α2-Adrenoreceptors Profile Modulation and High Antinociceptive Activity of (S)-(−)-2-[1-(Biphenyl-2-yloxy)ethyl]-4,5-dihydro-1H-imidazole
A number of derivatives structurally related to cirazoline (1) were synthesized and studied with the purpose of modulating α2-adrenoreceptors selectivity versus both α1-adrenoreceptors and I2 imidazoline binding sites. The most potent α2-agonist was 2-[1-(biphenyl-2-yloxy)ethyl]-4,5-dihydro-1H-imida...
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| Veröffentlicht in: | Journal of medicinal chemistry 2002-01, Vol.45 (1), p.32-40 |
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| creator | Gentili, Francesco Bousquet, Pascal Brasili, Livio Caretto, Mariangela Carrieri, Antonio Dontenwill, Monique Giannella, Mario Marucci, Gabriella Perfumi, Marina Piergentili, Alessandro Quaglia, Wilma Rascente, Carla Pigini, Maria |
| description | A number of derivatives structurally related to cirazoline (1) were synthesized and studied with the purpose of modulating α2-adrenoreceptors selectivity versus both α1-adrenoreceptors and I2 imidazoline binding sites. The most potent α2-agonist was 2-[1-(biphenyl-2-yloxy)ethyl]-4,5-dihydro-1H-imidazole (7), whose key pharmacophoric features closely matched those found in the α2-agonist 2-(3-exo-(3-phenylprop-1-yl)-2-exo-norbornyl)amino-2-oxazoline (15). (S)-(−)-7 was the most potent of the two enantiomers, confirming the stereospecificity of the interaction with α2-adrenoreceptors. This eutomer was tested on two algesiometric paradigms and, because of the interaction with α2-adrenoreceptors, showed a potent and long-lasting antinociceptive activity, since it was abolished by the selective α2-antagonist RX821002. |
| doi_str_mv | 10.1021/jm0110082 |
| format | Article |
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The most potent α2-agonist was 2-[1-(biphenyl-2-yloxy)ethyl]-4,5-dihydro-1H-imidazole (7), whose key pharmacophoric features closely matched those found in the α2-agonist 2-(3-exo-(3-phenylprop-1-yl)-2-exo-norbornyl)amino-2-oxazoline (15). (S)-(−)-7 was the most potent of the two enantiomers, confirming the stereospecificity of the interaction with α2-adrenoreceptors. This eutomer was tested on two algesiometric paradigms and, because of the interaction with α2-adrenoreceptors, showed a potent and long-lasting antinociceptive activity, since it was abolished by the selective α2-antagonist RX821002.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm0110082</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Analgesics ; Biological and medical sciences ; Medical sciences ; Neuropharmacology ; Pharmacology. Drug treatments</subject><ispartof>Journal of medicinal chemistry, 2002-01, Vol.45 (1), p.32-40</ispartof><rights>Copyright © 2002 American Chemical Society</rights><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm0110082$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm0110082$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13410594$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Gentili, Francesco</creatorcontrib><creatorcontrib>Bousquet, Pascal</creatorcontrib><creatorcontrib>Brasili, Livio</creatorcontrib><creatorcontrib>Caretto, Mariangela</creatorcontrib><creatorcontrib>Carrieri, Antonio</creatorcontrib><creatorcontrib>Dontenwill, Monique</creatorcontrib><creatorcontrib>Giannella, Mario</creatorcontrib><creatorcontrib>Marucci, Gabriella</creatorcontrib><creatorcontrib>Perfumi, Marina</creatorcontrib><creatorcontrib>Piergentili, Alessandro</creatorcontrib><creatorcontrib>Quaglia, Wilma</creatorcontrib><creatorcontrib>Rascente, Carla</creatorcontrib><creatorcontrib>Pigini, Maria</creatorcontrib><title>α2-Adrenoreceptors Profile Modulation and High Antinociceptive Activity of (S)-(−)-2-[1-(Biphenyl-2-yloxy)ethyl]-4,5-dihydro-1H-imidazole</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>A number of derivatives structurally related to cirazoline (1) were synthesized and studied with the purpose of modulating α2-adrenoreceptors selectivity versus both α1-adrenoreceptors and I2 imidazoline binding sites. The most potent α2-agonist was 2-[1-(biphenyl-2-yloxy)ethyl]-4,5-dihydro-1H-imidazole (7), whose key pharmacophoric features closely matched those found in the α2-agonist 2-(3-exo-(3-phenylprop-1-yl)-2-exo-norbornyl)amino-2-oxazoline (15). (S)-(−)-7 was the most potent of the two enantiomers, confirming the stereospecificity of the interaction with α2-adrenoreceptors. This eutomer was tested on two algesiometric paradigms and, because of the interaction with α2-adrenoreceptors, showed a potent and long-lasting antinociceptive activity, since it was abolished by the selective α2-antagonist RX821002.</description><subject>Analgesics</subject><subject>Biological and medical sciences</subject><subject>Medical sciences</subject><subject>Neuropharmacology</subject><subject>Pharmacology. 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Drug treatments</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gentili, Francesco</creatorcontrib><creatorcontrib>Bousquet, Pascal</creatorcontrib><creatorcontrib>Brasili, Livio</creatorcontrib><creatorcontrib>Caretto, Mariangela</creatorcontrib><creatorcontrib>Carrieri, Antonio</creatorcontrib><creatorcontrib>Dontenwill, Monique</creatorcontrib><creatorcontrib>Giannella, Mario</creatorcontrib><creatorcontrib>Marucci, Gabriella</creatorcontrib><creatorcontrib>Perfumi, Marina</creatorcontrib><creatorcontrib>Piergentili, Alessandro</creatorcontrib><creatorcontrib>Quaglia, Wilma</creatorcontrib><creatorcontrib>Rascente, Carla</creatorcontrib><creatorcontrib>Pigini, Maria</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gentili, Francesco</au><au>Bousquet, Pascal</au><au>Brasili, Livio</au><au>Caretto, Mariangela</au><au>Carrieri, Antonio</au><au>Dontenwill, Monique</au><au>Giannella, Mario</au><au>Marucci, Gabriella</au><au>Perfumi, Marina</au><au>Piergentili, Alessandro</au><au>Quaglia, Wilma</au><au>Rascente, Carla</au><au>Pigini, Maria</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>α2-Adrenoreceptors Profile Modulation and High Antinociceptive Activity of (S)-(−)-2-[1-(Biphenyl-2-yloxy)ethyl]-4,5-dihydro-1H-imidazole</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2002-01-03</date><risdate>2002</risdate><volume>45</volume><issue>1</issue><spage>32</spage><epage>40</epage><pages>32-40</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>A number of derivatives structurally related to cirazoline (1) were synthesized and studied with the purpose of modulating α2-adrenoreceptors selectivity versus both α1-adrenoreceptors and I2 imidazoline binding sites. The most potent α2-agonist was 2-[1-(biphenyl-2-yloxy)ethyl]-4,5-dihydro-1H-imidazole (7), whose key pharmacophoric features closely matched those found in the α2-agonist 2-(3-exo-(3-phenylprop-1-yl)-2-exo-norbornyl)amino-2-oxazoline (15). (S)-(−)-7 was the most potent of the two enantiomers, confirming the stereospecificity of the interaction with α2-adrenoreceptors. This eutomer was tested on two algesiometric paradigms and, because of the interaction with α2-adrenoreceptors, showed a potent and long-lasting antinociceptive activity, since it was abolished by the selective α2-antagonist RX821002.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><doi>10.1021/jm0110082</doi><tpages>9</tpages></addata></record> |
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| subjects | Analgesics Biological and medical sciences Medical sciences Neuropharmacology Pharmacology. Drug treatments |
| title | α2-Adrenoreceptors Profile Modulation and High Antinociceptive Activity of (S)-(−)-2-[1-(Biphenyl-2-yloxy)ethyl]-4,5-dihydro-1H-imidazole |
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