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Discovery of BMS-961955, an allosteric inhibitor of the hepatitis C virus NS5B polymerase. 2017
Barbara Zhizhen Zheng, and
Stanley V D'Andrea, and
Umesh Hanumegowda, and
Jay O Knipe, and
Kathy Mosure, and
Xiaoliang Zhuo, and
Julie A Lemm, and
Mengping Liu, and
Karen L Rigat, and
Ying-Kai Wang, and
Hua Fang, and
Chris Poronsky, and
Jingfang Cutrone, and
Dauh-Rurng Wu, and
Pirama Nayagam Arunachalam, and
T J Balapragalathan, and
Arunachalam Arumugam, and
Arvind Mathur, and
Nicholas A Meanwell, and
Min Gao, and
Susan B Roberts, and
John F Kadow
Department of Discovery Chemistry and Molecular Technologies, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States. Electronic address: zhizhenZheng@bms.com.
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 XimencyTM.
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