Synthesis of 5- and 6-Aminopyridin-3-ol Quinone Methide Precursors
2022
Online
Hochschulschrift
Organophosphorus (OP) nerve agents are compounds that contain phosphoryl or thiophosphoryl functional groups. These molecules have been continuously developed and prepared since the late 1930’s, with newer generations (V- and A-series) having much higher toxicity relative to the original G-series of OP nerve agents. OP pesticides are also the cause of many poisonings, attributed to over 100,000 suicide deaths per year. OP molecules act as covalent inhibitors of the enzyme acetylcholinesterase (AChE), but their therapeutic window for treatment is small due the rapid inhibition and also due to a subsequent and spontaneous O-dealkylation event. This O-dealkylation causes the “aging” of AChE, and current therapeutics are not able to regenerate the native enzyme. Quinone methide precursors (QMPs) are hypothesized to reverse the aged state of AChE through either an SN2 reaction or the formation of a quinone methide (QM) inside the active site of AChE. The focus of this thesis is the development and synthesis of 5-aminopyridin-3-ol and 6-aminopyridin-3-ol QMPs as potential therapeutic treatments for OP poisoning.
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Synthesis of 5- and 6-Aminopyridin-3-ol Quinone Methide Precursors
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Autor/in / Beteiligte Person: | Lind, Eli A. |
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Veröffentlichung: | 2022 |
Medientyp: | Hochschulschrift |
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