title: Indol-2-yl ethanones as novel indoleamine 2,3-dioxygenase (IDO) inhibitors.
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.
authors.affiliation: Drug design and Discovery Center, University of Namur, 61 Rue de Bruxelles, 5000 Namur, Belgium.
authors.forename: Eduard
authors.initials: E
authors.lastname: Dolušić
authors.forename: Pierre
authors.initials: P
authors.lastname: Larrieu
authors.forename: Sébastien
authors.initials: S
authors.lastname: Blanc
authors.forename: Frédéric
authors.initials: F
authors.lastname: Sapunaric
authors.forename: Bernadette
authors.initials: B
authors.lastname: Norberg
authors.forename: Laurence
authors.initials: L
authors.lastname: Moineaux
authors.forename: Delphine
authors.initials: D
authors.lastname: Colette
authors.forename: Vincent
authors.initials: V
authors.lastname: Stroobant
authors.forename: Luc
authors.initials: L
authors.lastname: Pilotte
authors.forename: Didier
authors.initials: D
authors.lastname: Colau
authors.forename: Thierry
authors.initials: T
authors.lastname: Ferain
authors.forename: Graeme
authors.initials: G
authors.lastname: Fraser
authors.forename: Moreno
authors.initials: M
authors.lastname: Galleni
authors.forename: Moreno
authors.initials: M
authors.lastname: Galeni
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Frère
authors.forename: Bernard
authors.initials: B
authors.lastname: Masereel
authors.forename: Benoît
authors.initials: B
authors.lastname: Van den Eynde
authors.forename: Johan
authors.initials: J
authors.lastname: Wouters
authors.forename: Raphaël
authors.initials: R
authors.lastname: Frédérick
mesh_terms: D020134:Catalytic Domain; D002460:Cell Line; D004980:Ethane / Q000737:chemistry*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D054730:Protein Interaction Domains and Motifs; D013329:Structure-Activity Relationship
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007211:Indoles; D004980:Ethane