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. Based upon crystallographic data of a previous furan-linked pterin, various expanded furans were synthesized, linked to the pterin and tested for inhibition. Concurrently, hetero-analogs of furan were explored, leading to the discovery of more potent triazol-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.
Department of Chemistry and Biochemistry, University of Texas at Austin, 1 University Station A1590, Austin, TX 78712, USA.
Jeff M
JM
Pruet
Ryota
R
Saito
Lawrence A
LA
Manzano
Karl R
KR
Jasheway
Paul A
PA
Wiget
Ishan
I
Kamat
Eric V
EV
Anslyn
Jon D
JD
Robertus