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

2 Citations (Scopus)

Abstract

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
Volume11
Issue number12
Early online date10 Nov 2020
DOIs
Publication statusPublished - 10 Dec 2020

Keywords

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

Fingerprint

Dive into the research topics of 'Escaping from Flatland: Antimalarial Activity of sp<sup>3</sup>-Rich Bridged Pyrrolidine Derivatives'. Together they form a unique fingerprint.

Cite this