Improved replicon cellular activity of non-nucleoside allosteric inhibitors of HCV NS5B polymerase: From benzimidazole to indole scaffolds

Beaulieu, Pierre L.; Gillard, James; Bykowski, Darren; Brochu, Christian; Dansereau, Nathalie; Duceppe, Jean‐Simon; Haché, Bruno; Jakalian, Araz; Lagacé, Lisette; LaPlante, Steven R.; McKercher, Ginette; Moreau, Elaine; Perreault, Stéphane; Stammers, Timothy A.; Thauvette, Louise; Warrington, J. V.; Kukolj, George

doi:10.1016/j.bmcl.2006.07.074

Cited by 77 publications

(46 citation statements)

References 17 publications

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“…Benzimidazole derivatives exhibit broad spectrum of biological activities, such as antifungal, 1) antibacterial, 2) antiviral, 3) and antitumoral activities, 4) and thus play an important role in agricultural and pharmaceutical fields. In the pesticide field, benzimidazole fungicides with carbendazim, benomyl and thiabendazole, for example, are still used as fungicides due to their high efficiency, broad spectrum and good systemic property.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and antifungal activity of 1-substitutedphenyl-3-(5-halobenzimidazol-2-yl) acylurea

et al. 2010

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Twelve novel compounds of 1-substitutedphenyl-3-(5-halobenzimidazol-2-yl) acylurea were synthesized by the reaction of 5-halobenzimidazol-2-yl acylisocyanate with substituted anilines in yields of 62.4-76.1%. The structures of the title compounds were characterized by IR, 1 H NMR spectra and elemental analysis. Antifungal activities against Botrytis cinerea and Sclerotinia sclerotiorum were also evaluated by the mycelium growth rate method in the lab. The results indicated that most of the title compounds exhibited excellent antifungal activities against Sclerotinia sclerotiorum, and their activities were higher than that of thiophanatemethyl.

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Section: Introductionmentioning

confidence: 99%

Synthesis and antifungal activity of 1-substitutedphenyl-3-(5-halobenzimidazol-2-yl) acylurea

et al. 2010

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“…Commercially available diamine (8) was acylated to a mono-amine (9), which was further converted into sulfonyl chloride (10) via diazotization according to an established procedure. 14,15 Coupling of 10 with Ad-NH 2 , followed by de-protection, yielded the desired intermediate (11), which was ultimately converted into the corresponding analog 5 using procedures described in Scheme 1.…”

Section: Infection By Hepatitis C Virus (Hcv) Is a Global Healthmentioning

confidence: 99%

“…4 Medicinal chemistry pursuits of this polymerase for anti-HCV drug-discovery have led to the identification of numerous classes of structurally diversified inhibitors. [5][6][7][8][9][10][11][12][13] One of the reported NS5B inhibitors, NM283, is currently in phase II clinical trials, 13 thus validating NS5B as a target for the discovery of anti-HCV drugs.We have previously described a series of allosteric inhibitors for HCV NS5B. 5,6 Our continued endeavors were focused on finding other mechanistically unique scaffolds.…”

mentioning

confidence: 99%

Isothiazoles as active-site inhibitors of HCV NS5B polymerase

Yan¹,

Appleby²,

Gunić³

et al. 2007

Bioorganic & Medicinal Chemistry Letters

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“…Recently, N-morpholinoacetyl-2-phenyl-indole-6-carboxylic acid was determined as a potent inhibitor of subgenomic hepatitis C virus replication with an IC 50 value of 0.127 μM (Harper et al, 2005). A structurally similar compound, Nmethyl-2-phenyl-3-cyclohexyl-indole-6-carboxylic acid was reported by another research group to be an allosteric inhibitor of the HCV virus with an IC 50 value of 0.009 μM (Beaulieu et al, 2006). Oxindole derivatives were also investigated as antiviral agents and some of them were found to be potent HIV-1 non-nucleoside reverse transcriptase inhibitors (Jiang et al, 2006).…”

Section: Introductionmentioning

confidence: 97%

A Study of 3-Substituted Benzylidene-1,3-dihydro-indoline Derivatives as Antimicrobial and Antiviral Agents

Ölgen

Özkan

2009

Zeitschrift Für Naturforschung C

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3-Substituted benzylidene-1,3-dihydro-indoline derivatives were tested for their in vitro antibacterial activity against the Gram-negative bacteria Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and the Gram-positive bacteria Bacillus subtilis, Staphylococcus aureus, and for their their in vitro antifungal activity against Candida krusei and Candida albicans. The minimum inhibitory concentration (MIC) values were determined by the 2-fold serial dilution technique in Mueller Hinton broth and Sabouraud dextrose agar using antibacterial and antifungal assays, respectively. For comparison of the antimicrobial activity, rifampicin, ampicillin trihydrate, gentamicin sulfate, and ofl oxacin were used as reference antibacterial agents, and fl uconazole and amphotericin B were employed as reference antifungal agents. The most active compound 10 showed notable inhibition against Bacillus subtilis, Staphylococcus aureus, and Candida krusei. Compounds 1 and 6 were found slightly effective against Klebsiella pneumoniae and Escherichia coli. In addition, compounds 13 and 14 showed inhibition against Bacillus subtilis and Staphylococcus aureus. Indole derivatives were also tested in vitro for replication of the HepAD38 cell line and compared with lamivudine (3TC, L-2′,3′-dideoxy-3′-thiacytidine). The IC 50 values of the compounds were found to be >1000 μM against HBV except for compound 13 which exhibited activity with an IC 50 value of 500 μM.

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Improved replicon cellular activity of non-nucleoside allosteric inhibitors of HCV NS5B polymerase: From benzimidazole to indole scaffolds

Cited by 77 publications

References 17 publications

Synthesis and antifungal activity of 1-substitutedphenyl-3-(5-halobenzimidazol-2-yl) acylurea

Synthesis and antifungal activity of 1-substitutedphenyl-3-(5-halobenzimidazol-2-yl) acylurea

Isothiazoles as active-site inhibitors of HCV NS5B polymerase

A Study of 3-Substituted Benzylidene-1,3-dihydro-indoline Derivatives as Antimicrobial and Antiviral Agents

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