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]
Marzag, Hamid [Auteur]
Knorr, Michael [Auteur]
Strohmann, Carsten [Auteur]
Lawson, Ata Martin [Auteur]
Ghinet, Alina [Auteur]
Lille Inflammation Research International Center (LIRIC) - U995
Dubois, Joelle [Auteur]
Farce, Amaury [Auteur]
Lille Inflammation Research International Center (LIRIC) - U995
Daich, Adam [Auteur]
Othman, Mohamed [Auteur]

Journal title :

Organic & Biomolecular Chemistry

Abbreviated title :

Org. Biomol. Chem.

Publication date :

2019-02-22

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 >

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
Inserm
Université de Lille

Collections :

• Lille Inflammation Research International Center (LIRIC) - U995

Research team(s) :

Therapeutic innovation targetting inflammation

Submission date :

2019-05-17T13:08:38Z