You, Youngsu Kim, Hee Sun Bae, Il Hak Lee, Seung Gi Jee, Min Hyeok Keum, Gyochang Jang, Sung Key Kim, B. Moon 2024-01-20T02:31:46Z 2024-01-20T02:31:46Z 2021-09-05 2017-01-05 0223-5234 https://pubs.kist.re.kr/handle/201004/123213 The discovery of a new series of potent hepatitis C virus (HCV) NS5A inhibitors containing biaryl sulfone or sulfate cores is reported. Structure-activity relationship (SAR) studies on inhibitors containing various substitution patterns of the sulfate or sulfone core structure established that m-,m'- substituted biaryl sulfate core-based inhibitors containing an amide moiety (compound 20) or an imidazole moiety (compound 24) showed extremely high potency. Compound 20 demonstrated double-digit pM potencies against both genotype 1b (GT-1b) and 2a (GT-2a). Compound 24 also exhibited double-digit pM potencies against GT-1b and sub nM potencies against GT-2a. Furthermore, compounds 20 and 24 exhibited no cardiotoxicity in an hERG ligand binding assay and showed acceptable plasma stability and no mutagenic potential in the Ames test. In addition, these compounds showed distinctive additive effects in combination treatment with the NS5B targeting drug sofosbuvir (Sovaldi (R)). The results of this study showed that the compounds 20 and 24 could be effective HCV inhibitors. (C) 2016 Elsevier Masson SAS. All rights reserved. English ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER HCV NS5A INHIBITORS NONSTRUCTURAL PROTEIN 5A DRUG DISCOVERY CELL-CULTURE REPLICATION INFECTION THERAPY ASSAY COMBINATION DACLATASVIR New potent biaryl sulfate-based hepatitis C virus inhibitors Article 10.1016/j.ejmech.2016.09.031 1 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v.125, pp.87 - 100 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 125 87 100 scie scopus 000390496600007 2-s2.0-84987984361 Chemistry, Medicinal Pharmacology & Pharmacy Article HCV NS5A INHIBITORS NONSTRUCTURAL PROTEIN 5A DRUG DISCOVERY CELL-CULTURE REPLICATION INFECTION THERAPY ASSAY COMBINATION DACLATASVIR HCV NS5A inhibitor Biaryl sulfate Structure-activity relationship