title: Design, synthesis and evaluation of novel anti-HCV molecules that deliver intracellularly three highly potent NS5A inhibitors.
abstract: The design and synthesis of new non-symmetrical NS5A inhibitors with sulfur containing amino acids is reported along with their ability to block HCV replication in an HCV 1b replicon system. These compounds display EC50 values in the picomolar range with a large therapeutic index (>10(6)). Moreover, cellular pharmacology studies show that our preferred compounds intracellularly deliver three potent NS5A inhibitors.
authors.affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Veterans Affairs Medical Center, Decatur, GA 30033, USA.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Boucle
authors.affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Veterans Affairs Medical Center, Decatur, GA 30033, USA.
authors.forename: Sijia
authors.initials: S
authors.lastname: Tao
authors.affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Veterans Affairs Medical Center, Decatur, GA 30033, USA.
authors.forename: Franck
authors.initials: F
authors.lastname: Amblard
authors.affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Veterans Affairs Medical Center, Decatur, GA 30033, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Stanton
authors.affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Veterans Affairs Medical Center, Decatur, GA 30033, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Nettles
authors.affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Veterans Affairs Medical Center, Decatur, GA 30033, USA.
authors.forename: Chengwei
authors.initials: C
authors.lastname: Li
authors.affiliation: CoCrystal Pharma, Inc., Tucker, GA 30084, USA.
authors.forename: Tamara R
authors.initials: TR
authors.lastname: McBrayer
authors.affiliation: CoCrystal Pharma, Inc., Tucker, GA 30084, USA.
authors.forename: Tony
authors.initials: T
authors.lastname: Whitaker
authors.affiliation: CoCrystal Pharma, Inc., Tucker, GA 30084, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Coats
authors.affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Veterans Affairs Medical Center, Decatur, GA 30033, USA. Electronic address: rschina@emory.edu.
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Schinazi
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D002219:Carbamates; D002460:Cell Line / Q000187:drug effects / Q000821:virology; D060326:Chemistry Techniques, Synthetic; D002522:Chlorocebus aethiops; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D058990:Molecular Targeted Therapy; D009154:Mutation; D011759:Pyrrolidines; D013329:Structure-Activity Relationship; D014633:Valine / Q000031:analogs & derivatives; D014709:Vero Cells / Q000187:drug effects; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D014633:Valine; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C549273:daclatasvir
keywords: Antiviral; HCV; NS5A