29289-18-7Relevant articles and documents
1-Aryl-3-(4-methoxybenzyl)ureas as potentially irreversible glycogen synthase kinase 3 inhibitors: Synthesis and biological evaluation
Venter, Jana,Perez, Concepción,van Otterlo, Willem A.L.,Martínez, Ana,Blackie, Margaret A.L.
, p. 1597 - 1600 (2019/05/02)
Glycogen synthase kinase 3 (GSK-3)has become known for its multifactorial involvement in the pathogenesis of Alzheimer's disease. In this study, a benzothiazole- and benzimidazole set of 1-aryl-3-(4-methoxybenzyl)ureas were synthesised as proposed Cys199-targeted covalent inhibitors of GSK-3β, through the incorporation of an electrophilic warhead onto their ring scaffolds. The nitrile-substituted benzimidazolylurea 2b (IC50 = 0.086 ± 0.023 μM)and halomethylketone-substituted benzimidazolylurea 9b (IC50 = 0.13 ± 0.060 μM)displayed high GSK-3β inhibitory activity, in comparison to reference inhibitor AR-A014418 (1, IC50 = 0.072 ± 0.043)in our assay. The results suggest further investigation of 2b and 9b as potential covalent inhibitors of GSK-3β, since a targeted interaction might provide improved kinase-selectivity.
Regioselective nitration of anilines with Fe(NO3)3·9H2O as a promoter and a nitro source
Gao, Yang,Mao, Yuanyou,Zhang, Biwei,Zhan, Yingying,Huo, Yanping
supporting information, p. 3881 - 3884 (2018/06/08)
An efficient Fe(NO3)3·9H2O promoted ortho-nitration reaction of aniline derivatives has been developed. This reaction may go through a nitrogen dioxide radical (NO2) intermediate, which is generated by the thermal decomposition of iron(iii) nitrate. The practicality of the present method using nontoxic and inexpensive iron reagents has been shown by the broad substrate scope and applications.
Design and synthesis of new benzimidazole-carbazole conjugates for the stabilization of human telomeric DNA, telomerase inhibition, and their selective action on cancer cells
Maji, Basudeb,Kumar, Krishan,Kaulage, Mangesh,Muniyappa,Bhattacharya, Santanu
supporting information, p. 6973 - 6988 (2014/10/16)
Cell-permeable small molecules that enhance the stability of the G-quadruplex (G4) DNA structures are currently among the most intensively pursued ligands for inhibition of the telomerase activity. Herein we report the design and syntheses of four novel benzimidazole-carbazole conjugates and demonstrate their high binding affinity to G4 DNA. S1 nuclease assay confirmed the ligand mediated G-quadruplex DNA protection. Additional evidence from Telomeric Repeat Amplification Protocol (TRAP-LIG) assay demonstrated efficient telomerase inhibition activity by the ligands. Two of the ligands showed IC 50 values in the sub-micromolar range in the TRAP-LIG assay, which are the best among the benzimidazole derivatives reported so far. The ligands also exhibited cancer cell selective nuclear internalization, nuclear condensation, fragmentation, and eventually antiproliferative activity in long-term cell viability assays. Annexin V-FITC/PI staining assays confirm that the cell death induced by the ligands follows an apoptotic pathway. An insight into the mode of ligand binding was obtained from the molecular dynamics simulations.
Reductive cyclization with baker's yeast of 4-alkyl-2-nitro-acetanilides to 6-alkylbenzimidazoles and 1-hydroxy-2-methyl-6-alkylbenzimidazoles
Navarro-Ocana,Olguin,Luna,Jimenez-Estrada,Barzana
, p. 2754 - 2756 (2007/10/03)
Reduction of 4-substituted 2-nitroacetanilides by baker's yeast in acid media effected cyclization, resulting in the formation of n-substituted 2-methylbenzimidazoles and 6-substituted 1-hydroxy-2-methylbenzimidazole via the chemo- and regioselective reduction of the 2-nitro aromatic group to amine or hydroxylamine.
Hypoxia-Selective Agents Derived from Quinoxaline 1,4-Di-N-oxides
Monge, Antonio,Palop, Juan A.,Cerain, Adela Lopez de,Senador, Virginia,Martinez-Crespo, Francisko J.,et al.
, p. 1786 - 1792 (2007/10/02)
Hypoxic cells, which are a common feature of solid tumors, but not normal tissues, are resistant to both anticancer drugs and radiation therapy.Thus the identification of drugs with selective toxicity toward hypoxic cells is an important objective in anticancer chemotherapy.The benzotriazine di-N-oxide (SR 4233, Tirapazamine) has been shown to be an efficient and selective cytotoxin for hypoxic cells.Since the bioreductive activation of Tirapazamine is thought to be due to the presence of the 1,4-di-N-oxide moiety, a series of 3-aminoquinoxaline-2-carbonitrile 1,4-di-N-oxides with a range of electron-donating and -withdrawing substituents in the 6- and /or 7- positions has been synthesized and evaluated for toxicity to hypoxic cells.Electrochemical studies of the quinoxaline di-N-oxides and Tirapazamine showed that as the electron-withdrawing nature of the 6(7)-substituent increases, the reduction potential becomes more positive and the compound is more readily reduced.Apart from the unsubstituted 6a and the 6,7-dimethyl derivative 6c, the quinoxaline di-N-oxide have reduction potentials significantly more positive than Tirapazamine (Epc -0.90 V).The most potent cytotoxins to cells in culture were the 6,7-dichloro and 6,7-difluoro derivatives 6i and 6l, which were 30-fold more potent than Tirapazamine.The 6(7)-fluoro and 6(7)-chloro compounds, 6e and 6h, showed the greatest hypoxia selectivity.Four of the compounds, 6e, 6f, 6h and 6i, killed the inner cells of multicellular tumor spheroids in vitro.In vivo Balb/c mice tolerated a dose of these four compounds twice the size of that of Tirapazamine.This study demonstrates that quinoxaline 1,4-di-N-oxides could provide useful hypoxia-selective therapeutic agents.
DNA Binding Compounds. V. Synthesis and Characterization of Boron-Containing Bibenzimidazoles Related to the DNA Minor Groove Binder, Hoechst 33258
Kelly, David P.,Bateman, Stuart A.,Martin, Roger F.,Reum, Monica E.,Rose, Michael,Whittaker, Antony R. D.
, p. 247 - 262 (2007/10/02)
The synthesis and characterization of four novel boron-containing bibenzimidazoles related to the DNA minor groove binder Hoechst 33258 are reported.Such compounds, particularly their 10B-enriched forms, have potential as agents for boron neutron capture therapy which is used in the treatment of cancers.
Structure, DNA minor groove binding, and base pair specificity of alkyl- and aryl-linked bis(amidinobenzimidazoles) and bis(amidinoindoles)
Fairley,Tidwell,Donkor,Naiman,Ohemeng,Lombardy,Bentley,Cory
, p. 1746 - 1753 (2007/10/02)
A series of bis(amidinobenzimidazoles) and bis(amidinoindoles) with varied linking chains connecting the aromatic groups and various modifications to the basic amidino groups have been prepared. The calf thymus (CT) DNA and nucleic acid homopolymer [poly(dA)·poly(dT), poly(dA-dT)·poly-(dA-dT), and poly(dG-dC)·poly(dG-dC)] binding properties of these compounds have been studied by thermal denaturation (ΔT(m)) and viscosity. The compounds show a greater affinity for poly(dA)·poly(dT) and poly(dA-dT)·poly(dA-dT) than for poly(dG-dC)·poly(dG-dC). Viscometric titrations indicate that the compounds do not bind by intercalation. Molecular modeling studies and the biophysical data suggest that the molecules bind to the minor groove of CT DNA and homopolymers. Analysis of the shape of the molecules is consistent with this mode of nucleic acid binding. Compounds with an even number of methylenes connecting the benzimidazole rings have a higher affinity for DNA than those with an odd number of methylenes. Molecular modeling calculations that determine the radius of curvature of four defined groups in the molecule show that the shape of the molecule, as a function of chain length, affects the strength of nucleic acid binding. Electronic effects from cationic substituents as well as hydrogen bonding from the imidazole nitrogens also contribute to the nucleic acid affinity. The bis(amidinoindoles) show no structurally associated differential in nucleic acid base pair specificity or affinity.
Substituted 1-sulfonylbenzimidazoles
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, (2008/06/13)
Certain 1-sulfonyl-2,5(6)-substituted-benzimidazole compounds are useful as antiviral agents.
