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ID: ALA1667850

Journal: Bioorg Med Chem

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

Authors: Dolušić 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 JM, Masereel B, Van den Eynde B, Wouters J, Frédérick R.

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.

CiteXplore: 21269836

DOI: 10.1016/j.bmc.2010.12.032