title: Discovery and synthesis of novel benzofurazan derivatives as inhibitors of influenza A virus.
abstract: The identification of a novel hit compound inhibitor of the protein-protein interaction between the influenza RNA-polymerase PA and PB1 subunits has been accomplished by means of high-throughput screening. A small family of structurally related molecules has been synthesized and biologically evaluated with most of the compounds showing micromolar potency of inhibition against viral replication.
authors.affiliation: PiKe Pharma GmbH, Zurich, Switzerland.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kessler
authors.forename: Daniele
authors.initials: D
authors.lastname: Castagnolo
authors.forename: Mafalda
authors.initials: M
authors.lastname: Pagano
authors.forename: Davide
authors.initials: D
authors.lastname: Deodato
authors.forename: Martina
authors.initials: M
authors.lastname: Bernardini
authors.forename: Beatrice
authors.initials: B
authors.lastname: Pilger
authors.forename: Charlene
authors.initials: C
authors.lastname: Ranadheera
authors.forename: Maurizio
authors.initials: M
authors.lastname: Botta
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D001583:Benzoxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry / Q000378:metabolism*; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D009980:Influenza A virus / Q000187:drug effects* / Q000201:enzymology; D061985:Madin Darby Canine Kidney Cells; D054730:Protein Interaction Domains and Motifs / Q000187:drug effects; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D001583:Benzoxazoles; D004791:Enzyme Inhibitors; D021122:Protein Subunits; C020160:benzofurazan; D012321:DNA-Directed RNA Polymerases
keywords: Antiviral agents; Benzofurazan; H1N1; Influenza virus; Viral RNA polymerase