- Homology modelling, molecular dynamics simulation and docking evaluation of β-tubulin of Schistosoma mansoni
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Schistosomiasis is one of the neglected diseases causing considerable morbidity and mortality throughout the world. Microtubules with its main component, tubulin play a vital role in helminthes including schistosomes. Benzimidazoles represent potential drug candidates by binding β-tubulin. The study aimed to generate a homology model for the β-tubulin of S. mansoni using the crystal structure of O vis aries (Sheep) β-tubulin (PDB ID: 3N2G D) as a template, then different β-tubulin models were generated and two previously reported benzimidazole derivatives (NBTP-F and NBTP-OH) were docked to the generated models, the binding results indicated that both S. mansoni, S. haematobium were susceptible to the two NBTP derivatives. Additionally, three mutated versions of S. mansoni β-tubulin wild-type were generated and the mutation (F185Y) seems to slightly enhance the ligand binding. Dynamics simulation experiments showed S. haematobium β-tubulin is highly susceptible to the tested compounds; similar to S. mansoni, moreover, mutated models of S. mansoni β-tubulin altered its NBTPs susceptibility. Moreover, additional seven new benzimidazole derivatives were synthesized and tested by molecular docking on the generated model binding site of S. mansoni β-tubulin and were found to have good interaction inside the pocket.
- El-Shehabi, Fouad,Mansour, Basem,Bayoumi, Waleed A.,El Bialy, Serry A.,Elmorsy, Mohammad A.,Eisa, Hassan M.,Taman, Amira
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- Synthesis of benzimidazole derivatives using heterogeneous ZnO nanoparticles
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A mild and efficient procedure for synthesis of benzimidazole derivatives in the presence of a catalytic amount of mechanochemically synthesized zinc oxide nanoparticles under solvent-free condition has been achieved.
- Alinezhad, Heshmatollah,Salehian, Fatemeh,Biparva, Pourya
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Read Online
- Multi-target inhibitor acting on QC and GSK-3[beta]
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The invention discloses a multi-target inhibitor acting on QC and GSK-3[beta], wherein the multi-target inhibitor has the structural general formula shown in the specification; according to active center crystal structures of target QC and GSK-3[beta] zymoprotein, with synthesis of multiple high-activity pharmacophores, the multi-target inhibitor capable of acting on QC and GSK-3[beta] at the sametime is prepared through skeletal transition and recombination design; the multi-target inhibitor is a high-activity molecule with multiple target points, the molecular structure diversity of a leaddrug is remarkably expanded, and research and development of innovative anti-AD drugs and AD diagnostic kits are actively promoted.
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Paragraph 0049; 0054; 0058; 0063; 0067; 0072
(2020/04/02)
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- Preparation method and application of multi-target inhibitor acting on QC and GSK-3beta
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The invention discloses a preparation method and application of a multi-target inhibitor acting on QC and GSK-3 beta. The structural general formula of the multi-target inhibitor prepared by the method is shown in the specification. According to the invention, according to active center crystal structures of target QC and GSK-3 beta zymoprotein, multiple high-activity pharmacophores are integrated, the multi-target inhibitor capable of acting on QC and GSK-3 beta at the same time is prepared through framework transition and recombination design, the multi-target inhibitor is molecules with multiple target points and high activity, the molecular structure diversity of a lead drug is remarkably expanded, and the research and development of innovative anti-AD drugs and AD diagnostic kits areactively promoted, and the preparation method of the multi-target inhibitor provided by the invention is simple and easy to operate.
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Paragraph 0058; 0063; 0067; 0072; 0076; 0081
(2020/04/17)
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- Halogen–metal exchange on bromoheterocyclics with substituents containing an acidic proton via formation of a magnesium intermediate
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A selective and practical bromine–metal exchange on bromoheterocyclics bearing substituents with an acidic proton under non-cryogenic conditions was developed by a simple modification of an existing protocol. Our protocol of using a combination of i-PrMgCl and n-BuLi has not only solved the problem of intermolecular quenching that often occurred when using alkyl lithium alone as the reagent for halogen–lithium exchange, but also offered a highly selective method for performing bromo–metal exchange on dibrominated arene compounds through chelation effect.
- Tian, Qingqiang,Shang, Suqin,Wang, Huajun,Shi, Guoqiang,Li, Zhiyao,Yuan, Jianyong
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supporting information
(2017/12/05)
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- Carbon Dioxide Mediated Novel Synthesis of Quinazoline-2,4(1H,3H)-dione in Water
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A novel, efficient, and scalable CO2 mediated synthesis of quinazoline-2,4(1H,3H)-dione was developed by a simple cyclization of 2-aminobenzonitrile with DMF in water as the solvent. This is the first report of its kind. DMF was used as the necessary carbon source in the synthesis of quinazoline-2,4(1H,3H)-dione. This synthetic protocol is very efficient; it gives >99% conversion with excellent selectivity. The product was isolated by filtration because of the highly insoluble nature of quinazoline-2,4(1H,3H)-dione in water. The co-product, dimethyl amine, also has industrial importance, and the CO2 that is used can be recycled. This protocol has wide-spread applications in the syntheses of benzimidazole and benzothiazole.
- Rasal, Kalidas B.,Yadav, Ganapati D.
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p. 2067 - 2073
(2016/12/24)
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- Synthesis method of Ramosetron
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The invention discloses a synthesis method of Ramosetron. According to the method, 3,4-diaminobenzoic acid is used as a starting raw material for finally preparing the Ramosetron through the synthesis of benzimidazole-5-carboxylic acid, benzimidazole-5-methyl carbonate sulfate, 4,5,6,7-tetrahydro benzimidazole-5-methyl carbonate sulfate, 4,5,6,7-tetrahydro benzimidazole-5-triazolylformate sulfate, N-[(4,5,6,7-tetrahydro benzimidazole-5-yl)] pyrrole hydrochloride and 5-[(1-methylindol -3-yl) carbonyl]-4,5,6,7-tetrahydro benzimidazole. Compared with the prior art, the method provided by the invention has the advantages that the reaction conditions are optimized; after the optimization, the reaction is really feasible; the yield of the 4,5,6,7-tetrahydro benzimidazole-5-methyl carbonate sulfate, the 4,5,6,7-tetrahydro benzimidazole-5-triazolylformate sulfate, the N-[(4,5,6,7-tetrahydro benzimidazole-5-yl)] pyrrole hydrochloride and the like is improved; the reaction total yield reaches more than 30 percent; higher economic benefits are realized.
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Paragraph 0076; 0077; 0125; 0126; 0127; 0128
(2016/10/09)
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- Gold-Catalyzed Reductive Transformation of Nitro Compounds Using Formic Acid: Mild, Efficient, and Versatile
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Developing new efficient catalytic systems to convert abundant and renewable feedstocks into valuable products in a compact, flexible, and target-specific manner is of high importance in modern synthetic chemistry. Here, we describe a versatile set of mild catalytic conditions utilizing a single gold-based solid catalyst that enables the direct and additive-free preparation of four distinct and important amine derivatives (amines, formamides, benzimidazoles, and dimethlyated amines) from readily available formic acid (FA) and nitro starting materials with high level of chemoselectivity. By controlling the stoichiometry of the employed FA, which has attracted considerable interest in the area of sustainable chemistry because of its potential as an entirely renewable hydrogen carrier and as a versatile C1 source, a facile atom- and step-efficient transformation of nitro compounds can be realized in a modular fashion. Renewable formic acid as a flexible feedstock: A versatile heterogeneous gold-based catalytic system has been developed for the controlled, flexible, and target-specific reductive transformation of nitro compounds using stoichiometric equivalents of formic acid as a key starting material under mild and convenient conditions. The overall operational simplicity, high chemoselectivity, functional-group tolerance, and reusability of the catalyst make this approach an attractive and reliable tool for organic and process chemists.
- Yu, Lei,Zhang, Qi,Li, Shu-Shuang,Huang, Jun,Liu, Yong-Mei,He, He-Yong,Cao, Yong
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p. 3029 - 3035
(2015/09/28)
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- SELECTIVE HDAC3 INHIBITORS
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Provided herein are HDAC3 inhibitors, as well as methods of treatment comprising administering these compounds to a subject in need thereof.
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Page/Page column 35
(2014/08/19)
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- Synthesis and antibacterial activity of novel 4″-O-benzimidazolyl clarithromycin derivatives
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Novel 4″-O-benzimidazolyl clarithromycin derivatives were designed, synthesized and evaluated for their in vitro antibacterial activities. These benzimidazolyl derivatives exhibited excellent activity against erythromycin-susceptible strains better than the references, and some of them showed greatly improved activity against erythromycin-resistant strains. Compounds 16 and 17, which have the terminal 2-(4-methylphenyl)benzimidazolyl and 2-(2-methoxyphenyl)benzimidazolyl groups on the C-4″ bishydrazide side chains, were the most active against erythromycin-resistant Staphylococcus pneumoniae expressing the erm gene and the mef gene. In addition, compound 17 exhibited the highest activity against erythromycin-susceptible S. pneumoniae ATCC49619 and Staphylococcus aureus ATCC25923 as well. It is worth noting that the 4″-O-(2-aryl)benzimidazolyl derivatives show higher activity against erythromycin-susceptible and erythromycin-resistant strains than the 4″-O-(2-alkyl)benzimidazolyl derivatives.
- Cong, Chao,Wang, Haiyang,Hu, Yue,Liu, Chen,Ma, Siti,Li, Xin,Cao, Jichao,Ma, Shutao
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supporting information; experimental part
p. 3105 - 3111
(2011/07/08)
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- Benzimidazole, Benzoxazole and Benzothiazole Derivatives, Optical Film Comprising them and Method of Producing thereof
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The present invention is relates to the synthesis of predominantly planar heterocyclic organic compound and the manufacture of optical films based on these compounds. Said organic compound has the general structural formula where Het is a predominantly planar heterocyclic molecular system possessing hydrophilic properties; B is a binding group; p is the number in the range from 3 to 8; S is a group providing solubility of the organic compound; m is a number in the range from 0 to 8. Said organic compound is transparent for electromagnetic radiation in the visible spectral range from 400 to 700 nm, and a solution of the compound or a salt thereof is capable of forming a substantially transparent optical layer on a substrate, with the heterocyclic molecular planes oriented predominantly parallel to the substrate surface.
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Page/Page column 13-14
(2010/12/29)
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- Rapid one-pot preparation of 2-substituted benzimidazoles from 2-nitroanilines using microwave conditions
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A high yielding one-pot procedure for the generation of 2-substituted benzimidazoles directly from 2-nitroanilines by in situ reduction and cyclization using a microwave procedure is described.
- VanVliet, David S.,Gillespie, Paul,Scicinski, Jan J.
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p. 6741 - 6743
(2007/10/03)
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