- An efficient hydrogenation of dinitrile to aminonitrile in supercritical carbon dioxide
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The highly selective hydrogenation of adiponitrile proceeds effectively in supercritical carbon dioxide (scCO2) to produce 6-aminocapronitrile with excellent selectivity of 100% over rhodium/alumina (Rh/Al2O 3) and without any additive, which is impossible in classical organic solvents. The presence of CO2 can be beneficial or mandatory for the exclusive formation of the aminonitrile as it can act as a solvent to enhance the activity and also as temporary protecting agent to increase the selectivity. These results successfully show the general concept of using scCO2 as a protective medium for the selectivity control of dinitrile to aminonitrile reactions. Recycling of the catalyst and further extension of this method to other dinitriles were also investigated.
- Chatterjee, Maya,Sato, Masahiro,Kawanami, Hajime,Yokoyama, Toshirou,Suzuki, Toshishige,Ishizaka, Takayuki
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Read Online
- Site-specific enzymatic introduction of a norbornene modified unnatural base into RNA and application in post-transcriptional labeling
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Inverse electron demand Diels-Alder cycloadditions have proven to be extremely useful for mild and additive-free orthogonal labeling of biomolecules, amongst others, for RNA labeling in vitro and in a cellular context. Here we present a method for site-specific introduction of an alkene modification into RNA via T7 in vitro transcription. For this, an unnatural, hydrophobic base pairing system developed by Romesberg and coworkers was modified introducing one or two norbornene moieties at predefined positions into RNA oligonucleotides in an in vitro transcription reaction. This allows post-transcriptional functionalization of these RNA molecules with tetrazine derivatives containing for instance fluorophores or biotin.
- Domnick, Christof,Eggert, Frank,Kath-Schorr, Stephanie
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- 2-IMIDAZOLYL-PYRIMIDINE SCAFFOLDS AS POTENT AND SELECTIVE INHIBITORS OF NEURONAL NITRIC OXIDE SYNTHASE
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Imidazolyl-pyrimidine and related compounds, as can utilize heme-iron coordination in the selective inhibition of neuronal nitric oxide synthase.
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Paragraph 0031
(2016/01/25)
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- Novel 2,4-disubstituted pyrimidines as potent, selective, and cell-permeable inhibitors of neuronal nitric oxide synthase
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Selective inhibition of neuronal nitric oxide synthase (nNOS) is an important therapeutic approach to target neurodegenerative disorders. However, the majority of the nNOS inhibitors developed are arginine mimetics and, therefore, suffer from poor bioavai
- Mukherjee, Paramita,Li, Huiying,Sevrioukova, Irina,Chreifi, Georges,Martásek, Pavel,Roman, Linda J.,Poulos, Thomas L.,Silverman, Richard B.
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supporting information
p. 1067 - 1088
(2015/03/04)
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- Photostimulated reduction of nitriles by SmI2
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Despite their high electron-withdrawing strength, nitriles are not good electron acceptors and therefore are hard to reduce. In this work, using photostimulation in the visible region, we examined the reactivity of aliphatic and aromatic, mono- and dicyano compounds in reaction with SmI2. A proton donor that complexes efficiently with SmI2 must be used. Maximum yield was obtained at ca.0.2 M MeOH. Aromatic nitriles were more reactive than aliphatic nitriles, which exhibited negligible yields. Phenylacetonitrile presents an intermediate reactivity. The mechanism of the reaction involves coordination of the SmI2 to the lone pair of the nitrile nitrogen followed by an inner sphere electron transfer. Surprisingly, m-dicyanobenzene was less reactive than the monocyano derivative benzonitrile. This was traced to the lower ability of the dicyano compound to coordinate to the SmI2 due to, as was shown by quantum mechanical calculations, its lone pair having an energy significantly lower than that of benzonitrile. It is noteworthy that at the SmI2 initial concentration used (0.04M), light penetrates only the 0.4 mm outer layer of the reaction mixture. Therefore the photostimulation effect observed was due to irradiation of only 4% of the total reaction volume, implying that under optimal conditions the effect should be 25 times larger.
- Rao, Chintada Nageswara,Hoz, Shmaryahu
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experimental part
p. 4029 - 4034
(2012/06/29)
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- One-pot primary aminomethylation of aryl and heteroaryl halides with sodium phthalimidomethyltrifluoroborate
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A one-pot primary aminomethylation of aryl halides, triflates, mesylates, and tosylates via Suzuki-Miyaura cross-coupling reactions with sodium phthalimidomethyltrifluoroborate followed by deamidation with ethylenediamine is reported.
- Murai, Norio,Miyano, Masayuki,Yonaga, Masahiro,Tanaka, Keigo
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supporting information; experimental part
p. 2818 - 2821
(2012/07/17)
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- PROCESS FOR PRODUCING XYLYLENEDIAMINE
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The invention provides a process for producing xylylenediamine, including supplying a solution of phthalonitrile dissolved in a solvent to a reactor filled with a catalyst and hydrogenating the phthalonitrile to produce xylylenediamine, characterized in that the process includes halting supply of the solution; (2) bringing a washing liquid into contact with the catalyst, the washing liquid having a phthalonitrile content of 3 mass% or less and a xylylenediamine content of 1 mass% or more; and after completion of the contact, resuming supply of the solution, and employing the catalyst continuously in hydrogenation. Through the production process of the invention, the catalyst can be employed continuously for a long period of time, and the catalyst-related cost can be considerably reduced.
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Page/Page column 8; 11
(2011/06/24)
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- (3-HYDROXY-4-AMINO-BUTAN-2-YL) -3- (2-THIAZOL-2-YL-PYRROLIDINE-1-CARBONYL) BENZAMIDE DERIVATIVES AND RELATED COMPOUNDS AS BETA-SECRETASE INHIBITORS FOR TREATING
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The present invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating of Alzheimer's disease. (Formula)
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Page/Page column 118
(2009/05/29)
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- PRODUCTION METHOD OF PRIMARY AMINES AND CATALYSTS FOR PRODUCING PRIMARY AMINES
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A method of producing a primary amine by the hydrogenation of a nitrile in the presence of a hydrogenation catalyst. The hydrogenation catalyst contains at least one metal selected from the group consisting of nickel, cobalt and iron. Before use in the hydrogenation of nitrile, the hydrogenation catalyst is pretreated with at least one treating agent selected from the group consisting of hydrocarbons, alcohols, ethers, esters and carbon monoxide at 150 to 500° C.
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Page/Page column 6
(2008/06/13)
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- Production of Xylylenediamines
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A method of producing xylylenediamine by a two-stage hydrogenation of a starting phthalonitrile in a solvent. The main steps of the method are a hydrogenation step 1 and a hydrogenation step 2. In the hydrogenation step 1, a solution of the starting phthalonitrile in the solvent containing liquid ammonia is fed to an inlet of a first reaction zone and the hydrogenation is carried out in the first reaction zone in the presence of a heterogeneous catalyst, to hydrogenate nitrile groups in the starting phthalonitrile to aminomethyl groups. A part of the hydrogenation product solution from the first reaction zone is circulated to the inlet of the first reaction zone and the rest is introduced into the hydrogenation step 2 where further undergoes the hydrogenation.
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Page/Page column 3-7
(2008/06/13)
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- Process for the preparation of amino compounds containing an aromatic ring by using a shell-type catalyst
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An aromatic dinitrile compound is hydrogenated in an amide solvent in the presence of a solid catalyst and in the absence of ammonia to produce an aromatic ring-containing amino compound by reducing at least one cyano group to aminomethyl group. The solid catalyst is a supported palladium catalyst in which palladium is substantially present on the outer surface of carrier and in a surface layer within a depth of 200 μm from the outer surface. Using such a solid catalyst, the aromatic dinitrile compound is efficiently hydrogenated to the aromatic ring-containing amino compound under mild conditions.
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Page/Page column 7-8
(2008/06/13)
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- Method for producing xylylenediamine
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A method of producing xylylenediamine of the present invention includes the steps of : subjecting a liquid mixture of phthalonitriles with liquid ammonia or a mixture of liquid ammonia and an organic solvent to a first catalytic hydrogenation treatment, thereby hydrogenating the phthalonitriles to obtain a reaction product (A), wherein a content of the liquid ammonia or the mixture of liquid ammonia and an organic solvent is 80 wt% or more; removing the liquid ammonia in the reaction product (A) to obtain a reaction product (B); subjecting the reaction product (B) to a second catalytic hydrogenation treatment, thereby hydrogenating cyanobenzylamine to obtain a reaction product (C); and distilling the reaction product (C) to purify xylylenediamine.
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Page/Page column 8
(2008/06/13)
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- Substituted pyridoxines as anti-platelet agents
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Compounds with antiplatelet aggregation characteristics for the treatment of cardiovascular and cardiovascular related disease, are described. The methods are directed to administering pharmaceutical compositions comprising a pyridoxine analogue.
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Page/Page column 11
(2008/06/13)
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- TETRAHYDROISOQUINOLINES AS FACTOR XA INHIBITORS
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The present invention is directed to compounds represented by Formula I and pharmaceutically acceptable salts, solvates, hydrates, and prodrugs thereof which are inhibitors of Factor Xa. The present invention is also directed to and intermediates used in making such compounds, pharmaceutical compositions containing such compounds, methods to prevent or treat a number of conditions characterized by undesired thrombosis and methods of inhibiting the coagulation of a blood sample.
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Page/Page column 37
(2008/06/13)
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- PYRAZOLOPYRIMIDINES AS CYCLIN-DEPENDENT KINASE INHIBITORS
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In its many embodiments, the present invention provides a novel class of pyrazolo[1,5-a]pyrimidine compounds as inhibitors of cyclin dependent kinases, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.
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- Process for production of xylylenediamine and/or cyanobenzylamine
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In the process of the present invention, xylylenediamine and/or cyanobenzylamine is produced by a catalytic liquid-phase hydrogenation of a phthalonitrile compound. The liquid-phase hydrogenation is performed by controlling the concentration of a benzamide compound to a specific level or lower. In a preferred embodiment, the concentration of a benzoic acid compound is further controlled to a specific level or lower. By the process, xylylenediamine and/or cyanobenzylamine is produced at high yields and the catalyst life is prolonged.
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- High-selective production method of di(aminomethyl)-substituted aromatic compound
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A di(aminomethyl)-substituted aromatic compound is produced by a two-stage hydrogenation. In the first stage, an aromatic dinitrile is hydrogenated into a cyano(aminomethyl)-substituted aromatic compound in the presence of a Pd-containing catalyst. The resultant cyano(aminomethyl)-substituted aromatic compound is then hydrogenated in the second stage into the target di(aminomethyl)-substituted aromatic compound in the presence of a Ni- and/or Co-containing catalyst. By the above method, the di(aminomethyl)-substituted aromatic compound is produced in a high selectivity and a sufficiently high yield without reducing the catalyst life.
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- Production method of xylylenediamine
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In the method of the present invention, xylylenediamine is produced by a two-stage hydrogenation of a dicyanobenzene compound. In a first stage (a), the hydrogenation is performed until a conversion of nitrile groups reaches 90 mol% or higher and less than 99.9 mol%. In a second stage (b), the hydrogenation is further continued at temperatures 10°C or more higher than in the step (a) until the conversion of nitrile groups reaches a level which is higher than that attained in the step (a) and equal to 99.5 mol% or more. In the present invention, a highly pure xylylenediamine containing a minimized amount of cyanobenzylamine is efficiently produced in a simple manner without needing a specific purification, and also without deteriorating the use efficiency of the catalyst while reducing the amount of the dicyanobenzene compound remaining not reacted and the generation of the intermediate cyanobenzylamine.
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- Process for production of xylylenediamine
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In the process of the present invention for producing a xylylenediamine by a liquid-phase hydrogenation of a dicyanobenzene in the presence of a catalyst, the catalyst having its activity decreased during the course of use in the hydrogenation is reactivated and a pressure drop through a fixed bed catalyst layer is got rid of, thereby regenerating the catalyst for reuse in the subsequent hydrogenation of the dicyanobenzene to produce the xylylenediamine. The catalyst is regenerated by brought into contact with a hydrogen-containing gas under controlled temperature conditions.
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- Novel pyrazolopyrimidines as cyclin dependent kinase inhibitors
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In its many embodiments, the present invention provides a novel class of pyrazolo[1,5-a]pyrimidine compounds as inhibitors of cyclin dependent kinases, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.
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- Unexpected enhancement of thrombin inhibitor potency with o-aminoalkylbenzylamides in the P1 position
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Thrombin inhibitors incorporating o-aminoalkylbenzylamides in the P1 position were designed, synthesized and found to have enhanced potency and selectivity in several different structural classes. X-ray crystallographic analysis of compound 24 bound in the α-thrombin-hirugen complex provides an explanation for these unanticipated results.
- Rittle, Kenneth E.,Barrow, James C.,Cutrona, Kellie J.,Glass, Kristen L.,Krueger, Julie A.,Kuo, Lawrence C.,Lewis, S. Dale,Lucas, Bobby J.,McMasters, Daniel R.,Morrissette, Matthew M.,Nantermet, Philippe G.,Newton, Christina L.,Sanders, William M.,Yan, Youwei,Vacca, Joseph P.,Selnick, Harold G.
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p. 3477 - 3482
(2007/10/03)
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- Syntheses of Quadruply Two- And Three-Atom, Aza-Bridged, Cofacial Bis(5,10,15,20-tetraphenylporphyrins)
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Several syntheses for quadruply aza-bridged, cofacial bis(5,10,15,20-tetraphenylporphyrins) were investigated. Reaction of 5,10,15,20-tetrakis(α-bromo-m-tolyl)porphyrin (2) with p-toluenesulfonamide or cyanamide and Cs2CO3 at high dilution in dimethylformamide produced the tosyl and cyano dimers 3a and 3b in 8% yield each. The method of choice was the reaction of porphyrin 2 with tosylamido porphyrin 5a under the same conditions to give dimer 3a in 38% yield. Biphenyl radical anion induced desulfonylation of 3a provided the amino dimer 3c (41%). Reaction of porphyrin 2 with tosylamido porphyrin 13 provided the dimer 14 (of reduced bridge length) in 1% yield. Other methods for the synthesis of 3a and 3c are also discussed. UV/vis and 1H NMR spectroscopic results suggest an eclipsed "screwed-down" preferred conformation for these dimers, and molecular models are used to illustrate this conformational possibility. (1) Several terms have been used to describe the orientation of one porphyrin ring parallel and coplanar on top of another (i.e., strati by Kagen,5b face to face by Collman,5a and cofacial by Chang3b). Whereas the term cofacial is now generally the most commonly used descriptor, we prefer the usage of strati (from stratum, Latin for covering) for the specific naming of compounds, since it allows for more detailed structural information than simple letter-number shorthand abreviations. Moreover, a new shorthand naming system will be presented in the body of this account,17 which derives naturally from the strati terminology used in the Experimental Section.
- Bookser, Brett C.,Bruice, Thomas C.
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p. 4208 - 4218
(2007/10/02)
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- Benzylamines: Synthesis and evaluation of antimycobacterial properties
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The synthesis of benzylamines with various N-alkyl chains and substituents in the aromatic system as well as their evaluation on Mycobacterium tuberculosis H 37 Ra are described. The most active compounds in this test, N-methyl-3-chlorobenzylamine (MIC 10.2 μg/mL), N-methyl-3,5-dichlorobenzylamine (93, MIC 10.2 μg/mL), and N-butyl-3,5-difluorobenzylamine (MIC 6.4 μg/mL), also exhibited a marked inhibitory effect on Mycobacterium marinum and Mycobacterium lufu used for the determination of antileprotic properties. The combination of 93 with aminosalicylic acid, streptomycin, or dapsone exert marked supra-additive effects on M. tuberculosis H 37 Ra.
- Meindl,Von Angerer,Schonenberger,Ruckdeschel
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p. 1111 - 1118
(2007/10/02)
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