2-hydroxyisoquinoline-1,3(2H,4H)-diones ...
Document type :
Article dans une revue scientifique
PMID :
Permalink :
Title :
2-hydroxyisoquinoline-1,3(2H,4H)-diones (HIDs) as human immunodeficiency virus type 1 integrase inhibitors: Influence of the alkylcarboxamide substitution of position 4
Author(s) :
Billamboz, Muriel [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Suchaud, Virginie [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Bailly, Fabrice [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Unité de Catalyse et de Chimie du Solide (UCCS) - UMR 8181
Lion, Cédric [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Andreola, Marie-Line [Auteur]
Microbiologie Fondamentale et Pathogénicité [MFP]
Christ, Frauke [Auteur]
Catholic University of Leuven = Katholieke Universiteit Leuven [KU Leuven]
Debyser, Zeger [Auteur]
Catholic University of Leuven = Katholieke Universiteit Leuven [KU Leuven]
Cotelle, Philippe [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Suchaud, Virginie [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Bailly, Fabrice [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Unité de Catalyse et de Chimie du Solide (UCCS) - UMR 8181
Lion, Cédric [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Andreola, Marie-Line [Auteur]
Microbiologie Fondamentale et Pathogénicité [MFP]
Christ, Frauke [Auteur]
Catholic University of Leuven = Katholieke Universiteit Leuven [KU Leuven]
Debyser, Zeger [Auteur]
Catholic University of Leuven = Katholieke Universiteit Leuven [KU Leuven]
Cotelle, Philippe [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Journal title :
European journal of medicinal chemistry
Abbreviated title :
Eur. J. Med. Chem.
Volume number :
117
Pages :
256-268
Publication date :
2016-07-19
ISSN :
0223-5234
English keyword(s) :
Two-metal binding pharmacophore
2-hydroxyisoquinoline-1,3(2H,4H)-diones
Antiretroviral
HIV-1 integrase
2-hydroxyisoquinoline-1,3(2H,4H)-diones
Antiretroviral
HIV-1 integrase
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Herein, we report further insight into the biological activities displayed by the 2-hydroxyisoquinoline-1,3(2H,4H)-dione (HID) scaffold. Previous studies have evidenced the marked fruitful effect of substitution of this ...
Show more >Herein, we report further insight into the biological activities displayed by the 2-hydroxyisoquinoline-1,3(2H,4H)-dione (HID) scaffold. Previous studies have evidenced the marked fruitful effect of substitution of this two-metal binding pharmacophore at position 4 by phenyl and benzyl carboxamido chains. Strong human immunodeficiency virus type 1 integrase (HIV-1 IN) inhibitors in the low nanomolar range with micromolar (even down to low nanomolar) anti-HIV activities were obtained. Keeping this essential 4-carboxamido function, we investigated the influence of the replacement of phenyl and benzyl groups by various alkyl chains. This study shows that the recurrent halogenobenzyl pharmacophore found in the INSTIs can be efficiently replaced by an n-alkyl group. With an optimal length of six carbons, we observed a biological profile and a high barrier to resistance equivalent to those of a previously reported hit compound bearing a 4-fluorobenzyl group.Show less >
Show more >Herein, we report further insight into the biological activities displayed by the 2-hydroxyisoquinoline-1,3(2H,4H)-dione (HID) scaffold. Previous studies have evidenced the marked fruitful effect of substitution of this two-metal binding pharmacophore at position 4 by phenyl and benzyl carboxamido chains. Strong human immunodeficiency virus type 1 integrase (HIV-1 IN) inhibitors in the low nanomolar range with micromolar (even down to low nanomolar) anti-HIV activities were obtained. Keeping this essential 4-carboxamido function, we investigated the influence of the replacement of phenyl and benzyl groups by various alkyl chains. This study shows that the recurrent halogenobenzyl pharmacophore found in the INSTIs can be efficiently replaced by an n-alkyl group. With an optimal length of six carbons, we observed a biological profile and a high barrier to resistance equivalent to those of a previously reported hit compound bearing a 4-fluorobenzyl group.Show less >
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
CNRS
Université de Lille
Université de Lille
Collections :
Research team(s) :
Therapeutic innovation targetting inflammation
Submission date :
2019-05-17T13:14:39Z
2021-03-19T08:08:02Z
2021-03-19T08:08:02Z