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991.
992.
Synthesis and Antiangiogenic Properties of Tetrafluorophthalimido and Tetrafluorobenzamido Barbituric Acids 下载免费PDF全文
Dr. Agnieszka Ambrożak Christian Steinebach Dr. Erin R. Gardner Shaunna L. Beedie Dr. Gregor Schnakenburg Dr. William D. Figg Prof. Dr. Michael Gütschow 《ChemMedChem》2016,11(23):2621-2629
The development of novel thalidomide derivatives as immunomodulatory and anti‐angiogenic agents has revived over the last two decades. Herein we report the design and synthesis of three chemotypes of barbituric acids derived from the thalidomide structure: phthalimido‐, tetrafluorophthalimido‐, and tetrafluorobenzamidobarbituric acids. The latter were obtained by a new tandem reaction, including a ring opening and a decarboxylation of the fluorine‐activated phthalamic acid intermediates. Thirty compounds of the three chemotypes were evaluated for their anti‐angiogenic properties in an ex vivo assay by measuring the decrease in microvessel outgrowth in rat aortic ring explants. Tetrafluorination of the phthalimide moiety in tetrafluorophthalimidobarbituric acids was essential, as all of the nonfluorinated counterparts lost anti‐angiogenic activity. An opening of the five‐membered ring and the accompanying increased conformational freedom, in case of the corresponding tetrafluorobenzamidobarbituric acids, was well tolerated. Their activity was retained, although their molecular structures differ in torsional flexibility and possible hydrogen‐bond networking, as revealed by comparative X‐ray crystallographic analyses. 相似文献
993.
4‐Biphenylalanine‐ and 3‐Phenyltyrosine‐Derived Hydroxamic Acids as Inhibitors of the JumonjiC‐Domain‐Containing Histone Demethylase KDM4A 下载免费PDF全文
Dr. Ludovica Morera Dr. Martin Roatsch Michael C. D. Fürst Dr. Inga Hoffmann Dr. Johanna Senger Mirjam Hau Dr. Henriette Franz Prof. Dr. Roland Schüle Prof. Dr. Markus R. Heinrich Prof. Dr. Manfred Jung 《ChemMedChem》2016,11(18):2063-2083
Overexpression of the histone lysine demethylase KDM4A, which regulates H3K9 and H3K36 methylation states, has been related to the pathology of several human cancers. We found that a previously reported hydroxamate‐based histone deacetylase (HDAC) inhibitor (SW55) was also able to weakly inhibit this demethylase with an IC50 value of 25.4 μm . Herein we report the synthesis and biochemical evaluations, with two orthogonal in vitro assays, of a series of derivatives of this lead structure. With extensive chemical modifications on the lead structure, also by exploiting the versatility of the radical arylation with aryldiazonium salts, we were able to increase the potency of the derivatives against KDM4A to the low‐micromolar range and, more importantly, to obtain demethylase selectivity with respect to HDACs. Cell‐permeable derivatives clearly showed a demethylase‐inhibition‐dependent antiproliferative effect against HL‐60 human promyelocytic leukemia cells. 相似文献
994.
995.
Integrating legacy soil phosphorus into sustainable nutrient management strategies for future food,bioenergy and water security 总被引:11,自引:0,他引:11
996.
Prof. Aaron R. Van Dyke Lily S. Etemad Michael J. Vessicchio George A. Naclerio Victoria Jedson 《Chembiochem : a European journal of chemical biology》2016,17(17):1602-1605
A strategy for labeling native enzymes in a manner that preserves their activity is reported: capture–tag–release (CTR). Key to this approach is the small molecule CTR probe that contains an enzyme inhibitor, benzophenone crosslinker, and aryl phosphine ester. After UV‐derived capture of the enzyme, addition of an azide‐containing tag triggers a Staudinger ligation that labels the enzyme. A further consequence of the Staudinger ligation is fragmentation of the CTR probe, thus releasing the inhibitor and restoring enzymatic activity. As a proof‐of‐principle, the CTR strategy was applied to the hydrolase β‐galactosidase. The enzyme was efficiently labeled with biotin, and the kinetic data for the biotinylated enzyme were comparable to those for unlabeled β‐galactosidase. The CTR probe exhibits excellent targeting specificity, as it selectively labeled β‐galactosidase in a complex protein mixture. 相似文献
997.
Patrick Walther Antje Ota Alexander Müller Frank Hermanutz Frank Gähr Michael R. Buchmeiser 《大分子材料与工程》2016,301(11):1337-1344
Chitin and its deacetylated derivative, chitosan, are nontoxic, antibacterial, biodegradable, and biocompatible biopolymers. Due to these properties, they are widely used for biomedical applications such as scaffolds for tissue engineering, wound dressings, separation membranes and antibacterial coatings. Unfortunately, there is still a lack of suitable solvent systems for the direct processing of chitin, e.g., into films and coatings. Such solvents must be nontoxic, noncorrosive, nondegrading, and allow for high chitin concentrations. Here, the potential of designed ionic liquids (IL) as solvents for chitin is outlined. Phosphonium‐ and imidazolium‐based ILs are synthesized, characterized and the influence of the cation on the solution process has been evaluated. It is shown that particularly imidazolium carboxylate‐based ILs are appropriate solvents for chitin and are suitable for the production of foils and coatings on both fabrics and foams.
998.
999.
1000.
Přemysl Beran Debashis Mukherji Pavel Strunz Ralph Gilles Michael Hofmann Lukas Karge Oleksandr Dolotko Joachim Rösler 《Metals and Materials International》2016,22(4):562-571
Neutron diffraction measurement was performed in-situ at high temperatures on Co-Re-Ta-C alloys with and without Cr addition. This included alloys containing different C content with the C/Ta ratio varying between 0.5 and 1.0. The Co-Re-solid solution matrix of the experimental alloys is polymorphic (like in pure cobalt) and transformed from low temperature hexagonal ? phase to high temperature cubic γ phase on heating. This transformation is reversible and show hysteresis. The main alloying addition, Re, stabilizes the ? Co-phase and increases the transformation temperature to above 1273 K. The onset of the \(\varepsilon \rightleftharpoons \gamma\) transformation during heating and cooling was found to differ depending on the alloy composition. In alloys without Cr addition the transformation was not completed on cooling and the high temperature γ phase was partly retained at room temperature in metastable state with the amount depending on the cooling rate from high temperature. The diffraction and microstructural results showed that Cr is ? stabilizer (similar as Re) but the role of Ta is not clear. The C/Ta ratio has no direct effect on the matrix phase transformation. Nevertheless, it influences indirectly by determining the amount of Ta which is freely available in the matrix. 相似文献