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A compound of formula (I) as well as pharmaceutically acceptable salt thereof, wherein R1 to R5 have the significance given in claim 1, can be used as a medicament.

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A new bifunctional fluorescent label, BRos, was synthesised in order to monitor protein dynamics using fluorescence microscopy, and the photophysical properties were compared with those of bifunctionalised rhodamine, BRho. In a labelling experiment with a model peptide of troponin C, which regulates muscle contraction and relaxation, it was found that BRos was bound to the peptide through two linkages and provided a homogeneous compound, whereas BRho gave a pair of diastereomers having different physical properties in NMR and HPLC analyses. This journal is The Royal Society of Chemistry.

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A mild method is presented for the formation of N-acylated oxazolidinones that employs acid fluorides and mild bases, such as iPr 2NEt and NEt3. Optimized reaction conditions for two types of substrates have been developed utilizing either the oxazolidinone itself or the corresponding in situ generated O-silyloxazolidinones resulting in the formation of the desired N-acylated products in high yields of up to 98%.

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Given the environmental concerns driving process developments and considering the size and scale of potential application of post combustion capture (PCC), it is important to fully understand process hazards. In this work we present an environmental, health and safety (EHS) hazard assessment framework for screening and comparing amine based PCC options. A multi-criteria assessment compares the performance of 7 m Monoethanolamine (MEA), 4 m Diethanolamine (DEA), 10 m Diglycolamine (DGA), 8 m Piperazine (PZ) and a blend of 7 m Methyldiethanolamine (MDEA) with 2 m PZ under a set of different process conditions. The EHS assessment takes into account varying circulating volumes, process conditions and potential for solvent degradation. The EHS assessment is also compared with operating costs and life cycle assessment (LCA) metrics. The EHS assessment is carried out on two levels. The first is less data intensive and provides a unified score that can be used to compare and screen process alternatives, while the second level studies the contribution of individual degradation products to different EHS hazard categories in detail. Results of the parametric study show that lean loading is an influential factor in determining first level EHS scores, process costs and environmental impacts and a trade-off is observed between EHS and LCA scores for some of the solvents. In the second level EHS assessment, the parent amine heavily influences most mass dependent hazard categories such as the fire/explosion, acute toxicity and air mediated effects category. Heat stable salts affect the solid waste category. Most degradation products are considered corrosive or irritant and therefore feature strongly in that category in addition to the parent amine. The second level EHS assessment is complemented with workplace exposure analysis to ensure the compliance with workplace threshold limits. Nitrosamines stand out for acute and chronic toxicity effects and are therefore used as an example to demonstrate the workplace exposure. Workplace amines and nitrosamine concentrations are estimated to assess long and potential short term worker exposure as a result of gas leakages and spills respectively. Indoor ventilation rates are inadequate to keep workplace amine and nitrosamine concentrations below the recommended guidelines. To reduce short term exposure effects, a steady state liquid nitrosamine concentration lower than 13.7 mM is required. The results of the parametric study show that changing process conditions can lower nitrosamine concentrations, but can also shift the contribution of the parent amine and degradation products of the other hazard categories and affect LCA metrics. The sensitivity of the EHS and LCA results to model assumptions and conditions are tested by varying inlet NOx, expected aerosols and solvent degradation levels. Low NOx levels in the flue gas are required for PZ and MDEA-PZ systems to meet the nitrosamine concentration thresholds for environmental and health concerns. This study also highlights the need to consider hazard effects during early process design phases, identifies degradation related data gaps and critical process parameters towards more environmentally benign PCC design.

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PROBLEM TO BE SOLVED: To provide a compound that has excellent glucokinase (GK) activating action and is useful as a pharmaceutical. SOLUTION: The present invention provides a 2-pyridone compound represented by formula [1], and a tautomer or stereoisomer of the compound, or their pharmacologically acceptable salts, or their solvates (where R1 is RA-ZA-; RA is any of a carboxy group, a sulfo group or formula [5]). COPYRIGHT: (C)2016,JPO&INPIT

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A compound of formula (I) as well as pharmaceutically acceptable salt thereof, wherein R1 to R4 have the significance given in claim 1, can be used as a modulator of AMPK

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Despite the remarkable advances in catalytic asymmetric aziridinations over the past decades, establishing a general procedure for the stereoselective synthesis of trisubstituted aziridines has remained an elusive goal. Chiral N-triflyl phosphoramide-catalyzed reactions of N-alpha-diazoacyl oxazolidinones and N-Boc imines were developed as a solution to this unmet challenge.

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Previous structure-activity relationship studies involving a series of lactone-based muscarinic ligands identified a lead compound containing a diphenylmethylpiperazine moiety (4; IC50 = 340 nM). The purpose of the present work is to investigate 1,3-benzodioxoles, 4,4-diethyl substituted tetrahydrofurans, 5-substituted oxazolidinones and chromones as bioisosteric replacements for the lactone ring in a novel series of muscarinic ligands. The approach provided compounds with improved % inhibition values and identified a non-selective muscarinic ligand with an IC50 value of 280 nM. The structure-activity relationship for this new series will be discussed. Selected compounds were evaluated in preliminary assays for subtype selectivity and were found to be non-selective.

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Described herein are 1,4-substituted piperidine compounds according to Formula (I) that have demonstrated activity as fatty acid synthase inhibitors. Also described herein are pharmaceutical compositions containing the described 1,4-substituted piperidine compounds, and methods of treating diseases mediated by fatty acid synthase, by administering one or more of the compounds or pharmaceutical formulations described herein. Also described herein are methods of synthesizing the compounds described, including the described 1,4-substituted piperidine compounds and synthetic intermediates useful in those syntheses.

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A practical and efficient synthetic route to construct a variety of 3-amidated quinoxalin-2(1H)-ones was developed via transition-metal free direct oxidative amidation of quinoxalin-2(1H)-ones with amidates using Selectfluor reagent as a mild oxidant. This protocol features mild reaction conditions, operational simplicity, broad substrate scope, and good to excellent yields.

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