Access to 3-spiroindolizines containing ...
Document type :
Article dans une revue scientifique
DOI :
PMID :
Permalink :
Title :
Access to 3-spiroindolizines containing an isoindole ring through intra-molecular arylation of spiro-N-acyliminium species: a new family of potent farnesyltransferase inhibitors.
Author(s) :
Pesquet, Anthony [Auteur]
Unité de Recherche en Chimie Organique et Macromoléculaire [URCOM]
Marzag, Hamid [Auteur]
Unité de Recherche en Chimie Organique et Macromoléculaire [URCOM]
Knorr, Michael [Auteur]
Univers, Théorie, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213) [UTINAM]
Strohmann, Carsten [Auteur]
Lawson, Ata Martin [Auteur]
Unité de Recherche en Chimie Organique et Macromoléculaire [URCOM]
Ghinet, Alina [Auteur]
1059196|||JUNIA [JUNIA]
498252|||Lille Inflammation Research International Center - U 995 [LIRIC]
Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167
Lille Inflammation Research International Center (LIRIC) - U995
Dubois, Joelle [Auteur]
Institut de Chimie des Substances Naturelles [ICSN]
Farce, Amaury [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Daich, Adam [Auteur]
Unité de Recherche en Chimie Organique et Macromoléculaire [URCOM]
Othman, Mohamed [Auteur]
Unité de Recherche en Chimie Organique et Macromoléculaire [URCOM]
Unité de Recherche en Chimie Organique et Macromoléculaire [URCOM]
Marzag, Hamid [Auteur]
Unité de Recherche en Chimie Organique et Macromoléculaire [URCOM]
Knorr, Michael [Auteur]
Univers, Théorie, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213) [UTINAM]
Strohmann, Carsten [Auteur]
Lawson, Ata Martin [Auteur]
Unité de Recherche en Chimie Organique et Macromoléculaire [URCOM]
Ghinet, Alina [Auteur]
1059196|||JUNIA [JUNIA]
498252|||Lille Inflammation Research International Center - U 995 [LIRIC]
Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167
Lille Inflammation Research International Center (LIRIC) - U995
Dubois, Joelle [Auteur]
Institut de Chimie des Substances Naturelles [ICSN]
Farce, Amaury [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Daich, Adam [Auteur]
Unité de Recherche en Chimie Organique et Macromoléculaire [URCOM]
Othman, Mohamed [Auteur]
Unité de Recherche en Chimie Organique et Macromoléculaire [URCOM]
Journal title :
Organic & Biomolecular Chemistry
Abbreviated title :
Org. Biomol. Chem.
Volume number :
17
Pages :
2798-2808
Publication date :
2019-02-07
ISSN :
1477-0539
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
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 ...
Show more >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.Show less >
Show more >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.Show less >
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
CHU Lille
Inserm
Université de Lille
Inserm
Université de Lille
Collections :
Research team(s) :
Therapeutic innovation targetting inflammation
Submission date :
2019-05-17T13:08:38Z
2024-01-30T12:12:32Z
2024-01-30T12:17:02Z
2024-01-30T12:12:32Z
2024-01-30T12:17:02Z