1531-25-5Relevant articles and documents
N-demethylation of dextromethorphan
Peet
, p. 1447 - 1448 (1980)
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Late-Stage Conversion of a Metabolically Labile Aryl Methyl Ether-Containing Natural Product to Fluoroalkyl Analogues
Altman, Ryan A.,Ambler, Brett R.,Sorrentino, Jacob P.
, p. 5416 - 5427 (2020/05/19)
We report the conversion of aryl methyl ethers and phenols into six fluoroalkyl analogues through late-stage functionalization of a natural product-derived FDA-approved therapeutic. This series of short synthetic sequences exploits a combination of both modern and traditional methods and demonstrates that some recently reported methods do not always work as well as desired on a natural product-like scaffold. Nonetheless, reaction optimization can deliver sufficient quantities of each target analogue for medicinal chemistry purposes. In some cases, classical reactions and synthetic sequences still outcompete modern organofluorine transformations, which should encourage the continued search for improved reactions. Overall, the project provides a valuable synthetic roadmap for medicinal chemists to access a range of fluorinated therapeutic candidates with distinct physicochemical properties relative to the original O-based analogue.
CYP2D6 allelic variants *34, *17-2, *17-3, and *53 and a Thr309Ala mutant display altered kinetics and NADPH coupling in metabolism of bufuralol and dextromethorphan and altered susceptibility to inactivation by SCH 66712
Glass, Sarah M.,Martell, Cydney M.,Oswalt, Alexandria K.,Osorio-Vasquez, Victoria,Cho, Christi,Hicks, Michael J.,Mills, Jacqueline M.,Fujiwara, Rina,Glista, Michael J.,Kamath, Sharat S.
supporting information, p. 1106 - 1117 (2018/08/12)
Metabolic phenotype can be affected by multiple factors, including allelic variation and interactions with inhibitors. Human CYP2D6 is responsible for approximately 20% of cytochrome P450–mediated drug metabolism but consists of more than 100 known varian
