Aromatic Substitution Reaction of 2-Chloropyridines Catalyzed by Microsomal Glutathione S-Transferase 1

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 gl...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Drug metabolism and disposition 2009-09, Vol.37 (9), p.1797-1800
Hauptverfasser: Inoue, Kazuko, Ohe, Tomoyuki, Mori, Kenichi, Sagara, Takeshi, Ishii, Yasuyuki, Chiba, Masato
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 1800
container_issue 9
container_start_page 1797
container_title Drug metabolism and disposition
container_volume 37
creator Inoue, Kazuko
Ohe, Tomoyuki
Mori, Kenichi
Sagara, Takeshi
Ishii, Yasuyuki
Chiba, Masato
description 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.
doi_str_mv 10.1124/dmd.109.027698
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_733968596</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0090955624021524</els_id><sourcerecordid>733968596</sourcerecordid><originalsourceid>FETCH-LOGICAL-c404t-886fbe8b32ff305da266cbdfbf499abe410c5ebfcf60c55e3b72ced87317cd853</originalsourceid><addsrcrecordid>eNp1kM1v1DAUxC0EosvClSPKBThlsZM4sY_VCgpSKyRaJG6WP543Rkm82A4o_evxkhU99fTm8JvRvEHoNcE7QqrmgxnNjmC-w1XXcvYEbQitSIkx__EUbfLBJae0vUAvYvyJMWmamj9HF4TThrCKbtDhMvhRJqeL21nF5NKcnJ-KbyD1P-FtUZX7fvDBH5fgjJsgFnuZ5LDcgynUUtw4HXzMIUNxNcxJpj77oLgt74KcooUgIxTkJXpm5RDh1flu0fdPH-_2n8vrr1df9pfXpW5wk0rGWquAqbqytsbUyKpttTJW2YZzqaAhWFNQVts2Cwq16ioNhnU16bRhtN6i92vuMfhfM8QkRhc1DIOcwM9RdHXNW0Z5m8ndSp7qxwBWHIMbZVgEweK0rcjbZs3Fum02vDlHz2oE84Cfx8zA2zMgo5aDzf9rF_9zFWGUdbnqFr1bud4d-j8ugDj2MoxS-8EfFlF3ggvS8RPIVhDyYr8dBBG1gyk_nE06CePdY2X_AjdUpG8</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>733968596</pqid></control><display><type>article</type><title>Aromatic Substitution Reaction of 2-Chloropyridines Catalyzed by Microsomal Glutathione S-Transferase 1</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Inoue, Kazuko ; Ohe, Tomoyuki ; Mori, Kenichi ; Sagara, Takeshi ; Ishii, Yasuyuki ; Chiba, Masato</creator><creatorcontrib>Inoue, Kazuko ; Ohe, Tomoyuki ; Mori, Kenichi ; Sagara, Takeshi ; Ishii, Yasuyuki ; Chiba, Masato</creatorcontrib><description>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.</description><identifier>ISSN: 0090-9556</identifier><identifier>EISSN: 1521-009X</identifier><identifier>DOI: 10.1124/dmd.109.027698</identifier><identifier>PMID: 19541825</identifier><identifier>CODEN: DMDSAI</identifier><language>eng</language><publisher>Bethesda, MD: Elsevier Inc</publisher><subject>Animals ; Biological and medical sciences ; Chlorobenzenes - metabolism ; Chromatography, High Pressure Liquid ; Glutathione - metabolism ; Glutathione Transferase - metabolism ; Hydrocarbons, Aromatic - metabolism ; Mass Spectrometry ; Medical sciences ; Microsomes, Liver - enzymology ; Molecular Conformation ; Nitro Compounds - metabolism ; Pharmacology. Drug treatments ; Pyridines - chemistry ; Pyridines - metabolism ; Rats ; Spectrophotometry, Ultraviolet</subject><ispartof>Drug metabolism and disposition, 2009-09, Vol.37 (9), p.1797-1800</ispartof><rights>2009 American Society for Pharmacology and Experimental Therapeutics</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c404t-886fbe8b32ff305da266cbdfbf499abe410c5ebfcf60c55e3b72ced87317cd853</citedby><cites>FETCH-LOGICAL-c404t-886fbe8b32ff305da266cbdfbf499abe410c5ebfcf60c55e3b72ced87317cd853</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=21858787$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19541825$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Inoue, Kazuko</creatorcontrib><creatorcontrib>Ohe, Tomoyuki</creatorcontrib><creatorcontrib>Mori, Kenichi</creatorcontrib><creatorcontrib>Sagara, Takeshi</creatorcontrib><creatorcontrib>Ishii, Yasuyuki</creatorcontrib><creatorcontrib>Chiba, Masato</creatorcontrib><title>Aromatic Substitution Reaction of 2-Chloropyridines Catalyzed by Microsomal Glutathione S-Transferase 1</title><title>Drug metabolism and disposition</title><addtitle>Drug Metab Dispos</addtitle><description>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.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Chlorobenzenes - metabolism</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Glutathione - metabolism</subject><subject>Glutathione Transferase - metabolism</subject><subject>Hydrocarbons, Aromatic - metabolism</subject><subject>Mass Spectrometry</subject><subject>Medical sciences</subject><subject>Microsomes, Liver - enzymology</subject><subject>Molecular Conformation</subject><subject>Nitro Compounds - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Pyridines - chemistry</subject><subject>Pyridines - metabolism</subject><subject>Rats</subject><subject>Spectrophotometry, Ultraviolet</subject><issn>0090-9556</issn><issn>1521-009X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kM1v1DAUxC0EosvClSPKBThlsZM4sY_VCgpSKyRaJG6WP543Rkm82A4o_evxkhU99fTm8JvRvEHoNcE7QqrmgxnNjmC-w1XXcvYEbQitSIkx__EUbfLBJae0vUAvYvyJMWmamj9HF4TThrCKbtDhMvhRJqeL21nF5NKcnJ-KbyD1P-FtUZX7fvDBH5fgjJsgFnuZ5LDcgynUUtw4HXzMIUNxNcxJpj77oLgt74KcooUgIxTkJXpm5RDh1flu0fdPH-_2n8vrr1df9pfXpW5wk0rGWquAqbqytsbUyKpttTJW2YZzqaAhWFNQVts2Cwq16ioNhnU16bRhtN6i92vuMfhfM8QkRhc1DIOcwM9RdHXNW0Z5m8ndSp7qxwBWHIMbZVgEweK0rcjbZs3Fum02vDlHz2oE84Cfx8zA2zMgo5aDzf9rF_9zFWGUdbnqFr1bud4d-j8ugDj2MoxS-8EfFlF3ggvS8RPIVhDyYr8dBBG1gyk_nE06CePdY2X_AjdUpG8</recordid><startdate>20090901</startdate><enddate>20090901</enddate><creator>Inoue, Kazuko</creator><creator>Ohe, Tomoyuki</creator><creator>Mori, Kenichi</creator><creator>Sagara, Takeshi</creator><creator>Ishii, Yasuyuki</creator><creator>Chiba, Masato</creator><general>Elsevier Inc</general><general>American Society for Pharmacology and Experimental Therapeutics</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20090901</creationdate><title>Aromatic Substitution Reaction of 2-Chloropyridines Catalyzed by Microsomal Glutathione S-Transferase 1</title><author>Inoue, Kazuko ; Ohe, Tomoyuki ; Mori, Kenichi ; Sagara, Takeshi ; Ishii, Yasuyuki ; Chiba, Masato</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c404t-886fbe8b32ff305da266cbdfbf499abe410c5ebfcf60c55e3b72ced87317cd853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Chlorobenzenes - metabolism</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Glutathione - metabolism</topic><topic>Glutathione Transferase - metabolism</topic><topic>Hydrocarbons, Aromatic - metabolism</topic><topic>Mass Spectrometry</topic><topic>Medical sciences</topic><topic>Microsomes, Liver - enzymology</topic><topic>Molecular Conformation</topic><topic>Nitro Compounds - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Pyridines - chemistry</topic><topic>Pyridines - metabolism</topic><topic>Rats</topic><topic>Spectrophotometry, Ultraviolet</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Inoue, Kazuko</creatorcontrib><creatorcontrib>Ohe, Tomoyuki</creatorcontrib><creatorcontrib>Mori, Kenichi</creatorcontrib><creatorcontrib>Sagara, Takeshi</creatorcontrib><creatorcontrib>Ishii, Yasuyuki</creatorcontrib><creatorcontrib>Chiba, Masato</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Drug metabolism and disposition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Inoue, Kazuko</au><au>Ohe, Tomoyuki</au><au>Mori, Kenichi</au><au>Sagara, Takeshi</au><au>Ishii, Yasuyuki</au><au>Chiba, Masato</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aromatic Substitution Reaction of 2-Chloropyridines Catalyzed by Microsomal Glutathione S-Transferase 1</atitle><jtitle>Drug metabolism and disposition</jtitle><addtitle>Drug Metab Dispos</addtitle><date>2009-09-01</date><risdate>2009</risdate><volume>37</volume><issue>9</issue><spage>1797</spage><epage>1800</epage><pages>1797-1800</pages><issn>0090-9556</issn><eissn>1521-009X</eissn><coden>DMDSAI</coden><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.</abstract><cop>Bethesda, MD</cop><pub>Elsevier Inc</pub><pmid>19541825</pmid><doi>10.1124/dmd.109.027698</doi><tpages>4</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0090-9556
ispartof Drug metabolism and disposition, 2009-09, Vol.37 (9), p.1797-1800
issn 0090-9556
1521-009X
language eng
recordid cdi_proquest_miscellaneous_733968596
source MEDLINE; Alma/SFX Local Collection
subjects Animals
Biological and medical sciences
Chlorobenzenes - metabolism
Chromatography, High Pressure Liquid
Glutathione - metabolism
Glutathione Transferase - metabolism
Hydrocarbons, Aromatic - metabolism
Mass Spectrometry
Medical sciences
Microsomes, Liver - enzymology
Molecular Conformation
Nitro Compounds - metabolism
Pharmacology. Drug treatments
Pyridines - chemistry
Pyridines - metabolism
Rats
Spectrophotometry, Ultraviolet
title Aromatic Substitution Reaction of 2-Chloropyridines Catalyzed by Microsomal Glutathione S-Transferase 1
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-24T18%3A15%3A07IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Aromatic%20Substitution%20Reaction%20of%202-Chloropyridines%20Catalyzed%20by%20Microsomal%20Glutathione%20S-Transferase%201&rft.jtitle=Drug%20metabolism%20and%20disposition&rft.au=Inoue,%20Kazuko&rft.date=2009-09-01&rft.volume=37&rft.issue=9&rft.spage=1797&rft.epage=1800&rft.pages=1797-1800&rft.issn=0090-9556&rft.eissn=1521-009X&rft.coden=DMDSAI&rft_id=info:doi/10.1124/dmd.109.027698&rft_dat=%3Cproquest_cross%3E733968596%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=733968596&rft_id=info:pmid/19541825&rft_els_id=S0090955624021524&rfr_iscdi=true