765-50-4Relevant academic research and scientific papers
Enhanced cytotoxicity of indenyl molybdenum(ii) compounds bearing a thiophene function
Mrózek, Ond?ej,Melounková, Lucie,Dostál, Libor,Císa?ová, Ivana,Eisner, Ale?,Havelek, Radim,Peterová, Eva,Honzí?ek, Jan,Vinklárek, Jaromír
, p. 11361 - 11373 (2019)
A series of six indenyl molybdenum compounds bearing a thiophenyl function in the side chain were prepared and characterized by analytical and spectroscopic methods. The structures of [(η5-C9H6CH2C4H3S)(η3-C3H5)Mo(CO)2] and [(η5-C9H6CH2C4H3S)Mo(CO)2(bpy)][BF4] were determined by single-crystal X-ray diffraction. The compounds bearing N,N-chelating ligands exhibit increased cytotoxic activity against human leukemia cell lines MOLT-4; up to two orders of magnitude lower IC50 values were observed compared to analogues with unsubstituted indenyl, which clearly demonstrates the strong effect of the indenyl ligand modification on the biological activity of the molybdenum(ii) compounds. The highest cytostatic potential was observed for the complex bearing 4,7-diphenyl-1,10-phenanthtoline [(η5-C9H6CH2C4H3S)Mo(CO)2(Ph2phen)][BF4] with IC50 (MOLT-4) = 0.19 ± 0.02 μM. Detailed regulation of the molecular and cellular mechanism by this derivative was investigated on the lung carcinoma cell line A549 and compared with the lung fibroblast cell line MRC-5. Rather unusual differences in the effects on tumor and non-tumor cell lines provide a unique insight into the cytostatic action of molybdenum(ii) complexes.
Diethyl(thiophen-2-ylmethyl)phosphonate: A novel multifunctional electrolyte additive for high voltage batteries
Zhu, Yunmin,Luo, Xueyi,Zhi, Huozhen,Liao, Youhao,Xing, Lidan,Xu, Mengqing,Liu, Xiang,Xu, Kang,Li, Weishan
, p. 10990 - 11004 (2018)
Carbonate-based electrolytes used in Li-ion batteries encounter various challenges in extreme electrochemical environments, and hence their application requires various additives, especially when used with high voltage cathode materials. These additives are designed to form protective interphases that prevent parasitic carbonate oxidation, while in certain cases they stabilize electrolytes from reduction at anode surfaces or even serve as flame-retardants that postpone the thermal runaway during overcharge. However, most of these additives casts negative effects, lowering ionic conductivity of electrolyte or impairing the compatibility between cathode and electrolyte. An ideal solution of minimizing the presence of these inert molecules is to identify an additive that structurally integrates these multiple functions into a single compound. In this work, we report a novel additive, diethyl(thiophen-2-ylmethyl)phosphonate (DTYP). Its 0.5% presence in a base electrolyte dramatically improves the capacity retention of a high voltage Li-ion cell using LiNi0.5Mn1.5O4 from 18% to 85% after 280 cycles at 1C at 60 °C, increases the endothermic reaction onset temperature from 193 °C to 223 °C, and reduces the self-extinguishing time of the electrolyte from 88 s to 77 s. Thus, such a multifunctional additive presents a cost-efficient solution to the issues often faced in high voltage lithium-ion batteries.
Convenient preparation of diethyl (2-thienyl)methanephosphonate
Davis, Matthew C.
, p. 2079 - 2083 (2005)
This article describes a convenient preparation of diethyl (2-thienyl)methanephosphonate in 88% overall yield. Copyright Taylor & Francis, Inc.
Structure-guided optimization of 1H-imidazole-2-carboxylic acid derivatives affording potent VIM-Type metallo-β-lactamase inhibitors
Yan, Yu-Hang,Li, Wenfang,Chen, Wei,Li, Chao,Zhu, Kai-Rong,Deng, Ji,Dai, Qing-Qing,Yang, Ling-Ling,Wang, Zhenling,Li, Guo-Bo
, (2021/11/17)
Production of metallo-β-lactamases (MBLs) in bacterial pathogens is an important cause of resistance to the ‘last-resort’ carbapenem antibiotics. Development of effective MBL inhibitors to reverse carbapenem resistance in Gram-negative bacteria is still needed. We herein report X-ray structure-guided optimization of 1H-imidazole-2-carboxylic acid (ICA) derivatives by considering how to engage with the active-site flexible loops and improve penetration into Gram-negative bacteria. Structure-activity relationship studies revealed the importance of appropriate substituents at ICA 1-position to achieve potent inhibition to class B1 MBLs, particularly the Verona Integron-encoded MBLs (VIMs), mainly by involving ingenious interactions with the flexible active site loops as observed by crystallographic analyses. Of the tested ICA inhibitors, 55 displayed potent synergistic antibacterial activity with meropenem against engineered Escherichia coli strains and even intractable clinically isolated Pseudomonas aeruginosa producing VIM-2 MBL. The morphologic and internal structural changes of bacterial cells after treatment further demonstrated that 55 crossed the outer membrane and reversed the activity of meropenem. Moreover, 55 showed good pharmacokinetic and safety profile in vivo, which could be a potential candidate for combating VIM-mediated Gram-negative carbapenem resistance.
Structure–Activity Studies of 3,9-Diazaspiro[5.5]undecane-Based γ-Aminobutyric Acid Type A Receptor Antagonists with Immunomodulatory Effect
Bavo, Francesco,de-Jong, Heleen,Petersen, Jonas,Falk-Petersen, Christina Birkedahl,L?ffler, Rebekka,Sparrow, Emma,Rostrup, Frederik,Eliasen, Jannik Nicklas,Wilhelmsen, Kristine S.,Barslund, Kasper,Bundgaard, Christoffer,Nielsen, Birgitte,Kristiansen, Uffe,Wellendorph, Petrine,Bogdanov, Yury,Fr?lund, Bente
, p. 17795 - 17812 (2022/01/03)
The 3,9-diazaspiro[5.5]undecane-based compounds 2027 and 018 have previously been reported to be potent competitive γ-aminobutyric acid type A receptor (GABAAR) antagonists showing low cellular membrane permeability. Given the emerging peripheral application of GABAAR ligands, we hypothesize 2027 analogs as promising lead structures for peripheral GABAAR inhibition. We herein report a study on the structural determinants of 2027 in order to suggest a potential binding mode as a basis for rational design. The study identified the importance of the spirocyclic benzamide, compensating for the conventional acidic moiety, for GABAAR ligands. The structurally simplified m-methylphenyl analog 1e displayed binding affinity in the high-nanomolar range (Ki = 180 nM) and was superior to 2027 and 018 regarding selectivity for the extrasynaptic α4βδ subtype versus the α1- and α2- containing subtypes. Importantly, 1e was shown to efficiently rescue inhibition of T cell proliferation, providing a platform to explore the immunomodulatory potential for this class of compounds.
Pd-catalyzed allylative dearomatisation using Grignard reagents
Boldrini, Cosimo,Harutyunyan, Syuzanna R.
supporting information, p. 11807 - 11810 (2021/11/30)
Pd-catalyzed allylative dearomatisation of naphthyl halides is shown to be feasible by employing Grignard reagents. The high reactivity of the nucleophile allows for fast reactions and low catalyst loading, while a plethora of successfully substituted compounds illustrate the broad scope. Five membered heteroaromatic compounds are also demonstrated to be reactive under similar conditions.
Method for continuously synthesizing 2-chloromethylthiophene by using micro-channel reactor
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Paragraph 0034; 0037-0052, (2021/07/08)
The invention discloses a method for continuously synthesizing 2-chloromethylthiophene by using a micro-channel reactor. The micro-channel reactor comprises a premixing temperature control module and a reaction module, the premixing temperature control module and the reaction module are connected in series, and each of the premixing temperature control module and the reaction module is formed by connecting more than two units in series through reaction. The invention relates to the technical field of organic compound preparation. According to the method for continuously synthesizing 2-chloromethylthiophene by using a micro-channel reactor, one-step synthesis can be realized, the operation is simple, the production process is simplified, and the reaction time is about 60 seconds. The reaction time of a traditional kettle type reactor is more than 4 hours, the reaction temperature is about 20 DEG C, and the traditional kettle type reactor needs a low-temperature reaction (about -10 DEG C). The yield of the produced 2-chloromethylthiophene reaches about 80%, the selectivity reaches about 90%, by-products are reduced, the amount of three wastes is small, and the mass transfer and heat transfer performances of the reaction are enhanced.
MUSCARINIC AGONISTS AS NON-STEROIDAL AND NON-OPIOID ANALGESICS AND METHODS OF USE THEREOF
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Paragraph 0060; 0073; 0076; 00106, (2020/09/19)
Novel Gi/o-biased muscarinic agonists selectively activate only one specific signaling pathway and are novel pharmacophores for development of new painkillers (analgesics). Methods of making and using these agonists are also described.
Novel M2-selective, Gi-biased agonists of muscarinic acetylcholine receptors
Randáková, Alena,Nelic, Dominik,Ungerová, Dana,Nwokoye, Peter,Su, Qiwen,Dole?al, Vladimír,El-Fakahany, Esam E.,Boulos, John,Jakubík, Jan
supporting information, p. 2073 - 2089 (2020/02/18)
Background and Purpose: More than 30% of currently marketed medications act via GPCRs. Thus, GPCRs represent one of the most important pharmacotherapeutic targets. In contrast to traditional agonists activating multiple signalling pathways, agonists activating a single signalling pathway represent a new generation of drugs with increased specificity and fewer adverse effects. Experimental Approach: We have synthesized novel agonists of muscarinic ACh receptors and tested their binding and function (on levels of cAMP and inositol phosphates) in CHO cells expressing individual subtypes of muscarinic receptors, primary cultures of rat aortic smooth muscle cells and suspensions of digested native tissues from rats. Binding of the novel compounds to M2 receptors was modelled in silico. Key Results: Two of the tested new compounds (1-(thiophen-2-ylmethyl)-3,6-dihydro-2H-pyridinium and 1-methyl-1-(thiophen-2-ylmethyl)-3,6-dihydro-2H-pyridinium) only inhibited cAMP synthesis in CHO cells, primary cultures, and native tissues, with selectivity for M2 muscarinic receptors and displaying bias towards the Gi signalling pathway at all subtypes of muscarinic receptors. Molecular modelling revealed interactions with the orthosteric binding site in a way specific for a given agonist followed by agonist-specific changes in the conformation of the receptor. Conclusions and Implications: The identified compounds may serve as lead structures in the search for novel non-steroidal and non-opioid analgesics acting via M2 and M4 muscarinic receptors with reduced side effects associated with activation of the phospholipase C signalling pathway.
Application of 1-substituted-1H-imidazole-2-carboxylic acid compounds in preparation of metal beta-lactamase inhibitors
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Paragraph 0231-0233, (2020/06/09)
The invention relates to application of 1-substituted-1H-imidazole-2-carboxylic acid compounds in preparation of metal beta-lactamase inhibitors, and particularly discloses application of compounds shown in a formula I in preparation of metal beta-lactamase inhibitors or antibacterial combined medicines. Experiments prove that the compounds provided by the invention can be used for effectively inhibiting the activity of various MBL enzymes including VIM-2, NDM-1, IMP-1, VIM-1 and VIM-5; the compounds, especially the compounds 11, 13, 14, 29, 30, 34, 37 and 40, have an IC50 value of 2.13 [mu] Mor less on the VIM-2 type MBL enzymes, have a more significant inhibition effect than positive control drugs, and have very good potential in the preparation of MBL enzyme inhibitors. Meanwhile, thecompounds disclosed by the invention are combined with beta-lactam antibiotics, so that metal beta-lactamase generated by drug-resistant bacteria can be effectively inhibited, the antibacterial activity of the antibiotics is enhanced, and the compounds have a very good application prospect in preparation of antibacterial combined medicines.
