Escaping from Flatland:
Antimalarial Activity of sp3-Rich Bridged Pyrrolidine
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Authors: | Brian Cox,James Duffy,Victor Zdorichenko,Corentin Bellanger,Jessica Hurcum,Benoî t Laleu,Kevin I. Booker-Milburn,Luke D. Elliott,Michael Robertson-Ralph,Christopher J. Swain,Stephen J. Bishop,Irene Hallyburton,Mark Anderson |
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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. |
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Keywords: | Drug discovery antimalarial photochemistry sp3-rich substituted bridged pyrrolidines 3D character |
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