21645-25-0Relevant articles and documents
Design, synthesis and biological evaluation of 2-substituted-6-[(4-substituted-1-piperidyl)methyl]-1H-benzimidazoles as inhibitors of ebola virus infection
Bessières, Maxime,Plebanek, El?bieta,Chatterjee, Payel,Shrivastava-Ranjan, Punya,Flint, Mike,Spiropoulou, Christina F.,Warszycki, Dawid,Bojarski, Andrzej J.,Roy, Vincent,Agrofoglio, Luigi A.
, (2021/02/06)
Novel 2-substituted-6-[(4-substituted-1-piperidyl)methyl]-1H-benzimidazoles were designed and synthesized as Ebola virus inhibitors. The proposed structures of the new prepared benzimidazole-piperidine hybrids were confirmed based on their spectral data and CHN analyses. The target compounds were screened in vitro for their anti-Ebola activity. Among tested molecules, compounds 26a (EC50=0.93 μM, SI = 10) and 25a (EC50=0.64 μM, SI = 20) were as potent as and more selective than Toremifene reference drug (EC50 = 0.38 μM, SI = 7) against cell line. Data suggests that the mechanism by which 25a and 26a block EBOV infection is through the inhibition of viral entry at the level of NPC1. Furthermore, a docking study revealed that several of the NPC1 amino acids that participate in binding to GP are involved in the binding of the most active compounds 25a and 26a. Finally, in silico ADME prediction indicates that 26a is an idealy drug-like candidate. Our results could enable the development of small molecule drug capable of inhibiting Ebola virus, especially at the viral entry step.
BENZIMIDAZOL DERIVATIVES FOR TREATING FILOVIRUS INFECTION
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Page/Page column 70; 71, (2018/04/13)
The present invention relates to compounds comprising a benzimidazole scaffold, and the use of such compounds for the treatment of viral diseases. The invention also relates to pharmaceutical compositions comprising said compounds as an active ingredient. In particular the compounds of the invention comprising a benzimidazole scaffold are used for the treatment of filoviruses or retroviruses, and preferably for the treatment of Ebola virus or HIV virus.
Highly efficient synthesis of tetra benzo spiro bis-crown ether
Moradgholi, Fatemeh,Vahedi, Hooshang,Lari, Jalil
, p. 85 - 90 (2015/06/23)
Novel spiro bis-crown ethers derivatives with four benzo units connected via one carbon bridges have been prepared. These compounds represent well preorganized cavities with interesting complexation abilities towards cations. These macrocyclic were prepared by a four-step via template method by utilizing simple precursors catechol, oliethylen glycol and penta erythritol tetra bromide in good yield. Additionally, cesium carbonate could be used as an excellent base for these reactions.
Inner workings of a cinchona alkaloid catalyzed oxa-Michael cyclization: Evidence for a concerted hydrogen-bond-network mechanism
Hintermann, Lukas,Ackerstaff, Jens,Boeck, Florian
supporting information, p. 2311 - 2321 (2013/04/10)
Cinchona alkaloids catalyze the oxa-Michael cyclization of 4-(2-hydroxyphenyl)-2-butenoates to benzo-2,3-dihydrofuran-2-yl acetates and related substrates in up to 99 % yield and 91 % ee (ee=enantiomeric excess). Catalyst and substrate variation studies reveal an important role of the alkaloid hydroxy group in the reaction mechanism, but not in the sense of a hydrogen-bonding activation of the carbonyl group of the substrate as assumed by the Hiemstra-Wynberg mechanism of bifunctional catalysis. Deuterium labeling at C-2 of the substrate shows that addition of RO-H to the alkenoate occurs with syn diastereoselectivity of ≥99:1, suggesting a mechanism-based specificity. A concerted hydrogen-bond network mechanism is proposed, in which the alkaloid hydroxy group acts as a general acid in the protonation of the α-carbanionic center of the product enolate. The importance of concerted hydrogen-bond network mechanisms in organocatalytic reactions is discussed. The relative stereochemistry of protonation is proposed as analytical tool for detecting concerted addition mechanisms, as opposed to ionic 1,4-additions. Secret of cyclization: The cinchona alkaloid catalyzed asymmetric oxa-Michael cyclization of 2′-hydroxyphenyl-2-butenoates to benzodihydrofurans proceeds by a highly enantio- and diastereoselective syn-specific addition mode (see scheme). Transition-state activation of the carbonyl group by hydrogen bonding to the catalyst is excluded. This represents a clear-cut demonstration of the importance of concerted hydrogen-bond network mechanisms in cinchona-based asymmetric organocatalysis. Copyright
Tuning the mesomorphic properties of liquid-crystalline dibenzotetraaza[14]annulenes - Discotic nematic phases of tetraalkoxy- substituted derivatives
Grolik, Jaros?aw,Dudek, ?ukasz,Eilmes, Julita
scheme or table, p. 5127 - 5130 (2012/09/25)
A homologous series of five tetrasubstituted dibenzotetraaza[14]annulene- based discotic mesogens was prepared and studied using polarizing optical microscopy (POM) and differential scanning calorimetry (DSC). A nematic phase was identified for the product bearing two peripheral isobutoxy and two dodecyloxy substituents.
Ruthenium(III) acetylacetonate [Ru(acac)3] - An efficient chemoselective catalyst for the tetrahydropyranylation (THP) of alcohols and phenols under solvent-free conditions
Varala, Ravi,Adapa, Srinivas R.
, p. 1174 - 1179 (2007/10/03)
A catalytic amount of ruthenium(III) acetylacetonate (2 mol%) [Ru(acac)3] enables solvent-free tetrahydropyranylation of different types of alcohols and phenols at ambient temperature in moderate to excellent yields. Notably, selective monoprotection of diols can be achieved chemoselectively. Furthermore, the catalyst could be recovered and reused if necessary.
Strategies for the synthesis of bi- and triarylic materials starting from commercially available phenols
Chopa, Alicia B.,Silbestri, Gustavo F.,Lockhart, María T.
, p. 3865 - 3877 (2007/10/03)
A series of arylstannanes have been synthesized, through an SRN1 mechanism, in good to excellent yields (74%-99%) by the photostimulated reaction of trimethyl stannyl ion with substrates supporting different nucleofugal groups. The arylstannanes thus obtained were suitable intermediates for Stille cross-coupling reactions leading to asymmetric bi- and triaryl compounds in acceptable global yields. An attractive feature of this route is that simple commercially available benzenediols, chloro- and methoxy phenols might be useful starting substrates, leading the latter to higher global yields of products in fewer steps. The strategies proposed open a broad synthetic tool.
Preparation of synthetic lignins with superior NMR characteristics via isotopically labeled monolignols
Ralph, John,Zhang, Yingsheng,Ede, Richard M.
, p. 2609 - 2613 (2007/10/03)
Synthetic lignins are particularly valuable for studying aspects of lignification, plant cell wall cross-linking, and lignin structure. If they are not too highly polymeric, they are soluble in normal lignin solvents and amenable to solution-state NMR studies. However, in the application of inverse-detected correlation experiments, particularly the popular HMQC and HMBC experiments, the spectra have annoying T1-noise ridges. These artifacts make it difficult to locate correlation peaks that are near the methoxy signal in the proton dimension. One solution is to use gradient-enhanced NMR but that requires additional hardware that is not yet ubiquitous. An alternative is to produce monolignols in which the atoms of the methoxy group are NMR-invisible. We have accomplished this by preparing coniferyl and sinapyl alcohols using 13C-depleted deuterated methyl iodide (12C2H3I). The methods, which incorporate steps simpler than have been used previously for labeled monolignols, are sufficiently low cost and straight-forward that these monomers can be utilized for any synthetic lignins destined for NMR studies. The NMR spectra of lignins derived from these 'methoxy-less' monomers are markedly superior to their normal-monomer counterparts. Several popular NMR experiments are illustrated for synthetic lignins derived from normal vs. isotopically labeled coniferyl alcohol, along with some useful experiments that have not been seen in lignin-related publications to date.
Chromogenic and fluorogenic crown ether compounds for the selective extraction and determination of Hg(II)
Vaidya, Bikas,Zak, Jerzy,Bastiaans, Glenn J.,Porter, Marc D.,Hallman, Johnny L.,Nabulsi, Nabeel A. R.,Utterback, Marty D.,Strzelbicka, Bozena,Bartsch, Richard A.
, p. 4101 - 4111 (2007/10/02)
Two novel crown ether compounds, N,N′-bis(2-hydroxy-5-nitrobenzyl)-4,13-diazadibenzo-18-crown-6 (CCE) and N,N′-bis(7-hydroxy-4-methylcoumarin-8-methylene)-4,13-diazadibenzo-18- crown-6 (FCE), have been synthesized as potential reagents for the selective e
Anticoccidial activity of crown polyethers
Brown,Foubister
, p. 590 - 592 (2007/10/02)
Anticoccidial activity in vitro against Eimeria tenella is reported for crown polyethers with ring sizes from 14 to 30 atoms. The most potent compounds, 4 and 9, were found active at 0.33 ppm, but none were active in vivo. Test results are discussed in te
