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Title: Investigation of a novel series of 2-hydroxyisoquinoline-1,3(2H,4H)-diones as human immunodeficiency virus type 1 integrase inhibitors
Authors: Suchaud, Virginie
Bailly, Fabrice
Lion, Cedric
Calmels, Christina
Andréola, Marie-Line
Christ, Frauke
Debyser, Zeger
Cotelle, Philippe # ×
Issue Date: Jun-2014
Series Title: Journal of medicinal chemistry vol:57 issue:11 pages:4640-60
Abstract: We report herein further insight into the biological activities displayed by a series of 2-hydroxyisoquinoline-1,3(2H,4H)-diones (HIDs). Substitution of the N-hydroxyimide two-metal binding pharmacophore at position 4 by carboxamido side chains was previously shown by us to be fruitful for this scaffold, since strong human immunodeficiency virus type 1 integrase (HIV-1 IN) inhibitors in the low nanomolar range associated with low micromolar anti-HIV activities were obtained. We investigated the influence of substitution at position 7 on biological activity. Introduction of electron-withdrawing functional groups such as the nitro moiety at position 7 led to a noticeable improvement of antiviral activity, down to low nanomolar anti-HIV potencies, with advantageous therapeutic indexes going close to those of the clinically used raltegravir and retained potencies against a panel of IN mutants.
URI: 
ISSN: 0022-2623
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Virology and Gene Therapy
× corresponding author
# (joint) last author

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