Further studies on hepatitis C virus NS5B RNA-dependent RNA polymerase inhibitors toward improved replicon cell activities: Benzimidazole and structurally related compounds bearing the 2-morpholinophenyl moiety

Hirashima, Shin‐ichi; Oka, Takahiro; Ikegashira, Kazutaka; Noji, Satoru; Yamanaka, Hiroshi; Hara, Yoshinori; Goto, Hiroyuki; Mizojiri, Ryo; Niwa, Yasushi; Noguchi, Tōru; Ando, Izuru; Ikeda, Satoru; Hashimoto, Harukichi

doi:10.1016/j.bmcl.2007.03.027

Cited by 33 publications

(17 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nonnucleoside polymerase inhibitors (NNIs) interact with four distinct allosteric sites on HCV polymerase (4). We previously reported the discovery of several HCV polymerase inhibitors with a benzimidazole and indole core based on highthroughput screening and structure-based drug design (14,15,18,19).…”

Section: H Epatitis C Virus (Hcv) Is the Major Cause Of Posttransfusimentioning

confidence: 99%

Preclinical Characterization of JTK-853, a Novel Nonnucleoside Inhibitor of the Hepatitis C Virus RNA-Dependent RNA Polymerase

Ando

Adachi

Ogura

et al. 2012

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

Section: H Epatitis C Virus (Hcv) Is the Major Cause Of Posttransfusimentioning

confidence: 99%

Preclinical Characterization of JTK-853, a Novel Nonnucleoside Inhibitor of the Hepatitis C Virus RNA-Dependent RNA Polymerase

Ando

Adachi

Ogura

et al. 2012

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

“…48 JTK-109 (Japan Tobacco Inc.) was advanced into clinical studies. 49,50 This chemotype has been further modified. 51-53 MK-3281 has been described as a potent 'finger loop' allosteric inhibitor of HCV NS5B, and safety and tolerability of the drug has been tested on HCV-infected male patients.…”

Section: Ns5b Polymerase As An Anti-hcv Drug Targetmentioning

confidence: 99%

Recent advances in drug discovery of benzothiadiazine and related analogs as HCV NS5B polymerase inhibitors

Das

Hong

Chen

et al. 2011

Bioorganic & Medicinal Chemistry

View full text Add to dashboard Cite

“…The inhibitors of NS5B are categorized as nucleosides (NIs) and non-nucleosides (NNIs) (Ni and Wagman, 2004). Several inhibitors with different scaffolds have appeared in the literature, including benzimidazole (Beaulieu et al, 2004;Hirashima et al, 2007;Ishida et al, 2006), indole (Harper et al, 2005;Stansfield et al, 2009), thiophene (Louise-May et al, 2007), acridone derivatives (Stankiewicz-Drogon et al, 2008), benzothiadiazine Donner et al, 2008;Krueger et al, 2006;Pratt et al, 2005;Rockway et al, 2006), and so on. However, all these studies focused on how to synthesize new structures and measure their inhibition activity, and this process is extremely time-consuming and expensive.…”

Section: Introductionmentioning

confidence: 99%

Simple and accurate approaches to predict the activity of benzothiadiazine derivatives as HCV inhibitors

et al. 2011

Med Chem Res

View full text Add to dashboard Cite

Quantitative structure-activity relationship (QSAR) models of Hepatitis C virus (HCV) inhibitors were developed for 118 benzothiadiazine derivatives based on linear and nonlinear approaches. The best multi-linear regression (BMLR) was utilized to select appropriate molecular descriptors and develop linear model. Using the same descriptors, radial basis function neural networks (RBFNN) and support vector machine (SVM) were employed to generate the non-linear models. When comparing with the simpler BMLR model, RBFNN and SVM models had more accurate results with the square of correlation coefficients (R 2 ) of 0.850 and 0.875 for the training set, and R 2 of 0.893 and 0.854 for the test set. It proved that RBFNN and SVM were useful tools to predict the biological activity of benzothiadiazine derivatives as HCV inhibitors. Meanwhile, those factors governing the biological activity of benzothiadiazine derivatives were discussed. The proposed methods will be of significance in the HCV inhibitors research, and can be expected to apply to other similar research fields.

show abstract

Further studies on hepatitis C virus NS5B RNA-dependent RNA polymerase inhibitors toward improved replicon cell activities: Benzimidazole and structurally related compounds bearing the 2-morpholinophenyl moiety

Cited by 33 publications

References 10 publications

Preclinical Characterization of JTK-853, a Novel Nonnucleoside Inhibitor of the Hepatitis C Virus RNA-Dependent RNA Polymerase

Preclinical Characterization of JTK-853, a Novel Nonnucleoside Inhibitor of the Hepatitis C Virus RNA-Dependent RNA Polymerase

Recent advances in drug discovery of benzothiadiazine and related analogs as HCV NS5B polymerase inhibitors

Simple and accurate approaches to predict the activity of benzothiadiazine derivatives as HCV inhibitors

Contact Info

Product

Resources

About