A New Structural Motif for μ-Opioid Antagonists
On the basis of the structural features of the Dmt-Tic pharmacophore, a new motif leading to a fairly potent μ-opioid antagonist is described. This motif contains the 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-one skeleton as a substitute for the Tic residue, which provides the conformational constr...
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| Veröffentlicht in: | Journal of medicinal chemistry 2005-05, Vol.48 (10), p.3644-3648 |
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| container_issue | 10 |
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| container_title | Journal of medicinal chemistry |
| container_volume | 48 |
| creator | Van den Eynde, Isabelle Laus, Georges Schiller, Peter W Kosson, Piotr Chung, Nga N Lipkowski, Andrzej W Tourwé, Dirk |
| description | On the basis of the structural features of the Dmt-Tic pharmacophore, a new motif leading to a fairly potent μ-opioid antagonist is described. This motif contains the 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-one skeleton as a substitute for the Tic residue, which provides the conformational constraint compatible with the μ-opioid receptor. The stereoselective synthesis of four stereoisomers is performed starting from homochiral 2‘,6‘-dimethyltyrosine (Dmt) and o-aminomethylphenylalanine. |
| doi_str_mv | 10.1021/jm0491795 |
| format | Article |
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This motif contains the 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-one skeleton as a substitute for the Tic residue, which provides the conformational constraint compatible with the μ-opioid receptor. The stereoselective synthesis of four stereoisomers is performed starting from homochiral 2‘,6‘-dimethyltyrosine (Dmt) and o-aminomethylphenylalanine.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm0491795</identifier><identifier>PMID: 15887972</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Animals ; Benzazepines - chemical synthesis ; Benzazepines - chemistry ; Benzazepines - pharmacology ; Biological and medical sciences ; Electric Stimulation ; Guinea Pigs ; Ileum - drug effects ; Ileum - physiology ; In Vitro Techniques ; Medical sciences ; Muscle Contraction ; Muscle, Smooth - drug effects ; Muscle, Smooth - physiology ; Neuropharmacology ; Neurotransmitters. Neurotransmission. Receptors ; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems ; Pharmacology. Drug treatments ; Propane - analogs & derivatives ; Propane - chemical synthesis ; Propane - chemistry ; Propane - pharmacology ; Radioligand Assay ; Receptors, Opioid, mu - antagonists & inhibitors ; Receptors, Opioid, mu - physiology ; Stereoisomerism ; Structure-Activity Relationship</subject><ispartof>Journal of medicinal chemistry, 2005-05, Vol.48 (10), p.3644-3648</ispartof><rights>Copyright © 2005 American Chemical Society</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a412t-568c5e09c02d41bbca9c344b3e8424c8b090aef58c28a25b2a78cc05673f561a3</citedby><cites>FETCH-LOGICAL-a412t-568c5e09c02d41bbca9c344b3e8424c8b090aef58c28a25b2a78cc05673f561a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm0491795$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm0491795$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16780558$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15887972$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Van den Eynde, Isabelle</creatorcontrib><creatorcontrib>Laus, Georges</creatorcontrib><creatorcontrib>Schiller, Peter W</creatorcontrib><creatorcontrib>Kosson, Piotr</creatorcontrib><creatorcontrib>Chung, Nga N</creatorcontrib><creatorcontrib>Lipkowski, Andrzej W</creatorcontrib><creatorcontrib>Tourwé, Dirk</creatorcontrib><title>A New Structural Motif for μ-Opioid Antagonists</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>On the basis of the structural features of the Dmt-Tic pharmacophore, a new motif leading to a fairly potent μ-opioid antagonist is described. This motif contains the 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-one skeleton as a substitute for the Tic residue, which provides the conformational constraint compatible with the μ-opioid receptor. The stereoselective synthesis of four stereoisomers is performed starting from homochiral 2‘,6‘-dimethyltyrosine (Dmt) and o-aminomethylphenylalanine.</description><subject>Animals</subject><subject>Benzazepines - chemical synthesis</subject><subject>Benzazepines - chemistry</subject><subject>Benzazepines - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Electric Stimulation</subject><subject>Guinea Pigs</subject><subject>Ileum - drug effects</subject><subject>Ileum - physiology</subject><subject>In Vitro Techniques</subject><subject>Medical sciences</subject><subject>Muscle Contraction</subject><subject>Muscle, Smooth - drug effects</subject><subject>Muscle, Smooth - physiology</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems</subject><subject>Pharmacology. Drug treatments</subject><subject>Propane - analogs & derivatives</subject><subject>Propane - chemical synthesis</subject><subject>Propane - chemistry</subject><subject>Propane - pharmacology</subject><subject>Radioligand Assay</subject><subject>Receptors, Opioid, mu - antagonists & inhibitors</subject><subject>Receptors, Opioid, mu - physiology</subject><subject>Stereoisomerism</subject><subject>Structure-Activity Relationship</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0MtKw0AUBuBBFFurC19AslFwET1zSybLWrxhtdVW6W6YTCeSmiZ1JkF9N5_BZ3KkxW4EYeAs5uPnnB-hfQwnGAg-nc2BJThO-AZqY04gZALYJmoDEBKSiNAW2nFuBgAUE7qNWpgLEScxaSPoBnfmLRjVttF1Y1UR3FZ1ngVZZYOvz3CwyKt8GnTLWj1XZe5qt4u2MlU4s7eaHfR4cT7uXYX9weV1r9sPFcOkDnkkNDeQaCBThtNUq0RTxlJqBCNMixQSUCbjQhOhCE-JioXWwKOYZjzCinbQ0TJ3YavXxrhaznOnTVGo0lSNk1EsCOU8_hfihAn_mIfHS6ht5Zw1mVzYfK7sh8Qgf3qUvz16e7AKbdK5ma7lqjgPDldAOa2KzKpS527t_HrAufAuXDrfnXn__Vf2xV9AYy7Hw5F8uDmb0Mn9kxyuc5V2clY1tvQl_7HgN9uKk7U</recordid><startdate>20050519</startdate><enddate>20050519</enddate><creator>Van den Eynde, Isabelle</creator><creator>Laus, Georges</creator><creator>Schiller, Peter W</creator><creator>Kosson, Piotr</creator><creator>Chung, Nga N</creator><creator>Lipkowski, Andrzej W</creator><creator>Tourwé, Dirk</creator><general>American Chemical Society</general><scope>BSCLL</scope><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>7TK</scope><scope>7X8</scope></search><sort><creationdate>20050519</creationdate><title>A New Structural Motif for μ-Opioid Antagonists</title><author>Van den Eynde, Isabelle ; Laus, Georges ; Schiller, Peter W ; Kosson, Piotr ; Chung, Nga N ; Lipkowski, Andrzej W ; Tourwé, Dirk</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a412t-568c5e09c02d41bbca9c344b3e8424c8b090aef58c28a25b2a78cc05673f561a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Benzazepines - chemical synthesis</topic><topic>Benzazepines - chemistry</topic><topic>Benzazepines - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Electric Stimulation</topic><topic>Guinea Pigs</topic><topic>Ileum - drug effects</topic><topic>Ileum - physiology</topic><topic>In Vitro Techniques</topic><topic>Medical sciences</topic><topic>Muscle Contraction</topic><topic>Muscle, Smooth - drug effects</topic><topic>Muscle, Smooth - physiology</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems</topic><topic>Pharmacology. Drug treatments</topic><topic>Propane - analogs & derivatives</topic><topic>Propane - chemical synthesis</topic><topic>Propane - chemistry</topic><topic>Propane - pharmacology</topic><topic>Radioligand Assay</topic><topic>Receptors, Opioid, mu - antagonists & inhibitors</topic><topic>Receptors, Opioid, mu - physiology</topic><topic>Stereoisomerism</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Van den Eynde, Isabelle</creatorcontrib><creatorcontrib>Laus, Georges</creatorcontrib><creatorcontrib>Schiller, Peter W</creatorcontrib><creatorcontrib>Kosson, Piotr</creatorcontrib><creatorcontrib>Chung, Nga N</creatorcontrib><creatorcontrib>Lipkowski, Andrzej W</creatorcontrib><creatorcontrib>Tourwé, Dirk</creatorcontrib><collection>Istex</collection><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>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Van den Eynde, Isabelle</au><au>Laus, Georges</au><au>Schiller, Peter W</au><au>Kosson, Piotr</au><au>Chung, Nga N</au><au>Lipkowski, Andrzej W</au><au>Tourwé, Dirk</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A New Structural Motif for μ-Opioid Antagonists</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2005-05-19</date><risdate>2005</risdate><volume>48</volume><issue>10</issue><spage>3644</spage><epage>3648</epage><pages>3644-3648</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>On the basis of the structural features of the Dmt-Tic pharmacophore, a new motif leading to a fairly potent μ-opioid antagonist is described. This motif contains the 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-one skeleton as a substitute for the Tic residue, which provides the conformational constraint compatible with the μ-opioid receptor. The stereoselective synthesis of four stereoisomers is performed starting from homochiral 2‘,6‘-dimethyltyrosine (Dmt) and o-aminomethylphenylalanine.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>15887972</pmid><doi>10.1021/jm0491795</doi><tpages>5</tpages></addata></record> |
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| subjects | Animals Benzazepines - chemical synthesis Benzazepines - chemistry Benzazepines - pharmacology Biological and medical sciences Electric Stimulation Guinea Pigs Ileum - drug effects Ileum - physiology In Vitro Techniques Medical sciences Muscle Contraction Muscle, Smooth - drug effects Muscle, Smooth - physiology Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems Pharmacology. Drug treatments Propane - analogs & derivatives Propane - chemical synthesis Propane - chemistry Propane - pharmacology Radioligand Assay Receptors, Opioid, mu - antagonists & inhibitors Receptors, Opioid, mu - physiology Stereoisomerism Structure-Activity Relationship |
| title | A New Structural Motif for μ-Opioid Antagonists |
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