5932-27-4Relevant articles and documents
Vinyldiazo Compounds as 3-Carbon Radical Acceptors: Synthesis of 4-Fluoroacridines via Visible-Light-Promoted Cascade Radical Cyclization
Li, Weiyu,Zhou, Lei
, p. 4279 - 4283 (2021)
Vinyldiazo reagents were developed as the radical acceptors in a visible-light-promoted sequential radical cyclization reaction, providing a mechanistically distinct pathway to achieve (3 + 3) cyclization. Using N-aryl chlorodifluoromethyl alkynyl ketoimines as the radical precursors, the reaction allows the introduction of a fluorine atom to the acridine skeleton during the construction of both the pyridine and benzene motifs from acyclic building blocks. The resulting 4-fluoroacridines exhibited pronounced fluorescent properties in the solid state.
Two new palladium and platinum complexes with a bidentate pyrazole-based ligand: Crystal structure, fluorescence and Hirshfeld surface analysis
Feng, Chao,Li, Xue-Jing,Zhang, Duo,Qu, Zhi-Rong,Zhao, Hong
, p. 823 - 830 (2016)
Two new precious metal coordination complexes [Pd(HL)2] (1) and [PtL2] (2) (where H2L is 1-(carboxymethyl)-1H-pyrazole-3-carboxylic acid) were synthesized by one-pot in situ hydrolysis. The complexes are assembled into a 3D structure by hydrogen bonding interactions and intermolecular contacts. The structures have been established by single-crystal X-ray diffraction, and characterized by FT-IR and liquid state fluorescent spectroscopy. Hirshfeld surface analysis reveals that the OH contacts outnumber the other contacts in both structures (49.4 % of the total interactions for 1 and 41.6 % for 2).
1-vinyl-3- and 1-vinyl-5-pyrazolecarboxylic acids. synthesis and anti-burn activity of their chitosan salts
Rstakyan,Akopyan,Saakyan,Attaryan,Asratyan
, p. 1945 - 1949 (2014)
The synthesis of 1-vinyl-3- and 1-vinyl-5-pyrazolcarboxylic acids is developed and the anti burn activity of the chitosan salts of 1-vinyl-3(5)-carboxylic acids is studied.
COMPOUNDS WITH COPPER- OR ZINC-ACTIVATED TOXICITY AGAINST MICROBIAL INFECTION
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, (2022/02/05)
Heterocyclic compounds with a novel pyrazole thioamide-based NNSN structural motif, having highly effective zinc- or copper-activated toxicity against microbial infections at micromolar or nanomolar minimum inhibitory concentrations (MIC), and methods of making and using same.
Design, synthesis and biological evaluation of ring-fused pyrazoloamino pyridine/pyrimidine derivatives as potential FAK inhibitors
Xie, Hongming,Lin, Xinglong,Zhang, Yingjun,Tan, Fuxing,Chi, Bo,Peng, Zhihong,Dong, Wanrong,An, Delie
supporting information, (2020/10/06)
We report herein the synthesis of novel ring-fused pyrazoloamino pyridine/pyrimidine derivatives as potential FAK inhibitors and the evaluation of pharmaceutical activity against five cancer cell lines (MDA-MB-231, BXPC-3, NCI-H1975, DU145 and 786O). Generally, the majority of compounds displayed strong anti-FAK enzymatic potencies (IC50 1 nM) and could effectively inhibit several class of cancer cell lines within the concentration of 3 μM in comparison with GSK2256098 as a reference. Among them, compound 4o is considered to be the most effective due to high sensitivity in antiproliferation. In culture, 4o could not only inhibit FAK Y397 phosphorylation in MDA-MB-231 cell line, but also trigger apoptosis in a dose-dependent manner. Furthermore, computational docking analysis also suggested that 4o and TAE-226 displayed the similar interaction with FAK kinase domain.
Structure-activity relationship studies for the development of inhibitors of murine adipose triglyceride lipase (ATGL)
Breinbauer, Rolf,Doler, Carina,Fuchs, Elisabeth,Grabner, Gernot F.,Mayer, Nicole,Melcher, Michaela-Christina,Migglautsch, Anna K.,Romauch, Matthias,Schweiger, Martina,Zechner, Rudolf,Zimmermann, Robert
supporting information, (2020/07/13)
High serum fatty acid (FA) levels are causally linked to the development of insulin resistance, which eventually progresses to type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) generalized in the term metabolic syndrome. Adipose triglyceride lipase (ATGL) is the initial enzyme in the hydrolysis of intracellular triacylglycerol (TG) stores, liberating fatty acids that are released from adipocytes into the circulation. Hence, ATGL-specific inhibitors have the potential to lower circulating FA concentrations, and counteract the development of insulin resistance and NAFLD. In this article, we report about structure–activity relationship (SAR) studies of small molecule inhibitors of murine ATGL which led to the development of Atglistatin. Atglistatin is a specific inhibitor of murine ATGL, which has proven useful for the validation of ATGL as a potential drug target.
Structure Kinetics Relationships and Molecular Dynamics Show Crucial Role for Heterocycle Leaving Group in Irreversible Diacylglycerol Lipase Inhibitors
Janssen, Antonius P.A.,Van Hengst, Jacob M.A.,Béquignon, Olivier J.M.,Deng, Hui,Van Westen, Gerard J.P.,Van Der Stelt, Mario
, p. 7910 - 7922 (2019/10/11)
Drug discovery programs of covalent irreversible, mechanism-based enzyme inhibitors often focus on optimization of potency as determined by IC50-values in biochemical assays. These assays do not allow the characterization of the binding activity (Ki) and reactivity (kinact) as individual kinetic parameters of the covalent inhibitors. Here, we report the development of a kinetic substrate assay to study the influence of the acidity (pKa) of heterocyclic leaving group of triazole urea derivatives as diacylglycerol lipase (DAGL)-α inhibitors. Surprisingly, we found that the reactivity of the inhibitors did not correlate with the pKa of the leaving group, whereas the position of the nitrogen atoms in the heterocyclic core determined to a large extent the binding activity of the inhibitor. This finding was confirmed and clarified by molecular dynamics simulations on the covalently bound Michaelis-Menten complex. A deeper understanding of the binding properties of covalent serine hydrolase inhibitors is expected to aid in the discovery and development of more selective covalent inhibitors.
Batch and Continuous-Flow One-Pot Processes using Amine Diazotization to Produce Silylated Diazo Reagents
Audubert, Clément,Gamboa Marin, Oscar Javier,Lebel, Hélène
supporting information, p. 6294 - 6297 (2017/05/19)
A novel synthesis of trimethylsilyldiazomethane (TMSCHN2) by diazotization of trimethylsilylmethylamine (TMSCH2NH2) is reported using batch and continuous flow synthesis. The latter affords a daily production of 275 g (2.4 mol) of TMSCHN2. Other silylated methylamines were also successfully reacted under the developed reaction conditions to furnish various silicon-bearing diazomethane reagents. The applicability of the process is highlighted by disclosure of batch and continuous flow one-pot esterification and 1,3-dipolar cycloaddition processes. Furthermore, the high-yielding esterification of carboxylic acids with silylated and substituted methylamines in continuous flow is disclosed. Finally, work-up and purification procedures are reported for the preparation of a 2-MeTHF solution of TMSCHN2, which can be used in rhodium-catalyzed methylenation and homologation reactions.
PYRROLOPYRIMIDINE COMPOUND
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Paragraph 0264; 0265, (2017/11/11)
The present application relates to the field of pharmaceutical chemistry, and in particular, to a pyrrolopyrimidine compound represented by general formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. The present invention further relates to a method for preparing the pyrrolopyrimidine compound represented by general formula (I), pharmaceutical compositions and an application of the pyrrolopyrimidine compound in treating diseases mediated by Janus Kinase.
Laboratory-Scale Membrane Reactor for the Generation of Anhydrous Diazomethane
Dallinger, Doris,Pinho, Vagner D.,Gutmann, Bernhard,Kappe, C. Oliver
, p. 5814 - 5823 (2016/07/26)
A configurationally simple and robust semibatch apparatus for the in situ on-demand generation of anhydrous solutions of diazomethane (CH2N2) avoiding distillation methods is presented. Diazomethane is produced by base-mediated decomposition of commercially available Diazald within a semipermeable Teflon AF-2400 tubing and subsequently selectively separated from the tubing into a solvent- and substrate-filled flask (tube-in-flask reactor). Reactions with CH2N2 can therefore be performed directly in the flask without dangerous and labor-intensive purification operations or exposure of the operator to CH2N2. The reactor has been employed for the methylation of carboxylic acids, the synthesis of α-chloro ketones and pyrazoles, and palladium-catalyzed cyclopropanation reactions on laboratory scale. The implementation of in-line FTIR technology allowed monitoring of the CH2N2 generation and its consumption. In addition, larger scales (1.8 g diazomethane per hour) could be obtained via parallelization (numbering up) by simply wrapping several membrane tubings into the flask.
