SAR and biological evaluation of 3-azabicyclo[3.1.0]hexane derivatives as μ opioid ligands
3-Azabicyclo[3.1.0]hexane compounds were designed as novel achiral μ opioid receptor ligands for the treatment of pruritus in dogs. In this paper, we describe the SAR of this class of opioid ligand, highlighting changes to the lead structure which led to compounds having picomolar binding affinity,...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2012-03, Vol.22 (6), p.2200-2203 |
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| creator | Lunn, Graham Roberts, Lee R. Content, Stephane Critcher, Douglas J. Douglas, Sara Fenwick, Ashley E. Gethin, David M. Goodwin, Graham Greenway, David Greenwood, Sean Hall, Kim Thomas, Martin Thompson, Stephen Williams, David Wood, Gavin Wylie, Andrew |
| description | 3-Azabicyclo[3.1.0]hexane compounds were designed as novel achiral μ opioid receptor ligands for the treatment of pruritus in dogs. In this paper, we describe the SAR of this class of opioid ligand, highlighting changes to the lead structure which led to compounds having picomolar binding affinity, selective for the μ receptor over δ and κ subtypes. Some subtleties of functional activity will also be described.
3-Azabicyclo[3.1.0]hexane compounds were designed as novel achiral μ opioid receptor ligands for the treatment of pruritus in dogs. In this paper, we describe the SAR of this class of opioid ligand, highlighting changes to the lead structure which led to compounds having picomolar binding affinity, selective for the μ receptor over δ and κ subtypes. Some subtleties of functional activity will also be described. |
| doi_str_mv | 10.1016/j.bmcl.2012.01.099 |
| format | Article |
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3-Azabicyclo[3.1.0]hexane compounds were designed as novel achiral μ opioid receptor ligands for the treatment of pruritus in dogs. In this paper, we describe the SAR of this class of opioid ligand, highlighting changes to the lead structure which led to compounds having picomolar binding affinity, selective for the μ receptor over δ and κ subtypes. Some subtleties of functional activity will also be described.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2012.01.099</identifier><identifier>PMID: 22357342</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>Animals ; Antipruritics - chemical synthesis ; Antipruritics - pharmacology ; binding capacity ; Biological and medical sciences ; Bridged Bicyclo Compounds, Heterocyclic - chemical synthesis ; Bridged Bicyclo Compounds, Heterocyclic - pharmacology ; chemistry ; Dogs ; Guinea Pigs ; hexane ; Hexanes - chemical synthesis ; Hexanes - pharmacology ; Humans ; In Vitro Techniques ; Kinetics ; Ligands ; Medical sciences ; Opioid ; Pharmacology. Drug treatments ; pruritus ; Pruritus - drug therapy ; Pruritus - metabolism ; Receptors, Opioid, delta - antagonists & inhibitors ; Receptors, Opioid, delta - metabolism ; Receptors, Opioid, kappa - antagonists & inhibitors ; Receptors, Opioid, kappa - metabolism ; Receptors, Opioid, mu - antagonists & inhibitors ; Receptors, Opioid, mu - metabolism ; Structure-Activity Relationship ; μ Opioid</subject><ispartof>Bioorganic & medicinal chemistry letters, 2012-03, Vol.22 (6), p.2200-2203</ispartof><rights>2012 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2012 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c441t-ef9eb8118ef5d2c9d6db874be62879edfea747f1806cffb83d6e7c66fcf067b43</citedby><cites>FETCH-LOGICAL-c441t-ef9eb8118ef5d2c9d6db874be62879edfea747f1806cffb83d6e7c66fcf067b43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmcl.2012.01.099$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25696938$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22357342$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lunn, Graham</creatorcontrib><creatorcontrib>Roberts, Lee R.</creatorcontrib><creatorcontrib>Content, Stephane</creatorcontrib><creatorcontrib>Critcher, Douglas J.</creatorcontrib><creatorcontrib>Douglas, Sara</creatorcontrib><creatorcontrib>Fenwick, Ashley E.</creatorcontrib><creatorcontrib>Gethin, David M.</creatorcontrib><creatorcontrib>Goodwin, Graham</creatorcontrib><creatorcontrib>Greenway, David</creatorcontrib><creatorcontrib>Greenwood, Sean</creatorcontrib><creatorcontrib>Hall, Kim</creatorcontrib><creatorcontrib>Thomas, Martin</creatorcontrib><creatorcontrib>Thompson, Stephen</creatorcontrib><creatorcontrib>Williams, David</creatorcontrib><creatorcontrib>Wood, Gavin</creatorcontrib><creatorcontrib>Wylie, Andrew</creatorcontrib><title>SAR and biological evaluation of 3-azabicyclo[3.1.0]hexane derivatives as μ opioid ligands</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>3-Azabicyclo[3.1.0]hexane compounds were designed as novel achiral μ opioid receptor ligands for the treatment of pruritus in dogs. In this paper, we describe the SAR of this class of opioid ligand, highlighting changes to the lead structure which led to compounds having picomolar binding affinity, selective for the μ receptor over δ and κ subtypes. Some subtleties of functional activity will also be described.
3-Azabicyclo[3.1.0]hexane compounds were designed as novel achiral μ opioid receptor ligands for the treatment of pruritus in dogs. In this paper, we describe the SAR of this class of opioid ligand, highlighting changes to the lead structure which led to compounds having picomolar binding affinity, selective for the μ receptor over δ and κ subtypes. Some subtleties of functional activity will also be described.</description><subject>Animals</subject><subject>Antipruritics - chemical synthesis</subject><subject>Antipruritics - pharmacology</subject><subject>binding capacity</subject><subject>Biological and medical sciences</subject><subject>Bridged Bicyclo Compounds, Heterocyclic - chemical synthesis</subject><subject>Bridged Bicyclo Compounds, Heterocyclic - pharmacology</subject><subject>chemistry</subject><subject>Dogs</subject><subject>Guinea Pigs</subject><subject>hexane</subject><subject>Hexanes - chemical synthesis</subject><subject>Hexanes - pharmacology</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Kinetics</subject><subject>Ligands</subject><subject>Medical sciences</subject><subject>Opioid</subject><subject>Pharmacology. Drug treatments</subject><subject>pruritus</subject><subject>Pruritus - drug therapy</subject><subject>Pruritus - metabolism</subject><subject>Receptors, Opioid, delta - antagonists & inhibitors</subject><subject>Receptors, Opioid, delta - metabolism</subject><subject>Receptors, Opioid, kappa - antagonists & inhibitors</subject><subject>Receptors, Opioid, kappa - metabolism</subject><subject>Receptors, Opioid, mu - antagonists & inhibitors</subject><subject>Receptors, Opioid, mu - metabolism</subject><subject>Structure-Activity Relationship</subject><subject>μ Opioid</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcGKFDEQhoMo7rj6Ah40F9lTt5V0Ot0BL8viqrAguC4Ii4R0Uhkz9HTGZGZwfTafwWcyzYx601MuX_1_5StCnjKoGTD5clUPazvWHBivgdWg1D2yYEKKqhHQ3icLUBKqXolPJ-RRzisAJkCIh-SE86btGsEX5Pb6_AM1k6NDiGNcBmtGinsz7sw2xIlGT5vKfDdDsHd2jLdNXXo-f8FvZkLqMIV94faYqcn05w8aNyEGR8ewLJH5MXngzZjxyfE9JTeXrz9evK2u3r95d3F-VVkh2LZCr3DoGevRt45b5aQb-k4MKHnfKXQeTSc6z3qQ1vuhb5zEzkrprQfZDaI5JWeH3E2KX3eYt3odssVxLEvGXdZK9qwDgPb_JJctdKztC8kPpE0x54Reb1JYm3SnGejZvl7p2b6e7WtgutgvQ8-O8bthje7PyG_dBXhxBEwupn0ykw35L9dKJVUztz8_cN5EbZapMDfXpaktJ2wkg_nPrw4EFrH7gElnG3Cy6EJCu9Uuhn9t-guj9Kyt</recordid><startdate>20120315</startdate><enddate>20120315</enddate><creator>Lunn, Graham</creator><creator>Roberts, Lee R.</creator><creator>Content, Stephane</creator><creator>Critcher, Douglas J.</creator><creator>Douglas, Sara</creator><creator>Fenwick, Ashley E.</creator><creator>Gethin, David M.</creator><creator>Goodwin, Graham</creator><creator>Greenway, David</creator><creator>Greenwood, Sean</creator><creator>Hall, Kim</creator><creator>Thomas, Martin</creator><creator>Thompson, Stephen</creator><creator>Williams, David</creator><creator>Wood, Gavin</creator><creator>Wylie, Andrew</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>FBQ</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>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20120315</creationdate><title>SAR and biological evaluation of 3-azabicyclo[3.1.0]hexane derivatives as μ opioid ligands</title><author>Lunn, Graham ; Roberts, Lee R. ; Content, Stephane ; Critcher, Douglas J. ; Douglas, Sara ; Fenwick, Ashley E. ; Gethin, David M. ; Goodwin, Graham ; Greenway, David ; Greenwood, Sean ; Hall, Kim ; Thomas, Martin ; Thompson, Stephen ; Williams, David ; Wood, Gavin ; Wylie, Andrew</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c441t-ef9eb8118ef5d2c9d6db874be62879edfea747f1806cffb83d6e7c66fcf067b43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Antipruritics - chemical synthesis</topic><topic>Antipruritics - pharmacology</topic><topic>binding capacity</topic><topic>Biological and medical sciences</topic><topic>Bridged Bicyclo Compounds, Heterocyclic - chemical synthesis</topic><topic>Bridged Bicyclo Compounds, Heterocyclic - pharmacology</topic><topic>chemistry</topic><topic>Dogs</topic><topic>Guinea Pigs</topic><topic>hexane</topic><topic>Hexanes - chemical synthesis</topic><topic>Hexanes - pharmacology</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Kinetics</topic><topic>Ligands</topic><topic>Medical sciences</topic><topic>Opioid</topic><topic>Pharmacology. Drug treatments</topic><topic>pruritus</topic><topic>Pruritus - drug therapy</topic><topic>Pruritus - metabolism</topic><topic>Receptors, Opioid, delta - antagonists & inhibitors</topic><topic>Receptors, Opioid, delta - metabolism</topic><topic>Receptors, Opioid, kappa - antagonists & inhibitors</topic><topic>Receptors, Opioid, kappa - metabolism</topic><topic>Receptors, Opioid, mu - antagonists & inhibitors</topic><topic>Receptors, Opioid, mu - metabolism</topic><topic>Structure-Activity Relationship</topic><topic>μ Opioid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lunn, Graham</creatorcontrib><creatorcontrib>Roberts, Lee R.</creatorcontrib><creatorcontrib>Content, Stephane</creatorcontrib><creatorcontrib>Critcher, Douglas J.</creatorcontrib><creatorcontrib>Douglas, Sara</creatorcontrib><creatorcontrib>Fenwick, Ashley E.</creatorcontrib><creatorcontrib>Gethin, David M.</creatorcontrib><creatorcontrib>Goodwin, Graham</creatorcontrib><creatorcontrib>Greenway, David</creatorcontrib><creatorcontrib>Greenwood, Sean</creatorcontrib><creatorcontrib>Hall, Kim</creatorcontrib><creatorcontrib>Thomas, Martin</creatorcontrib><creatorcontrib>Thompson, Stephen</creatorcontrib><creatorcontrib>Williams, David</creatorcontrib><creatorcontrib>Wood, Gavin</creatorcontrib><creatorcontrib>Wylie, Andrew</creatorcontrib><collection>AGRIS</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>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lunn, Graham</au><au>Roberts, Lee R.</au><au>Content, Stephane</au><au>Critcher, Douglas J.</au><au>Douglas, Sara</au><au>Fenwick, Ashley E.</au><au>Gethin, David M.</au><au>Goodwin, Graham</au><au>Greenway, David</au><au>Greenwood, Sean</au><au>Hall, Kim</au><au>Thomas, Martin</au><au>Thompson, Stephen</au><au>Williams, David</au><au>Wood, Gavin</au><au>Wylie, Andrew</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SAR and biological evaluation of 3-azabicyclo[3.1.0]hexane derivatives as μ opioid ligands</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2012-03-15</date><risdate>2012</risdate><volume>22</volume><issue>6</issue><spage>2200</spage><epage>2203</epage><pages>2200-2203</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>3-Azabicyclo[3.1.0]hexane compounds were designed as novel achiral μ opioid receptor ligands for the treatment of pruritus in dogs. In this paper, we describe the SAR of this class of opioid ligand, highlighting changes to the lead structure which led to compounds having picomolar binding affinity, selective for the μ receptor over δ and κ subtypes. Some subtleties of functional activity will also be described.
3-Azabicyclo[3.1.0]hexane compounds were designed as novel achiral μ opioid receptor ligands for the treatment of pruritus in dogs. In this paper, we describe the SAR of this class of opioid ligand, highlighting changes to the lead structure which led to compounds having picomolar binding affinity, selective for the μ receptor over δ and κ subtypes. Some subtleties of functional activity will also be described.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>22357342</pmid><doi>10.1016/j.bmcl.2012.01.099</doi><tpages>4</tpages></addata></record> |
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| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2012-03, Vol.22 (6), p.2200-2203 |
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| language | eng |
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| subjects | Animals Antipruritics - chemical synthesis Antipruritics - pharmacology binding capacity Biological and medical sciences Bridged Bicyclo Compounds, Heterocyclic - chemical synthesis Bridged Bicyclo Compounds, Heterocyclic - pharmacology chemistry Dogs Guinea Pigs hexane Hexanes - chemical synthesis Hexanes - pharmacology Humans In Vitro Techniques Kinetics Ligands Medical sciences Opioid Pharmacology. Drug treatments pruritus Pruritus - drug therapy Pruritus - metabolism Receptors, Opioid, delta - antagonists & inhibitors Receptors, Opioid, delta - metabolism Receptors, Opioid, kappa - antagonists & inhibitors Receptors, Opioid, kappa - metabolism Receptors, Opioid, mu - antagonists & inhibitors Receptors, Opioid, mu - metabolism Structure-Activity Relationship μ Opioid |
| title | SAR and biological evaluation of 3-azabicyclo[3.1.0]hexane derivatives as μ opioid ligands |
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