Discovery of BMS-961955, an allosteric inhibitor of the hepatitis C virus NS5B polymerase. Issue 15 (1st August 2017)

• Record Type: Journal Article
• Authors: Zheng, Barbara Zhizhen; D'Andrea, Stanley V.; Hanumegowda, Umesh; Knipe, Jay O.; Mosure, Kathy; Zhuo, Xiaoliang; Lemm, Julie A.; Liu, Mengping; Rigat, Karen L.; Wang, Ying-Kai; Fang, Hua; Poronsky, Chris; Cutrone, Jingfang; Wu, Dauh-Rurng; Arunachalam, Pirama Nayagam; Balapragalathan, T.J.; Arumugam, Arunachalam; Mathur, Arvind; Meanwell, Nicholas A.; Gao, Min; Roberts, Susan B.; Kadow, John F.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 15(2017)
• Page Start: 3294
• Page End: 3300
• Publication Date: 2017-08-01
• Subjects: HCV NS5B -- Polymerase -- Cyclopropyl-fused indolobenzazepine -- Metabolic stability -- Direct-acting antiviral agent -- Antiviral agent; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.06.024
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: The synthesis, structure-activity relationship (SAR) data, and further optimization of the metabolic stability and pharmacokinetic (PK) properties for a previously disclosed class of cyclopropyl-fused indolobenzazepine HCV NS5B polymerase inhibitors are described. These efforts led to the discovery of BMS-961955 as a viable contingency backup to beclabuvir which was recently approved in Japan for the treatment of HCV as part of a three drug, single pill combination marketed as Ximency TM .