Investigation of the mode of binding of a novel series of N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamides to the hepatitis C virus polymerase

Journal Article · Wed Nov 20 04:00:00 EST 2013 · Bioorg. Med. Chem. Lett.

DOI:https://doi.org/10.1016/j.bmcl.2011.03.011· OSTI ID:1025626

Gentles, Robert G.; Sheriff, Steven; Beno, Brett R.; Wan, Changhong; Kish, Kevin; Ding, Min; Zheng, Xiaofan; Chupak, Louis; Poss, Michael A.; Witmer, Mark R.; Morin, Paul; Wang, Ying-Kai; Rigat, Karen; Lemm, Julie; Voss, Stacey; Liu, Mengping; Pelosi, Lenore; Roberts, Susan B.; Gao, Min; Kadow, John F. ^[1]

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1. BMS

Structure based rationales for the activities of potent N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamide inhibitors of the hepatitis C viral polymerase are described herein. These compounds bind to the hepatitis C virus non-structural protein 5B (NS5B), and co-crystal structures of select examples from this series with NS5B are reported. Comparison of co-crystal structures of a potent analog with both NS5B genotype 1a and genotype 1b provides a possible explanation for the genotype-selectivity observed with this compound class and suggests opportunities for the further optimization of the series.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: INDUSTRY
• OSTI ID: 1025626
• Journal Information: Bioorg. Med. Chem. Lett., Journal Name: Bioorg. Med. Chem. Lett. Journal Issue: (8) ; 04, 2011 Vol. 21
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
GENOTYPE
HEPATITIS
OPTIMIZATION
POLYMERASES
PROTEINS