Synthesis and potassium KV7 channel opening activity of thioether analogues of the analgesic flupirtine
| العنوان: | Synthesis and potassium KV7 channel opening activity of thioether analogues of the analgesic flupirtine |
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| المؤلفون: | Lukas Schulig, Kristin Beirow, Anja Bodtke, Abdrrahman Shemsu Surur, Patrick J. Bednarski, Christian Bock, Andreas Link |
| المصدر: | Organic & Biomolecular Chemistry. 16:8695-8699 |
| بيانات النشر: | Royal Society of Chemistry (RSC), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Liver injury, 010405 organic chemistry, Potassium, Organic Chemistry, Analgesic, chemistry.chemical_element, Sulfoxide, Voltage-gated potassium channel, Pharmacology, medicine.disease, 01 natural sciences, Biochemistry, 0104 chemical sciences, Sulfone, 010404 medicinal & biomolecular chemistry, chemistry.chemical_compound, chemistry, Thioether, medicine, Physical and Theoretical Chemistry, Flupirtine, medicine.drug |
| الوصف: | Flupirtine, an opener of neuronal voltage gated potassium channels (KV7.2/3), has been used as a therapeutic alternative for pain treatment in patients refractory to NSAIDs and opioids. Because flupirtine is associated with rare but fatal drug-induced liver injury that may result from the formation of toxic metabolites upon metabolic oxidation, we synthesized novel derivatives with the goal of identifying equally active and ultimately safer KV7.2/3 channel openers. Four thioether analogues were designed to lack a nitrogen atom that would be a prerequisite for the formation of toxic para-quinone diimines, and form sulfoxide and sulfone metabolites instead. KV7.2/3 channel opening activity and hepatotoxicity data of twelve novel flupirtine analogues, four thioethers and their respective sulfoxide and sulfone metabolites are reported. |
| تدمد: | 1477-0539 1477-0520 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::6ca87da5eea7ff7a8f48dbde13006103Test https://doi.org/10.1039/c8ob02530dTest |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi...........6ca87da5eea7ff7a8f48dbde13006103 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14770539 14770520 |
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