title: Functionalized triazines as potent HCV entry inhibitors.
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 EC50values in the HCV pseudotype particle (HCVpp) assay.
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States. Electronic address: eric_mull@hotmail.com.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Mull
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Li-Qiang
authors.initials: LQ
authors.lastname: Sun
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Virology Discovery Biology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Betsy
authors.initials: B
authors.lastname: Eggers
authors.affiliation: Department of Virology Discovery Biology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Kevin
authors.initials: K
authors.lastname: Pokornowski
authors.affiliation: Department of Virology Discovery Biology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Zhai
authors.affiliation: Department of Computer-Assisted Drug Design, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Rajamani
authors.affiliation: Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Susan
authors.initials: S
authors.lastname: Jenkins
authors.affiliation: Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Melissa
authors.initials: M
authors.lastname: Kramer
authors.affiliation: Department of Lead Evaluation, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Ying-Kai
authors.initials: YK
authors.lastname: Wang
authors.affiliation: Department of Lead Evaluation, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Hua
authors.initials: H
authors.lastname: Fang
authors.affiliation: Department of Virology Discovery Biology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Tenney
authors.affiliation: Department of Virology Discovery Biology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Baldick
authors.affiliation: Department of Virology Discovery Biology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Mark I
authors.initials: MI
authors.lastname: Cockett
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Meanwell
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Scola
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects*; D051381:Rats; D013329:Structure-Activity Relationship; D014227:Triazines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D014227:Triazines
keywords: Acyl sulfonamide; Entry inhibitor; Hepatitis C virus; Triazine