Retention Mechanism of Imidazoles in Connective Tissue. III. Aldehyde Adduct Formation of a 4(5H)(or 5(4H))-Imidazolone Product in Vitro
スポンサーリンク
概要
- 論文の詳細を見る
2-Methylimidazole (2MI), as well as imidazole, has been though to undergo cupro-ascorbate (Cu-VC)-catalyzed oxidative transformation in vitro to become a reactive species capable of combining with aldehydes intrinsic to connective-tissue proteins. We attempted to seize the essence of the above reaction through obtaining the structural information of an aldehyde-bonding species. As major products from 2MI in the in vitro Cu-VC system, 2-hydroxymethylimidazole (2(OH)MI) and 2-methyl-4-(5H)(or 5(4H))-imidazolone (2MIone) were identified by mass-spectral and chromatographic comparison with the corresponding authentic standards synthesized. The in situ addition of acetaldehyde or propionaldehyde as a simple protein-aldehyde model to the system resulted in the deducible formation of an aldol condensate, 2-methyl-4(or 5)-ethylidene-4(5H)(or 5(4H))-imidazolone (2MEIone) or its possible analogue with a propylidene moiety, respectively. The authentic compound of 2MIone directly reacted with acetaldehyde and easily afforded the products assignable to the isomers of 2MEIone through the ethylidfene moiety at physiological pH and temperature, whereas neither 2MI or 2(OH)MI reacted at all. These results suggest that a 4(5H)(or 5(4H))-imidazolone product, although simply a monooxygenated form, is sufficiently reactive to give aldol condensation-typed covalent adducts with aldehydes, even under physiological conditions, probably having an activated methylene moiety in the ring strucuture. Based on the present results, we discussed the mechanism of the retention of imidazole-containing drugs in connective tissue.
- 公益社団法人日本薬学会の論文
- 1998-09-15
著者
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AWAZU Shoji
Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Science
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AKIMOTO Masayuki
Department of Ophtahalmology, Sinshu University Medical School
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Yamaguchi Jun-ichi
Department of Cardiology, Saitama Cardiovascular and Respiratory Center
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AKIMOTO Masayuki
Faculty of Pharmaceutical Sciences, Josai International University
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SUWA Toshio
Department of Drug Development Science & Clinical Evaluation, Kyoritsu University of Pharmacy
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KOHNO Yoshiro
Department of Drug Metabolism, Medicinal Research Laboratory, Taisho Pharmaceutical Co., Ltd.
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Kohno Yoshiro
大正製薬(株)開発研究所薬物動態研究室
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Kohno Yoshiro
Department Of Drug Metabolism Medicinal Research Laboratory Taisho Pharmaceutical Co. Ltd.
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Yamaguchi Jun-ichi
Department Of Drug Metabolism Taisho Pharmaceutical Research Center
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AWAZU Shoji
東京薬科大学薬学部 薬物動態制御学教室
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Awazu S
Tokyo Coll. Pharmacy Tokyo Jpn
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Awazu Shoji
Department Of Biopharmaceutics Tokyo College Of Pharmacy:department Of Pharmaceutics Research Center
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Suwa T
大正製薬(株)開発研究所薬物動態研究室
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Suwa Toshio
Dept.of Biochemistry Tokyo College Of Pharmacy:(present Address) Research Center Taisho Pharmaceutic
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Ohya Kumiko
Department Of Clinical Pharmacology And Toxicology Showa Pharmaceutical University
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Fukumoto Kyoko
Department Of Pharmacokinetics Kyoto Pharmaceutical University
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Yamaguchi Jun-ichi
Department Of Applied Chemistry Faculty Of Engineering Kanagawa Institute Of Technology
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Awazu Shoji
Deparment Of Biopharmaceutics Tokyo College Of Pharmacy
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OHTA Katsuji
Department of Drug Metabolism, Taisho Pharmaceutical Research Center
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FUKASAWA Yoshiki
Department of Drug Metabolism, Taisho Pharmaceutical Research Center
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FUKUSHIMA Kiyomi
Department of Drug Metabolism, Taisho Pharmaceutical Research Center
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Fukushima K
大正製薬(株)開発研究所薬物動態研究室
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Fukasawa Y
Showa Pharmaceutical Univ. Tokyo Jpn
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Akimoto Masayuki
Fac. Of Pharmaceutical Sciences Josai International Univ.
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Akimoto Masayuki
Department Of Ophtahalmology Sinshu University Medical School
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Awazu S
Department Of Biopharmaceutics School Of Pharmacy Tokyo University Of Pharmacy And Life Science
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