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141.
Jürgen Allwohn Martin Brumm Gernot Frenking Matthias Hornivius Werner Massa Friedrich W. Steubert Sigrid Wocadlo 《Advanced Synthesis \u0026amp; Catalysis》1993,335(6):503-514
Synthesis and Conformational Analysis of Pyranophanones and Pyrylophanium Compounds with Intraannular Substituents The synthesis of [3.3]dithiapyranophanone 6 and 11 is accomplished by use of the two-components-dilution-principle. Pyrolysis of their bis(sulfones) 7 and 12 gives the [2.2]pyranophanones 8 , 9 and 13 . Under preservation of conformation the intraannular carbonyl-function is used for the synthesis of methylpyranophanoles 14 , 16 and 17 . The synthesis of pyrylophanium compounds 15 and 18 is possible by elimination in trifluoroacetic acid. 6 exhibits anti-conformation within its crystal-structure and like 7 reveals temperature-dependent behavior in solution. Using 6 as an example, a combination of 13C-NMR-spectroscopy, forcefield-calculation and computer-simulation is applied for the first time to give evidence for molecular-dynamic processes of cyclophanes. 8 and 9 are the syn- and anti-conformers of the desired product, as shown by X-ray structural analysis. 13 reveals anti-conformation within its crystal structure as well as in solution. The conformational analysis of other new phanes described here is based on the 1H-NMR-spectra of these pyrolysis products. As expected the intraannular substituents of Pyrylophanium-lons 15 and 18 show the characteristic upfield-shift within their 1H-NMR-spectra. 相似文献
142.
Binucleophilic biogenic α-aminoacids 1 such as cysteine, penicillamine, serine, and threonine react with lactam acetals 2 by condensation to bridged α-amidinoacids 3 or by condensation/ring transformation to 2-(ω-aminoalkyl)-1,3-azoline-4-carboxylic acids 6. Corresponding reactions with lactim ethers 7 afford analogous α-amidinoacids 8 , condensed imidazolones 10 as their derivatives, ω-aminoalkyl-1,3-azolines 13 and, by further reaction with lactim ether 7 , modified ω-amidinoalkyl-1,3-azolines 14 . 相似文献
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145.
Cindy Bay Gzona Bajraktari-Sylejmani Walter E. Haefeli Jürgen Burhenne Johanna Weiss Max Sauter 《International journal of molecular sciences》2022,23(7)
The solute carrier L-type amino acid transporter 1 (LAT-1/SLC7A5) is a viable target for drug delivery to the central nervous system (CNS) and tumors due to its high abundance at the blood–brain barrier and in tumor tissue. LAT-1 is only localized on the cell surface as a heterodimer with CD98, which is not required for transporter function. To support future CNS drug-delivery development based on LAT-1 targeting, we established an ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) assay for stable isotopically labeled leucine ([13C6, 15N]-L-leucine), with a dynamic range of 0.1–1000 ng/mL that can be applied for the functional testing of LAT-1 activity when combined with specific inhibitors and, consequently, the LAT-1 inhibition capacity of new compounds. The assay was established in a 96-well format, facilitating high-throughput experiments, and, hence, can support the screening for novel inhibitors. Applicable recommendations of the US Food and Drug Administration and European Medicines Agency for bioanalytical method validation were followed to validate the assay. The assay was applied to investigate the IC50 of two well-known LAT-1 inhibitors on hCMEC/D3 cells: the highly specific LAT-1 inhibitor JPH203, which was also used to demonstrate LAT-1 specific uptake, and the general system L inhibitor BCH. In addition, the [13C6, 15N]-L-leucine uptake was determined on two human brain capillary endothelial cell lines (NKIM-6 and hCMEC/D3), which were characterized for their expressional differences of LAT-1 at the protein and mRNA level and the surface amount of CD98. The IC50 values of the inhibitors were in concordance with previously reported values. Furthermore, the [13C6, 15N]-L-leucine uptake was significantly higher in hCMEC/D3 cells compared to NKIM-6 cells, which correlated with higher expression of LAT-1 and a higher surface amount of CD98. Therefore, the UPLC-MS/MS quantification of ([13C6, 15N]-L-leucine is a feasible strategy for the functional characterization of LAT-1 activity in cells or tissue. 相似文献
146.
Yo‐Han Seo Jurij Koruza Andreja Benčan Barbara Malič Jürgen Rödel Kyle G. Webber 《Journal of the American Ceramic Society》2014,97(5):1582-1588
The influence of second phase zirconia particles on the electrical properties and fracture behavior of various polycrystalline soft Pb(Zr1?xTix)O3 (PZT) compositions was investigated. PZT composites with yttria‐stabilized tetragonal zirconia particles exhibited enhanced crack resistance in comparison to monolithic compositions, regardless of the PZT composition. The addition of zirconia, however, was found to change the PZT composition through the diffusion of zirconium, resulting in variations in the observed piezoelectric and ferroelectric responses. Through the tailoring of the PZT matrix composition, the large electromechanical response and enhanced fracture toughness could be retained. The variation in both small and large signal properties is contrasted to fracture results and crystal structure changes, as determined by X‐ray diffraction. 相似文献
147.
148.
Jürgen Liebscher Alemayehu Areda Berhanu Abegaz 《Advanced Synthesis \u0026amp; Catalysis》1983,325(5):689-694
149.
Michael Singh Serhat Akkaya Mark Preuß Franziska Rademacher Mersedeh Tohidnezhad Yusuke Kubo Peter Behrendt Jan-Tobias Weitkamp Thilo Wedel Ralph Lucius Regine Glser Jürgen Harder Andreas Bayer 《International journal of molecular sciences》2022,23(5)
Platelet-released growth factors (PRGFs) or other thrombocyte concentrate products, e.g., Platelet-Rich Fibrin (PRF), have become efficient tools of regenerative medicine in many medical disciplines. In the context of wound healing, it has been demonstrated that treatment of chronic or complicated wounds with PRGF or PRF improves wound healing in the majority of treated patients. Nevertheless, the underlying cellular and molecular mechanism are still poorly understood. Therefore, we aimed to analyze if PRGF-treatment of human keratinocytes caused the induction of genes encoding paracrine factors associated with successful wound healing. The investigated genes were Semaphorin 7A (SEMA7A), Angiopoietin-like 4 (ANGPLT4), Fibroblast Growth Factor-2 (FGF-2), Interleukin-32 (IL-32), the CC-chemokine-ligand 20 (CCL20), the matrix-metalloproteinase-2 (MMP-2), the chemokine C-X-C motif chemokine ligand 10 (CXCL10) and the subunit B of the Platelet-Derived Growth Factor (PDGFB). We observed a significant gene induction of SEMA7A, ANGPLT4, FGF-2, IL-32, MMP-2 and PDGFB in human keratinocytes after PRGF treatment. The CCL20- and CXCL10 gene expressions were significantly inhibited by PRGF therapy. Signal transduction analyses revealed that the PRGF-mediated gene induction of SEMA7A, ANGPLT4, IL-32 and MMP-2 in human keratinocytes was transduced via the IL-6 receptor pathway. In contrast, EGF receptor signaling was not involved in the PRGF-mediated gene expression of analyzed genes in human keratinocytes. Additionally, treatment of ex vivo skin explants with PRGF confirmed a significant gene induction of SEMA7A, ANGPLT4, MMP-2 and PDGFB. Taken together, these results describe a new mechanism that could be responsible for the beneficial wound healing properties of PRGF or related thrombocytes concentrate products such as PRF. 相似文献
150.
N-(3-Aminothioacryloyl)-formamidines 3 react with primary amines to give either 4(1H)-pyrimidinthiones 6 or transaminated N-(3-aminothioacryloyl)-formamidines 5 . Alkylation of the latter compounds gives rise to cyclised 6(1H)-pyrimidinimines 7 . The 4(1H)-pyrimidinthiones 6 can be S-alkylated to 4-alkylmercaptopyrimidinium salts 8 . Subsequent substitution of the alkylmercapto group of the 8 results in the formation of 4-aminopyrimidinium salts 9 , which can also be obtained starting from the 3 by a reversed reaction sequence that is first by S-alkylation to 3-alkylmercapto-2-azapentamethinium salts 10 and subsequent reaction with primary amines. 相似文献