- Design, synthesis and biological evaluation of 2-substituted-6-[(4-substituted-1-piperidyl)methyl]-1H-benzimidazoles as inhibitors of ebola virus infection
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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.
- 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.
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- Bimetal complex with aryloxy ether skeleton, and preparation method and application thereof
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The invention provides a bimetallic complex with an aryloxy ether skeleton, and a preparation method and application of the bimetallic complex. The bimetallic complex has a structural expression as shown in the specification. A catalytic system of the bimetallic complex shows very good catalytic activity and thermal stability when being used for catalyzing olefin homopolymerization or olefin/alphaolefin copolymerization reactions, and a polymerization product generated by catalysis has relatively high molecular weight and a high alpha-olefin insertion rate and has a very good industrial application prospect.
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Paragraph 0129; 0143-0144
(2020/11/26)
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- IVB group-containing bimetallic complex catalyst as well as preparation method and application thereof
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The invention provides an IVB group-containing bimetallic complex catalyst as well as a preparation method and application of the catalyst. The IVB group-containing bimetallic complex has a structuralexpression shown in the specification. The IVB group-co
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Paragraph 0111; 0113; 0122-0125
(2020/11/23)
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- Asymmetric Transfer Hydrogenation of o-Hydroxyphenyl Ketones: Utilizing Directing Effects That Optimize the Asymmetric Synthesis of Challenging Alcohols
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A systematic range of o-hydroxyphenyl ketones were reduced under asymmetric transfer hydrogenation conditions using the C3-tethered catalyst 2. Two directing effects, i.e., an o-hydroxyphenyl coupled to a bulky aromatic on the opposite side of the ketone substrate, combine in a matched manner to deliver reduction products with very high enantiomeric excess.
- Clarkson, Guy J.,Wills, Martin,Zheng, Ye
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supporting information
(2020/05/05)
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- Metal complex, preparation method and application thereof
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The invention provides a metal complex, a preparation method and application thereof. The metal complex has the following structural expression shown as the specification. The invention has the technical advantages that: the invention puts forward the O,
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Paragraph 0125; 0136-0140
(2020/10/20)
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- Enantioselective (3+2) cycloaddition: Via N-heterocyclic carbene-catalyzed addition of homoenolates to cyclic N -sulfonyl trifluoromethylated ketimines: Synthesis of fused N-heterocycle γ-lactams
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An enantioselective (3+2) cycloaddition of enals and cyclic N-sulfonyl trifluoromethyl ketimines via N-heterocyclic carbene-catalyzed homoenolate addition is described. This reaction can efficiently construct fused N-heterocycle γ-lactams bearing two adjacent chiral centers with >20?:?1 dr and 94-99% ee, with one chiral center as a trifluoromethylated α-tetrasubstituted carbon stereocenter.
- Zhang, Zhen-Zhen,Zhang, Yongna,Duan, Hui-Xin,Deng, Zhuo-Fei,Wang, You-Qing
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supporting information
p. 1553 - 1556
(2020/02/13)
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- Cascade Claisen and Meinwald Rearrangement for One-Pot Divergent Synthesis of Benzofurans and 2 H-Chromenes
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A new cascade approach has been developed for the one-pot four-step divergent synthesis of polysubstituted benzofurans and 2H-chromenes, featuring a novel cascade aromatic Claisen rearrangement/Meinwald rearrangement/dehydrative or oxidative cyclization. This new method was demonstrated with 39 examples tolerating different substitutions at an epoxide, allylic ether, and aromatic ring, and we showcased its utility with the first total synthesis of natural product liparacid A in seven steps.
- Song, Liyan,Su, Qian,Lin, Xi,Du, Zhihui,Xu, Huiyou,Ouyang, Ming-An,Yao, Hongliang,Tong, Rongbiao
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supporting information
p. 3004 - 3009
(2020/04/20)
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- Formation and Activation of Zr/Hf Bis(phenolate-ether) Precatalysts
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Zr and Hf complexes of bis(phenolate-ether) (“O4”) ligands feature high activity, stereoselectivity and molecular weight capability for propene polymerization at high temperature. Here we report a simplified ligand synthesis and several new examples of O4
- Cuthbert, Eric N. T.,Busico, Vincenzo,Herbert, David E.,Budzelaar, Peter H. M.
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supporting information
p. 3396 - 3410
(2019/08/12)
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- Ru(II)-catalyzed C-H activation and annulation of salicylaldehydes with monosubstituted and disubstituted alkynes
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The Ru(ii)-catalyzed C-H activation and annulation reaction of salicylaldehydes and disubstituted alkynes affords chromones in high yields. This reaction also works with terminal alkynes and tolerates a wide range of sensitive functional groups. The selectivity pattern of this Ru(ii)-catalyzed annulation reaction is different from the known Au(i), Rh(iii)-catalyzed annulation reactions of salicylaldehydes and terminal alkynes.
- Baruah, Swagata,Kaishap, Partha Pratim,Gogoi, Sanjib
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supporting information
p. 13004 - 13007
(2016/11/11)
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- Synthesis of Phenanthrene Derivatives by Intramolecular Cyclization Utilizing the [1,2]-Phospha-Brook Rearrangement Catalyzed by a Bronsted Base
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The synthesis of functionalized phenanthrene derivatives was achieved by intramolecular cyclization utilizing the [1,2]-phospha-Brook rearrangement under Bronsted base catalysis. Treatment of biaryl compounds having an α-ketoester moiety and an alkyne moiety at the 2 and 2′ positions, respectively, with diisopropyl phosphite in the presence of a catalytic amount of phosphazene base P2-tBu provides 9,10-disubstituted phenanthrene derivatives in high yields. This reaction involves the generation of an ester enolate through an umpolung process, that is, addition of diisopropyl phosphite to a keto moiety followed by the [1,2]-phospha-Brook rearrangement, the intramolecular addition to an alkyne, and the [3,3] rearrangement of the allylic phosphate moiety in a consecutive fashion.
- Kondoh, Azusa,Aoki, Takuma,Terada, Masahiro
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supporting information
p. 12577 - 12580
(2015/09/01)
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- 1-Benzyl-4-phenyl-1H-1,2,3-triazoles improve the transcriptional functions of estrogen-related receptor γ and promote the browning of white adipose
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The estrogen-related receptor γ (ERRγ) is a potential molecular target for the development of small molecules to stimulate the adipose browning process, which may represent a novel attractive strategy to treat obesity related disorders. The receptor possesses a very small ligand binding cavity and therefore identification of small molecule ERRγ modulators is a considerable challenge. We have successfully designed and synthesized a series of 1-benzyl-4-phenyl-1H-1,2,3-triazoles and demonstrated that they improve the transcriptional functions of ERRγ, potently elevating both the mRNA levels and the protein levels of ERRγ downstream targets. One of the most promising compounds, 4-(1-(4-iso-propylbenzyl)-1H-1,2,3-triazol-4-yl)benzene-1,2-diol (2e) was further shown to directly bind with the ERRγ ligand binding domain (ERRγ-LBD) in an isothermal calorimetric (ITC) assay and to thermally stabilize ERRγ-LBD protein by increasing its melting temperature (Tm) as demonstrated by circular dichroism (CD) spectroscopy. Furthermore, 2e potently stimulates the adipocyte browning process and induces mitochondrial biogenesis both in vitro and in vivo, suggesting the considerable therapeutic potential of this compound for the treatment of obesity and related disorders.
- Xu, Shilin,Mao, Liufeng,Ding, Ping,Zhuang, Xiaoxi,Zhou, Yang,Yu, Lei,Liu, Yingxue,Nie, Tao,Xu, Tingting,Xu, Yong,Liu, Jinsong,Smaill, Jeff,Ren, Xiaomei,Wu, Donghai,Ding, Ke
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p. 3751 - 3760
(2015/07/27)
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- Simple and efficient method for tetrahydropyranylation of alcohols and phenols by using silica supported sodium hydrogen sulphate as a catalyst
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A Simple and efficient process for tetrahydropyranylation of alcohols and phenols has been developed by reacting with dihydropyran at room temperature in presence of catalytic amount of silica supported sodium hydrogen sulphate.
- Ravi Kumar,Satyanarayana,Srinivasa Reddy
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experimental part
p. 3876 - 3878
(2012/09/21)
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- Traceless solid-phase synthesis of trifluoromethylarenes
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Save the best for last: In the first method for the trifluoromethylation of immobilized arenes, the aryl halides are attached through a dithioester linkage to the Merrifield resin and then functionalized by means of numerous reactions including transition
- Doebele, Marion,Wiehn, Matthias S.,Braese, Stefan
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supporting information; experimental part
p. 11533 - 11535
(2012/01/11)
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- Bridged bi-aromatic ligands, catalysts, processes for polymerizing and polymers therefrom
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New ligands and compositions with bridged bis-aromatic ligands are disclosed that catalyze the polymerization of monomers into polymers. These catalysts with metal centers have high performance characteristics, including higher comonomer incorporation int
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- 2-Methoxy-2H-chromenes from 2-Bromophenols and 3-Trimethylsilyloxyacroleins
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The preparation of 2-methoxy-2H-chromenes 6 from 2-bromophenols 1 and 3-trimethylsilyloxyacroleins 4 as C3 anellation reagents is described.Heterocyclization involves C-C linkage of ortho-lithiated 2-phenoxytetrahydropyrans 3 with 3-trimethylsilyloxyacrol
- Ulrich, Friedrich-Wilhelm,Breitmaier, Eberhard
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p. 951 - 953
(2007/10/02)
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- Hydroxy derivatives of tamoxifen
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In the exploration of the structural features that affect the RBA (binding affinity for the estrogen receptor of rat uterus relative to that of estradiol) in the tamoxifen [trans-(Z)-1-[4-(dimethylamino)ethoxy]-1,2-diphenyl-1-butene] series, several derivatives variously substituted in the 1-phenyl group have been synthesized. In the tamoxifen series, the descriptors E and Z, which define the configuration of the geometrical isomers and depend on the location and nature of substituents in the aromatic moieties and the ethyl group, may vary, although the relative configuration (cis or trans) does not. In order to avoid confusion the terms cis and trans will be used in this paper to refer to the relative positions of the 4-[2-(dimethylamino)ethoxy]phenyl and ethyl (or hydroxyethyl, hydroxypropyl, or bromo) substituents attached to the ethene moiety]. The final stage of each synthesis involved acid-catalyzed dehydration of a tertiary alcohol, and, in contrast to the known 3- and 4-hydroxy derivatives which were obtained as near-equimolar cis,trans mixtures, only the trans forms of the 2-hydroxy, 2-methyl, 2,4-dihydroxy, and 4-hydroxy-2-methyl derivatives were obtained. Also, in contrast to the trans forms of the 3- and 4-hydroxy derivatives, which are readily equilibrated to cis,trans mixtures, the trans 2-hydroxy derivative could not be isomerized. Tamoxifen and 2-methyltamoxifen had similar RBA's (~1% of that of E2), but that of 2-hydroxytamoxifen was much lower (0.1%). Introduction of a second hydroxyl group (2,4-dihydroxy derivative) enhanced the RBA, and for the 4-hydroxy-2-methyl derivative, the RBA and growth inhibitory activity against the MCF-7 mammary tumor cell line in vitro were high and comparable to those of 4-hydroxytamoxifen, a metabolite of the parent drug. Tamoxifen derivatives hydroxylated at positions 3 or 4 of the 1-butene moiety and the 5-hydroxy-1-pentene analogue were also synthesized, but they had very low RBA values.
- Foster,Jarman,Leung,McCague,Leclercq,Devleeschouwer
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p. 1491 - 1497
(2007/10/02)
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