Synthesis and Identification of the Quaternary Ammonium-Linked Glucuronide of 1-Phenylimidazole in Human Liver Microsomes and Investigation of the Human UDP-Glucuronosyltransferases Involved
1-Phenylimidazole was investigated as a potential model substrate with respect to formation of a quaternary ammonium-linked glucuronide (N + -glucuronide) at an aromatic type tertiary amine. A reference sample of the potential N + -glucuronide metabolite of 1-phenylimidazole was obtained by organic...
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| Published in | Drug metabolism and disposition Vol. 28; no. 9; pp. 1009 - 1013 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
Bethesda, MD
American Society for Pharmacology and Experimental Therapeutics
01.09.2000
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| Subjects | |
| Online Access | Get full text |
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| Abstract | 1-Phenylimidazole was investigated as a potential model substrate with respect to formation of a quaternary ammonium-linked
glucuronide (N + -glucuronide) at an aromatic type tertiary amine. A reference sample of the potential N + -glucuronide metabolite of 1-phenylimidazole was obtained by organic synthesis. The structural identity of the metabolite
formed by incubation of 1-phenylimidazole with human liver microsomes was proven to be the N + -glucuronide by exhibiting the same HPLC retention time and electrospray ionization mass spectrum as the reference sample.
The screening of 1-phenylimidazole against a panel of nine expressed human UDP-glucuronosyltransferases indicated the involvement
of UGT1A3 and UGT1A4 in the formation of the N + -glucuronide metabolite. |
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| AbstractList | 1-Phenylimidazole was investigated as a potential model substrate with respect to formation of a quaternary ammonium-linked
glucuronide (N + -glucuronide) at an aromatic type tertiary amine. A reference sample of the potential N + -glucuronide metabolite of 1-phenylimidazole was obtained by organic synthesis. The structural identity of the metabolite
formed by incubation of 1-phenylimidazole with human liver microsomes was proven to be the N + -glucuronide by exhibiting the same HPLC retention time and electrospray ionization mass spectrum as the reference sample.
The screening of 1-phenylimidazole against a panel of nine expressed human UDP-glucuronosyltransferases indicated the involvement
of UGT1A3 and UGT1A4 in the formation of the N + -glucuronide metabolite. 1-Phenylimidazole was investigated as a potential model substrate with respect to formation of a quaternary ammonium-linked glucuronide (N(+)-glucuronide) at an aromatic type tertiary amine. A reference sample of the potential N(+)-glucuronide metabolite of 1-phenylimidazole was obtained by organic synthesis. The structural identity of the metabolite formed by incubation of 1-phenylimidazole with human liver microsomes was proven to be the N(+)-glucuronide by exhibiting the same HPLC retention time and electrospray ionization mass spectrum as the reference sample. The screening of 1-phenylimidazole against a panel of nine expressed human UDP-glucuronosyltransferases indicated the involvement of UGT1A3 and UGT1A4 in the formation of the N(+)-glucuronide metabolite. |
| Author | Gordon McKay Sarvesh C. Vashishtha Denis J. McCann Edward M. Hawes |
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| Keywords | Human Imidazole derivatives UDP-glucuronosyltransferase Enzyme Transferases Liver Glycosyltransferases Glucuronic acid conjugation Metabolism In vitro Glucuroconjugate Quaternary ammonium compound Tertiary amine Hexosyltransferases Aromatic compound |
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| Snippet | 1-Phenylimidazole was investigated as a potential model substrate with respect to formation of a quaternary ammonium-linked
glucuronide (N + -glucuronide) at... 1-Phenylimidazole was investigated as a potential model substrate with respect to formation of a quaternary ammonium-linked glucuronide (N(+)-glucuronide) at... |
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| SubjectTerms | Biological and medical sciences Chromatography, High Pressure Liquid General pharmacology Glucuronides - chemistry Glucuronides - metabolism Glucuronosyltransferase - metabolism Humans Imidazoles - chemistry Imidazoles - metabolism Imidazoles - pharmacokinetics Kinetics Magnetic Resonance Spectroscopy Medical sciences Microsomes, Liver - metabolism Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions Pharmacology. Drug treatments Quaternary Ammonium Compounds - chemistry |
| Title | Synthesis and Identification of the Quaternary Ammonium-Linked Glucuronide of 1-Phenylimidazole in Human Liver Microsomes and Investigation of the Human UDP-Glucuronosyltransferases Involved |
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