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排序方式: 共有885条查询结果,搜索用时 15 毫秒
881.
882.
Dr. Maximilian Barth Dr. Stefan Rudolph Jan Kampschulze Dr. Imke Meyer zu Vilsendorf Walburga Hanekamp Dr. Dennis Mulac Prof. Dr. Klaus Langer Prof. Dr. Matthias Lehr 《ChemMedChem》2022,17(9):e202100757
A series of hexafluoroisopropyl carbamates with indolylalkyl- and azaindolylalkyl-substituents at the carbamate nitrogen was synthesized and evaluated for inhibition of the endocannabinoid degrading enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). The synthesized derivatives with butyl to heptyl spacers between the heteroaryl and the carbamate moiety were inhibitors of both enzymes. For investigated compounds in which the alkyl chain was partially incorporated into a piperidine ring, different results were obtained. Compounds with a methylene spacer between the piperidine ring and the heteroaromatic system were found to be selective MAGL inhibitors, while an extension of the alkyl spacer to two to four atoms resulted in dual inhibition of FAAH/MAGL. The only small change in enzyme inhibitory activity with variation of the heteroaromatic system indicates that the reactive hexafluoroisopropyl carbamate group is mainly responsible for the strength of the inhibitory effect of the compounds. Selected derivatives were also tested for hydrolytic stability in aqueous solution, liver homogenate and blood plasma as well as for aqueous solubility and for permeability in a Caco-2 cell model. Some compounds showed a slightly higher MAGL inhibitory effect than the known selective MAGL inhibitor ABX-1431 and also partly surpassed this substance with regard to certain physicochemical and biochemical properties such as water solubility and cell permeability. 相似文献
883.
Julia Feye Jessica Matthias Alena Fischer David Rudolph Jens Treptow Radian Popescu Jochen Franke Annemarie L. Exarhos Zoe A. Boekelheide Dagmar Gerthsen Claus Feldmann Peter W. Roesky Esther S. Rösch 《Small (Weinheim an der Bergstrasse, Germany)》2023,19(38):2301997
Magnetic particle imaging (MPI) is a powerful and rapidly growing tomographic imaging technique that allows for the non-invasive visualization of superparamagnetic nanoparticles (NPs) in living matter. Despite its potential for a wide range of applications, the intrinsic quantitative nature of MPI has not been fully exploited in biological environments. In this study, a novel NP architecture that overcomes this limitation by maintaining a virtually unchanged effective relaxation (Brownian plus Néel) even when immobilized is presented. This superparamagnetic magnetite architecture made of phenolic resin hollow spheres coated with Eu(III) containing silica nanoparticles (SMART RHESINs) was synthesized and studied. Magnetic particle spectroscopy (MPS) measurements confirm their suitability for potential MPI applications. Photobleaching studies show an unexpected photodynamic due to the fluorescence emission peak of the europium ion in combination with the phenol formaldehyde resin (PFR). Cell metabolic activity and proliferation behavior are not affected. Colocalization experiments reveal the distinct accumulation of SMART RHESINs near the Golgi apparatus. Overall, SMART RHESINs show superparamagnetic behavior and special luminescent properties without acute cytotoxicity, making them suitable for bimodal imaging probes for medical use like cancer diagnosis and treatment. SMART RHESINs have the potential to enable quantitative MPS and MPI measurements both in mobile and immobilized environments. 相似文献
884.
Dr. Adrian Richter Dr. Gagandeep Narula Dr. Ines Rudolph Dr. Rüdiger W. Seidel Dr. Christoph Wagner Prof. Dr. Yossef Av-Gay Prof. Dr. Peter Imming 《ChemMedChem》2022,17(6):e202100733
8-Nitrobenzothiazinones (BTZs) are a promising class of antimycobacterial agents currently under investigation in clinical trials. Starting from thiourea derivatives, a new synthetic pathway to BTZs was established. It allows the formation of the thiazinone ring system in one synthetic step and is applicable for preparation of a wide variety of BTZ analogues. The synthetic procedure furthermore facilitates the replacement of the sulphur atom in the thiazinone ring system by oxygen or nitrogen to afford the analogous benzoxazinone and quinazolinone systems. 36 BTZ analogues were prepared and tested in luminescence-based assays for in vitro activity against Mycobacterium tuberculosis (Mtb) using the microdilution broth method and a high-throughput macrophage infection assay. 相似文献
885.
A. Stephen K. Hashmi Christian Lothschütz Ren Dpp Martin Ackermann Janosc De Buck Becker Matthias Rudolph Christian Scholz Frank Rominger 《Advanced Synthesis \u0026amp; Catalysis》2012,354(1):133-147
Two substrates containing an aryl iodide and an allenoate ester were prepared and the gold‐induced cycloisomerisation to vinylgold(I) species and their proto‐deauration as well as the intramolecular palladium‐catalysed cross‐coupling reactions were investigated. Switching to catalytic amounts of gold and palladium and stoichiometric amounts of silver did indeed furnish the product of a cycloisomerisation/intramolecular cross‐coupling. Control experiments revealed that silver cannot substitute for gold or palladium in these reactions, but a different palladium catalyst in a different oxidation state also afforded the cycloisomerisation/intramolecular cross‐coupling products in only slightly reduced yields. By ICP analysis the palladium was shown to contain gold only at the sub‐ppm level. This shows how carefully results obtained with such systems have to be interpreted. Then a series of allylic and benzylic o‐alkynylbenzoates were investigated in gold‐ and palladium‐catalysed reactions. For esters of benzyl alcohol and cinnamyl alcohol no palladium co‐catalyst was needed for the conversion. All reagents were thoroughly checked for palladium traces by ICP analysis in order to thoroughly exclude a gold/palladium co‐catalysis. Optimisation of the gold complex, counter ion and solvent showed that gold(I) isonitrile pre‐catalysts and silver triflate as activator in dioxane are suitable to convert a number of substrates with aryl, alkyl and even cyclopropyl substituents. Crossover experiments proved an intermolecular allyl transfer. 相似文献