The discovery of a pan-genotypic, primer grip inhibitor of HCV NS5B polymeraseThe authors declare no competing interests.Electronic supplementary information (ESI) available. See DOI: 10.1039/c6md00636a

The development of a series of novel 7-azabenzofurans exhibiting pan-genotype inhibition of HCV NS5B polymerase via binding to the primer grip site is presented. Many challenges, including poor oral bioavailability, high clearance, bioactivation, high human serum shift, and metabolic stability were...

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Main Authors: Eastman, Kyle J, Parcella, Kyle, Yeung, Kap-Sun, Grant-Young, Katharine A, Zhu, Juliang, Wang, Tao, Zhang, Zhongxing, Yin, Zhiwei, Beno, Brett R, Sheriff, Steven, Kish, Kevin, Tredup, Jeffrey, Jardel, Adam G, Halan, Vivek, Ghosh, Kaushik, Parker, Dawn, Mosure, Kathy, Fang, Hua, Wang, Ying-Kai, Lemm, Julie, Zhuo, Xiaoliang, Hanumegowda, Umesh, Rigat, Karen, Donoso, Maria, Tuttle, Maria, Zvyaga, Tatyana, Haarhoff, Zuzana, Meanwell, Nicholas A, Soars, Matthew G, Roberts, Susan B, Kadow, John F
Format: Article
Language:English
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Summary:The development of a series of novel 7-azabenzofurans exhibiting pan-genotype inhibition of HCV NS5B polymerase via binding to the primer grip site is presented. Many challenges, including poor oral bioavailability, high clearance, bioactivation, high human serum shift, and metabolic stability were encountered and overcome through SAR studies. This work culminated in the selection of BMS-986139 ( 43 ) as a preclinical candidate. A series of novel 7-azabenzofurans exhibiting pan-genotype inhibition of HCV NS5B polymerase via binding to the primer grip site is presented.
ISSN:2040-2503
2040-2511
DOI:10.1039/c6md00636a