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A crude enzyme extracts of two halohydrin dehalogenases(HheC and HheA-N178A) for biocatalytic transformations with different substrates have been prepared. Racemic epoxides, oxazolidinones, azidoalcohols, cyanohydrins and bromoalcohols for substrates and/or standards for enzymatic reactions have been synthesized. Analytical methods of high performance liquid chromatography and gas chromatography on columns with chiral stationary phases for monitoring conversion, regio- and enantioselectivity of enzymatic reactions have been developed. Kinetic and dinamic kinetic resolution of racemic epibromohydrins in enzymatic reactions with different nucleophiles (cyanate, cyanide and azide) catalysed by halohydrin dehalogenase HheC have been studied. Catalytic activity of genetically modified halohydrin dehalogenase HheA-N178A in reactions of azidolysis of aromatic epoxides has been explored. As a result of this research, optically active 2-oxazolidinones and β-azidoalcohols have been ...
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The synthesis of racemic Carvedilol ((±)-1) has been achieved starting from 2-(chloromethyl) oxirane ((±)-2) in a four-step sequence. 5-(Chloromethyl) oxazolidin-2-one ((±)-3) and 5-((9H-carbazol-4-yloxy) methyl) oxazolidin-2-one ((±)-4) are intermediates. A similar sequence starting from (R)- or (S)-2-(chloromethyl)oxirane 2 give corresponding chiral 5-((9H-carbazol-4-yloxy)methyl) oxazolidin-2-one 4 followed by chiral Carvedilol 1. The synthetic sequence followed avoids the formation of impurity B (bis impurity). This approach can be useful for the preparation of pharmaceutically important moieties containing β-amino alcohols without formation of bis impurity ...
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The main use of linezolid is the treatment of severe infections caused by Gram-positive bacteria that are resistant to other antibiotics; it should not be used against bacteria that are sensitive to drugs with a narrower spectrum of activity, such as penicillins and cephalosporins. In both the popular press and the scientific literature, linezolid has been called a "reserve antibiotic"-one that should be used sparingly so that it will remain effective as a drug of last resort against potentially intractable infections.. In the United States, the indications for linezolid use approved by the U.S. Food and Drug Administration (FDA) are the treatment of vancomycin-resistant Enterococcus faeciuminfections, with or without bacterial invasion of the bloodstream; nosocomial pneumonia (hospital-acquired) and community-acquired pneumonia caused by S. aureus or S. pneumoniae; complicated skin and skin structure infections (cSSSI) caused by susceptible bacteria, including diabetic foot infection, unless ...
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In order to assess the frequency of clinically relevant linezolid-resistant staphylococcal isolates, and the role of linezolid in maintaining and coselecting multiple resistance mechanisms (cfr, 23S rRNA, L3/L4 mutations), a prospective Italian study was performed from 2010 to 2011 to confirm the diffusion of three major multidrug-resistant clones (ST2, ST5, ST23).
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Abstract: : Purpose: post-operative endophthalmitis is most frequently due to infection with gram positive bacteria, particularly coagulase negative Staphylococci. In the past, direct intra-ocular injection of antibiotics was necessary as penetration into the eye from the bloodstream was restricted by the blood-ocular barrier. The few antibiotics that may have achieved therapeutic intra-ocular concentrations following systemic administration had largely gram negative activity. An antibiotic with broad spectrum gram positive activity, which reaches therapeutic levels in the eye following intravenous or oral administration, would offer a significant advance in the treatment of endophthalmitis. Linezolid is the first licensed representative of a new class of antibiotics, the oxazolidinones. Its spectrum of activity is primarily against gram positive bacteria. Our aim was to establish pharmacokinetic curves for intraocular penetration of Linezolid following oral administration. Methods: a single ...
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Susan Todd, writing this morning for the New Jersey Star Ledger, has a very balanced view of the Merck CETP inhibitor's chances -- including the idea that Roche's CETP candidate may beat Merck's to market by more than two years -- do go read it all: . . . .The drugmaker will move anacetrapib into…
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Whole blood samples from healthy subjects will be incubated with MRSA bacterium or bacterial toxins in the presence and absence of either linezolid or vancomycin. Final concentrations will mimic physiologic conditions. Platelets and leukocytes will be isolated and assayed for the presence of absence of activation and pre-mRNA splicing ...
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