synthesis of α-Aminoboronic acid peptides using a 1-glycerol polystyrene resin is described. Standard Fmoc solid-phase peptide chemistry is carried out to construct bortezomib and ixazomib. This approach eliminates the need for liquid-liquid extractions, silica gel column chromatography, and HPLC purifications, as products are isolated in high purity after direct cleavage from the resin.
- Daniels, Blake E.,Stivala, Craig E.
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- Borate compound and pharmaceutically acceptable salt thereof, and preparation method and application of boric acid ester compound and pharmaceutically acceptable salt thereof
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The invention relates to a borate compound as shown in a formula (1), a pharmaceutically acceptable salt thereof, a preparation method and application thereof. The borate compound is novel in structure and has a proteasome inhibition function. The stability of the borate compound disclosed by the invention in a solution is far higher than that of Ixazomib. Especially when the pH is 1.2 and the pH is 6.8, the stability of the compound provided by the invention is more advantageous. Besides, microsome stability results show that the compound has good stability in five different liver microsomes, the half-life period of the microsomes of Ixazomib in cynomolgus monkeys is too long, the medicine is basically not metabolized, and serious toxicity can be caused. The compound can be used for preparing medicines for treating inflammation, immune-related diseases, cancers or hyperproliferative diseases and changing antigen peptides generated by proteasomes in organisms.
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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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supporting information
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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Paragraph 0004; 0012
(2019/11/04)
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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; 0208-0209; 0210-0212
(2019/12/25)
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- Novel boric acid salicylate derivatives and pharmaceutical composition thereof
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The invention discloses novel boric acid salicylate derivatives and pharmaceutical composition thereof and also provides pharmaceutically acceptable salt, a preparation method, an application of the pharmaceutical composition of the derivatives. The provided compounds have a remarkable inhibition function on tumor cells, can be used for preventing and/or treating tumor-related diseases, especiallymultiple myeloma and have broad application prospects.
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Paragraph 0096; 0118-0122
(2019/08/06)
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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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- CU-AND NI-CATALYZED DECARBOXYLATIVE BORYLATION REACTIONS
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The invention is directed to methods of converting a carboxylic acid group in a compound, via a redox active ester, to a corresponding boronic ester by treatment with bis(pinacolato)diboron-alkyllithium complex in the presence of a ligand, a Ni(ll) salt or a copper salt, and an Mg(ll) salt, in the presence of an alkyllithium or a lithium hydroxide or alkoxide salt. The product pinacolato boronate ester can be cleaved to provide a boronic acid. The invention is also directed to methods of preparing various compounds of medical value comprising boronic acid groups, and to novel boronic-acid containing compounds of medicinal value, including an atorvastatin boronic acid analog, a vancomycin aglycone boronic acid analog, and boronic acid containing elastase inhibitors mCBK319, mCBK320, mCBK323, and RPX-7009.
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Page/Page column 93; 95-96
(2018/10/19)
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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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Paragraph 0156; 0165; 0166
(2017/08/30)
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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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- 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 0185; 0186; 0187; 0189
(2016/12/01)
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- PROTEASOME INHIBITORS
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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 26-27
(2009/04/25)
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- Proteasome inhibitors
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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 25
(2008/12/04)
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