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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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*  NOPR: Synthesis of racemic and chiral Carvedilol starting from corresponding 5-(chloromethyl)oxazolidin-2-one
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 Vitro Activity of TR-700, the Active Ingredient of the Antibacterial Prodrug TR-701, a Novel Oxazolidinone Antibacterial...
PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.
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Safety of long-term use of linezolid: results of an open-label study Jose A Vazquez,1 Anthony C Arnold,2 Robert N Swanson,3 Pinaki Biswas,3 Matteo Bassetti4 1Section of Infectious Diseases, Medical College of Georgia, Georgia Regents University, Augusta, GA, USA; 2UCLA Department of Ophthalmology, Jules Stein Eye Institute, Los Angeles, CA, USA; 3Clinical Research, Global Innovative Pharmaceutical, Pfizer Inc., New York, NY, USA; 4Infectious Diseases Division, Santa Maria della Misericordia University Hospital, Udine, Italy Objective: The objective of this study was to assess the long-term safety of linezolid in patients with chronic infections requiring treatment for ≥6 weeks. Enhanced monitoring for optic neuropathy was included to characterize the early development of this side effect and to identify ophthalmologic tests that might be valuable in early detection of this event. Methods: This was a multicenter, open-label, pilot study of patients aged ≥18 years on long-term linezolid therapy.
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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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There will be no CETP heart drug miracle in the works at Merck.. The pharma giant looked over a set of positive but troublesome Phase III data for its drug anacetrapib and concluded today that they will relegate it to the same graveyard that has greeted every other CETP heart drug so far.. The decision underscores a tidal shift in drug developer's standards for launching a big new drug into a major market, where the data has to point to a compelling market opportunity. Failing that, marginal drugs don't stand a chance, even if they might pass muster at the FDA.. "Unfortunately, after comprehensive evaluation, we have concluded that the clinical profile for anacetrapib does not support regulatory filings," said Roger Perlmutter, president of Merck Research Laboratories. "During the past half-century, Merck has made numerous, important contributions to the treatment of cardiovascular disease. Our work in cardiovascular research continues.". Once upon a time, CETP offered a bright prospect for some ...
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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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*  Single Dose Safety, Tolerability And Pharmacokinetics Of Escalating Intravenous Doses Of Linezolid Followed By Evaluation Of...
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