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191.
Synthesis and Structure–Activity Relationship Studies of 2‐(1,3,4‐Oxadiazole‐2(3H)‐thione)‐3‐amino‐5‐arylthieno[2,3‐b]pyridines as Inhibitors of DRAK2 下载免费PDF全文
Dr. Piotr Leonczak Dr. Ling‐Jie Gao Dr. Anna Teresa Ramadori Prof. Eveline Lescrinier Prof. Jef Rozenski Dr. Steven De Jonghe Prof. Piet Herdewijn 《ChemMedChem》2014,9(11):2587-2601
In recent years, DAPK‐related apoptosis‐inducing protein kinase 2 (DRAK2) has emerged as a promising target for the treatment of a variety of autoimmune diseases and for the prevention of graft rejection after organ transplantation. However, medicinal chemistry optimization campaigns for the discovery of novel small‐molecule inhibitors of DRAK2 have not yet been published. Screening of a proprietary compound library led to the discovery of a benzothiophene analogue that displays an affinity constant (Kd) value of 0.25 μM . Variation of the core scaffold and of the substitution pattern afforded a series of 5‐arylthieno[2,3‐b]pyridines with strong binding affinity (Kd=0.008 μM for the most potent representative). These compounds also show promising activity in a functional biochemical DRAK2 enzyme assay, with an IC50 value of 0.029 μM for the most potent congener. Selectivity profiling of the most potent compounds revealed that they lack selectivity within the DAPK family of kinases. However, one of the less potent analogues is a selective ligand for DRAK2 and can be used as starting point for the synthesis of selective and potent DRAK2 inhibitors. 相似文献
192.
Songlin Ran Shuigen G. Huang Omer Van der Biest Jef Vleugels 《Journal of the European Ceramic Society》2012,32(10):2537-2543
Fully densified ZrB2-based ceramic composites were produced by reactive pulsed electric current sintering (PECS) of ZrB2–ZrH2 powders within a total thermal cycle time of only 35 min. The composition of the final composite was directly influenced by the initial ZrH2 content in the starting powder batch. With increasing ZrH2 content, ZrB2–ZrO2, ZrB2–ZrB–ZrO2 and ZrB2–ZrB–Zr3O composites were obtained. The ZrB2–ZrB–ZrO2 composite derived from a 9.8 wt% ZrH2 starting powder exhibited an excellent flexural strength of 1382 MPa combined with a Vickers hardness of 17.1 GPa and a fracture toughness of 5.0 MPa m1/2. The high strength was attributed to a fine grain size and the removal of B2O3 through reaction with Zr. Higher ZrH2 content starting powders were densified through solution-reprecipitation resulting in the formation of coarser angular ZrB2–ZrB composites with a Zr3O grain boundary phase with a fracture toughness of 5.0 MPa m1/2 and an acceptable strength in the 852–939 MPa range. 相似文献
193.
用一种新的液相掺杂技术制备Y2O3的ZrO2纳米粉体,在水-乙醇溶剂中,干燥由硝酸铝,硝酸钇和单斜相氧化锆粉体组成的悬浮液,然后在600℃热分解,可以制备出粒度小于100nm的Y2O3掺杂单斜相ZrO2粉体,这种粉体可以在0.1Pa的真空中,经1450℃热压烧结成致密化Y-TZP材料,此材料的断裂韧性(KIC)为9.9MPa.m^1/2,Vickers硬度(HV100N)为11.720GPa。 相似文献
194.
Ping-an Fang Hui Gu Pei-ling Wang Jef Van Landuyt Jef Vleugels Omer Van der Biest 《Journal of the American Ceramic Society》2005,88(7):1929-1934
The phase and microstructure relationship of 12 mol% CeO2 -stabilized ZrO2 ceramics prepared from coated powder was investigated using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy-dispersed X-ray spectroscopy (EDS). As compared with the sample prepared with co-precipitated method, which exhibited a similar grain size distribution, the EDS analysis revealed that the powder coating induced a wide distribution of CeO2 solubility, which decreases monotonically with the increase of grain size. This variation of stabilizer content from grain to grain rendered many large grains in the monoclinic phase. Stronger cerium segregation to grain boundaries was observed between large grains, which often form thin amorphous films there. The inhomogeneous CeO2 distribution keeps more tetragonal ZrO2 grains close to the phase boundary to facilitate the transforming toughness. Addition of an Al2 O3 precursor in coated powders effectively raises the overall CeO2 stabilizer content in the grains and preserves more transformable tetragonal phase in the microstructure, which further enhanced the fracture toughness. The dependence of CeO2 solubility on grain size may be explained in a simple coating-controlled diffusion and growth process that deserves further investigation. 相似文献
195.
Koenraad Bonny Patrick De Baets Pieter Samyn Filip Lobbestael Jozef Vleugels Bert Lauwers Weidong Liu 《Lubrication Science》2009,21(9):378-396
Hot‐pressed, laboratory‐made, ZrO2‐based composites with 40 vol. % WC, TiCN or TiN were surface finished by electrical discharge machining in order to compare their reciprocating sliding friction and wear response against WC–6wt%Co cemented carbide in unlubricated conditions. Sliding experiments were performed using a Plint TE77 pin‐on‐flat wear test rig, revealing a strong impact of the secondary phase on the tribological behaviour of the ZrO2‐based composites. The worn surfaces and wear debris were characterised by scanning electron microscopy, energy dispersive X‐ray analysis and surface topography scanning, pointing out abrasion, polishing and adhesion as main wear mechanisms. The most favourable friction and wear characteristics were encountered with ZrO2–WC composites compared to the other grades with equal amount of volumetric secondary phase. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献