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Your search keyword '"Seiler, Peter"' showing total 9 results
Start Over Author "Seiler, Peter" Publisher american chemical society
9 results on '"Seiler, Peter"'

1. Discovery and Structure–Activity Relationship of Cadazolid: A First-In-Class Quinoxolidinone Antibiotic for the Treatment of Clostridioides difficile Infection.

Author

Rueedi, Georg, Panchaud, Philippe, Friedli, Astrid, Specklin, Jean-Luc, Hubschwerlen, Christian, Blumstein, Anne-Catherine, Caspers, Patrick, Enderlin-Paput, Michel, Jacob, Loïc, Kohl, Christopher, Locher, Hans H., Pfaff, Philippe, Schmitt, Christine, Seiler, Peter, and Ritz, Daniel

Published
2024
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2. Optimization of LpxC Inhibitor Lead Compounds Focusing on Efficacy and Formulation for High Dose Intravenous Administration.

Author

Panchaud, Philippe, Surivet, Jean-Philippe, Diethelm, Stefan, Blumstein, Anne-Catherine, Gauvin, Jean-Christophe, Jacob, Loïc, Masse, Florence, Mathieu, Gaëlle, Mirre, Azely, Schmitt, Christine, Enderlin-Paput, Michel, Lange, Roland, Gnerre, Carmela, Seeland, Swen, Herrmann, Charlyse, Locher, Hans H., Seiler, Peter, Ritz, Daniel, and Rueedi, Georg

Published
2020
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3. Discovery of Novel Inhibitors of LpxC Displaying Potent in Vitro Activity against Gram-Negative Bacteria.

Author

Surivet, Jean-Philippe, Panchaud, Philippe, Specklin, Jean-Luc, Diethelm, Stefan, Blumstein, Anne-Catherine, Gauvin, Jean-Christophe, Jacob, Loïc, Masse, Florence, Mathieu, Gaëlle, Mirre, Azely, Schmitt, Christine, Lange, Roland, Tidten-Luksch, Naomi, Gnerre, Carmela, Seeland, Swen, Herrmann, Charlyse, Seiler, Peter, Enderlin-Paput, Michel, Mac Sweeney, Aengus, and Wicki, Micha

Published
2020
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4. Synthesis and Characterization of Tetrahydropyran-Based Bacterial Topoisomerase Inhibitors with Antibacterial Activity against Gram-Negative Bacteria.

Author

Surivet, Jean-Philippe, Zumbrunn, Cornelia, Bruyère, Thierry, Bur, Daniel, Kohl, Christopher, Locher, Hans H., Seiler, Peter, Ertel, Eric A., Hess, Patrick, Enderlin-Paput, Michel, Enderlin-Paput, Stéphanie, Gauvin, Jean-Christophe, Mirre, Azely, Hubschwerlen, Christian, Ritz, Daniel, and Rueedi, Georg

Published
2017
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6. Novel Tetrahydropyran-BasedBacterial Topoisomerase Inhibitors with Potent Anti-Gram PositiveActivity and Improved Safety Profile.

Author

Surivet, Jean-Philippe, Zumbrunn, Cornelia, Rueedi, Georg, Bur, Daniel, Bruyère, Thierry, Locher, Hans, Ritz, Daniel, Seiler, Peter, Kohl, Christopher, Ertel, Eric A., Hess, Patrick, Gauvin, Jean-Christophe, Mirre, Azely, Kaegi, Verena, Dos Santos, Marina, Kraemer, Stéphanie, Gaertner, Mika, Delers, Jonathan, Enderlin-Paput, Michel, and Weiss, Maria

Published
2015
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7. Design,Synthesis, and Characterization of Novel Tetrahydropyran-BasedBacterial Topoisomerase Inhibitors with Potent Anti-Gram-PositiveActivity.

Author

Surivet, Jean-Philippe, Zumbrunn, Cornelia, Rueedi, Georg, Hubschwerlen, Christian, Bur, Daniel, Bruyère, Thierry, Locher, Hans, Ritz, Daniel, Keck, Wolfgang, Seiler, Peter, Kohl, Christopher, Gauvin, Jean-Christophe, Mirre, Azely, Kaegi, Verena, Dos Santos, Marina, Gaertner, Mika, Delers, Jonathan, Enderlin-Paput, Michel, and Boehme, Maria

Published
2013
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8. Novel tetrahydropyran-based bacterial topoisomerase inhibitors with potent anti-gram positive activity and improved safety profile.

Author

Surivet JP, Zumbrunn C, Rueedi G, Bur D, Bruyère T, Locher H, Ritz D, Seiler P, Kohl C, Ertel EA, Hess P, Gauvin JC, Mirre A, Kaegi V, Dos Santos M, Kraemer S, Gaertner M, Delers J, Enderlin-Paput M, Weiss M, Sube R, Hadana H, Keck W, and Hubschwerlen C

Subjects
Animals, Anti-Bacterial Agents pharmacology, Guinea Pigs, Hemodynamics drug effects, Humans, Male, Mice, Microbial Sensitivity Tests, Pyrans pharmacology, Rats, Rats, Wistar, Structure-Activity Relationship, Topoisomerase II Inhibitors pharmacology, Anti-Bacterial Agents chemical synthesis, Gram-Positive Bacteria drug effects, Pyrans chemical synthesis, Topoisomerase II Inhibitors chemical synthesis
Abstract

Novel antibacterial drugs that are effective against infections caused by multidrug resistant pathogens are urgently needed. In a previous report, we have shown that tetrahydropyran-based inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) display potent antibacterial activity and exhibit no target-mediated cross-resistance with fluoroquinolones. During the course of our optimization program, lead compound 5 was deprioritized due to adverse findings in cardiovascular safety studies. In the effort of mitigating these findings and optimizing further the pharmacological profile of this class of compounds, we have identified a subseries of tetrahydropyran-based molecules that are potent DNA gyrase and topoisomerase IV inhibitors and display excellent antibacterial activity against Gram positive pathogens, including clinically relevant resistant isolates. One representative of this class, compound 32d, elicited only weak inhibition of hERG K(+) channels and hNaV1.5 Na(+) channels, and no effects were observed on cardiovascular parameters in anesthetized guinea pigs. In vivo efficacy in animal infection models has been demonstrated against Staphylococcus aureus and Streptococcus pneumoniae strains.

Published
2015
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9. Design, synthesis, and characterization of novel tetrahydropyran-based bacterial topoisomerase inhibitors with potent anti-gram-positive activity.

Author

Surivet JP, Zumbrunn C, Rueedi G, Hubschwerlen C, Bur D, Bruyère T, Locher H, Ritz D, Keck W, Seiler P, Kohl C, Gauvin JC, Mirre A, Kaegi V, Dos Santos M, Gaertner M, Delers J, Enderlin-Paput M, and Boehme M

Subjects
Animals, Anti-Bacterial Agents metabolism, Anti-Bacterial Agents pharmacokinetics, Chemistry Techniques, Synthetic, DNA Gyrase chemistry, DNA Gyrase metabolism, DNA Topoisomerase IV antagonists & inhibitors, DNA Topoisomerase IV chemistry, DNA Topoisomerase IV metabolism, DNA Topoisomerases chemistry, Female, Gram-Positive Bacteria enzymology, Humans, Inhibitory Concentration 50, Mice, Molecular Docking Simulation, Protein Conformation, Pyrans metabolism, Pyrans pharmacokinetics, Rats, Structure-Activity Relationship, Topoisomerase II Inhibitors, Topoisomerase Inhibitors chemical synthesis, Topoisomerase Inhibitors metabolism, Topoisomerase Inhibitors pharmacokinetics, Topoisomerase Inhibitors pharmacology, Anti-Bacterial Agents chemical synthesis, Anti-Bacterial Agents pharmacology, DNA Topoisomerases metabolism, Drug Design, Gram-Positive Bacteria drug effects, Pyrans chemical synthesis, Pyrans pharmacology
Abstract

There is an urgent need for new antibacterial drugs that are effective against infections caused by multidrug-resistant pathogens. Novel nonfluoroquinolone inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) have the potential to become such drugs because they display potent antibacterial activity and exhibit no target-mediated cross-resistance with fluoroquinolones. Bacterial topoisomerase inhibitors that are built on a tetrahydropyran ring linked to a bicyclic aromatic moiety through a syn-diol linker show potent anti-Gram-positive activity, covering isolates with clinically relevant resistance phenotypes. For instance, analog 49c was found to be a dual DNA gyrase-topoisomerase IV inhibitor, with broad antibacterial activity and low propensity for spontaneous resistance development, but suffered from high hERG K(+) channel block. On the other hand, analog 49e displayed lower hERG K(+) channel block while retaining potent in vitro antibacterial activity and acceptable frequency for resistance development. Furthermore, analog 49e showed moderate clearance in rat and promising in vivo efficacy against Staphylococcus aureus in a murine infection model.

Published
2013
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