Optimized 5-Membered Heterocycle-Linked Pterins for the Inhibition of Ricin Toxin A

The optimization of a series of pterin amides for use as Ricin Toxin A (RTA) inhibitors is reported. On the basis of crystallographic data of a previous furan-linked pterin, various expanded furans were synthesized, linked to the pterin, and tested for inhibition. Concurrently, heteroanalogues of fu...

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Published in:ACS medicinal chemistry letters 2012-07, Vol.3 (7), p.588-591
Main Authors: Pruet, Jeff M, Saito, Ryota, Manzano, Lawrence A, Jasheway, Karl R, Wiget, Paul A, Kamat, Ishan, Anslyn, Eric V, Robertus, Jon D
Format: Article
Language:English
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Letter
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Summary:The optimization of a series of pterin amides for use as Ricin Toxin A (RTA) inhibitors is reported. On the basis of crystallographic data of a previous furan-linked pterin, various expanded furans were synthesized, linked to the pterin, and tested for inhibition. Concurrently, heteroanalogues of furan were explored, leading to the discovery of more potent triazole-linked pterins. Additionally, we discuss a dramatic improvement in the synthesis of these pterin amides via a dual role by diazabicycloundecene (DBU). This synthetic enhancement facilitates rapid diversification of the previously challenging pterin heterocycle, potentially aiding future medicinal research involving this structure.
ISSN:1948-5875
1948-5875
DOI:10.1021/ml300099t