Aromatic substitution reaction of 2-chloropyridines catalyzed by microsomal glutathione S-transferase 1

Kazuko Inoue; Tomoyuki Ohe; Kenichi Mori; Takeshi Sagara; Yasuyuki Ishii; Masato Chiba

doi:10.1124/dmd.109.027698

Aromatic substitution reaction of 2-chloropyridines catalyzed by microsomal glutathione S-transferase 1

Kazuko Inoue, Tomoyuki Ohe, Kenichi Mori, Takeshi Sagara, Yasuyuki Ishii, Masato Chiba

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

Abstract

We investigated the substitution reaction of a series of 2-chloropyridine derivatives catalyzed by rat liver microsomal glutathione S-transferase 1. Various 2-chloropyridine derivatives were metabolized to the corresponding substituted glutathione conjugates via displacement of chlorine atom with glutathione. The reaction was affected by the electron-withdrawing strength and position of the substituents. Molecular orbital calculations on the change in Gibbs free energy between the initial and transition states verified the presence of a Meisenheimer complex and its influence on the reaction rate.

Original language	English
Pages (from-to)	1797-1800
Number of pages	4
Journal	Drug Metabolism and Disposition
Volume	37
Issue number	9
DOIs	https://doi.org/10.1124/dmd.109.027698
Publication status	Published - 2009 Sep 21
Externally published	Yes

ASJC Scopus subject areas

Pharmacology
Pharmaceutical Science

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AU - Inoue, Kazuko

AU - Ohe, Tomoyuki

AU - Mori, Kenichi

AU - Sagara, Takeshi

AU - Ishii, Yasuyuki

AU - Chiba, Masato

PY - 2009/9/21

Y1 - 2009/9/21

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AB - We investigated the substitution reaction of a series of 2-chloropyridine derivatives catalyzed by rat liver microsomal glutathione S-transferase 1. Various 2-chloropyridine derivatives were metabolized to the corresponding substituted glutathione conjugates via displacement of chlorine atom with glutathione. The reaction was affected by the electron-withdrawing strength and position of the substituents. Molecular orbital calculations on the change in Gibbs free energy between the initial and transition states verified the presence of a Meisenheimer complex and its influence on the reaction rate.

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Aromatic substitution reaction of 2-chloropyridines catalyzed by microsomal glutathione S-transferase 1

Abstract

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