Structural investigation of the naphthyridone scaffold: identification of a 1,6-naphthyridone derivative with potent and selective anti-HIV activity

ChemMedChem
Oriana TabarriniChristophe Pannecouque

Abstract

Building upon a large, previously reported series of anti-HIV 6-desfluoroquinolones endowed with a peculiar mechanism of action, the inhibition of Tat-mediated transcription, replacement of the quinolone nucleus with a naphthyridone core was shown to be very productive. In this work, the naphthyridone scaffold was investigated in depth by synthesizing various analogues. This led to the identification of NM13 as the most selective derivative obtained in MT-4 cells. It is the result of the successful combination of the 1,6-naphthyridone nucleus and the C7 benzothiazolpiperazine group, which, for the first time, not only grants potent anti-HIV activity but displays very high selectivity. Further studies aimed at a more thorough investigation of the anti-HIV profile of this new derivative are in progress.

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Citations

Jun 7, 2014·Journal of Medicinal Chemistry·Manuela DonalisioOriana Tabarrini
Aug 16, 2014·Bioorganic & Medicinal Chemistry·Luca SancinetoOriana Tabarrini
Dec 3, 2014·European Journal of Medicinal Chemistry·Rangappa S KeriSrinivasa Budagumpi
Jan 1, 2012·Biology·Guillaume Mousseau, Susana Valente
Oct 27, 2018·Journal of Enzyme Inhibition and Medicinal Chemistry·Serena MassariOriana Tabarrini
Jul 6, 2019·Archiv der Pharmazie·Ruo WangWeixiong Shi
Nov 7, 2019·Journal of Virology·Lisa J HendersonAvindra Nath
Dec 5, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ming-Shu WangNeng-Fang She
Jun 12, 2020·European Journal of Medicinal Chemistry·Maria Giulia NiziOriana Tabarrini

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