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

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.

SUBMITTER: Cox B

PROVIDER: S-EPMC7734793 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Escaping from Flatland: Substituted Bridged Pyrrolidine Fragments with Inherent Three-Dimensional Character.

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