The Discovery of Novel Antimalarial Aminoxadiazoles as a Promising Nonendoperoxide Scaffold
Since the appearance of resistance to the current front-line antimalarial treatments, ACTs (artemisinin combination therapies), the discovery of novel chemical entities to treat the disease is recognized as a major global health priority. From the GSK antimalarial set, we identified an aminoxadiazole with an antiparasitic profile comparable with artemisinin (1), with no cross-resistance in a resistant strains panel and a potential new mode of action. A medicinal chemistry program allowed delivery of compounds such as 19 with high solubility in aqueous media, an acceptable toxicological profile, and oral efficacy. Further evaluation of the lead compounds showed that in vivo genotoxic degradants might be generated. The compounds generated during this medicinal chemistry program and others from the GSK collection were used to build a pharmacophore model which could be used in the virtual screening of compound collections and potentially identify new chemotypes that could deliver the same antiparasitic profile.
| Errataetall: |
ErratumIn: J Med Chem. 2017 Dec 14;60(23):9911. - PMID 29164877 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:60 |
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| Enthalten in: |
Journal of medicinal chemistry - 60(2017), 16 vom: 24. Aug., Seite 6880-6896 |
| Sprache: |
Englisch |
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| Links: |
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| Anmerkungen: |
Date Completed 26.09.2017 Date Revised 13.01.2019 published: Print-Electronic ErratumIn: J Med Chem. 2017 Dec 14;60(23):9911. - PMID 29164877 Citation Status MEDLINE |
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| doi: |
10.1021/acs.jmedchem.6b01441 |
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NLM27479442X |
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| 245 | 1 | 4 | |a The Discovery of Novel Antimalarial Aminoxadiazoles as a Promising Nonendoperoxide Scaffold |
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| 500 | |a ErratumIn: J Med Chem. 2017 Dec 14;60(23):9911. - PMID 29164877 | ||
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| 520 | |a Since the appearance of resistance to the current front-line antimalarial treatments, ACTs (artemisinin combination therapies), the discovery of novel chemical entities to treat the disease is recognized as a major global health priority. From the GSK antimalarial set, we identified an aminoxadiazole with an antiparasitic profile comparable with artemisinin (1), with no cross-resistance in a resistant strains panel and a potential new mode of action. A medicinal chemistry program allowed delivery of compounds such as 19 with high solubility in aqueous media, an acceptable toxicological profile, and oral efficacy. Further evaluation of the lead compounds showed that in vivo genotoxic degradants might be generated. The compounds generated during this medicinal chemistry program and others from the GSK collection were used to build a pharmacophore model which could be used in the virtual screening of compound collections and potentially identify new chemotypes that could deliver the same antiparasitic profile | ||
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