- Direct carbamoylation of aryl halides
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(Equation presented) A carbamoylsilane is shown to carry out the direct carbamoylation of aryl chlorides, bromides, and iodides under catalysis by phosphinepalladium-(0) complexes.
- Cunico, Robert F.,Maity, Bikash C.
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Read Online
- KCNT1 INHIBITORS AND METHODS OF USE
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The present invention is directed to, in part, compounds and compositions useful for preventing and/or treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene (e.g., KCNT1). Methods of treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene such as KCNT1 are also provided herein.
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Paragraph 000317
(2020/11/23)
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- Novel Human Aminopeptidase N Inhibitors: Discovery and Optimization of Subsite Binding Interactions
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Aminopeptidase N (APN/CD13) is a zinc-dependent M1 aminopeptidase that contributes to cancer progression by promoting angiogenesis, metastasis, and tumor invasion. We have previously identified hydroxamic acid-containing analogues that are potent inhibitors of the APN homologue from the malarial parasite Plasmodium falciparum M1 aminopeptidase (PfA-M1). Herein, we describe the rationale that underpins the repurposing of PfA-M1 inhibitors as novel APN inhibitors. A series of novel hydroxamic acid analogues were developed using a structure-based design approach and evaluated their inhibition activities against APN. N-(2-(Hydroxyamino)-2-oxo-1-(3′,4′,5′-trifluoro-[1,1′-biphenyl]-4-yl)ethyl)-4-(methylsulfonamido)benzamide (6ad) proved to be an extremely potent inhibitor of APN activity in vitro, selective against other zinc-dependent enzymes such as matrix metalloproteases, and possessed limited cytotoxicity against Ad293 cells and favorable physicochemical and metabolic stability properties. The combined results indicate that compound 6ad may be a useful lead for the development of anticancer agents.
- Lee, Jisook,Vinh, Natalie B.,Drinkwater, Nyssa,Yang, Wei,Kannan Sivaraman, Komagal,Schembri, Luke S.,Gazdik, Michelle,Grin, Peter M.,Butler, Georgina S.,Overall, Christopher M.,Charman, Susan A.,McGowan, Sheena,Scammells, Peter J.
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supporting information
p. 7185 - 7209
(2019/08/28)
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- Novel betrixaban intermediate and preparation method and application thereof
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The invention discloses a novel betrixaban intermediate and a preparation method and application thereof. The structure of the intermediate is shown in formula I. The intermediate can achieve efficient and high-yield construction of an N,N-dimethylcarbamimidoyl structure fragment in the betrixaban structure through a bio-enzyme catalysis method, and has the advantages of being green and environmentally friendly.
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Paragraph 0061; 0062; 0064
(2019/07/10)
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- MONONUCLEAR IRON COMPLEX AND ORGANIC SYNTHESIS REACTION USING SAME
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Provided is a mononuclear iron complex that comprises an iron-silicon bond that is represented by formula (1) and that exhibits excellent catalyst activity in each of a hydrosilylation reaction, a hydrogenation reaction, and reduction of a carbonyl compound. In formula (1), R1-R6 either independently represent an alkyl group, an aryl group, an aralkyl group or the like that may be substituted with a hydrogen atom or X, or represent a crosslinking substituent in which at least one pair comprising one of R1-R3 and one of R4-R6 is combined. X represents a halogen atom, an organoxy group, or the like. L represents a two-electron ligand other than CO. When a plurality of L are present, the plurality of L may be the same as or different from each other. When two L are present, the two L may be bonded to each other. n and m independently represent an integer of 1 to 3 with the stipulation that n+m equals 3 or 4.
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- Copper-catalyzed amide bond formation from formamides and carboxylic acids
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A highly efficient copper-catalyzed approach to form amide bonds from formamides and carboxylic acids was developed. This protocol shows broad substrate scopes and high yields in the presence of 1 mol% catalyst and 4.0 equiv. formamides.
- Liu, Hong-Qiang,Liu, Jun,Zhang, Yang-Hui,Shao, Chang-Dong,Yu, Jing-Xun
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- Syntheses of amides via iodine-catalyzed multiple sp3 C-H bonds oxidation of methylarenes and sequential coupling with N,N-dialkylformamides
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The oxidative coupling of methylarenes and N,N-dialkylformamides was developed, and the appropriate reaction conditions were established. By using I2 as the catalyst, and tert-butyl hydroperoxide (TBHP) as the oxidant, the reaction provided N,N
- Du, Bingnan,Sun, Peipei
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p. 1176 - 1182
(2014/08/18)
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- Cross coupling of acyl and aminyl radicals: Direct synthesis of amides catalyzed by Bu4NI with TBHP as an oxidant
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A radical solution: A Bu4NI/tert-butyl hydroperoxide (TBHP) catalyzed synthesis of amides through a cross-coupling reaction between acyl and aminyl radicals is described. This method involves the combination of aldehyde C-H bond functionalization and decarbonylation of N,N-disubstituted formamides (see scheme). The cross-coupling is metal-free, has a wide substrate scope, operational simplicity, and gives high yields on scale-up. Copyright
- Liu, Zhaojun,Zhang, Jie,Chen, Shulin,Shi, Erbo,Xu, Yuan,Wan, Xiaobing
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experimental part
p. 3231 - 3235
(2012/05/05)
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- NOVEL PIPERAZINE ANALOGS AS BROAD-SPECTRUM INFLUENZA ANTIVIRALS
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A compound of Formula (I) is set forth, including pharmaceutically acceptable salts thereof, wherein Het is a 5 or 6-membered heterocycle with -N, -O, or -S adjacent to the -Ar substituent or adjacent to the point of attachment for the -Ar substituent; Ar
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Page/Page column 63
(2012/03/27)
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- Identification of a potent sodium hydrogen exchanger isoform 1 (NHE1) inhibitor with a suitable profile for chronic dosing and demonstrated cardioprotective effects in a preclinical model of myocardial infarction in the rat
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Sodium-hydrogen exchanger isoform 1 (NHE1) is a ubiquitously expressed transmembrane ion channel responsible for intracellular pH regulation. During myocardial ischemia, low pH activates NHE1 and causes increased intracellular calcium levels and aberrant cellular processes, leading to myocardial stunning, arrhythmias, and ultimately cell damage and death. The role of NHE1 in cardiac injury has prompted interest in the development of NHE1 inhibitors for the treatment of heart failure. This report outlines our efforts to identify a compound suitable for once daily, oral administration with low drug-drug interaction potential starting from NHE1 inhibitor sabiporide. Substitution of a piperidine for the piperazine of sabiporide followed by replacement of the pyrrole moiety and subsequent optimization to improve potency and eliminate off-target activities resulted in the identification of N-[4-(1-acetyl- piperidin-4-yl)-3-trifluoromethyl-benzoyl]-guanidine (60). Pharmacological evaluation of 60 revealed a remarkable ability to prevent ischemic damage in an ex vivo model of ischemia reperfusion injury in isolated rat hearts.
- Huber, John D.,Bentzien, J?rg,Boyer, Stephen J.,Burke, Jennifer,De Lombaert, Stéphane,Eickmeier, Christian,Guo, Xin,Haist, James V.,Hickey, Eugene R.,Kaplita, Paul,Karmazyn, Morris,Kemper, Raymond,Kennedy, Charles A.,Kirrane, Thomas,Madwed, Jeffrey B.,Mainolfi, Elizabeth,Nagaraja, Nelamangara,Soleymanzadeh, Fariba,Swinamer, Alan,Eldrup, Anne B.
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p. 7114 - 7140
(2012/11/07)
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- Selective deprotection and amidation of 2-pyridyl esters via N-methylation
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The 2-pyridyl residue serves as a protecting group for various carboxylic acids. The protecting group is selectively cleaved under mild conditions via N-methylation of the pyridyl group. During the deprotection process, the various functional groups as we
- Yamada, Shinji,Abe, Misato
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experimental part
p. 8667 - 8671
(2011/01/04)
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- Zinc-catalyzed reduction of amides: Unprecedented selectivity and functional group tolerance
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(Chemical Equation Presented) A novel zinc-catalyzed reduction of tertiary amides was developed. This system shows remarkable chemoselectivity and substrate scope tolerating ester, ether, nitro, cyano, azo, and keto substituents. Copyright
- Das, Shoubhik,Addis, Daniele,Zhou, Shaolin,Junge, Kathrin,Beller, Matthias
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supporting information; experimental part
p. 1770 - 1771
(2010/04/25)
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- Practical access to amines by platinum-catalyzed reduction of carboxamides with hydrosilanes: Synergy of dual Si-H groups leads to high efficiency and selectivity
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The synergetic effect of two Si-H groups leads to efficient reduction of carboxamides to amines by platinum catalysts under mild conditions. The rate of the reaction is dependent on the distance of two Si-H groups; 1,1,3,3-tetramethyldisiloxane (TMDS) and 1,2-bis(dimethylsilyl)benzene are found to be an effective reducing reagent. The reduction of amides having other reducible functional groups such as NO2, CO2R, CN, CdC, Cl, and Br moieties proceeds with these groups remaining intact, providing a reliable method for the access to functionalized amine derivatives. The platinum-catalyzed reduction of amides with polymethylhydrosiloxane (PMHS) also proceeds under mild conditions. The reaction is accompanied by automatic removal of both platinum and silicon wastes as insoluble silicone resin, and the product is obtained by simple extraction. A mechanism involving double oxidative addition of TMDS to a platinum center is discussed.
- Hanada, Shiori,Tsutsumi, Emi,Motoyama, Yukihiro,Nagashima, Hideo
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supporting information; experimental part
p. 15032 - 15040
(2010/01/29)
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- Hydrosilane reduction of tertiary carboxamides by iron carbonyl catalysts
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Fox in the carboxamide: Reduction of tertiary carboxamides to their corresponding amines is catalyzed by [Fe(CO)5] or [Fe 3(CO)12], using 1,1,3,3tetramethyldlsiloxane (TMDS) as the reducing agent. The reaction proceeds under either thermal or photochemical conditions. Unlike the hydrosilane reduction of amides using platinum or ruthenlum catalysts, TMDS preferentially reduces a nitro group, even in the presence of competing amides.
- Sunada, Yusuke,Kawakami, Hiroko,Imaoka, Tsuyoshi,Motoyama, Yukihiro,Nagashima, Hideo
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supporting information; experimental part
p. 9511 - 9514
(2010/03/24)
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- Functional group-selective poisoning of molecular catalysts: A ruthenium cluster-catalysed highly amide-selective silane reduction that does not affect ketones or esters
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The addition of amines eliminates the catalytic activity of a triruthenium cluster in the hydrosilane reduction of ketones and esters without affecting the rate of reduction of amides; selective reduction of the amide group in amido ketones and amido esters is accomplished. The Royal Society of Chemistry.
- Sasakuma, Hidehiro,Motoyama, Yukihiro,Nagashima, Hideo
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p. 4916 - 4918
(2008/09/17)
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