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

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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. © 2011 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	1550-1561
Number of pages	12
Journal	Bioorganic and Medicinal Chemistry
Volume	19
Issue number	4
DOIs	https://doi.org/10.1016/j.bmc.2010.12.032
Publication status	Published - 15 Feb 2011
Event	JFB 2011. - Liege, Belgium Duration: 19 May 2011 → …

Keywords

Anticancer
IDO
Immunotherapy
Indoleamine 2,3-dioxygenase

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmc.2010.12.032

BMC 8927 corrSubmitted manuscript, 2.07 MB

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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, 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 and 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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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 and Medicinal Chemistry, vol. 19, no. 4, pp. 1550-1561. https://doi.org/10.1016/j.bmc.2010.12.032

TY - JOUR

T1 - Indol-2-yl ethanones as novel indoleamine 2,3-dioxygenase (IDO) inhibitors

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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U2 - 10.1016/j.bmc.2010.12.032

DO - 10.1016/j.bmc.2010.12.032

M3 - Article

C2 - 21269836

SN - 0968-0896

VL - 19

SP - 1550

EP - 1561

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 4

T2 - JFB 2011.

Y2 - 19 May 2011

ER -

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

Abstract

Keywords

UN SDGs

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

Abstract

Keywords

UN SDGs

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