1. Synthesis and structural assignment of two major metabolites of the LTA4H inhibitor DG-051.
- Author
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Enache LA, Zhang J, Sullins DW, Kennedy I, Onua E, Zembower DE, Muellner FW, Singh J, and Kiselyov AS
- Subjects
- Anesthetics, Dissociative, Animals, Chromatography, High Pressure Liquid, Cytochrome P-450 CYP3A metabolism, Dogs, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors pharmacology, Humans, Mass Spectrometry methods, Metabolomics, Molecular Structure, Rats, Small Molecule Libraries, Spectrometry, Mass, Electrospray Ionization methods, Tandem Mass Spectrometry methods, Enzyme Inhibitors chemistry, Epoxide Hydrolases antagonists & inhibitors, Microsomes, Liver metabolism, Spectrophotometry, Ultraviolet methods
- Abstract
The same two major CYP mediated metabolites of DG-051 were produced in the presence of rat, dog, monkey and human liver microsomes. Their respective structures were hypothesized based on mass spectrometry data correlated with the parent structure and confirmed by comparison with authentic synthetic samples. The number of regioisomers synthesized as candidates for metabolite M1 was narrowed down using a metabolic study of a selectively deuterated DG-051 analogue.
- Published
- 2009
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