The discovery of long-acting saligenin beta sub(2 adrenergic receptor agonists incorporating hydantoin or uracil rings)
A series of novel, potent and selective human beta sub(2 adrenoceptor agonists incorporating a hydantoin or a uracil ring on the right-hand side phenyl ring of (R)-salmeterol is presented. Hydantoin 12a had long duration of action in vitro on guinea pig trachea, and 12 h in guinea pigs in vivo at it...
Gespeichert in:
| Veröffentlicht in: | Bioorganic & medicinal chemistry 2011-07, Vol.19 (14), p.4192-4201 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 4201 |
|---|---|
| container_issue | 14 |
| container_start_page | 4192 |
| container_title | Bioorganic & medicinal chemistry |
| container_volume | 19 |
| creator | Procopiou, Panayiotis A Barrett, Victoria J Bevan, Nicola J Butchers, Peter R Conroy, Richard Emmons, Amanda d, Alison J Jeulin, Severine Looker, Brian E Lunniss, Gillian E Morrison, Valerie S Mutch, Peter J Perciaccante, Rossana Ruston, Mark Smith, Claire E Somers, Graham Xepfqmjboitfns-Sanmltnesa-N, InChiKey |
| description | A series of novel, potent and selective human beta sub(2 adrenoceptor agonists incorporating a hydantoin or a uracil ring on the right-hand side phenyl ring of (R)-salmeterol is presented. Hydantoin 12a had long duration of action in vitro on guinea pig trachea, and 12 h in guinea pigs in vivo at its EC) sub(9)0 25 mu M. It had lower oral absorption than salmeterol in rats, and lower bioavailability than salmeterol in vivo in both rats and dogs (2% and 5%, respectively). An improved method for measuring the absorbed fraction of analogues dosed to rats, which considers the glucuronidated fraction is presented. Compound 12a was metabolised in human liver microsomes and hepatocytes to the active hydantoic acid 12m. |
| doi_str_mv | 10.1016/j.bmc.2011.05.064 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest</sourceid><recordid>TN_cdi_proquest_miscellaneous_883032688</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>883032688</sourcerecordid><originalsourceid>FETCH-proquest_miscellaneous_8830326883</originalsourceid><addsrcrecordid>eNqNjk1OwzAQRr0AifJzAHazAxYx47REyRqBOED3leNMXVeuHWYcUG-PhTgAq7f43pM-pe4NaoOmez7q8eR0i8ZofNHYbS7UCoeub7Afuit1LXJExHYzmJX63h4IpiAufxGfIe8h5uQb60pIHsTG4CmFBCMVC7KMjy3YiSkR--CAydFcMoP1OQUpAiG5zHNm-9sfzpNNJde-OgtbFyJwHeTpVl3ubRS6--ONenh_275-NDPnz4Wk7E71FMVoE-VFdn2_xnXbVfzf_AFgJVbt</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>883032688</pqid></control><display><type>article</type><title>The discovery of long-acting saligenin beta sub(2 adrenergic receptor agonists incorporating hydantoin or uracil rings)</title><source>Access via ScienceDirect (Elsevier)</source><creator>Procopiou, Panayiotis A ; Barrett, Victoria J ; Bevan, Nicola J ; Butchers, Peter R ; Conroy, Richard ; Emmons, Amanda ; d, Alison J ; Jeulin, Severine ; Looker, Brian E ; Lunniss, Gillian E ; Morrison, Valerie S ; Mutch, Peter J ; Perciaccante, Rossana ; Ruston, Mark ; Smith, Claire E ; Somers, Graham ; Xepfqmjboitfns-Sanmltnesa-N, InChiKey</creator><creatorcontrib>Procopiou, Panayiotis A ; Barrett, Victoria J ; Bevan, Nicola J ; Butchers, Peter R ; Conroy, Richard ; Emmons, Amanda ; d, Alison J ; Jeulin, Severine ; Looker, Brian E ; Lunniss, Gillian E ; Morrison, Valerie S ; Mutch, Peter J ; Perciaccante, Rossana ; Ruston, Mark ; Smith, Claire E ; Somers, Graham ; Xepfqmjboitfns-Sanmltnesa-N, InChiKey</creatorcontrib><description>A series of novel, potent and selective human beta sub(2 adrenoceptor agonists incorporating a hydantoin or a uracil ring on the right-hand side phenyl ring of (R)-salmeterol is presented. Hydantoin 12a had long duration of action in vitro on guinea pig trachea, and 12 h in guinea pigs in vivo at its EC) sub(9)0 25 mu M. It had lower oral absorption than salmeterol in rats, and lower bioavailability than salmeterol in vivo in both rats and dogs (2% and 5%, respectively). An improved method for measuring the absorbed fraction of analogues dosed to rats, which considers the glucuronidated fraction is presented. Compound 12a was metabolised in human liver microsomes and hepatocytes to the active hydantoic acid 12m.</description><identifier>ISSN: 0968-0896</identifier><identifier>DOI: 10.1016/j.bmc.2011.05.064</identifier><language>eng</language><ispartof>Bioorganic & medicinal chemistry, 2011-07, Vol.19 (14), p.4192-4201</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Procopiou, Panayiotis A</creatorcontrib><creatorcontrib>Barrett, Victoria J</creatorcontrib><creatorcontrib>Bevan, Nicola J</creatorcontrib><creatorcontrib>Butchers, Peter R</creatorcontrib><creatorcontrib>Conroy, Richard</creatorcontrib><creatorcontrib>Emmons, Amanda</creatorcontrib><creatorcontrib>d, Alison J</creatorcontrib><creatorcontrib>Jeulin, Severine</creatorcontrib><creatorcontrib>Looker, Brian E</creatorcontrib><creatorcontrib>Lunniss, Gillian E</creatorcontrib><creatorcontrib>Morrison, Valerie S</creatorcontrib><creatorcontrib>Mutch, Peter J</creatorcontrib><creatorcontrib>Perciaccante, Rossana</creatorcontrib><creatorcontrib>Ruston, Mark</creatorcontrib><creatorcontrib>Smith, Claire E</creatorcontrib><creatorcontrib>Somers, Graham</creatorcontrib><creatorcontrib>Xepfqmjboitfns-Sanmltnesa-N, InChiKey</creatorcontrib><title>The discovery of long-acting saligenin beta sub(2 adrenergic receptor agonists incorporating hydantoin or uracil rings)</title><title>Bioorganic & medicinal chemistry</title><description>A series of novel, potent and selective human beta sub(2 adrenoceptor agonists incorporating a hydantoin or a uracil ring on the right-hand side phenyl ring of (R)-salmeterol is presented. Hydantoin 12a had long duration of action in vitro on guinea pig trachea, and 12 h in guinea pigs in vivo at its EC) sub(9)0 25 mu M. It had lower oral absorption than salmeterol in rats, and lower bioavailability than salmeterol in vivo in both rats and dogs (2% and 5%, respectively). An improved method for measuring the absorbed fraction of analogues dosed to rats, which considers the glucuronidated fraction is presented. Compound 12a was metabolised in human liver microsomes and hepatocytes to the active hydantoic acid 12m.</description><issn>0968-0896</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNqNjk1OwzAQRr0AifJzAHazAxYx47REyRqBOED3leNMXVeuHWYcUG-PhTgAq7f43pM-pe4NaoOmez7q8eR0i8ZofNHYbS7UCoeub7Afuit1LXJExHYzmJX63h4IpiAufxGfIe8h5uQb60pIHsTG4CmFBCMVC7KMjy3YiSkR--CAydFcMoP1OQUpAiG5zHNm-9sfzpNNJde-OgtbFyJwHeTpVl3ubRS6--ONenh_275-NDPnz4Wk7E71FMVoE-VFdn2_xnXbVfzf_AFgJVbt</recordid><startdate>20110715</startdate><enddate>20110715</enddate><creator>Procopiou, Panayiotis A</creator><creator>Barrett, Victoria J</creator><creator>Bevan, Nicola J</creator><creator>Butchers, Peter R</creator><creator>Conroy, Richard</creator><creator>Emmons, Amanda</creator><creator>d, Alison J</creator><creator>Jeulin, Severine</creator><creator>Looker, Brian E</creator><creator>Lunniss, Gillian E</creator><creator>Morrison, Valerie S</creator><creator>Mutch, Peter J</creator><creator>Perciaccante, Rossana</creator><creator>Ruston, Mark</creator><creator>Smith, Claire E</creator><creator>Somers, Graham</creator><creator>Xepfqmjboitfns-Sanmltnesa-N, InChiKey</creator><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20110715</creationdate><title>The discovery of long-acting saligenin beta sub(2 adrenergic receptor agonists incorporating hydantoin or uracil rings)</title><author>Procopiou, Panayiotis A ; Barrett, Victoria J ; Bevan, Nicola J ; Butchers, Peter R ; Conroy, Richard ; Emmons, Amanda ; d, Alison J ; Jeulin, Severine ; Looker, Brian E ; Lunniss, Gillian E ; Morrison, Valerie S ; Mutch, Peter J ; Perciaccante, Rossana ; Ruston, Mark ; Smith, Claire E ; Somers, Graham ; Xepfqmjboitfns-Sanmltnesa-N, InChiKey</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-proquest_miscellaneous_8830326883</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Procopiou, Panayiotis A</creatorcontrib><creatorcontrib>Barrett, Victoria J</creatorcontrib><creatorcontrib>Bevan, Nicola J</creatorcontrib><creatorcontrib>Butchers, Peter R</creatorcontrib><creatorcontrib>Conroy, Richard</creatorcontrib><creatorcontrib>Emmons, Amanda</creatorcontrib><creatorcontrib>d, Alison J</creatorcontrib><creatorcontrib>Jeulin, Severine</creatorcontrib><creatorcontrib>Looker, Brian E</creatorcontrib><creatorcontrib>Lunniss, Gillian E</creatorcontrib><creatorcontrib>Morrison, Valerie S</creatorcontrib><creatorcontrib>Mutch, Peter J</creatorcontrib><creatorcontrib>Perciaccante, Rossana</creatorcontrib><creatorcontrib>Ruston, Mark</creatorcontrib><creatorcontrib>Smith, Claire E</creatorcontrib><creatorcontrib>Somers, Graham</creatorcontrib><creatorcontrib>Xepfqmjboitfns-Sanmltnesa-N, InChiKey</creatorcontrib><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</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Procopiou, Panayiotis A</au><au>Barrett, Victoria J</au><au>Bevan, Nicola J</au><au>Butchers, Peter R</au><au>Conroy, Richard</au><au>Emmons, Amanda</au><au>d, Alison J</au><au>Jeulin, Severine</au><au>Looker, Brian E</au><au>Lunniss, Gillian E</au><au>Morrison, Valerie S</au><au>Mutch, Peter J</au><au>Perciaccante, Rossana</au><au>Ruston, Mark</au><au>Smith, Claire E</au><au>Somers, Graham</au><au>Xepfqmjboitfns-Sanmltnesa-N, InChiKey</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The discovery of long-acting saligenin beta sub(2 adrenergic receptor agonists incorporating hydantoin or uracil rings)</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><date>2011-07-15</date><risdate>2011</risdate><volume>19</volume><issue>14</issue><spage>4192</spage><epage>4201</epage><pages>4192-4201</pages><issn>0968-0896</issn><abstract>A series of novel, potent and selective human beta sub(2 adrenoceptor agonists incorporating a hydantoin or a uracil ring on the right-hand side phenyl ring of (R)-salmeterol is presented. Hydantoin 12a had long duration of action in vitro on guinea pig trachea, and 12 h in guinea pigs in vivo at its EC) sub(9)0 25 mu M. It had lower oral absorption than salmeterol in rats, and lower bioavailability than salmeterol in vivo in both rats and dogs (2% and 5%, respectively). An improved method for measuring the absorbed fraction of analogues dosed to rats, which considers the glucuronidated fraction is presented. Compound 12a was metabolised in human liver microsomes and hepatocytes to the active hydantoic acid 12m.</abstract><doi>10.1016/j.bmc.2011.05.064</doi></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0968-0896 |
| ispartof | Bioorganic & medicinal chemistry, 2011-07, Vol.19 (14), p.4192-4201 |
| issn | 0968-0896 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_883032688 |
| source | Access via ScienceDirect (Elsevier) |
| title | The discovery of long-acting saligenin beta sub(2 adrenergic receptor agonists incorporating hydantoin or uracil rings) |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T22%3A10%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20discovery%20of%20long-acting%20saligenin%20beta%20sub(2%20adrenergic%20receptor%20agonists%20incorporating%20hydantoin%20or%20uracil%20rings)&rft.jtitle=Bioorganic%20&%20medicinal%20chemistry&rft.au=Procopiou,%20Panayiotis%20A&rft.date=2011-07-15&rft.volume=19&rft.issue=14&rft.spage=4192&rft.epage=4201&rft.pages=4192-4201&rft.issn=0968-0896&rft_id=info:doi/10.1016/j.bmc.2011.05.064&rft_dat=%3Cproquest%3E883032688%3C/proquest%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=883032688&rft_id=info:pmid/&rfr_iscdi=true |