Discovery of Orally Active 3-Pyridinyl-tropane As a Potent Nociceptin Receptor Agonist for the Management of Cough
A series of 3-pyridinyl-tropane analogues based on previously reported compound 1 have been synthesized and shown to bind to the nociceptin receptor with high affinity. From the SAR study and our lead optimization efforts, compound 10 was found to possess potent oral antitussive activity in the caps...
Gespeichert in:
| Veröffentlicht in: | Journal of medicinal chemistry 2009-09, Vol.52 (17), p.5323-5329 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 5329 |
|---|---|
| container_issue | 17 |
| container_start_page | 5323 |
| container_title | Journal of medicinal chemistry |
| container_volume | 52 |
| creator | Yang, Shu-Wei Ho, Ginny Tulshian, Deen Greenlee, William J Anthes, John Fernandez, Xiomara McLeod, Robbie L Hey, John A Xu, Xiaoying |
| description | A series of 3-pyridinyl-tropane analogues based on previously reported compound 1 have been synthesized and shown to bind to the nociceptin receptor with high affinity. From the SAR study and our lead optimization efforts, compound 10 was found to possess potent oral antitussive activity in the capsaicin-induced guinea pig model. The rationale for compound selection and the biological profile of the optimized lead (10) are disclosed. |
| doi_str_mv | 10.1021/jm9008218 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67628522</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>67628522</sourcerecordid><originalsourceid>FETCH-LOGICAL-a434t-2b129165984686584e99dbd755fa5177175afce75f1870d4fa747400b62243303</originalsourceid><addsrcrecordid>eNpt0E1v1DAQBmALgehSOPAHkC8gcQgdT_yV42r5lPolBOfI69hbr5J4sZ1K-ffNqqv2wmnm8OgdzUvIewZfGCC72A8NgEamX5AVEwgV18BfkhUAYoUS6zPyJuc9ANQM69fkjDVSacn5iqSvIdt479JMo6c3yfT9TNe2hHtH6-p2TqEL49xXJcWDGR1dZ2robSxuLPQ62mDdoYSR_nbHJSa63sUx5EL9spc7R6_MaHZuOPIlfxOn3d1b8sqbPrt3p3lO_n7_9mfzs7q8-fFrs76sDK95qXDLsGFSNJpLLYXmrmm6baeE8EYwpZgSxlunhGdaQce9UVxxgK1E5HUN9Tn59Jh7SPHf5HJph-VX1_fLH3HKrVQStUBc4OdHaFPMOTnfHlIYTJpbBu2x4Pap4MV-OIVO28F1z_LU6AI-noDJ1vQ-mdGG_OQQodFMsmdnbG73cUrj0sV_Dj4A5kmM6g</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>67628522</pqid></control><display><type>article</type><title>Discovery of Orally Active 3-Pyridinyl-tropane As a Potent Nociceptin Receptor Agonist for the Management of Cough</title><source>MEDLINE</source><source>ACS Publications</source><creator>Yang, Shu-Wei ; Ho, Ginny ; Tulshian, Deen ; Greenlee, William J ; Anthes, John ; Fernandez, Xiomara ; McLeod, Robbie L ; Hey, John A ; Xu, Xiaoying</creator><creatorcontrib>Yang, Shu-Wei ; Ho, Ginny ; Tulshian, Deen ; Greenlee, William J ; Anthes, John ; Fernandez, Xiomara ; McLeod, Robbie L ; Hey, John A ; Xu, Xiaoying</creatorcontrib><description>A series of 3-pyridinyl-tropane analogues based on previously reported compound 1 have been synthesized and shown to bind to the nociceptin receptor with high affinity. From the SAR study and our lead optimization efforts, compound 10 was found to possess potent oral antitussive activity in the capsaicin-induced guinea pig model. The rationale for compound selection and the biological profile of the optimized lead (10) are disclosed.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm9008218</identifier><identifier>PMID: 19678644</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Columbus, OH: American Chemical Society</publisher><subject>Administration, Oral ; Animals ; Antitussive Agents - administration & dosage ; Antitussive Agents - chemistry ; Antitussive Agents - pharmacology ; Antitussive Agents - therapeutic use ; Biological and medical sciences ; Cough - drug therapy ; Dogs ; Drug Discovery ; Guinea Pigs ; Humans ; Medical sciences ; Neuropharmacology ; Neurotransmitters. Neurotransmission. Receptors ; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems ; Pharmacology. Drug treatments ; Pyridines - administration & dosage ; Pyridines - chemistry ; Pyridines - pharmacology ; Pyridines - therapeutic use ; Rats ; Receptors, Opioid - agonists ; Receptors, Opioid - metabolism ; Receptors, Steroid - antagonists & inhibitors ; Structure-Activity Relationship ; Trans-Activators - antagonists & inhibitors ; Transcriptional Regulator ERG ; Tropanes - administration & dosage ; Tropanes - chemistry ; Tropanes - pharmacology ; Tropanes - therapeutic use ; Vocalization, Animal - drug effects</subject><ispartof>Journal of medicinal chemistry, 2009-09, Vol.52 (17), p.5323-5329</ispartof><rights>Copyright © 2009 American Chemical Society</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a434t-2b129165984686584e99dbd755fa5177175afce75f1870d4fa747400b62243303</citedby><cites>FETCH-LOGICAL-a434t-2b129165984686584e99dbd755fa5177175afce75f1870d4fa747400b62243303</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/jm9008218$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm9008218$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,777,781,2752,27057,27905,27906,56719,56769</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22098161$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19678644$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Shu-Wei</creatorcontrib><creatorcontrib>Ho, Ginny</creatorcontrib><creatorcontrib>Tulshian, Deen</creatorcontrib><creatorcontrib>Greenlee, William J</creatorcontrib><creatorcontrib>Anthes, John</creatorcontrib><creatorcontrib>Fernandez, Xiomara</creatorcontrib><creatorcontrib>McLeod, Robbie L</creatorcontrib><creatorcontrib>Hey, John A</creatorcontrib><creatorcontrib>Xu, Xiaoying</creatorcontrib><title>Discovery of Orally Active 3-Pyridinyl-tropane As a Potent Nociceptin Receptor Agonist for the Management of Cough</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>A series of 3-pyridinyl-tropane analogues based on previously reported compound 1 have been synthesized and shown to bind to the nociceptin receptor with high affinity. From the SAR study and our lead optimization efforts, compound 10 was found to possess potent oral antitussive activity in the capsaicin-induced guinea pig model. The rationale for compound selection and the biological profile of the optimized lead (10) are disclosed.</description><subject>Administration, Oral</subject><subject>Animals</subject><subject>Antitussive Agents - administration & dosage</subject><subject>Antitussive Agents - chemistry</subject><subject>Antitussive Agents - pharmacology</subject><subject>Antitussive Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Cough - drug therapy</subject><subject>Dogs</subject><subject>Drug Discovery</subject><subject>Guinea Pigs</subject><subject>Humans</subject><subject>Medical sciences</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>Pyridines - administration & dosage</subject><subject>Pyridines - chemistry</subject><subject>Pyridines - pharmacology</subject><subject>Pyridines - therapeutic use</subject><subject>Rats</subject><subject>Receptors, Opioid - agonists</subject><subject>Receptors, Opioid - metabolism</subject><subject>Receptors, Steroid - antagonists & inhibitors</subject><subject>Structure-Activity Relationship</subject><subject>Trans-Activators - antagonists & inhibitors</subject><subject>Transcriptional Regulator ERG</subject><subject>Tropanes - administration & dosage</subject><subject>Tropanes - chemistry</subject><subject>Tropanes - pharmacology</subject><subject>Tropanes - therapeutic use</subject><subject>Vocalization, Animal - drug effects</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0E1v1DAQBmALgehSOPAHkC8gcQgdT_yV42r5lPolBOfI69hbr5J4sZ1K-ffNqqv2wmnm8OgdzUvIewZfGCC72A8NgEamX5AVEwgV18BfkhUAYoUS6zPyJuc9ANQM69fkjDVSacn5iqSvIdt479JMo6c3yfT9TNe2hHtH6-p2TqEL49xXJcWDGR1dZ2robSxuLPQ62mDdoYSR_nbHJSa63sUx5EL9spc7R6_MaHZuOPIlfxOn3d1b8sqbPrt3p3lO_n7_9mfzs7q8-fFrs76sDK95qXDLsGFSNJpLLYXmrmm6baeE8EYwpZgSxlunhGdaQce9UVxxgK1E5HUN9Tn59Jh7SPHf5HJph-VX1_fLH3HKrVQStUBc4OdHaFPMOTnfHlIYTJpbBu2x4Pap4MV-OIVO28F1z_LU6AI-noDJ1vQ-mdGG_OQQodFMsmdnbG73cUrj0sV_Dj4A5kmM6g</recordid><startdate>20090910</startdate><enddate>20090910</enddate><creator>Yang, Shu-Wei</creator><creator>Ho, Ginny</creator><creator>Tulshian, Deen</creator><creator>Greenlee, William J</creator><creator>Anthes, John</creator><creator>Fernandez, Xiomara</creator><creator>McLeod, Robbie L</creator><creator>Hey, John A</creator><creator>Xu, Xiaoying</creator><general>American Chemical Society</general><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></search><sort><creationdate>20090910</creationdate><title>Discovery of Orally Active 3-Pyridinyl-tropane As a Potent Nociceptin Receptor Agonist for the Management of Cough</title><author>Yang, Shu-Wei ; Ho, Ginny ; Tulshian, Deen ; Greenlee, William J ; Anthes, John ; Fernandez, Xiomara ; McLeod, Robbie L ; Hey, John A ; Xu, Xiaoying</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a434t-2b129165984686584e99dbd755fa5177175afce75f1870d4fa747400b62243303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Administration, Oral</topic><topic>Animals</topic><topic>Antitussive Agents - administration & dosage</topic><topic>Antitussive Agents - chemistry</topic><topic>Antitussive Agents - pharmacology</topic><topic>Antitussive Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Cough - drug therapy</topic><topic>Dogs</topic><topic>Drug Discovery</topic><topic>Guinea Pigs</topic><topic>Humans</topic><topic>Medical sciences</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>Pyridines - administration & dosage</topic><topic>Pyridines - chemistry</topic><topic>Pyridines - pharmacology</topic><topic>Pyridines - therapeutic use</topic><topic>Rats</topic><topic>Receptors, Opioid - agonists</topic><topic>Receptors, Opioid - metabolism</topic><topic>Receptors, Steroid - antagonists & inhibitors</topic><topic>Structure-Activity Relationship</topic><topic>Trans-Activators - antagonists & inhibitors</topic><topic>Transcriptional Regulator ERG</topic><topic>Tropanes - administration & dosage</topic><topic>Tropanes - chemistry</topic><topic>Tropanes - pharmacology</topic><topic>Tropanes - therapeutic use</topic><topic>Vocalization, Animal - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Shu-Wei</creatorcontrib><creatorcontrib>Ho, Ginny</creatorcontrib><creatorcontrib>Tulshian, Deen</creatorcontrib><creatorcontrib>Greenlee, William J</creatorcontrib><creatorcontrib>Anthes, John</creatorcontrib><creatorcontrib>Fernandez, Xiomara</creatorcontrib><creatorcontrib>McLeod, Robbie L</creatorcontrib><creatorcontrib>Hey, John A</creatorcontrib><creatorcontrib>Xu, Xiaoying</creatorcontrib><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><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Shu-Wei</au><au>Ho, Ginny</au><au>Tulshian, Deen</au><au>Greenlee, William J</au><au>Anthes, John</au><au>Fernandez, Xiomara</au><au>McLeod, Robbie L</au><au>Hey, John A</au><au>Xu, Xiaoying</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discovery of Orally Active 3-Pyridinyl-tropane As a Potent Nociceptin Receptor Agonist for the Management of Cough</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2009-09-10</date><risdate>2009</risdate><volume>52</volume><issue>17</issue><spage>5323</spage><epage>5329</epage><pages>5323-5329</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>A series of 3-pyridinyl-tropane analogues based on previously reported compound 1 have been synthesized and shown to bind to the nociceptin receptor with high affinity. From the SAR study and our lead optimization efforts, compound 10 was found to possess potent oral antitussive activity in the capsaicin-induced guinea pig model. The rationale for compound selection and the biological profile of the optimized lead (10) are disclosed.</abstract><cop>Columbus, OH</cop><pub>American Chemical Society</pub><pmid>19678644</pmid><doi>10.1021/jm9008218</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 2009-09, Vol.52 (17), p.5323-5329 |
| issn | 0022-2623 1520-4804 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_67628522 |
| source | MEDLINE; ACS Publications |
| subjects | Administration, Oral Animals Antitussive Agents - administration & dosage Antitussive Agents - chemistry Antitussive Agents - pharmacology Antitussive Agents - therapeutic use Biological and medical sciences Cough - drug therapy Dogs Drug Discovery Guinea Pigs Humans Medical sciences Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems Pharmacology. Drug treatments Pyridines - administration & dosage Pyridines - chemistry Pyridines - pharmacology Pyridines - therapeutic use Rats Receptors, Opioid - agonists Receptors, Opioid - metabolism Receptors, Steroid - antagonists & inhibitors Structure-Activity Relationship Trans-Activators - antagonists & inhibitors Transcriptional Regulator ERG Tropanes - administration & dosage Tropanes - chemistry Tropanes - pharmacology Tropanes - therapeutic use Vocalization, Animal - drug effects |
| title | Discovery of Orally Active 3-Pyridinyl-tropane As a Potent Nociceptin Receptor Agonist for the Management of Cough |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-18T13%3A27%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Discovery%20of%20Orally%20Active%203-Pyridinyl-tropane%20As%20a%20Potent%20Nociceptin%20Receptor%20Agonist%20for%20the%20Management%20of%20Cough&rft.jtitle=Journal%20of%20medicinal%20chemistry&rft.au=Yang,%20Shu-Wei&rft.date=2009-09-10&rft.volume=52&rft.issue=17&rft.spage=5323&rft.epage=5329&rft.pages=5323-5329&rft.issn=0022-2623&rft.eissn=1520-4804&rft.coden=JMCMAR&rft_id=info:doi/10.1021/jm9008218&rft_dat=%3Cproquest_cross%3E67628522%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=67628522&rft_id=info:pmid/19678644&rfr_iscdi=true |