Palladium-catalyzed carbonylative transformations of bromhexine into bioactive compounds as glucocerebrosidase inhibitors

Muhammad Sharif, Anahit Pews-Davtyan, Jan Lukas, Johannes Schranck, Peter Langer, Arndt Rolfs, Matthias Beller

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

A general synthesis for dicarbonylated derivatives of the parent drug bromhexine is described. By using the commercially available Pd(OAc) 2/BuPAd2 (CataCXium A, Ad = adamantyl) catalyst system, the carbonylative arylation, amination, and alkoxylation of bromhexine proceeded with up to 79 % product yield. Selected synthesized derivatives of bromhexine showed improved effects as glucocerebrosidase inhibitors. The first palladium-catalyzed carbonylative Suzuki-Miyaura arylations as well as alkoxy-and aminocarbonylations of the parent drug bromhexine were successfully performed. Some of the resulting new carbonylated products showed significant inhibition towards the glucocerebrosidase enzyme.

Original languageEnglish
Pages (from-to)222-230
Number of pages9
JournalEuropean Journal of Organic Chemistry
Volume2014
Issue number1
DOIs
StatePublished - Jan 2014
Externally publishedYes

Keywords

  • Biological activity
  • Carbonylation
  • Cross-coupling
  • Inhibitors
  • Medicinal chemistry
  • Palladium

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