title: Discovery of small-molecule inhibitors of the ATPase activity of human papillomavirus E1 helicase.
abstract: The Boehringer Ingelheim compound collection was screened for inhibitors of the ATPase activity of human papillomavirus E1 helicase to develop antiviral agents that inhibit human papillomavirus (HPV) DNA replication. This screen led to the discovery of (biphenyl-4-sulfonyl)acetic acid 1, which inhibits the ATPase activity of HPV type 6 E1 helicase with a low micromolar IC(50) value. A hit-to-lead exercise rapidly converted 1 into a low nanomolar lead series.
authors.affiliation: Boehringer Ingelheim (Canada) Ltd., Research and Development, 2100 Cunard Street, Laval (Québec), Canada, H7S 2G5. amfaucher@lav.boehringer-ingelheim.com
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Faucher
authors.forename: Peter W
authors.initials: PW
authors.lastname: White
authors.forename: Christian
authors.initials: C
authors.lastname: Brochu
authors.forename: Chantal
authors.initials: C
authors.lastname: Grand-Maître
authors.forename: Jean
authors.initials: J
authors.lastname: Rancourt
authors.forename: Gulrez
authors.initials: G
authors.lastname: Fazal
mesh_terms: D000085:Acetates / Q000138:chemical synthesis* / Q000737:chemistry; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000037:antagonists & inhibitors* / Q000737:chemistry; D027383:Papillomaviridae / Q000201:enzymology*; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000085:Acetates; D000998:Antiviral Agents; D001713:Biphenyl Compounds; C118861:E1 protein, Human papillomavirus type 6; D009856:Oncogene Proteins, Viral; D013450:Sulfones; D000251:Adenosine Triphosphatases