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排序方式: 共有119条查询结果,搜索用时 500 毫秒
1.
Samuel K Yin W Stearns RA Tang YS Chaudhary AG Jewell JP Lanza T Lin LS Hagmann WK Evans DC Kumar S 《Journal of mass spectrometry : JMS》2003,38(2):211-221
Metabolic activation of drug candidates to electrophilic reactive metabolites that can covalently modify cellular macromolecules may result in acute and/or idiosyncratic immune system-mediated toxicities in humans. This presents a significant potential liability for the future development of these compounds as safe therapeutic agents. We present here an example of an approach where sites of metabolic activation within a new drug candidate series were rapidly identified using online liquid chromatography/multi-stage mass spectrometry on an ion trap mass spectrometer. This was accomplished by trapping the reactive intermediates formed upon incubation of compounds with rat and human liver microsomes as their corresponding glutathione conjugates and mass spectral characterization of these thiol adducts. Based on the structures of the GSH adducts identified, potential sites and mechanisms of bioactivation within the chemical structure were proposed. These metabolism studies were interfaced with iterative structural modifications of the chemical series in order to block these bioactivation sites within the molecule. This strategy led to a significant reduction in the propensity of the compounds to undergo metabolic activation as evidenced by reductions in the irreversible binding of radioactivity to liver microsomal material upon incubation of tritium-labeled compounds with this in vitro system. With the efficiency and throughput achievable with such an approach, it appears feasible to identify and address the metabolic activation potential of new drug leads during routine metabolite identification studies in an early drug discovery setting. 相似文献
2.
Harry R. Chobanian Ping Liu Marc D. Chioda Yan Guo Linus S. Lin 《Tetrahedron letters》2007,48(7):1213-1216
We report an expedient method for the heteroarylation of acetone under tin-free conditions. The coupling is performed using the commercially available enol silane of acetone (2-trimethylsilyloxypropene) and a corresponding aryl bromide, chloride or triflate under microwave-assisted conditions, with tris(dibenzylideneacetone)dipalladium (Pd2(dba)3) or palladium acetate (Pd(OAc)2) and 2-(2′,6′-dimethoxybiphenyl)dicyclohexylphosphine (S-Phos) as the catalyst system. 相似文献
3.
A titration unit for automatic analysis systems is described. The titrator performs different titrations specified by strings of digital parameters. It has 4 independent titration stations with individual electrode systems. A multiburette with 20 cylinders provides all stations with the necessary reagents. End-point titrations, and incremental and equilibrium titrations are controlled by a microcomputer. In combination with a sample transport and a desk calculator, the titrator can be used to process automatically samples of different natures which require different treatment. 相似文献
4.
The enantioselective reduction of 2-pentanone to (R)- and (S)-2-pentanol by Thermoanaerobacter (formerly Thermoanaerobium) brockii alcohol dehydrogenase (TBADH) in mixtures of water and water-miscible organic solvents was investigated. Significant enzymatic activity was retained in up to 87% methanol, ethanol and acetonitrile. The changes in enzyme activity as a function of organic solvent were correlated to structural alterations of TBADH with a series of spectroscopic studies (fluorescence, fluorescence quenching and circular dichroism (CD)). Interestingly, this study shows that the tetrameric form of TBADH is not critical for catalytic performance. 相似文献
5.
Dr. Stefanie Neubauer Dr. Florian Rechenmacher Dr. Ambros J. Beer Dr. Flavio Curnis Karolin Pohle Dr. Calogero D'Alessandria Prof. Dr. Hans‐Jürgen Wester Prof. Dr. Ute Reuning Prof. Dr. Angelo Corti Prof. Dr. Markus Schwaiger Prof. Dr. Horst Kessler 《Angewandte Chemie (International ed. in English)》2013,52(44):11666-11666
6.
Linus H. Leung Stephanie Fan Hani E. Naguib 《Journal of Polymer Science.Polymer Physics》2012,50(4):242-249
The fabrication of three‐dimensional (3D) electrospun composite scaffolds was presented in this study. Layers of electrospun meshes made from composites of poly(lactide‐co‐glycolide acid) (PLGA) and hydroxyapatite (HA) were stacked and sintered using pressurized gas. Three HA concentrations of 5, 10, and 20 wt % were tested, and the addition of the HA nanoparticles decreased the tensile mechanical properties of the meshes with 20 wt % HA. However, after the gas absorption process, the fibers within the mesh sintered, which improved the mechanical properties more than twofold. The fabrication of 3D, porous, electrospun scaffolds was also demonstrated. The resulting 3D scaffolds had open porosity of up to 70% and modulus of ~20 MPa. This technique improves on the current electrospinning technology by overcoming the challenges of depositing a thick, 3D structure. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011 相似文献
7.
De La Rosa Nathaly Kristiansson Per Nilsson E. J. Charlotta Ros Linus Pallon Jan Skogby Henrik 《Journal of Radioanalytical and Nuclear Chemistry》2018,317(1):253-259
Journal of Radioanalytical and Nuclear Chemistry - Proton-induced reaction (p,α) is one type of nuclear reaction analysis (NRA) suitable especially for light element quantification.... 相似文献
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9.
Various composites have been proposed in the literature for the fabrication of bioscaffolds for bone tissue engineering. These materials include poly(ε‐caprolactone) (PCL) with hydroxyapatite (HA). Since the biomaterial acts as the medium that transfers mechanical signals from the body to the cells, the fundamental properties of the biomaterials should be characterized. Furthermore, in order to control the processing of these materials into scaffolds, the characterization of the fundamental properties is also necessary. In this study, the physical, thermal, mechanical, and viscoelastic properties of the PCL‐HA micro‐ and nano‐composites were characterized. Although the addition of filler particles increased the compressive modulus by up to 450%, the thermal and viscoelastic properties were unaffected. Furthermore, although the presence of water plasticized the polymer, the viscoelastic behavior was only minimally affected. Testing the composites under various conditions showed that the addition of HA can strengthen PCL without changing its viscoelastic response. The results found in this study can be used to further understand and approximate the time‐dependent behavior of scaffolds for bone tissue engineering. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
10.