Primary and secondary alcohols are oxidized smoothly under mild conditions and in high yields to the corresponding aldehydes and ketones by 1 (see scheme), the first polymer‐supported IBX.

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Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that catalyzes the rate-limiting step in the kynurenine pathway of tryptophan (TRP) metabolism.As an inflammation-induced immunoregulatory enzyme, pharmacological inhibition of IDO1 activity is currently being pursued as a potential therapeutic tool for the treatment of cancer and other disease states. As such, a detailed understanding of the mechanism of action of established and novel IDO1 inhibitors remains of great interest. Comparison of a newly-developed IDO1 inhibitor (GSK5628) to the existing best-in-class compound, epacadostat (Incyte), allows us to report on a novel inhibition mechanism for IDO1. Here, we demonstrate that GSK5628 inhibits IDO1 by competing with heme for binding to a heme-free conformation of the enzyme (apo-IDO1) while epacadostat coordinates its binding with the iron atom of the IDO1 heme cofactor. Comparison of these two compounds in cellular systems reveals a long-lasting inhibitory effect of GSK5628, undescribed for other known IDO1 inhibitors. Detailed characterization of this novel binding mechanism for IDO1 inhibition may help design superior inhibitors or may confer a unique competitive advantage over other IDO1 inhibitors vis-àvis specificity and pharmacokinetic parameters.

Tabelle 1. Oxidationen von Alkoholen mit 7. SubstratProdukt Reinheit [%] [a] Quant. [b] 97 96 86 [b] 84 [b] 90 [b] 94 [b] 92 [b] 83 [b] 80 82[a] Reinheit mittels GC-MS bestimmt.[b] Ausbeute nach S‰ulenchromatographie an Kieselgel.