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Literature DB >> 16824756

Identification and structure-based optimization of novel dihydropyrones as potent HCV RNA polymerase inhibitors.

Hui Li¹, John Tatlock, Angelica Linton, Javier Gonzalez, Allen Borchardt, Peter Dragovich, Tanya Jewell, Tom Prins, Ru Zhou, Julie Blazel, Hans Parge, Robert Love, Michael Hickey, Chau Doan, Stephanie Shi, Rohit Duggal, Cristina Lewis, Shella Fuhrman.

Abstract

A novel class of non-nucleoside HCV NS5B polymerase inhibitors has been identified from screening. A co-crystal structure revealed an allosteric binding site in the protein that required a unique conformational change to accommodate inhibitor binding. Herein we report the structure-activity relationships (SARs) of this novel class of dihydropyrone-containing compounds that show potent inhibitory activities against the HCV RNA polymerase in biochemical assays.

Entities: Chemical

Mesh：

Substances：

Year: 2006 PMID： 16824756 DOI： 10.1016/j.bmcl.2006.06.065

Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823

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Cited

12 in total

Review 1. 1,2,4-Triazolo[1,5-a]pyrimidines in drug design.

Authors: Killian Oukoloff; Bobby Lucero; Karol R Francisco; Kurt R Brunden; Carlo Ballatore
Journal: Eur J Med Chem Date: 2019-01-14 Impact factor: 6.514

2. In vitro resistance study of AG-021541, a novel nonnucleoside inhibitor of the hepatitis C virus RNA-dependent RNA polymerase.

Authors: Stephanie T Shi; Koleen J Herlihy; Joanne P Graham; Shella A Fuhrman; Chau Doan; Hans Parge; Michael Hickey; Jingjin Gao; Xiu Yu; Fannie Chau; Javier Gonzalez; Hui Li; Cristina Lewis; Amy K Patick; Rohit Duggal
Journal: Antimicrob Agents Chemother Date: 2007-12-10 Impact factor: 5.191

3. Alcohol-assisted phosphine catalysis: one-step syntheses of dihydropyrones from aldehydes and allenoates.

Authors: Gardner S Creech; Ohyun Kwon
Journal: Org Lett Date: 2008-01-04 Impact factor: 6.005

4. Preclinical characterization of PF-00868554, a potent nonnucleoside inhibitor of the hepatitis C virus RNA-dependent RNA polymerase.

Authors: Stephanie T Shi; Koleen J Herlihy; Joanne P Graham; Jim Nonomiya; Sadayappan V Rahavendran; Heather Skor; Rebecca Irvine; Susan Binford; John Tatlock; Hui Li; Javier Gonzalez; Angelica Linton; Amy K Patick; Cristina Lewis
Journal: Antimicrob Agents Chemother Date: 2009-03-23 Impact factor: 5.191

Identification and structure-based optimization of novel dihydropyrones as potent HCV RNA polymerase inhibitors.

Review 1. 1,2,4-Triazolo[1,5-a]pyrimidines in drug design.

2. In vitro resistance study of AG-021541, a novel nonnucleoside inhibitor of the hepatitis C virus RNA-dependent RNA polymerase.

3. Alcohol-assisted phosphine catalysis: one-step syntheses of dihydropyrones from aldehydes and allenoates.

4. Preclinical characterization of PF-00868554, a potent nonnucleoside inhibitor of the hepatitis C virus RNA-dependent RNA polymerase.

5. Structure-based virtual screening, synthesis and SAR of novel inhibitors of hepatitis C virus NS5B polymerase.

6. Allosteric inhibitors have distinct effects, but also common modes of action, in the HCV polymerase.

7. Combination of pharmacophore hypothesis and molecular docking to identify novel inhibitors of HCV NS5B polymerase.

Review 8. Recent advances in the discovery of potent RNA-dependent RNA-polymerase (RdRp) inhibitors targeting viruses.

9. Thumb inhibitor binding eliminates functionally important dynamics in the hepatitis C virus RNA polymerase.

10. Inhibitors for the hepatitis C virus RNA polymerase explored by SAR with advanced machine learning methods.