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

Eduard Dolušić; Pierre Larrieu; Sébastien Blanc; Frédéric Sapunaric; Bernadette Norberg; Laurence Moineaux; Delphine Colette; Vincent Stroobant; Luc Pilotte; Didier Colau; Thierry Ferain; Graeme Fraser; Moreno Galeni; Jean Marie Frre; Bernard Masereel; Benoît Van Den Eynde; Johan Wouters; Raphaël Frédérick

doi:10.1016/j.bmc.2010.12.032

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

Eduard Dolušić, Pierre Larrieu, Sébastien Blanc, Frédéric Sapunaric, Bernadette Norberg, Laurence Moineaux, Delphine Colette, Vincent Stroobant, Luc Pilotte, Didier Colau, Thierry Ferain, Graeme Fraser, Moreno Galeni, Jean Marie Frre, Bernard Masereel, Benoît Van Den Eynde, Johan Wouters, Raphaël Frédérick

Résultats de recherche: Contribution à un journal/une revue › Article › Revue par des pairs

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Résumé

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. © 2011 Elsevier Ltd. All rights reserved.

langue originale	Anglais
Pages (de - à)	1550-1561
Nombre de pages	12
journal	Bioorganic & medicinal chemistry
Volume	19
Numéro de publication	4
Les DOIs	https://doi.org/10.1016/j.bmc.2010.12.032
Etat de la publication	Publié - 15 févr. 2011
Evénement	JFB 2011. - Liege, Belgique Durée: 19 mai 2011 → …

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10.1016/j.bmc.2010.12.032

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38 Citations
5 Poster
2 Article
1 Article dans les actes d'une conférence/un colloque
1 Revue de documentation

Indoleamine 2,3-dioxygenase inhibitors: a patent review (2008-2012)
Dolušić, E. & Frédérick, R., 1 oct. 2013, Dans: Expert opinion on therapeutic targets. 23, 10, p. 1367-1381 15 p.
Résultats de recherche: Contribution à un journal/une revue › Revue de documentation › Revue par des pairs
Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A
Dolušić, E., Larrieu, P., Meinguet, C., Colette, D., Rives, A., Blanc, S., Ferain, T., Pilotte, L., Stroobant, V., Wouters, J., Van Den Eynde, B., Masereel, B., Delfourne, E. & Frédérick, R., 1 janv. 2013, Dans: Bioorganic & Medicinal Chemistry Letters. 23, 1, p. 47-54 8 p.
Résultats de recherche: Contribution à un journal/une revue › Article › Revue par des pairs
3 Téléchargements (Pure)
Discovery and preliminary SARs of keto-indoles as novel indoleamine 2,3-dioxygenase (IDO) inhibitors
Dolušić, E., Larrieu, P., Blanc, S., Sapunaric, F., Pouyez, J., 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, Dans: European Journal of Medicinal Chemistry. 46, 7, p. 3058-3065 8 p.
Résultats de recherche: Contribution à un journal/une revue › Article › Revue par des pairs

1 Terminé

CANTOL: Conception et synthèse d'inhibiteurs de l'indolaminedioxygénase (IDO) pour le traitement du cancer
Masereel, B. (Responsable du Projet), Wouters, J. (Responsable du Projet), Dolušić, E. (Chercheur), FREDERICK, R. (Chercheur), POUYEZ, J. (Chercheur), Van den Eynde, B. J. (Co-investigateur), Frère, J.-M. (Co-investigateur), Moser, M. (Co-investigateur), Jean-Marie, B. (Co-investigateur), Combalbert, J. (Responsable du Projet) & Stephenne, J. (Co-investigateur)
1/04/08 → 31/03/12
Projet: Recherche

Physico-chimie et caractérisation (PC2)
Wouters, J. (!!Manager), Aprile, C. (!!Manager) & Fusaro, L. (!!Manager)
Plateforme technologique Caracterisation physico-chimiques
Equipement/installations: Plateforme technolgique

5 Participation à une conférence, un congrès

47th RICT: Drug Discovery and Selection.
Dolusic, E. (Poster)
6 juil. 2011 → 8 juil. 2011
Activité: Participation ou organisation d'un événement › Participation à une conférence, un congrès
JFB 2011.
Dolusic, E. (Conférencier)
19 mai 2011 → 20 mai 2011
Activité: Participation ou organisation d'un événement › Participation à une conférence, un congrès
XVIIIeme JOURNEE JEUNES CHERCHEURS
Dolusic, E. (Poster)
4 févr. 2011
Activité: Participation ou organisation d'un événement › Participation à une conférence, un congrès

CCDC 794451: Experimental Crystal Structure Determination
Dolusic, E. (Contributeur), Larrieu, P. (Contributeur), Blanc, S. (Contributeur), Sapunaric, F. (Contributeur), Norberg, B. (Contributeur), Moineaux, L. (Contributeur), Colette, D. (Contributeur), Stroobant, V. (Contributeur), Pilotte, L. (Contributeur), Colau, D. (Contributeur), Ferain, T. (Contributeur), Fraser, G. (Contributeur), Galeni, M. (Contributeur), Frere, J.-M. (Contributeur), Masereel, B. (Contributeur), Benoit, V. D. E. (Contributeur), Wouters, J. (Contributeur) & Frederick, R. (Contributeur), Cambridge Crystallographic Data Centre, 1 janv. 2011
DOI: 10.5517/ccvnpgm, http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccvnpgm&sid=DataCite
Ensemble de données
CCDC 794450: Experimental Crystal Structure Determination
Dolusic, E. (Contributeur), Larrieu, P. (Contributeur), Blanc, S. (Contributeur), Sapunaric, F. (Contributeur), Norberg, B. (Contributeur), Moineaux, L. (Contributeur), Colette, D. (Contributeur), Stroobant, V. (Contributeur), Pilotte, L. (Contributeur), Colau, D. (Contributeur), Ferain, T. (Contributeur), Fraser, G. (Contributeur), Galeni, M. (Contributeur), Frere, J.-M. (Contributeur), Masereel, B. (Contributeur), Benoit, V. D. E. (Contributeur), Wouters, J. (Contributeur) & Frederick, R. (Contributeur), Cambridge Crystallographic Data Centre, 1 janv. 2011
DOI: 10.5517/ccvnpfl, http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccvnpfl&sid=DataCite
Ensemble de données

Contient cette citation

Dolušić, E., Larrieu, P., Blanc, S., Sapunaric, F., Norberg, B., Moineaux, L., Colette, D., Stroobant, V., Pilotte, L., Colau, D., Ferain, T., Fraser, G., Galeni, M., Frre, 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, 19(4), 1550-1561. https://doi.org/10.1016/j.bmc.2010.12.032

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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. {\textcopyright} 2011 Elsevier Ltd. All rights reserved.",

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author = "Eduard Dolu{\v s}i{\'c} and Pierre Larrieu and S{\'e}bastien Blanc and Fr{\'e}d{\'e}ric Sapunaric and Bernadette Norberg and Laurence Moineaux and Delphine Colette and Vincent Stroobant and Luc Pilotte and Didier Colau and Thierry Ferain and Graeme Fraser and Moreno Galeni and Frre, {Jean Marie} and Bernard Masereel and {Van Den Eynde}, Beno{\^i}t and Johan Wouters and Rapha{\"e}l Fr{\'e}d{\'e}rick",

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Dolušić, E, Larrieu, P, Blanc, S, Sapunaric, F, Norberg, B , Moineaux, L, Colette, D, Stroobant, V, Pilotte, L, Colau, D, Ferain, T, Fraser, G, Galeni, M, Frre, JM, 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, VOL. 19, Numéro 4, p. 1550-1561. https://doi.org/10.1016/j.bmc.2010.12.032

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AU - Dolušić, Eduard

AU - Larrieu, Pierre

AU - Blanc, Sébastien

AU - Sapunaric, Frédéric

AU - Norberg, Bernadette

AU - Moineaux, Laurence

AU - Colette, Delphine

AU - Stroobant, Vincent

AU - Pilotte, Luc

AU - Colau, Didier

AU - Ferain, Thierry

AU - Fraser, Graeme

AU - Galeni, Moreno

AU - Frre, Jean Marie

AU - Masereel, Bernard

AU - Van Den Eynde, Benoît

AU - Wouters, Johan

AU - Frédérick, Raphaël

PY - 2011/2/15

Y1 - 2011/2/15

N2 - 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. © 2011 Elsevier Ltd. All rights reserved.

AB - 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. © 2011 Elsevier Ltd. All rights reserved.

KW - Anticancer

KW - IDO

KW - Immunotherapy

KW - Indoleamine 2,3-dioxygenase

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SN - 0968-0896

VL - 19

SP - 1550

EP - 1561

JO - Bioorganic & medicinal chemistry

JF - Bioorganic & medicinal chemistry

IS - 4

T2 - JFB 2011.

Y2 - 19 May 2011

ER -

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

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