- NB2001, a novel antibacterial agent with broad-spectrum activity and enhanced potency against β-lactamase-producing strains
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Enzyme-catalyzed therapeutic activation (ECTA) is a novel prodrug strategy to overcome drug resistance resulting from enzyme overexpression. β-Lactamase overexpression is a common mechanism of bacterial resistance to β-lactam antibiotics. We present here the results for one of the β-lactamase ECTA compounds, NB2001, which consists of the antibacterial agent triclosan in a prodrug form with a cephalosporin scaffold. Unlike conventional β-lactam antibiotics, where hydrolysis of the β-lactam ring inactivates the antibiotic, hydrolysis of NB2001 by β-lactamase releases triclosan. Evidence supporting the proposed mechanism is as follows. (i) NB2001 is a substrate for TEM-1 β-lactamase, forming triclosan with a second-order rate constant (kcat/Km) of greater than 77,000 M-1 s-1. (ii) Triclosan is detected in NB2001-treated, β-lactamase-producing Escherichia coli but not in E. coli that does not express β-lactamase. (iii) NB2001 activity against β-lactamase-producing E. coli is decreased in the presence of the β-lactamase inhibitor clavulanic acid. NB2001 was similar to or more potent than reference antibiotics against clinical isolates of Staphylococcus aureus (including MRSA), Staphylococcus epidermidis, Streptococcus pneumoniae, vancomycin-resistant Enterococcus faecalis, Moraxella catarrhalis and Haemophilus influenzae. NB2001 is also active against Klebsiella pneumoniae, Enterobacter aerogenes, and Enterobacter cloacae. The results indicate that NB2001 is a potent, broad-spectrum antibacterial agent and demonstrate the potential of ECTA in overcoming β-lactamase-mediated resistance.
- Li, Qing,Lee, Jean Y.,Castillo, Rosario,Hixon, Mark S.,Pujol, Catherine,Doppalapudi, Venkata Ramana,Shepard, H. Michael,Wahl, Geoffrey M.,Lobl, Thomas J.,Chan, Ming Fai
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- Synthesis method of triclosan
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The invention provides a triclosan synthesis method, and relates to the technical field of chemical synthesis. The synthesis method of triclosan comprises the following steps: (a) reacting 2-halogenated-5-chlorophenol with a silanization reagent and an alkali to obtain an intermediate I; (b) reacting the intermediate I with 2,4-dichlorophenol, iodinated alkali metal salt and an alkali to obtain anintermediate II; and (c) reacting the intermediate II with copper salt and water to obtain triclosan. The triclosan synthesis method provided by the invention has the advantages that the reaction conditions are mild, the reaction can be carried out without strong acid, strong alkali and high-temperature conditions, and the generation of a large amount of acid liquor and alkali liquor and high-temperature operation can be avoided; flammable and explosive toxic gas is not needed, so that the safety coefficient is high; and a diazonium salt is not needed, so that a large amount of carcinogenic substances such as benzofuran and dioxin can be prevented from being generated in the hydrolysis process, the obtained triclosan is low in impurity content and high in purity, and the requirements of pharmacopeia standards and ICH on raw material medicines can be met.
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- Computational and Experimental Studies of Phthaloyl Peroxide-Mediated Hydroxylation of Arenes Yield a More Reactive Derivative, 4,5-Dichlorophthaloyl Peroxide
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The oxidation of arenes by the reagent phthaloyl peroxide provides a new method for the synthesis of phenols. A new, more reactive arene oxidizing reagent, 4,5-dichlorophthaloyl peroxide, computationally predicted and experimentally determined to possess enhanced reactivity, has expanded the scope of the reaction while maintaining a high level of tolerance for diverse functional groups. The reaction proceeds through a novel "reverse-rebound" mechanism with diradical intermediates. Mechanistic insight was achieved through isolation and characterization of minor byproducts, determination of linear free energy correlations, and computational analysis of substituent effects of arenes, each of which provided additional support for the reaction proceeding through the diradical pathway.
- Camelio, Andrew M.,Liang, Yong,Eliasen, Anders M.,Johnson, Trevor C.,Yuan, Changxia,Schuppe, Alex W.,Houk,Siegel, Dionicio
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p. 8084 - 8095
(2015/09/01)
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- CYCLIC PEROXIDE OXIDATION OF AROMATIC COMPOUND PRODUCTION AND USE THEREOF
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The present invention provides a method for converting an aromatic hydrocarbon to a phenol by providing an aromatic hydrocarbon comprising one or more aromatic C-H bonds and one or more activated C-H bonds in a solvent; adding a phthaloyl peroxide to the solvent; converting the phthaloyl peroxide to a di-radical; contacting the di-radical with the one or more aromatic C-H bonds; oxidizing selectively one of the one or more aromatic C-H bonds in preference to the one or more activated C-H bonds; adding a hydroxyl group to the one of the one or more aromatic C-H bonds to form one or more phenols; and purifying the one or more phenols.
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Page/Page column 10
(2014/10/15)
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- MEDICAL ADHESIVE COMPOSITIONS
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A medical adhesive composition comprising, based upon the total weight of the composition, from about 50 wt. % to about 99.9 wt. % of one or more α-cyanoacrylate monomers and from about 0.1 wt. % to about 5 wt. % of one or more non-steroidal anti-inflammatory drugs (NSAIDs). Suitable NSAIDs include ibuprofen and acetaminophen. The resulting compositions provide enhances fibroblast proliferation and reduced cytotoxicity compared to compositions that do not contain NSAID.
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- ALKYLPOLYGLUCOSIDES CONTAINING DISINFECTANT COMPOSITIONS ACTIVE AGAINST PSEUDOMONAS MICROORGANISM
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An antiseptic cleansing composition comprising an antimicrobial agent, an effective amount of an alkylpolysaccharide surfactant, at least one alkyl alcohol and at least one aryl alcohol. Suitable surfactant alkylpolysaccharides may contain one or more sugar units selected from the group consisting of maltose, arabinose, xylose, mannose, galactose, gulose, idose, talose, allose, altrose, sucrose, fructose, sorbose, levulose, lactose, allulose, tagatose, alloheptulose, sedoheptulose, glucoheptulose, mannoheptulose, guloheptulose, idoheptulose, galactoheptulose, taloheptulose and derivatives thereof. Suitable antimicrobial agents include chlorhexidine, chlorhexidine salt, chlorophenol derivative, octenidindihydrochloride (CH3-(CH2)7-NHON-(CH2)10-NO-NH(CH2)7-CH2 or any other salt thereof, and quaternary ammonium compounds.
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- Process for the preparation of halogenated hydroxydiphenyl compounds
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A process for the preparation of halohydroxydiphenyl compounds useful for protecting organic materials and articles from microorganisms, of the formula by acylation of a halogenated benzene compound (first stage), etherification of the acylated compound with a halogenated phenol compound (second stage), oxidation of the etherified compound (third stage) and hydrolysis of the oxidized compound in a fourth stage, according to the following reaction scheme: in which R1 and R2 independently of one another are F, Cl or Br; R3 and R4 independently of one another are hydrogen; or C1-C4alkyl; m is 1 to 3; and n is 1 or 2.
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- Polymeric delivery and release systems for oral care actives
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A polymer useful in oral care compositions which has a reactive group covalently bonded to a bactericide, flavorant and/or essential oil compound, said bond being hydrolyzable in aqueous solution to slowly release said compound into said composition.
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- Antibacterial antiplaque mouthwash composition
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An oral composition mouthwash or liquid dentifrice containing an aqueous vehicle acceptable vehicle including an alcohol, a substantially water-insoluble noncationic antibacterial antiplaque agent, such as 2,4,4'-trichloro-21'-hydroxy-diphenyl ether (triclosan) wherein the antiplague agent is entirely dissolved in the solvent and the weight ratio of water to alcohol is in excess of about 10:1.
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- Antiplaque oral hygiene composition
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An oral hygiene composition in the form of a dentifrice or a mouthwash, comprising: (a) from 0.01 to 2% by weight of the composition of an antibacterial compound of formula (I): STR1 in which R1 is oxygen, sulphur or an alkylene group of from 1 to 6 carbon atoms, each of R2 to R6 and R2 ' to R6 ' is hydrogen, hydroxyl or halogen; (b) from 0 to 90% by weight of a dentally acceptable abrasive, (c) from 0.1% to 15% by weight of a dialkali or tetra-alkali metal pyrophosphate salt or a mixture thereof and (d) water.
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- 3-Imino-1,2,4-benzotriazine-1-oxides
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New 3-Imino-1,2,4-benzotriazine-1-oxides of formula I SPC1 wherein R represents an alkyl, alkenyl or haloalkyl radical, a phenyl or aralkyl radical optionally substituted by alkyl, alkoxy, haloalkyl, halogen or hydroxy, X and Y each independently represent hydrogen, halogen, an alkyl or alkoxy radical, or one of the two symbols represents a phenoxy or phenylsulphonyl radical optionally substituted by halogen, alkyl, haloalkyl and/or alkoxy which are active against harmful microorganisms are disclosed.
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