Bae, Il Hak Kim, Hee Sun You, Youngsu Chough, Chieyeon Choe, Weonu Seon, Min Kyung Lee, Seung Gi Keum, Gyochang Jang, Sung Key Kim, B. Moon 2024-01-20T06:31:03Z 2024-01-20T06:31:03Z 2021-09-05 2015-08-28 0223-5234 https://pubs.kist.re.kr/handle/201004/125110 Our study describes the discovery of a series of highly potent hepatitis C virus (HCV) NS5A inhibitors based on symmetrical prolinamide derivatives of benzidine and diaminofluorene. Through modification of benzidine, L-proline, and diaminofluorene derivatives, we developed novel inhibitor structures, which allowed us to establish a library of potent HCV NS5A inhibitors. After optimizing the benzidine prolinamide backbone, we identified inhibitors embedding meta-substituted benzidine core structures that exhibited the most potent anti-HCV activities. Furthermore, through a battery of studies including hERG ligand binding assay, CYP450 binding assay, rat plasma stability test, human liver microsomal stability test, and pharmacokinetic studies, the identified compounds 24, 26, 27, 42, and 43 are found to be nontoxic, and are expected to be effective therapeutic anti-HCV agents. (C) 2015 Elsevier Masson SAS. All rights reserved. English ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER NONSTRUCTURAL PROTEIN 5A REPLICATION COMPLEX INHIBITOR ACTING ANTIVIRAL AGENTS RNA REPLICATION BIOLOGICAL EVALUATION CRYSTAL-STRUCTURE STABILITY ASSAY SMALL MOLECULES DRUG DISCOVERY DOMAIN-III Novel benzidine and diaminofluorene prolinamide derivatives as potent hepatitis C virus NS5A inhibitors Article 10.1016/j.ejmech.2015.06.033 1 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v.101, pp.163 - 178 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 101 163 178 scie scopus 000360771900016 2-s2.0-84933532815 Chemistry, Medicinal Pharmacology & Pharmacy Article NONSTRUCTURAL PROTEIN 5A REPLICATION COMPLEX INHIBITOR ACTING ANTIVIRAL AGENTS RNA REPLICATION BIOLOGICAL EVALUATION CRYSTAL-STRUCTURE STABILITY ASSAY SMALL MOLECULES DRUG DISCOVERY DOMAIN-III HCV NS5A inhibitor Benzidine Diaminofluorene Structure-activity relationship