B Cox et al Antimalarial Actvity of SP3-rich bridged pyrrolidine derivatives.pdf (1.03 MB)
Escaping from flatland: antimalarial activity of sp3-rich bridged pyrrolidine derivatives
journal contribution
posted on 2023-06-09, 22:27 authored by 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 AndersonWe 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.
History
Publication status
- Published
File Version
- Accepted version
Journal
ACS Medicinal Chemistry LettersISSN
1948-5875Publisher
American Chemical SocietyExternal DOI
Issue
12Volume
11Page range
2497-2503Department affiliated with
- Chemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2020-12-15First Open Access (FOA) Date
2021-11-11First Compliant Deposit (FCD) Date
2020-12-15Usage metrics
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