2524-52-9Relevant articles and documents
Homarine Alkyl Ester Derivatives as Promising Acetylcholinesterase Inhibitors
Jo?o, Karen G.,Videira, Romeu A.,Paiva-Martins, Fátima,Valent?o, Patrícia,Pereira, David M.,Andrade, Paula B.
, p. 3315 - 3325 (2021/08/30)
Reversible acetylcholinesterase (AChE) inhibitors are key therapeutic tools to modulate the cholinergic connectivity compromised in several degenerative pathologies. In this work, four alkyl esters of homarine were synthesized and screened by using Electrophorus electricus AChE and rat brain AChE-rich fraction. Results showed that all homarine alkyl esters are able to inhibit AChE by a competitive inhibition mode. The effectiveness of AChE inhibition increases with the alkyl side chain length of the homarine esters, being HO?C16 (IC50=7.57±3.32 μM and Ki=18.96±2.28 μM) the most potent inhibitor. The fluorescence quenching studies confirmed that HO?C16 is the compound with higher selectivity and affinity for the tryptophan residues in the catalytic active site of AChE. Preliminary cell viability studies showed that homarine esters display no toxicity for human neuronal SH-SY5Y cells. Thus, the long-chain homarine esters emerge as new anti-cholinesterase agents, with potential to be considered for therapeutic applications development.
Design, synthesis, in vitro and in vivo evaluation against MRSA and molecular docking studies of novel pleuromutilin derivatives bearing 1, 3, 4-oxadiazole linker
Liu, Jie,Zhang, Guang-Yu,Zhang, Zhe,Li, Bo,Chai, Fei,Wang, Qi,Zhou, Zi-Dan,Xu, Ling-Ling,Wang, Shou-Kai,Jin, Zhen,Tang, You-Zhi
, (2021/05/17)
A class of pleuromutilin derivatives containing 1, 3, 4-oxadiazole were designed and synthesized as potential antibacterial agents against Methicillin-resistant staphylococcus aureus (MRSA). The ultrasound-assisted reaction was proposed as a green chemistry method to synthesize 1, 3, 4-oxadiazole derivatives (intermediates 85–110). Among these pleuromutilin derivatives, compound 133 was found to be the strongest antibacterial derivative against MRSA (MIC = 0.125 μg/mL). Furthermore, the result of the time-kill curves displayed that compound 133 could inhibit the growth of MRSA in vitro quickly (- 4.36 log10 CFU/mL reduction). Then, compound 133 (- 1.82 log10 CFU/mL) displayed superior in vivo antibacterial efficacy than tiamulin (- 0.82 log10 CFU/mL) in reducing MRSA load in mice thigh model. Besides, compound 133 exhibited low cytotoxicity to RAW 264.7 cells. Molecular docking studies revealed that compound 133 was successfully localized in the binding pocket of 50S ribosomal subunit (ΔGb = -10.50 kcal/mol). The results indicated that these pleuromutilin derivatives containing 1, 3, 4-oxadiazole might be further developed into novel antibiotics against MRSA.
Pleuromutilin derivative with 1, 3, 4-oxadiazole side chain and preparation and application thereof
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Paragraph 0055-0056; 0070; 0090; 0092; 0095; 0102, (2021/07/24)
The invention belongs to the field of medicinal chemistry, and particularly relates to a pleuromutilin derivative with a 1, 3, 4-oxadiazole side chain and preparation and application thereof The pleuromutilin derivative with the 1, 3, 4-oxadiazole side chain is a compound shown in a formula 2 or a pharmaceutically acceptable salt thereof, and a solvent compound, an enantiomer, a diastereoisomer and a tautomer of the compound shown in the formula 2 or the pharmaceutically acceptable salt thereof or a mixture of the solvent compound, the enantiomer, the diastereoisomer and the tautomer in any proportion, including a racemic mixture. The pleuromutilin derivative has good antibacterial activity, is especially suitable for being used as a novel antibacterial agent for systemic system infection of animals or human beings, and has good water solubility.
4-Amino-1,2,4-triazole-3-thione-derived Schiff bases as metallo-β-lactamase inhibitors
Baud, Damien,Bebrone, Carine,Becker, Katja,Benvenuti, Manuela,Cerboni, Giulia,Chelini, Giulia,Cutolo, Giuliano,De Luca, Filomena,Docquier, Jean-Denis,Feller, Georges,Fischer, Marina,Galleni, Moreno,Gavara, Laurent,Gresh, Nohad,Kwapien, Karolina,Legru, Alice,Mangani, Stefano,Mercuri, Paola,Pozzi, Cecilia,Sannio, Filomena,Sevaille, Laurent,Tanfoni, Silvia,Verdirosa, Federica,Berthomieu, Dorothée,Bestgen, Beno?t,Frère, Jean-Marie,Hernandez, Jean-Fran?ois
supporting information, (2020/09/16)
Resistance to β-lactam antibiotics in Gram-negatives producing metallo-β-lactamases (MBLs) represents a major medical threat and there is an extremely urgent need to develop clinically useful inhibitors. We previously reported the original binding mode of 5-substituted-4-amino/H-1,2,4-triazole-3-thione compounds in the catalytic site of an MBL. Moreover, we showed that, although moderately potent, they represented a promising basis for the development of broad-spectrum MBL inhibitors. Here, we synthesized and characterized a large number of 4-amino-1,2,4-triazole-3-thione-derived Schiff bases. Compared to the previous series, the presence of an aryl moiety at position 4 afforded an average 10-fold increase in potency. Among 90 synthetic compounds, more than half inhibited at least one of the six tested MBLs (L1, VIM-4, VIM-2, NDM-1, IMP-1, CphA) with Ki values in the μM to sub-μM range. Several were broad-spectrum inhibitors, also inhibiting the most clinically relevant VIM-2 and NDM-1. Active compounds generally contained halogenated, bicyclic aryl or phenolic moieties at position 5, and one substituent among o-benzoic, 2,4-dihydroxyphenyl, p-benzyloxyphenyl or 3-(m-benzoyl)-phenyl at position 4. The crystallographic structure of VIM-2 in complex with an inhibitor showed the expected binding between the triazole-thione moiety and the dinuclear centre and also revealed a network of interactions involving Phe61, Tyr67, Trp87 and the conserved Asn233. Microbiological analysis suggested that the potentiation activity of the compounds was limited by poor outer membrane penetration or efflux. This was supported by the ability of one compound to restore the susceptibility of an NDM-1-producing E. coli clinical strain toward several β-lactams in the presence only of a sub-inhibitory concentration of colistin, a permeabilizing agent. Finally, some compounds were tested against the structurally similar di-zinc human glyoxalase II and found weaker inhibitors of the latter enzyme, thus showing a promising selectivity towards MBLs.
Lanthanoid pyridyl-β-diketonate 'triangles'. New examples of single molecule toroics
Caporale, Chiara,Fuller, Rebecca O.,Massi, Massimiliano,Murray, Keith S.,Ogden, Mark I.,Phonsri, Wasinee,Rajaraman, Gopalan,Sobolev, Alexandre N.,Swain, Abinash
supporting information, p. 17421 - 17432 (2020/12/28)
Trinuclear lanthanoid clusters have been synthesised and investigated as toroidal spin systems. A pyridyl functionalised β-diketonate, 1,3-bis(pyridin-2-yl)propane-1,3-dione (o-dppdH) has been used to synthesise a family of clusters of the form [Dy3(OH)2(o-dppd)3Cl2(H2O)4]Cl2·7H2O (1), [Tb3(o-dppd)3(μ3-OH)2(CH3CH2OH)3Cl3][Tb3(o-dppd)3(μ3-OH)2(H2O)(CH3CH2OH)2Cl3]Cl2·H2O (2), [Ho3(OH)2(o-dppd)3Cl(H2O)5]Cl3·3H2O (3) and [Er3(OH)2(o-dppd)3Cl2(H2O)3(CH3OH)]Cl2·3H2O·CH3OH (4). Despite the previous occurrence of this structural motif in the literature, these systems have not been widely investigated in terms of torodic behaviour. Magnetic studies were used to further characterise the complexes. DC susceptibility studies support weak antiferromagnetic exchange in the complexes. Slow magnetic relaxation behaviour is observed in the dynamic AC magnetic studies for complex 1. Theoretical studies predict that complex 1 and 3 have a non-magnetic ground state based on a toroidal arrangement of spins. Changes to the coordination environment in 2 do not support a toroic spin state. The prolate nature of the ErIII centres in complex 4 and large transverse anisotropy do not support the toroidal arrangement of lanthanoid spins in the complex.
Construction of Esters through Sulfuryl Fluoride (SO 2 F 2) Mediated Dehydrative Coupling of Carboxylic Acids with Alcohols at Room Temperature
Qin, Hua-Li,S Alharbi, Njud,Wang, Shi-Meng
, p. 3901 - 3907 (2019/10/11)
A facile method for the construction of esters through dehydrative coupling of carboxylic acids with alcohols is developed. The reactions are mediated by sulfuryl fluoride (SO 2 F 2) at room temperature and proceed with high efficiency. The method has several advantages including broad substrate scope, mild conditions, excellent functional group compatibility and affords high yields, even on gram scale.
Synthesis of novel indole derivatives containing double 1,3,4-oxadiazole moiety as efficient bactericides against phytopathogenic bacterium Xanthomonas oryzae
Tian, Kun,Li, Xiao-Qin,Zhang, Li,Gan, Yi-Yuan,Meng, Jiao,Wu, Shou-Qun,Wan, Jin-Lin,Xu, Yang,Cai, Chao-Ting,Ouyang, Gui-Ping,Wang, Zhen-Chao
, p. 17 - 25 (2019/02/12)
Abstract: A series of novel indole derivatives containing double 1,3,4-oxadiazole moiety was designed, synthesized and evaluated for their antibacterial activities in vitro. These compounds were fully characterized by 1H NMR, 13C NMR, and HRMS. Bioassay results indicated that most of title compounds exhibited excellent antibacterial activities against rice bacterial pathogen Xanthomonas oryzae (Xoo). For example, compounds 7d, 7h, 7i, 7j, 7k, 7l and 7m had the half-maximal effective concentration (EC50) values of 52.31, 54.12, 40.65, 38.80, 51.13, 52.75 and 50.66?μg/mL, respectively, which was better than that of commercial product bismerthiazol (BMT) (85.18?μg/mL). The experimental results proved that indole derivatives bearing double 1,3,4-oxadiazole unit are promising candidates for the development of new agricultural bactericides against pathogenic bacterium Xoo. Graphical abstract: [Figure not available: see fulltext.].
Oxadiazole derivative and application thereof
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Paragraph 0061-0063, (2019/03/24)
The invention provides an oxadiazole derivative and application thereof. The oxadiazole derivative provided by the invention uses oxadiazole and pyridine as electron acceptors and uses carbazole as anelectron donor to form molecules with different steric hindrances and different conjugated degrees by different connection modes. The molecules have higher triplet state energy level, have both charge and hole transport functions, and can be used as blue or green main body type materials in the field of organic electroluminescence. When the material as a main body is applied to a blue light organic device using FIrpic as an object, a light-emitting device with an external quantum efficiency being 14.6 to 20.8 percent can be obtained. When the material as the main body is applied into a greenorganic light-emitting device using Ir(ppy)3 as the object, a light-emitting device with the external quantum efficiency being 10.6 to 21.8 percent can be obtained.
Copper-Promoted Oxidative Intramolecular C–H Amination of Hydrazones to Synthesize 1H-Indazoles and 1H-Pyrazoles Using a Cleavable Directing Group
Zhang, Guofu,Fan, Qiankun,Zhao, Yiyong,Ding, Chengrong
supporting information, p. 5801 - 5806 (2019/08/02)
A facile and efficient synthesis of 1H-indazoles and 1H-pyrazoles through a copper-promoted oxidative intramolecular C–H amination of hydrazones using a cleavable directing group was developed. This reaction is characterized by its mild conditions, operational simplicity, readily available reagents, and excellent yields. A tentative mechanism for Cu-mediated C–H oxidative amination was proposed.
