The discovery of a pan-genotypic, primer grip inhibitor of HCV NS5B polymerase

Eastman, Kyle J.; Parcella, Kyle; Yeung, Kap‐Sun; Grant-Young, Katharine A.; Zhu, Juliang; Wang, Tao; Zhang, Zhongxing; Yin, Zhiwei; Beno, Brett R.; Sheriff, S.; Kish, Kevin; Tredup, Jeffrey; Jardel, Adam; Halan, Vivek; Ghosh, Kaushik; Parker, Dawn D.; Mosure, Kathy; Fang, Hua; Wang, Ying-Kai; Lemm, Julie A.; Zhuo, Xianlu; Hanumegowda, Umesh; Rigat, Karen; Donoso, Maria; Tuttle, Maria; Zvyaga, Tatyana; Haarhoff, Zuzana; Meanwell, Nicholas A.; Soars, Matthew G.; Roberts, Susan B.; Kadow, John F.

doi:10.1039/c6md00636a

Cited by 16 publications

(12 citation statements)

References 12 publications

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“…In 2014, BMS scientists reported a class of tetrasubstituted 7‐azabenzofurans ( 1 , Scheme ) exhibiting pan‐genotype inhibition of HCV NS5B polymerase . The preparation of this series of compounds, exemplified by compound 5 , a potent HCV NS5B polymerase inhibitor, is shown in Scheme . The caveat in this synthesis lies in the construction of the 7‐azabenzofuran core and the attachment of the four substituents.…”

Section: Methodsmentioning

confidence: 99%

Facile and Efficient Synthesis of Tri‐ and Tetrasubstituted 7‐Azabenzofuran Derivatives

Fu¹,

Shen

et al. 2020

Asian J Org Chem

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Section: Methodsmentioning

confidence: 99%

Facile and Efficient Synthesis of Tri‐ and Tetrasubstituted 7‐Azabenzofuran Derivatives

Fu¹,

Shen

et al. 2020

Asian J Org Chem

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“…Finally, deprotonation and rearomatization provide the target products, 336 . Our group applied this method to the efficient synthesis of the potent HCV NS5B polymerase inhibitor, 341 (Scheme 101), [134] providing six times greater total yield than that obtained through the original synthesis developed by BMS scientists, [135] who used Pd‐catalyzed cyclization to construct the 7‐azabenzofuran core.…”

Section: Annulation Of C3‐substituted Pyridine/quinoline N‐oxidesmentioning

confidence: 99%

Recent Advances in the Synthesis of C2‐Functionalized Pyridines and Quinolines Using N‐Oxide Chemistry

et al. 2020

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While remarkable progress has recently been made for the direct C−H‐functionalization of azines, its application is still limited by a lack of accessible functional groups (primarily carbon‐based) and poor regioselectivity. In contrast, C2‐functionalized pyridines and quinolines can be easily synthesized by treating readily available N‐oxides with various reagents under appropriate activation conditions. This review seeks to comprehensively document the available synthetic methods for introducing functional groups at the C2 position of pyridines and quinolines. In this work, we highlight recent developments in the C2‐functionalization of pyridine and quinoline N‐oxides and address both the mechanisms and regioselectivity of the reactions. We also describe the pathways and reactive species involved in these processes and highlight a number of medically relevant nitrogen heteroaromatics.

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“…Over the last decade, rapid progress has been made in cell culture‐based HCV models, and high resolution structural biology of various therapeutically important HCV‐encoded proteins . This has made it possible to investigate the molecular basis of HCV infection as well as host responses, and in doing so accelerated the pace of target‐oriented drug development against HCV.…”

Section: Introductionmentioning

confidence: 99%

Evolution of efficacious pangenotypic hepatitis C virus therapies

Ashraf

Iman

Khalid

et al. 2018

Medicinal Research Reviews

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Hepatitis C compromises the quality of life of more than 350 million individuals worldwide. Over the last decade, therapeutic regimens for treating hepatitis C virus (HCV) infections have undergone rapid advancements. Initially, structure-based drug design was used to develop molecules that inhibit viral enzymes. Subsequently, establishment of cell-based replicon systems enabled investigations into various stages of HCV life cycle including its entry, replication, translation, and assembly, as well as role of host proteins. Collectively, these approaches have facilitated identification of important molecules that are deemed essential for HCV life cycle. The expanded set of putative virus and host-encoded targets has brought us one step closer to developing robust strategies for efficacious, pangenotypic, and well-tolerated medicines against HCV. Herein, we provide an overview of the development of various classes of virus and host-directed therapies that are currently in use along with others that are undergoing clinical evaluation.

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The discovery of a pan-genotypic, primer grip inhibitor of HCV NS5B polymerase

Cited by 16 publications

References 12 publications

Facile and Efficient Synthesis of Tri‐ and Tetrasubstituted 7‐Azabenzofuran Derivatives

Facile and Efficient Synthesis of Tri‐ and Tetrasubstituted 7‐Azabenzofuran Derivatives

Recent Advances in the Synthesis of C2‐Functionalized Pyridines and Quinolines Using N‐Oxide Chemistry

Evolution of efficacious pangenotypic hepatitis C virus therapies

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