- From PARP1 to TNKS2 inhibition: A structure-based approach
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Tankyrases (TNKSs) have recently gained great consideration as potential targets in Wnt/β-catenin pathway-dependent solid tumors. Previously, we reported the 2-mercaptoquinazolin-4-one MC2050 as a micromolar PARP1 inhibitor. Here we show how the resolution of the X-ray structure of PARP1 in complex with MC2050, combined with the computational investigation of the structural differences between TNKSs and PARP1/2 active sites, provided the rationale for a structure-based drug design campaign that with a limited synthetic effort led to the discovery of the bis-quinazolinone 5 as a picomolar and selective TNKS2 inhibitor, endowed with antiproliferative effects in a colorectal cancer cell line (DLD-1) where the Wnt pathway is constitutively activated.
- Tomassi, Stefano,Pfahler, Julian,Mautone, Nicola,Rovere, Annarita,Esposito, Chiara,Passeri, Daniela,Pellicciari, Roberto,Novellino, Ettore,Pannek, Martin,Steegborn, Clemens,Paiardini, Alessandro,Mai, Antonello,Rotili, Dante
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supporting information
p. 862 - 868
(2020/06/30)
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- Continuous N-alkylation reactions of amino alcohols using γ-Al2O3 and supercritical CO2: Unexpected formation of cyclic ureas and urethanes by reaction with CO2
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The use of γ-Al2O3 as a heterogeneous catalyst in scCO2 has been successfully applied to the amination of alcohols for the synthesis of N-alkylated heterocycles. The optimal reaction conditions (temperature and substrate flow rate) were determined using an automated self-optimising reactor, resulting in moderate to high yields of the target products. Carrying out the reaction in scCO2 was shown to be beneficial, as higher yields were obtained in the presence of CO2 than in its absence. A surprising discovery is that, in addition to cyclic amines, cyclic ureas and urethanes could be synthesised by incorporation of CO2 from the supercritical solvent into the product.
- Streng, Emilia S.,Lee, Darren S.,George, Michael W.,Poliakoff, Martyn
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p. 329 - 337
(2017/03/15)
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- Method for producing N-alkylpiperazine
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PROBLEM TO BE SOLVED: To provide a method for producing N-alkyl piperazines in high yield by selectively alkylating one amino group.SOLUTION: In the method for producing N-alkyl piperazines, piperazines represented by general formula (1) are reacted with a specific alkylating agent in the presence of an acid. In the formula: R-Rare each independently a hydrogen atom, a methyl group, an ethyl group, a 3-8C linear alkyl group or the like, a hydroxyethyl group, a hydroxypropyl group, a dihydroxypropyl group, a methoxy group, an ethoxy group, a phenyl group, a benzyl group, a 2-phenylethyl group, or the like.
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Paragraph 0056; 0062; 0065
(2017/02/09)
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- PREPARATION OF DIHYDROXYETHYL PIPERAZINE
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A process for selectively preparing dihydroxyethyl piperazine by reacting hydroxyethyloxazolidinone with an acid catalyst wherein the selectivity of hydroxyethyloxazolidinone to dihydroxyethyl piperazine is at least 55%.
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Paragraph 32
(2014/03/26)
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- IMPROVED PROCESS FOR MAKING ALKOXYLATED PIPERAZINE COMPOUNDS
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The present invention relates to an improved process for making mono- and di-alkoxylated piperazine compounds especially dihydroxyethylpiperazine. The improvement comprises the addition of an acid to the piperazine compound prior to the addition of an alkylene oxide to a reactor wherein the alkoxylated piperazine compound is prepared. Said improvement reduces the concentration of undesirable glycol ether byproducts which contribute undesirable color and foaming of the alkoxylated piperazine compounds.
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Page/Page column 7
(2013/03/28)
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- Iridium-catalyzed condensation of amines and vicinal diols to substituted piperazines
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A straightforward procedure is described for the synthesis of piperazines from amines and 1,2-diols. The heterocyclization is catalyzed by [Cp*IrCl2]2 and sodium hydrogen carbonate and can be achieved with either toluene or water as solvent. The transformation does not require any stoichiometric additives and only produces water as the byproduct. The reaction can be performed between a 1,2-diamine and a 1,2-diol or by a double condensation between a primary alkylamine and a 1,2-diol. At least one substituent is required on the piperazine ring to achieve the cyclization in good yield. The mechanism is believed to involve dehydrogenation of the 1,2-diol to the α-hydroxy aldehyde, which condenses with the amine to form the α-hydroxy imine. The latter rearranges to the corresponding α-amino carbonyl compound, which then reacts with another amine followed by reduction of the resulting imine. Piperazines are prepared by [Cp*IrCl 2]2-catalyzed heterocyclization of 1,2-diols with either 1,2-diamines or primary alkylamines. The reaction is performed in toluene or water and requires no stoichiometric additive. The key step in the mechanism is believed to be the isomerization of an α-hydroxy imine to the corresponding α-amino carbonyl compound. Copyright
- Lorentz-Petersen, Linda L. R.,Nordstrom, Lars Ulrik,Madsen, Robert
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p. 6752 - 6759
(2013/01/15)
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- PROCESS FOR PREPARING 1,4-BISHYDROXYETHYLPIPERAZINE
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Process for preparing 1,4-bishydroxyethylpiperazine (BHEPIP) of the formula I wherein diethanolamine (DEOA) of the formula II is reacted in the liquid phase in a reactor at a temperature in the range from 130 to 300° C. in the presence of a copper-comprising, chromium-free heterogeneous catalyst.
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Page/Page column 6
(2012/05/07)
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- NOVEL THIENOPYRIMIDINE DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, PROCESS FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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The present invention relates to a novel thienopyrimidine derivative having an excellent anti? inflammatory and anti-cancer activity, or a pharmaceutically acceptable salt thereof, a process for the preparation thereof and a pharmaceutical composition comprising the same. The compound according to the present invention strongly inhibits IKB kinase-β (IKK-β) involved in the activation of a transcriptional factor, NF-κB, which is associated with inducing various immune and inflammatory diseases, whereby a composition comprising the compound is a useful therapeutic agent against inflammatory diseases, in particular, arthritis and cancer.
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Page/Page column 110
(2010/11/28)
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- Process for converting heat stable amine salts to heat regenerable amine salts
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Processes are disclosed for converting heat stable amine salts to heat regenerable amine salts using a modified electrodialysis zone (140). The processes of the present invention can be used to reduce the level of heat stable salts in a lean solvent stream in an acid gas removal process and can be integrated with the acid gas removal process to utilize process streams as a source of ions.
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- Process for the preparation of N,N'-bis-(2-hydroxy-ethyl) piperazine
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A new process for preparing N,N'-bis-(2-hydroxyethyl)-piperazine (I) STR1 is described which involves reaction of oxamide with excess diethanolamine at a temperature of from 50° to 268° C.
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- Process for the preparation of N,N'-bis-(2-Hydroxy-ethyl)-piperazine
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A new process for preparing N,N?-bis-(2-hydroxyethyl)--piperazine (I) is described which involves reaction of oxamide with excess diethanolamine at a temperature of from 50 to 268°C.
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- Production of triethylenediamine
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An ethanolamine, preferably diethanolamine, is converted to triethylenediamine or 1,4-bis(2-hydroxyethyl)piperazine, or both by pyrolysis using a B-subgroup metal oxide such as titanium dioxide or zirconium dioxide, as catalyst. In addition it has also been discovered that 1,4-bis(2-hydroxyethyl)piperazine and N-(2-hydroxyethyl)piperazine can be converted in high yields and conversions into triethylenediamine by pyrolysis using the same type of catalyst. When using an ethanolamine as the feedstock and a Group IV-B metal oxide as the catalyst, the process usually results in the coproduction of triethylenediamine and 1,4-bis(2-hydroxyethyl)piperazine, and the latter can be recovered and used as a raw material for the production of additional triethylenediamine, as by recycle to the same reactor or as feedstock to an additional pyrolysis reactor.
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- Hydroxyethylation of Macrocyclic Polyamines; Inhibition by Partial Protonation
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The hydroxyethylation of macrocyclic crown-type polyamines with ethylene oxide in water is very sensitive to ring size and chemical structure.When the ring is 12-membered, the reaction is remarkably fast for the free amine, but completely inhibited for the monoprotonated species.Neutralization curves for these polyamines in water also reveal the special properties of the 12-membered ring, being more basic than the others in the first and second step, while further protonation could not be detected.
- Buoeen, Solfrid,Dale, Johannes,Krane, Jostein
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p. 773 - 778
(2007/10/02)
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- Dyestuff-containing microscopic capsule dispersion for record materials
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A dyestuff-containing microscopic capsule dispersion for record materials, which comprises at least one methine dyestuff represented by the general formula (I): STR1 wherein X means a phenyl, naphthyl, indolyl, β-styryl, pyridyl, pyrimidyl or pyrazinyl group which may optionally be substituted, R1 -R6 are individually an amino, substituted amino, lower alkyl, cycloalkyl, lower alkoxy or lower haloalkyl group or a halogen or hydrogen atom, R7 and R8 are each a hydrogen or halogen atom or a lower alkoxy group and may be coupled together to form a ring, and said methine dyestuff contains at least one substituted amino group at a position para to the central methine group in the molecule thereof, said methine dyestuff being contained in microscopic capsules; and alkanolamine represented by the general formula (II): STR2 wherein R denotes a lower alkylene, hydroxyalkylene or poly(oxyalkylene) group, R' and R" mean individually a hydrogen atom, an alkyl, hydroxyalkyl, aryl, aralkyl, acyl, or ω-hydroxyalkyl-polyoxyalkylene group or a lower alkyl ether of an ω-hydroxyalkyl-polyoxyalkylene group, and R' and R" may be coupled together to form a ring, and/or a metal ion sequestering agent, said alkanolamine and/or metal ion sequestering agent being contained in said microscopic capsules and/or a liquid medium wherein said microscopic capsules are dispersed.
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