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A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
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Functionalized triazines as potent HCV entry inhibitors.

Eric S Mull1, Li-Qiang Sun1, Qian Zhao1

  • 1Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States.

Bioorganic & Medicinal Chemistry Letters
|January 17, 2017
PubMed
Summary
This summary is machine-generated.

Researchers developed novel acylsulfonamide triazines as potent inhibitors of Hepatitis C virus (HCV) entry. These compounds exhibit sub-nanomolar efficacy in cellular assays, offering a promising new avenue for antiviral drug discovery.

Keywords:
Acyl sulfonamideEntry inhibitorHepatitis C virusTriazine

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Area of Science:

  • Medicinal Chemistry
  • Virology
  • Drug Discovery

Background:

  • Hepatitis C virus (HCV) entry is a critical target for antiviral therapies.
  • Previous research identified a lead compound for HCV entry inhibition.

Purpose of the Study:

  • To synthesize and evaluate novel acylsulfonamide-bearing triazines as HCV entry inhibitors.
  • To explore structure-activity relationships (SARs) of this new chemical series.

Main Methods:

  • Synthesis of a novel series of acylsulfonamide-bearing triazines.
  • Evaluation of compound activity using the HCV pseudotype particle (HCVpp) assay.
  • Structure-activity relationship (SAR) analysis to identify key structural features.

Main Results:

  • Discovery of potent analogues with sub-nanomolar EC50 values in the HCVpp assay.
  • Identification of the acylsulfonamide moiety as crucial for enhanced activity.
  • The modification projected an additional vector, driving improved antiviral potency.

Conclusions:

  • Acylsulfonamide-bearing triazines represent a promising class of HCV entry inhibitors.
  • The SAR study provides valuable insights for further optimization of these compounds.
  • This work may lead to the development of new therapeutic agents against HCV.