Isosteric exchange of the acylsulfonamide moiety in Abbott's Bcl-X(L) protein interaction antagonist

Alexander Doemling*, Walfrido Antuch, Barbara Beck, Vesna Schauer-Vukasinovic

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)

Abstract

A multi-component reaction strategy was used for the fast and efficient synthesis of amide isosteres of known Bcl-2 inhibitors capable of disrupting protein-protein interactions. Ugi reaction and a subsequent nucleophilic aromatic substitution reaction provide a versatile path to libraries of compounds similar to Abbott's acylsulfonamides. Modeling arguments are used to explain the inferior activity of the amide as opposed to the sulfonamide series. (c) 2008 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)4115-4117
Number of pages3
JournalBioorganic & Medicinal Chemistry Letters
Volume18
Issue number14
DOIs
Publication statusPublished - 15-Jul-2008
Externally publishedYes

Keywords

  • multi-component reaction
  • protein-protein interaction
  • Bcl
  • cancer
  • apoptosis
  • isocyanide
  • structure-based design
  • PARALLEL SYNTHESIS
  • INHIBITOR
  • BCL-X(L)
  • DESIGN

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