Design of gp120 HIV-1 entry inhibitors by scaffold hopping via isosteric replacements.

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  • Additional Information
    • Source:
      Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 0420510 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1768-3254 (Electronic) Linking ISSN: 02235234 NLM ISO Abbreviation: Eur J Med Chem Subsets: MEDLINE
    • Publication Information:
      Publication: Paris : Editions Scientifiques Elsevier
      Original Publication: Paris, S.E.C.T. [etc.]
    • Subject Terms:
      Drug Design*; HIV Envelope Protein gp120/*antagonists & inhibitors ; HIV Fusion Inhibitors/*chemistry ; HIV-1/*metabolism; Binding Sites ; Cell Line ; Cell Survival/drug effects ; HIV Envelope Protein gp120/metabolism ; HIV Fusion Inhibitors/metabolism ; HIV Fusion Inhibitors/pharmacology ; HIV-1/drug effects ; Humans ; Molecular Docking Simulation ; Structure-Activity Relationship ; Thiazoles/chemistry ; Thiazoles/metabolism ; Thiazoles/pharmacology ; Virus Internalization/drug effects
    • Abstract:
      We present the development of alternative scaffolds and validation of their synthetic pathways as a tool for the exploration of new HIV gp120 inhibitors based on the recently discovered inhibitor of this class, NBD-14136. The new synthetic routes were based on isosteric replacements of the amine and acid precursors required for the synthesis of NBD-14136, guided by molecular modeling and chemical feasibility analysis. To ensure that these synthetic tools and new scaffolds had the potential for further exploration, we eventually tested few representative compounds from each newly designed scaffold against the gp120 inhibition assay and cell viability assays.
      Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)
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    • Grant Information:
      R01 AI104416 United States AI NIAID NIH HHS
    • Contributed Indexing:
      Keywords: Drug discovery; HIV; Lead optimization; Screening; Synthesis; gp120
    • Accession Number:
      0 (HIV Envelope Protein gp120)
      0 (HIV Fusion Inhibitors)
      0 (Thiazoles)
    • Publication Date:
      Date Created: 20210711 Date Completed: 20211026 Latest Revision: 20221116
    • Publication Date:
      20231215
    • Accession Number:
      PMC8511295
    • Accession Number:
      10.1016/j.ejmech.2021.113681
    • Accession Number:
      34246921