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

A series of novel 7-azabenzofurans exhibiting pan-genotype inhibition of HCV NS5B polymerase via binding to the primer grip site is presented. 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 presen...

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Published in:MedChemComm 2017-02, Vol.8 (4), p.796-806
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
Subjects:
Chemistry
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Summary:A series of novel 7-azabenzofurans exhibiting pan-genotype inhibition of HCV NS5B polymerase via binding to the primer grip site is presented. 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.
ISSN:2040-2503
2040-2511
DOI:10.1039/c6md00636a