Escaping from flatland: antimalarial activity of sp<sup>3</sup>-rich bridged pyrrolidine derivatives

Cox, Brian, Duffy, James, Zdorichenko, Victor, Bellanger, Corentin, Hurcum, Jessica, Laleu, Benoît, Booker-Milburn, Kevin I, Elliott, Luke D, Robertson-Ralph, Michael, Swain, Christopher J, Bishop, Stephen J, Hallyburton, Irene and Anderson, Mark (2020) Escaping from flatland: antimalarial activity of sp<sup>3</sup>-rich bridged pyrrolidine derivatives. ACS Medicinal Chemistry Letters, 11 (12). pp. 2497-2503. ISSN 1948-5875

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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.

Item Type: Article
Schools and Departments: School of Life Sciences > Chemistry
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 15 Dec 2020 10:32
Last Modified: 19 Jul 2021 10:41
URI: http://sro.sussex.ac.uk/id/eprint/95712

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