Discovery of small-molecule inhibitors of the ATPase activity of human papillomavirus E1 helicase.
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.
Faucher
Anne-Marie
AM
Boehringer Ingelheim (Canada) Ltd., Research and Development, 2100 Cunard Street, Laval (Québec), Canada, H7S 2G5. amfaucher@lav.boehringer-ingelheim.com
White
Peter W
PW
Brochu
Christian
C
Grand-Maître
Chantal
C
Rancourt
Jean
J
Fazal
Gulrez
G
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
D000085:Acetates; D000998:Antiviral Agents; D001713:Biphenyl Compounds; C118861:E1 protein, Human papillomavirus type 6; D009856:Oncogene Proteins, Viral; D013450:Sulfones; D000251:Adenosine Triphosphatases