Access to 3-spiroindolizines containing ...
Type de document :
Article dans une revue scientifique
DOI :
PMID :
URL permanente :
Titre :
Access to 3-spiroindolizines containing an isoindole ring through intra-molecular arylation of spiro-N-acyliminium species: a new family of potent farnesyltransferase inhibitors.
Auteur(s) :
Pesquet, Anthony [Auteur]
Marzag, Hamid [Auteur]
Knorr, Michael [Auteur]
Strohmann, Carsten [Auteur]
Lawson, Ata Martin [Auteur]
Ghinet, Alina [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Dubois, Joelle [Auteur]
Farce, Amaury [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Daich, Adam [Auteur]
Othman, Mohamed [Auteur]
Marzag, Hamid [Auteur]
Knorr, Michael [Auteur]
Strohmann, Carsten [Auteur]
Lawson, Ata Martin [Auteur]
Ghinet, Alina [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Dubois, Joelle [Auteur]
Farce, Amaury [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Daich, Adam [Auteur]
Othman, Mohamed [Auteur]
Titre de la revue :
Organic & Biomolecular Chemistry
Nom court de la revue :
Org. Biomol. Chem.
Date de publication :
2019-02-22
ISSN :
1477-0539
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [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 ...
Lire la suite >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.Lire moins >
Lire la suite >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.Lire moins >
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
CHU Lille
Inserm
Université de Lille
Inserm
Université de Lille
Équipe(s) de recherche :
Therapeutic innovation targetting inflammation
Date de dépôt :
2019-05-17T13:08:38Z