title: Synthesis and structural assignment of two major metabolites of the LTA4H inhibitor DG-051.
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.
authors.affiliation: DeCODE Chemistry, Inc., 2501 Davey Road, Woodridge, IL 60517, USA. lenache@decode.com
authors.forename: Livia A
authors.initials: LA
authors.lastname: Enache
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: David W
authors.initials: DW
authors.lastname: Sullins
authors.forename: Isaac
authors.initials: I
authors.lastname: Kennedy
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Onua
authors.forename: David E
authors.initials: DE
authors.lastname: Zembower
authors.forename: Frank W
authors.initials: FW
authors.lastname: Muellner
authors.forename: Jasbir
authors.initials: J
authors.lastname: Singh
authors.forename: Alex S
authors.initials: AS
authors.lastname: Kiselyov
mesh_terms: D000778:Anesthetics, Dissociative; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004285:Dogs; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D055432:Metabolomics; D008862:Microsomes, Liver / Q000378:metabolism*; D015394:Molecular Structure; D051381:Rats; D054852:Small Molecule Libraries; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000778:Anesthetics, Dissociative; D004791:Enzyme Inhibitors; D054852:Small Molecule Libraries; D051544:Cytochrome P-450 CYP3A; D004851:Epoxide Hydrolases; C043134:leukotriene A4 hydrolase