Indol-2-yl ethanones as novel indoleamine 2,3-dioxygenase (IDO) inhibitors

Dolusic, Eduard;Larrieu, Pierre;Blanc, Sébastien;Sapunaric, Frédéric;Frédérick, Raphaël;et.al.
(2011) Bioorganic & Medicinal Chemistry : the tetrahedron journal for research at the interface of chemistry and biology — Vol. 19, n° 4, p. 1550-1561 (2011)

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Abstract
Indoleamine 2,3-dioxygenase (IDO) is a heme dioxygenase which has been shown to be involved in the pathological immune escape of diseases such as cancer. The synthesis and structure-activity relationships (SAR) of a novel series of IDO inhibitors based on the indol-2-yl ethanone scaffold is described. In vitro and in vivo biological activities have been evaluated, leading to compounds with IC(50) values in the micromolar range in both tests. Introduction of small substituents in the 5- and 6-positions of the indole ring, indole N-methylation and variations of the aromatic side chain are all well tolerated. An iron coordinating group on the linker is a prerequisite for biological activity, thus corroborating the virtual screening results.
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Dolusic, E., Larrieu, P., Blanc, S., Sapunaric, F., Norberg, B., Moineaux, L., Colette, D., Stroobant, V., Pilotte, L., Colau, D., Ferain, T., Fraser, G., Galleni, M., Frère, J.-M., Masereel, B., Van den Eynde, B., Wouters, J., & Frédérick, R. (2011). Indol-2-yl ethanones as novel indoleamine 2,3-dioxygenase (IDO) inhibitors. Bioorganic & Medicinal Chemistry : the tetrahedron journal for research at the interface of chemistry and biology, 19(4), 1550-1561. https://doi.org/10.1016/j.bmc.2010.12.032 (Original work published 2011)