Functionalized triazines as potent HCV entry inhibitors. Issue 4 (15th February 2017)

• Record Type: Journal Article
• Authors: Mull, Eric S.; Sun, Li-Qiang; Zhao, Qian; Eggers, Betsy; Pokornowski, Kevin; Zhai, Guangzhi; Rajamani, Ramkumar; Jenkins, Susan; Kramer, Melissa; Wang, Ying-Kai; Fang, Hua; Tenney, Daniel; Baldick, Carl J.; Cockett, Mark I.; Meanwell, Nicholas A.; Scola, Paul M.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 4(2017)
• Page Start: 1089
• Page End: 1093
• Publication Date: 2017-02-15
• Subjects: Hepatitis C virus -- Entry inhibitor -- Acyl sulfonamide -- Triazine; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.12.038
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: A series of potent and novel acylsulfonamide-bearing triazines were synthesized and the structure-activity relationships (SARs) as HCV entry inhibitors were evaluated. This acylsulfonamide series was derived from an early lead, 4-(4-(1-(4-chlorophenyl)cyclopropylamino)-6-(2, 2, 2-trifluoroethoxy)-1, 3, 5-triazin-2-ylamino)benzoic acid wherein the carboxylic acid was replaced with an acylsulfonamide moiety. This structural modification provided a class of compounds which projected an additional vector off the terminus of the acylsulfonamide functionality as a means to drive activity. This effort led to the discovery of potent analogues within this series that demonstrated sub-nanomolar EC50 values in the HCV pseudotype particle (HCVpp) assay.