title: Discovery of pentacyclic compounds as potent inhibitors of hepatitis C virus NS5B RNA polymerase.
abstract: We report a new series of inhibitors for hepatitis C virus NS5B RNA polymerase containing a constrained pentacyclic scaffold. Our SAR studies led to the identification of hexahydroindolo[2,1-a]pyrrolo[3,2-d][2]benzazepines exposing basic groups. The compounds displayed a high activity in the enzyme assay and displayed good activity in the cell-based (replicon) assay in the presence of serum proteins.
authors.affiliation: Department of Medicinal Chemistry, IRBM P. Angeletti S.p.A., Merck Research Laboratories Rome, Via Pontina km 30,600, I-00040 Pomezia, Rome, Italy. jorg_habermann@merck.com
authors.forename: Jörg
authors.initials: J
authors.lastname: Habermann
authors.forename: Elena
authors.initials: E
authors.lastname: Capitò
authors.forename: Maria del Rosario Rico
authors.initials: Mdel R
authors.lastname: Ferreira
authors.forename: Uwe
authors.initials: U
authors.lastname: Koch
authors.forename: Frank
authors.initials: F
authors.lastname: Narjes
mesh_terms: D001552:Benzazepines / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008099:Liver / Q000187:drug effects / Q000821:virology; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D012367:RNA, Viral / Q000235:genetics; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D001552:Benzazepines; D012321:DNA-Directed RNA Polymerases; D004791:Enzyme Inhibitors; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase