Journal of Medicinal Chemistry, volume 61, issue 8, pages 3565-3581
Imidazopyrazinones (IPYs): Non-Quinolone Bacterial Topoisomerase Inhibitors Showing Partial Cross-Resistance with Quinolones
Jeannot Frederic
1
,
Taillier Thomas
1
,
Despeyroux Pierre
1
,
Renard Stéphane
1
,
Rey Astrid
1
,
Mourez Michael
1
,
Poeverlein Christoph
2
,
Khichane Imène
3
,
Perrin Marc Antoine
3
,
Versluys Stéphanie
4
,
Stavenger Robert A.
5
,
Huang Jianzhong
5
,
Germe Thomas
6
,
Maxwell Anthony
6
,
Cao Sha
7
,
Huseby Doug
7
,
Hughes Diarmaid
7
,
Bacqué Eric
1
1
Therapeutic Area Infectious Diseases, Sanofi R&D, 1541 Avenue Marcel Mérieux, 69280 Marcy L’Etoile, France
|
2
R&D, Integrated Drug Discovery, Sanofi-Aventis Deutschland GmbH, Industriepark Hoechst, 65926 Frankfurt am Main, Germany
|
3
LGCR, Analytical Sciences, Sanofi R&D, 13 Quai Jules Guesde, 94400 Vitry sur Seine, France
|
4
Evotec France, 195 Route d’Espagne, BP 13669, 31036 Toulouse Cedex 1, France
|
5
Antibacterial DPU, GlaxoSmithKline, 1250 Collegeville Road, Collegeville, Pennsylvania 19426, United States
|
6
Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, U.K.
|
Publication type: Journal Article
Publication date: 2018-03-29
Journal:
Journal of Medicinal Chemistry
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 7.3
ISSN: 00222623, 15204804
Drug Discovery
Molecular Medicine
Abstract
In our quest for new antibiotics able to address the growing threat of multidrug 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 Innovative Medicines Initiative (IMI) European Gram Negative Antibacterial Engine (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 fluoroquinolones (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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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Jeannot F. et al. Imidazopyrazinones (IPYs): Non-Quinolone Bacterial Topoisomerase Inhibitors Showing Partial Cross-Resistance with Quinolones // Journal of Medicinal Chemistry. 2018. Vol. 61. No. 8. pp. 3565-3581.
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Jeannot F., Taillier T., Despeyroux P., Renard S., Rey A., Mourez M., Poeverlein C., Khichane I., Perrin M. A., Versluys S., Stavenger R. A., Huang J., Germe T., Maxwell A., Cao S., Huseby D., Hughes D., Bacqué E. Imidazopyrazinones (IPYs): Non-Quinolone Bacterial Topoisomerase Inhibitors Showing Partial Cross-Resistance with Quinolones // Journal of Medicinal Chemistry. 2018. Vol. 61. No. 8. pp. 3565-3581.
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TY - JOUR
DO - 10.1021/acs.jmedchem.7b01892
UR - https://doi.org/10.1021%2Facs.jmedchem.7b01892
TI - Imidazopyrazinones (IPYs): Non-Quinolone Bacterial Topoisomerase Inhibitors Showing Partial Cross-Resistance with Quinolones
T2 - Journal of Medicinal Chemistry
AU - Jeannot, Frederic
AU - Taillier, Thomas
AU - Despeyroux, Pierre
AU - Renard, Stéphane
AU - Rey, Astrid
AU - Mourez, Michael
AU - Poeverlein, Christoph
AU - Khichane, Imène
AU - Perrin, Marc Antoine
AU - Versluys, Stéphanie
AU - Stavenger, Robert A.
AU - Huang, Jianzhong
AU - Maxwell, Anthony
AU - Bacqué, Eric
AU - Germe, Thomas
AU - Cao, Sha
AU - Huseby, Doug
AU - Hughes, Diarmaid
PY - 2018
DA - 2018/03/29 00:00:00
PB - American Chemical Society (ACS)
SP - 3565-3581
IS - 8
VL - 61
SN - 0022-2623
SN - 1520-4804
ER -
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@article{2018_Jeannot,
author = {Frederic Jeannot and Thomas Taillier and Pierre Despeyroux and Stéphane Renard and Astrid Rey and Michael Mourez and Christoph Poeverlein and Imène Khichane and Marc Antoine Perrin and Stéphanie Versluys and Robert A. Stavenger and Jianzhong Huang and Anthony Maxwell and Eric Bacqué and Thomas Germe and Sha Cao and Doug Huseby and Diarmaid Hughes},
title = {Imidazopyrazinones (IPYs): Non-Quinolone Bacterial Topoisomerase Inhibitors Showing Partial Cross-Resistance with Quinolones},
journal = {Journal of Medicinal Chemistry},
year = {2018},
volume = {61},
publisher = {American Chemical Society (ACS)},
month = {mar},
url = {https://doi.org/10.1021%2Facs.jmedchem.7b01892},
number = {8},
pages = {3565--3581},
doi = {10.1021/acs.jmedchem.7b01892}
}
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Jeannot, Frederic, et al. “Imidazopyrazinones (IPYs): Non-Quinolone Bacterial Topoisomerase Inhibitors Showing Partial Cross-Resistance with Quinolones.” Journal of Medicinal Chemistry, vol. 61, no. 8, Mar. 2018, pp. 3565-3581. https://doi.org/10.1021%2Facs.jmedchem.7b01892.