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Discovery of BMS-961955, an allosteric inhibitor of the hepatitis C virus NS5B polymerase |
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| Authors: | Barbara Zhizhen Zheng Stanley V D&#x;Andrea Umesh Hanumegowda Jay O Knipe Kathy Mosure Xiaoliang Zhuo Julie A Lemm Mengping Liu Karen L Rigat Ying-Kai Wang Hua Fang Chris Poronsky Jingfang Cutrone Dauh-Rurng Wu Pirama Nayagam Arunachalam TJ Balapragalathan Arunachalam Arumugam Arvind Mathur John F Kadow |
| Institution: | 1. Department of Discovery Chemistry and Molecular Technologies, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States;2. Department of Preclinical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States;3. Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States;4. Department of Lead Evaluation, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States;5. Department of Discovery Synthesis, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, United States;6. Biocon Bristol-Myers Squibb R&D Center, Biocon Park, Bommasandra IV phase, Jigani Link Road, Bengaluru 560099, India |
| 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 XimencyTM. |
| Keywords: | HCV NS5B Polymerase Cyclopropyl-fused indolobenzazepine Metabolic stability Direct-acting antiviral agent Antiviral agent |
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