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Imidazopyrazinones (IPYs): non-quinolone bacterial topoisomerase inhibitors showing partial cross-resistance with quinolones.

08:00 EDT 29th March 2018 | BioPortfolio

Summary of "Imidazopyrazinones (IPYs): non-quinolone bacterial topoisomerase inhibitors showing partial cross-resistance with quinolones."

In our quest for new antibiotics able to address the growing threat of multi-drug resistant infections caused by Gram-negative bacteria, we have investigated an unprecedented series of non-quinolone bacterial topoisomerase inhibitors from the Sanofi patrimony, named IPYs for ImidazoPYrazinones as part of the IMI ENABLE organization. Hybridization of these historical compounds with the quinazolinediones, a known series of topoisomerase inhibitors, led us to a novel series of tricyclic IPYs that demonstrated potential for broad spectrum activity, in vivo efficacy and a good developability profile although later profiling revealed a genotoxicity risk. Resistance studies revealed partial cross-resistance with fluoro-quinolones (FQs) suggesting that IPYs bind to the same region of bacterial topoisomerases as FQs and interact with at least some of the keys residues involved in FQ binding.

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This article was published in the following journal.

Name: Journal of medicinal chemistry
ISSN: 1520-4804
Pages:

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