Structure–activity relationship (SAR) optimization of 6-(indol-2-yl) pyridine-3-sulfonamides: Identification of potent, selective, and orally bioavailable small molecules …

…, N Almstead, S Venkatraman, FG Njoroge…

Index: Zhang, Nanjing; Zhang, Xiaoyan; Zhu, Jin; Turpoff, Anthony; Chen, Guangming; Morrill, Christie; Huang, Song; Lennox, William; Kakarla, Ramesh; Liu, Ronggang; Li, Chunshi; Ren, Hongyu; Almstead, Neil; Venkatraman, Srikanth; Njoroge, F. George; Gu, Zhengxian; Clausen, Valerie; Graci, Jason; Jung, Stephen P.; Zheng, Yingcong; Colacino, Joseph M.; Lahser, Fred; Sheedy, Josephine; Mollin, Anna; Weetall, Marla; Nomeir, Amin; Karp, Gary M. Journal of Medicinal Chemistry, 2014 , vol. 57, # 5 p. 2121 - 2135

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Citation Number: 15

Abstract

A novel, potent, and orally bioavailable inhibitor of hepatitis C RNA replication targeting NS4B, compound 4t (PTC725), has been identified through chemical optimization of the 6- (indol-2-yl) pyridine-3-sulfonamide 2 to improve DMPK and safety properties. The focus of the SAR investigations has been to identify the optimal combination of substituents at the indole N-1, C-5, and C-6 positions and the sulfonamide group to limit the potential for in ...