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Structural and theoretical studies of [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid as HIV-1 integrase inhibitor.

par Vandurm, Pierre;Cauvin, Christine;Guiguen, Allan ;Georges, Benoît;Le Van, Kiet ;Martinelli, Valérie ;Cardona, Christelle ;Mbemba, Gladys;Mouscadet, Jean-François;Hevesi, László;Van Lint, Carine ;Wouters, Johan
Référence Bioorganic & medicinal chemistry letters, 19, 16, page (4806-4809)
Publication Publié, 2009

Article révisé par les pairs

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Résumé :

Ethyl [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl]-4-hydroxy-2-oxo-3-butenoate 1 and [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid 2 were synthesized as potential HIV-1 integrase inhibitors and evaluated for their enzymatic and antiviral activity, acidic compound 2 being more potent than ester compound 1. X-ray diffraction analyses and theoretical calculations show that the diketoacid chain of compound 2 is preferentially coplanar with the quinolinone ring (dihedral angle of 0-30 degrees ). Docking studies suggest binding modes in agreement with structure-activity relationships.