Boron-Based Functionalities Enhance, the Potency of 2,5-Dimethylfuran-Based IDO1 Inhibitors.

Abstract

Indoleamine-2,3-dioxygenase-1 (IDO1) is a critical immunoregulatory enzyme responsible for the metabolism of tryptophan during inflammation and disease. Based on a 2,5-dimethylfuran framework, examples of indoleamine-2,3-dioxygenase 1 (IDO1) inhibitors containing a diverse set of boron-based functional groups (closo-1,2- and 1,7-carborane, boronic acids and esters, and benzoxaboroles) are reported. The novel boron derivatives display low micrometer affinity for the human recombinant enzyme, with IC50 values ranging from 8 to 60 μM. Superior results are observed for the closo-carborane compounds which demonstrate a significant improvement in potency over their phenyl analogues, with inhibition of the IDO1 enzyme increasing by up to ≈80%.