Effect of deuteration on the metabolism and clearance of some pharmacologically active compounds-synthesis and in vitro metabolism of deuterated derivatives of dronedadrone
The synthesis and in vitro metabolism studies of a family of specifically deuterated derivatives of dronedarone are described. Metabolic stability and clearance of the parent compound are not sensitive to deuterium substitution, irrespective of the position of the heavy label. A series of eight site...
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| Veröffentlicht in: | Journal of labelled compounds & radiopharmaceuticals 2013-07, Vol.56 (9-10), p.504-512 |
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| container_issue | 9-10 |
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| container_title | Journal of labelled compounds & radiopharmaceuticals |
| container_volume | 56 |
| creator | Schofield, Joseph Brasseur, Denis de Bruin, Béatrice Vassal, Thierry Klieber, Sylvie Arabeyre, Catherine Bourrié, Martine Sadoun, Freddy Fabre, Gérard |
| description | The synthesis and in vitro metabolism studies of a family of specifically deuterated derivatives of dronedarone are described. Metabolic stability and clearance of the parent compound are not sensitive to deuterium substitution, irrespective of the position of the heavy label.
A series of eight site specifically deuterated analogues of dronedaraone (R1−R5 = H or D) were synthesised and the in vitro metabolic behaviour of each compound investigated using human hepatocyte preparations. Compared to the unlabelled parent compound, no significant differences in metabolic stability and clearance could be detected across the series of derivatives. |
| doi_str_mv | 10.1002/jlcr.3090 |
| format | Article |
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A series of eight site specifically deuterated analogues of dronedaraone (R1−R5 = H or D) were synthesised and the in vitro metabolic behaviour of each compound investigated using human hepatocyte preparations. Compared to the unlabelled parent compound, no significant differences in metabolic stability and clearance could be detected across the series of derivatives.</description><identifier>ISSN: 0362-4803</identifier><identifier>EISSN: 1099-1344</identifier><identifier>DOI: 10.1002/jlcr.3090</identifier><identifier>PMID: 24285529</identifier><identifier>CODEN: JLCRD4</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Amiodarone - analogs & derivatives ; Amiodarone - chemical synthesis ; Amiodarone - chemistry ; Amiodarone - metabolism ; antiarrhythmic ; Chemistry Techniques, Synthetic ; deuterium ; Deuterium - chemistry ; deuterium labelling ; Hepatocytes - metabolism ; Humans ; in vitro metabolism ; isotope effect ; Metabolism ; stable labelled synthesis ; Structure-Activity Relationship</subject><ispartof>Journal of labelled compounds & radiopharmaceuticals, 2013-07, Vol.56 (9-10), p.504-512</ispartof><rights>Copyright © 2013 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4570-d7ce70d71077abbe186ef475b0f9bc5bf8ce8034764deebd68f0d2900292c1763</citedby><cites>FETCH-LOGICAL-c4570-d7ce70d71077abbe186ef475b0f9bc5bf8ce8034764deebd68f0d2900292c1763</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjlcr.3090$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjlcr.3090$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24285529$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schofield, Joseph</creatorcontrib><creatorcontrib>Brasseur, Denis</creatorcontrib><creatorcontrib>de Bruin, Béatrice</creatorcontrib><creatorcontrib>Vassal, Thierry</creatorcontrib><creatorcontrib>Klieber, Sylvie</creatorcontrib><creatorcontrib>Arabeyre, Catherine</creatorcontrib><creatorcontrib>Bourrié, Martine</creatorcontrib><creatorcontrib>Sadoun, Freddy</creatorcontrib><creatorcontrib>Fabre, Gérard</creatorcontrib><title>Effect of deuteration on the metabolism and clearance of some pharmacologically active compounds-synthesis and in vitro metabolism of deuterated derivatives of dronedadrone</title><title>Journal of labelled compounds & radiopharmaceuticals</title><addtitle>J. Label Compd. Radiopharm</addtitle><description>The synthesis and in vitro metabolism studies of a family of specifically deuterated derivatives of dronedarone are described. Metabolic stability and clearance of the parent compound are not sensitive to deuterium substitution, irrespective of the position of the heavy label.
A series of eight site specifically deuterated analogues of dronedaraone (R1−R5 = H or D) were synthesised and the in vitro metabolic behaviour of each compound investigated using human hepatocyte preparations. Compared to the unlabelled parent compound, no significant differences in metabolic stability and clearance could be detected across the series of derivatives.</description><subject>Amiodarone - analogs & derivatives</subject><subject>Amiodarone - chemical synthesis</subject><subject>Amiodarone - chemistry</subject><subject>Amiodarone - metabolism</subject><subject>antiarrhythmic</subject><subject>Chemistry Techniques, Synthetic</subject><subject>deuterium</subject><subject>Deuterium - chemistry</subject><subject>deuterium labelling</subject><subject>Hepatocytes - metabolism</subject><subject>Humans</subject><subject>in vitro metabolism</subject><subject>isotope effect</subject><subject>Metabolism</subject><subject>stable labelled synthesis</subject><subject>Structure-Activity Relationship</subject><issn>0362-4803</issn><issn>1099-1344</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kd9qFDEUh4Modq1e-AIS8KZeTJuZyUwml7K2q7K04F_wJmSSMzZrZrImmW33nXxIM7vbUgQhcALnO1_C-SH0MienOSHF2coqf1oSTh6hWU44z_KS0sdoRsq6yGhDyiP0LIQVIalH6VN0VNCiqaqCz9Cf864DFbHrsIYxgpfRuAGnE68B9xBl66wJPZaDxsqC9HJQMOHB9YDX19L3Ujnrfholrd1iqaLZAFauX7tx0CEL2yGpggk7hRnwxkTvHqofvA06Xb3ZyEkSdh3vBtByV56jJ520AV4c6jH6enH-Zf4-W14tPszfLjNFK0YyzRQwollOGJNtC3lTQ0dZ1ZKOt6pqu0ZBWgplNdUAra6bjuiCp03yQuWsLo_Ryd679u73CCGK3gQF1soB3BhETusiYXXDE_r6H3TlRj-k3yWqZJxzxppEvdlTyrsQPHRi7U0v_VbkREwRiilCMUWY2FcH49j2oO_Ju8wScLYHboyF7f9N4uNy_umgzPYTJkS4vZ-Q_peoWckq8f1yIarLd9-Wn8sfYlH-BWmrub8</recordid><startdate>201307</startdate><enddate>201307</enddate><creator>Schofield, Joseph</creator><creator>Brasseur, Denis</creator><creator>de Bruin, Béatrice</creator><creator>Vassal, Thierry</creator><creator>Klieber, Sylvie</creator><creator>Arabeyre, Catherine</creator><creator>Bourrié, Martine</creator><creator>Sadoun, Freddy</creator><creator>Fabre, Gérard</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>201307</creationdate><title>Effect of deuteration on the metabolism and clearance of some pharmacologically active compounds-synthesis and in vitro metabolism of deuterated derivatives of dronedadrone</title><author>Schofield, Joseph ; Brasseur, Denis ; de Bruin, Béatrice ; Vassal, Thierry ; Klieber, Sylvie ; Arabeyre, Catherine ; Bourrié, Martine ; Sadoun, Freddy ; Fabre, Gérard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4570-d7ce70d71077abbe186ef475b0f9bc5bf8ce8034764deebd68f0d2900292c1763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Amiodarone - analogs & derivatives</topic><topic>Amiodarone - chemical synthesis</topic><topic>Amiodarone - chemistry</topic><topic>Amiodarone - metabolism</topic><topic>antiarrhythmic</topic><topic>Chemistry Techniques, Synthetic</topic><topic>deuterium</topic><topic>Deuterium - chemistry</topic><topic>deuterium labelling</topic><topic>Hepatocytes - metabolism</topic><topic>Humans</topic><topic>in vitro metabolism</topic><topic>isotope effect</topic><topic>Metabolism</topic><topic>stable labelled synthesis</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schofield, Joseph</creatorcontrib><creatorcontrib>Brasseur, Denis</creatorcontrib><creatorcontrib>de Bruin, Béatrice</creatorcontrib><creatorcontrib>Vassal, Thierry</creatorcontrib><creatorcontrib>Klieber, Sylvie</creatorcontrib><creatorcontrib>Arabeyre, Catherine</creatorcontrib><creatorcontrib>Bourrié, Martine</creatorcontrib><creatorcontrib>Sadoun, Freddy</creatorcontrib><creatorcontrib>Fabre, Gérard</creatorcontrib><collection>Istex</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>Journal of labelled compounds & radiopharmaceuticals</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schofield, Joseph</au><au>Brasseur, Denis</au><au>de Bruin, Béatrice</au><au>Vassal, Thierry</au><au>Klieber, Sylvie</au><au>Arabeyre, Catherine</au><au>Bourrié, Martine</au><au>Sadoun, Freddy</au><au>Fabre, Gérard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of deuteration on the metabolism and clearance of some pharmacologically active compounds-synthesis and in vitro metabolism of deuterated derivatives of dronedadrone</atitle><jtitle>Journal of labelled compounds & radiopharmaceuticals</jtitle><addtitle>J. Label Compd. Radiopharm</addtitle><date>2013-07</date><risdate>2013</risdate><volume>56</volume><issue>9-10</issue><spage>504</spage><epage>512</epage><pages>504-512</pages><issn>0362-4803</issn><eissn>1099-1344</eissn><coden>JLCRD4</coden><abstract>The synthesis and in vitro metabolism studies of a family of specifically deuterated derivatives of dronedarone are described. Metabolic stability and clearance of the parent compound are not sensitive to deuterium substitution, irrespective of the position of the heavy label.
A series of eight site specifically deuterated analogues of dronedaraone (R1−R5 = H or D) were synthesised and the in vitro metabolic behaviour of each compound investigated using human hepatocyte preparations. Compared to the unlabelled parent compound, no significant differences in metabolic stability and clearance could be detected across the series of derivatives.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>24285529</pmid><doi>10.1002/jlcr.3090</doi><tpages>9</tpages></addata></record> |
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| ispartof | Journal of labelled compounds & radiopharmaceuticals, 2013-07, Vol.56 (9-10), p.504-512 |
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| subjects | Amiodarone - analogs & derivatives Amiodarone - chemical synthesis Amiodarone - chemistry Amiodarone - metabolism antiarrhythmic Chemistry Techniques, Synthetic deuterium Deuterium - chemistry deuterium labelling Hepatocytes - metabolism Humans in vitro metabolism isotope effect Metabolism stable labelled synthesis Structure-Activity Relationship |
| title | Effect of deuteration on the metabolism and clearance of some pharmacologically active compounds-synthesis and in vitro metabolism of deuterated derivatives of dronedadrone |
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