title: Allosteric inhibitors of hepatitis C virus NS5B polymerase thumb domain site II: structure-based design and synthesis of new templates.
abstract: Chronic hepatitis C virus (HCV) infections are a significant medical problem worldwide. The NS5B Polymerase of HCV plays a central role in virus replication and is a prime target for the discovery of new treatment options. We recently disclosed 1H-benzo[de]isoquinoline-1,3(2H)-diones as allosteric inhibitors of NS5B Polymerase. Structural and SAR information guided us in the modification of the core structure leading to new templates with improved activity and toxicity/activity window.
authors.affiliation: IRBM - Merck Research Laboratories Rome, Via Pontina km 30,600, Pomezia (Rome) 00040, Italy. savinamal@libero.it
authors.forename: Savina
authors.initials: S
authors.lastname: Malancona
authors.forename: Monica
authors.initials: M
authors.lastname: Donghi
authors.forename: Marco
authors.initials: M
authors.lastname: Ferrara
authors.forename: Josè I
authors.initials: JI
authors.lastname: Martin Hernando
authors.forename: Marco
authors.initials: M
authors.lastname: Pompei
authors.forename: Silvia
authors.initials: S
authors.lastname: Pesci
authors.forename: Jesus M
authors.initials: JM
authors.lastname: Ontoria
authors.forename: Uwe
authors.initials: U
authors.lastname: Koch
authors.forename: Michael
authors.initials: M
authors.lastname: Rowley
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Summa
mesh_terms: D000494:Allosteric Regulation; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008968:Molecular Conformation; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase