Discovery of BMS-961955, an allosteric inhibitor of the hepatitis C virus NS5B polymerase.

Autor: Zheng BZ; 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., D'Andrea SV; Department of Discovery Chemistry and Molecular Technologies, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States., Hanumegowda U; Department of Preclinical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States., Knipe JO; Department of Preclinical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States., Mosure K; Department of Preclinical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States., Zhuo X; Department of Preclinical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States., Lemm JA; Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States., Liu M; Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States., Rigat KL; Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States., Wang YK; Department of Lead Evaluation, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States., Fang H; Department of Lead Evaluation, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States., Poronsky C; Department of Preclinical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States., Cutrone J; Department of Preclinical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States., Wu DR; Department of Discovery Synthesis, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, United States., Arunachalam PN; Biocon Bristol-Myers Squibb R&D Center, Biocon Park, Bommasandra IV phase, Jigani Link Road, Bengaluru 560099, India., Balapragalathan TJ; Biocon Bristol-Myers Squibb R&D Center, Biocon Park, Bommasandra IV phase, Jigani Link Road, Bengaluru 560099, India., Arumugam A; Biocon Bristol-Myers Squibb R&D Center, Biocon Park, Bommasandra IV phase, Jigani Link Road, Bengaluru 560099, India., Mathur A; Department of Discovery Synthesis, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, United States., Meanwell NA; Department of Discovery Chemistry and Molecular Technologies, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States., Gao M; Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States., Roberts SB; Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States., Kadow JF; Department of Discovery Chemistry and Molecular Technologies, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2017 Aug 01; Vol. 27 (15), pp. 3294-3300. Date of Electronic Publication: 2017 Jun 11.
DOI: 10.1016/j.bmcl.2017.06.024
Abstrakt: 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 .
(Copyright © 2017 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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