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Journal articles
Access to 3-spiroindolizines containing an isoindole ring through intra-molecular arylation of spiro-N-acyliminium species: a new family of potent farnesyltransferase inhibitors
Anthony Pesquet
1
Hamid Marzag
1
Michael Knorr
2
Carsten Strohmann
3
Ata Martin Lawson
1
Alina Ghinet
4, 5, 6
Joëlle Dubois
7
Farce Amaury
6
Adam Daïch
1, *
Mohamed Othman
1
*
Corresponding author
Ata Martin Lawson 1
Author IdHAL : ata-martin-lawson ORCID : https://orcid.org/0000-0002-1641-4190
Alina Ghinet 4, 5, 6
Author
Joëlle Dubois 7
Author
Farce Amaury 6
Author
Adam Daïch 1
Correspondent author IdHAL : adam-daich ORCID : https://orcid.org/0000-0002-6942-0519
Mohamed Othman 1
Author IdHAL : mohamed-othman ORCID : https://orcid.org/0000-0002-8379-5704
1
URCOM - Unité de Recherche en Chimie Organique et Macromoléculaire (25 rue Philippe Lebon
- BP 1123
- 76063 Le Havre Cedex - France)
- ULH - Université Le Havre Normandie : EA3221 (25 rue Philippe Lebon - BP 1123 - 76063 Le Havre Cedex France - France)
- NU - Normandie Université (Esplanade de la Paix - CS 14032 - 14032 Caen Cedex 5 - France)
2
UTINAM - Univers, Transport, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213) (16, route de Gray 25030 BESANCON CEDEX France - France)
- INSU - CNRS - Institut national des sciences de l'Univers (INSU-CNRS 3 rue Michel-Ange, 75794 Paris Cedex 16 - France)
- CNRS - Centre National de la Recherche Scientifique : UMR6213 (France)
- UFC - Université de Franche-Comté (1 rue Goudimel 25030 Besançon cedex - France)
3
TU - Technische Universität Dortmund [Dortmund] (44221 Dortmund - Germany)
4
ICPAL - Institut de Chimie Pharmaceutique Albert Lespagnol (Université de Lille II 3, rue du Professeur Laguesse F-59006 Lille - France)
- Université de Lille, Droit et Santé : EA4481 (42 rue Paul Duez 59000 Lille - France)
5
HEI - Hautes Etudes d’Ingénieur [Lille] (13 rue de Toul
BP41290
59014 Lille Cedex - France)
6
LIRIC - Lille Inflammation Research International Center - U 995 (Faculté de médecine -
Pôle recherche-4ème étage -
Place de Verdun -
F-59045 Lille Cedex - - France)
- Institut Pasteur de Lille : U995 (1 Rue du Professeur Calmette - Lille Cedex - 59019 - France)
- RIIP - Réseau International des Instituts Pasteur (25, rue du Dr Roux 75724 Paris Cedex 15 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U995 (101, rue de Tolbiac, 75013 Paris - France)
- Université de Lille (Lille - France)
- CHRU Lille - Centre Hospitalier Régional Universitaire [Lille] : U995 (2, avenue Oscar Lambret - 59037 Lille Cedex - France)
7
ICSN - Institut de Chimie des Substances Naturelles (Avenue de la terrasse 91198 Gif-sur-Yvette cedex - France)
- CNRS - Centre National de la Recherche Scientifique : UPR2301 (France)
Abstract : Based on N-acyliminium species, two efficient and rapid approaches to diversify spirocyclic systems connected by two different carbon centers to the isoindole ring have been developed. The imide reduction and the tandem oxidative cleavage of olefin/formyl-amide equilibration were at first selected as the key steps for these strategies. Ultimately the intramolecular α-amidoalkylation reaction was achieved through the arylation of α-acetoxy lactams or α-hydroxy lactams using, respectively, a Lewis acid or a Brønsted acid depending on the nature of N-acyliminium precursors. The latter led, in addition to the spiro-6-membered aza-heterocycles, to the formation of scarce spiro-5-membered analogues which show promising inhibitory activities on human farnesyltransferase in the nanomolar range demonstrating improved IC50 values of up to 1.5 nM.
Document type :
Journal articles
Complete list of metadata
https://hal-normandie-univ.archives-ouvertes.fr/hal-02332627
Contributor : Ata Martin Lawson Connect in order to contact the contributor
Submitted on : Thursday, October 24, 2019 - 9:26:02 PM
Last modification on : Wednesday, November 3, 2021 - 7:50:52 AM
Contributor : Ata Martin Lawson Connect in order to contact the contributor
Submitted on : Thursday, October 24, 2019 - 9:26:02 PM
Last modification on : Wednesday, November 3, 2021 - 7:50:52 AM
Identifiers
- HAL Id : hal-02332627, version 1
- DOI : 10.1039/c8ob02612b
- PUBMED : 30793727
Collections
COMUE-NORMANDIE | RIIP | RIIP_LILLE | UNIV-FCOMTE | ICSN | CNRS | INC-CNRS | INSU | UNIV-LILLE | UNILEHAVRE | URCOM | UTINAM | GS-CHIMIE | GS-HEALTH-DRUG-SCIENCES
Citation
Anthony Pesquet, Hamid Marzag, Michael Knorr, Carsten Strohmann, Ata Martin Lawson, et al.. Access to 3-spiroindolizines containing an isoindole ring through intra-molecular arylation of spiro-N-acyliminium species: a new family of potent farnesyltransferase inhibitors. Organic and Biomolecular Chemistry, Royal Society of Chemistry, 2019, 17 (10), pp.2798-2808. ⟨10.1039/c8ob02612b⟩. ⟨hal-02332627⟩
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