Escaping from Flatland: Antimalarial Activity of sp3-Rich Bridged Pyrrolidine Derivatives

Brian Cox, James Duffy, Victor Zdorichenko, Corentin Bellanger, Jessica Hurcum, Benoît Laleu, Kevin I. Booker-Milburn, Luke D. Elliott, Michael Robertson-Ralph, Christopher J. Swain, Stephen J. Bishop, Irene Hallyburton, Mark Anderson

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


We utilized synthetic photochemistry to generate novel sp3-rich scaffolds and report the design, synthesis, and biological testing of a diverse series of amides based on the 1-(amino-methyl)-2-benzyl-2-aza-bicyclo[2.1.1]hexane scaffold. Preliminary antimalarial screening of the library provided promising compounds with activity in the 1-5 μM range with an enhanced hit rate. Further evaluation (solubility, drug metabolism and pharmacokinetics (DMPK), and toxicity) of a selected compound (9) suggested that this series represents an excellent opportunity for further optimization with the framework offering multiple opportunities for the addition of uniquely vectorally positioned extra functionality.

Original languageEnglish
Pages (from-to)2497-2503
Number of pages7
JournalACS Medicinal Chemistry Letters
Issue number12
Early online date10 Nov 2020
Publication statusPublished - 10 Dec 2020


  • 3D character
  • antimalarial
  • Drug discovery
  • photochemistry
  • sp-rich substituted bridged pyrrolidines

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry


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