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排序方式: 共有1004条查询结果,搜索用时 15 毫秒
31.
Dr. Holger Siebeneicher Dr. Arwed Cleve Dr. Hartmut Rehwinkel Dr. Roland Neuhaus Dr. Iring Heisler Dr. Thomas Müller Dr. Marcus Bauser Dr. Bernd Buchmann 《ChemMedChem》2016,11(20):2261-2271
Despite the long‐known fact that the facilitative glucose transporter GLUT1 is one of the key players safeguarding the increase in glucose consumption of many tumor entities even under conditions of normal oxygen supply (known as the Warburg effect), only few endeavors have been undertaken to find a GLUT1‐selective small‐molecule inhibitor. Because other transporters of the GLUT1 family are involved in crucial processes, these transporters should not be addressed by such an inhibitor. A high‐throughput screen against a library of ~3 million compounds was performed to find a small molecule with this challenging potency and selectivity profile. The N‐(1H‐pyrazol‐4‐yl)quinoline‐4‐carboxamides were identified as an excellent starting point for further compound optimization. After extensive structure–activity relationship explorations, single‐digit nanomolar inhibitors with a selectivity factor of >100 against GLUT2, GLUT3, and GLUT4 were obtained. The most promising compound, BAY‐876 [N4‐[1‐(4‐cyanobenzyl)‐5‐methyl‐3‐(trifluoromethyl)‐1H‐pyrazol‐4‐yl]‐7‐fluoroquinoline‐2,4‐dicarboxamide], showed good metabolic stability in vitro and high oral bioavailability in vivo. 相似文献
32.
William C. Guenther 《技术计量学》2013,55(3):483-498
The linear cost model previously formalized by Hald [4], [5], [9] is reviewed. Techniques are described which permit easy determination of sampling plans based on that model. The degenerate, the beta, and the two point distributions are considered as prior distributions of p, the process fraction defective. For calculations only standard tables and a desk calculator are required. 相似文献
33.
Alf Mews Chaoyang Jiang Thomas Schuessler Guenther Philipp Y. Fan Marko Burghard 《Israel journal of chemistry》2001,41(1):15-22
The oxidation process of single-walled carbon nanotubes via nitric acid treatment was followed by IR-, UV-Vis-NIR, and single bundle Raman spectroscopy. The introduction of functional, oxygen-containing groups is revealed by an additional absorption band at 1725 cm−1, characteristic of carbonyl stretch vibrations. No significant shift of the optical absorption bands could be detected after oxidation. The combination of atomic force microscopy and confocal scanning resonance-enhanced Raman microscopy was used to investigate thin bundles and, eventually, individual nanotubes in detail. These experiments enabled determination of the dependence of the Raman intensity of the G-line (around 1590 cm−1) on the bundle height for both non-oxidized and oxidized tubes. The Raman cross-section of the oxidized tubes was found to be reduced by a factor of ˜4, compared to the pristine tubes. This observation is ascribed to all tubes within a bundle that are oxidized to the same degree. 相似文献
34.
Syed Safdar Ali Khalid Mohammed Khan Hartmut Echner Wolfgang Voelter Mashooda Hasan Atta-ur-Rahman 《Advanced Synthesis \u0026amp; Catalysis》1995,337(1):12-17
Two new synthons, Fmoc-L-Arg(biphenyl-4-sulphonyl)-OH ( 8 ) and Fmoc-Arg(4-methoxy-3-t-butylbenzenesulphonyl)-OH ( 14 ), are prepared for the synthesis of arginine-containing peptides. These groups are cleaved by commonly employed trifluoroacetic acid and methanesulphonic acid. Kinetic studies reveal that extended bicyclic aromatic conjugation, as in biphenyl, slightly improves the acid lability compared to the electron-donating t-butyl group. 相似文献
35.
Peter Mechnich Martin Schmücker Hartmut Schneider 《Journal of the American Ceramic Society》1999,82(9):2517-2522
A promising technique for the fabrication of mullite ceramics and mullite-matrix composites with low dimensional changes ("near-net-shape processing") is reaction bonding using Si metal and α-Al2 O3 as starting materials, because sintering-induced shrinkage is compensated by Si-oxidation-induced volume expansion. A mullite reaction bonding (RBM) route which proceeds at much lower temperatures (lessthan equal to1350°C) than in conventional RBM systems (greaterthan equal to1500°C) is based on Ce doping which provides accelerated Si oxidation and mullite formation due to the formation of transient, low-viscosity Ce-Al-Si-O liquids. The present study shows that the required Ce-Al-Si-O liquids form in a reducing environment with Ce occurring as Ce3+ . In an oxidizing environment, Ce is present as Ce4+ , giving rise to precipitation of crystalline CeO2 . Ce3+ left and right arrow Ce4+ redox reactions in the temperature range under consideration appear to be controlled by the presence of nonoxidized Si in the samples. According to the present investigation the amount of CeO2 added to the starting powders must be tailored carefully: Exaggerated CeO2 content produces large amounts of low-viscosity Ce-Al-Si-O liquids which may have the disadvantage of excessive sealing of the open porosity. This slows the oxygen diffusion velocity into the specimen considerably, with the consequence that nonoxidized Si and a residual Ce-Al-Si-O glass coexist in the ceramics after processing. A solution to this problem is to simultaneously enhance mullite crystal growth through seeding which works against excessive liquid-phase-induced shrinkage of the samples. This in turn enables complete oxidation and recrystallization of all liquid phases. 相似文献
36.
Patrick J. Riss Dr. Fabian Debus Dr. René Hummerich Ulrich Schmidt Dr. Patrick Schloss Dr. Hartmut Lueddens Dr. Frank Roesch Dr. 《ChemMedChem》2009,4(9):1480-1487
N‐4‐Fluorobut‐2‐yn‐1‐yl‐2β‐carbomethoxy‐3β‐phenyltropane (PR04.MZ) has been developed as dopamine transporter (DAT) ligand for molecular imaging. It contains a terminally fluorinated, conformationally constrained nitrogen substituent that is well suited for the introduction of fluorine‐18. The present report describes the pharmacological characterisation of [18F]PR04.MZ. The ligand shows an IC50 value of 2 nM against human DAT, whereas the IC50 value against human serotonin transporter and human noradrenalin transporter are lower (110 nM and 22 nM , respectively). Furthermore, its ex vivo organ distribution, its binding profile in the rat brain and reversibility of binding were examined. A μPET study illuminates a fast kinetic profile and specific binding to rat DAT. 相似文献
37.
Guenther Fuellerer Karl F. Doerner Richard F. Hartl Manuel Iori 《Computers & Operations Research》2009
In this paper a combination of the two most important problems in distribution logistics is considered, known as the two-dimensional loading vehicle routing problem. This problem combines the loading of the freight into the vehicles, and the successive routing of the vehicles along the road network, with the aim of satisfying the demands of the customers. 相似文献
38.
39.
Joachim Mittendorf Prof. Dr. Stefan Weigand Dr. Cristina Alonso‐Alija Dr. Erwin Bischoff Dr. Achim Feurer Dr. Michael Gerisch Dr. Armin Kern Dr. Andreas Knorr Dr. Dieter Lang Dr. Klaus Muenter Dr. Martin Radtke Dr. Hartmut Schirok Dr. Karl‐Heinz Schlemmer Dr. Elke Stahl Dr. Alexander Straub Dr. Frank Wunder Dr. Johannes‐Peter Stasch Dr. 《ChemMedChem》2009,4(5):693-693
40.
Guenther K Heinke V Thiele B Kleist E Prast H Raecker T 《Environmental science & technology》2002,36(8):1676-1680
4-Nonylphenols (NPs) are common products of biodegradation of a widely used group of nonionic surfactants, the nonylphenol ethoxylates (NPEs). These compounds are known to be persistent, toxic, and estrogen active. There is a worldwide scientific and public discussion on the potential consequences of human long term dietary exposure to such endocrine disrupters. Despite numerous determinations of NPs in environmental samples no systematical reports exist relating to concentrations of NPs in food. We analyzed NPs in 60 different foodstuff commercially available in Germany. The results indicate that NPs are ubiquitous in food. The concentrations of NPs on a fresh weight basis varied between 0.1 and 19.4 microg/kg regardless of the fat content of the foodstuff. Based on data on German food consumption rates and these first analyses of NPs in food, the daily intake for an adult was calculated to be 7.5 microg/day NPs. For infants exclusively fed with breast milk or infant formulas daily intakes of 0.2 microg/day and 1.4 microg/day NPs, respectively, can be estimated. 相似文献