Convenient synthesis of alternatively bridged tryptophan ketopiperazines and their activities against trypanosomatid parasites
Abstract
There is an urgent need for the development of new treatments against trypanosomatid parasites; the causative agents of some of the most debilitating diseases in the developing world. This work targets an interesting 6-5-6-6 fused carboline scaffold, accessing a range of substituted derivatives through stereospecific intramolecular Pictet-Spengler condensation. Modification of the cyclisation conditions allowed retention of the carbamate protecting group and gave insight into the reaction mechanism. Compounds' bioactivities were measured against T. brucei, T. cruzi, L. major and HeLa cells. We have identified promising pan-trypanocidal lead compounds based on the core scaffold, and highlight key SAR trends which will be useful for the future development of these compounds as potent trypanocidal agents.
Citation
Cockram , P E , Turner , C , Slawin , A M Z & Smith , T 2022 , ' Convenient synthesis of alternatively bridged tryptophan ketopiperazines and their activities against trypanosomatid parasites ' , ChemMedChem , vol. Early View , e202100664 . https://doi.org/10.1002/cmdc.202100664
Publication
ChemMedChem
Status
Peer reviewed
ISSN
1860-7179Type
Journal article
Rights
Copyright © 2021 Wiley-VCH GmbH. This work has been made available online in accordance with publisher policies or with permission. Permission for further reuse of this content should be sought from the publisher or the rights holder. This is the author created accepted manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://doi.org/10.1002/cmdc.202100664
Description
This work was supported through funding from the EPSRC (grant number EP/J500549/1) and the University of St Andrews School of Chemistry.Collections
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