Characterization of Novel Selective H1-Antihistamines for Clinical Evaluation in the Treatment of Insomnia
Analogues of the known H1-antihistamine R-dimethindene were profiled as potential agents for the treatment of insomnia. Several highly selective compounds were efficacious in rodent sleep models. On the basis of overall profile, indene 1d and benzothiophene 2a had pharmacokinetic properties suitable...
Gespeichert in:
| Veröffentlicht in: | Journal of medicinal chemistry 2009-09, Vol.52 (17), p.5307-5310 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 5310 |
|---|---|
| container_issue | 17 |
| container_start_page | 5307 |
| container_title | Journal of medicinal chemistry |
| container_volume | 52 |
| creator | Moree, Wilna J Li, Bin-Feng Jovic, Florence Coon, Timothy Yu, Jinghua Gross, Raymond S Tucci, Fabio Marinkovic, Dragan Zamani-Kord, Said Malany, Siobhan Bradbury, Margaret J Hernandez, Lisa M O’Brien, Zhihong Wen, Jianyun Wang, Hua Hoare, Samuel R. J Petroski, Robert E Sacaan, Aida Madan, Ajay Crowe, Paul D Beaton, Graham |
| description | Analogues of the known H1-antihistamine R-dimethindene were profiled as potential agents for the treatment of insomnia. Several highly selective compounds were efficacious in rodent sleep models. On the basis of overall profile, indene 1d and benzothiophene 2a had pharmacokinetic properties suitable for evaluation in night time dosing. Compound 2a did not show an in vivo cardiovascular effect from weak hERG channel inhibition. |
| doi_str_mv | 10.1021/jm900933k |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_67626645</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>67626645</sourcerecordid><originalsourceid>FETCH-LOGICAL-a250t-e0ccf73d8dfdd26f092d0c45e2028b3754befb165a6236883efe1b34045c2c1c3</originalsourceid><addsrcrecordid>eNpFkbFOwzAURS0EoqUw8APIC2yBZztxkxFVhVaqYADmyHGeVZfEAdupBF9PKkqZ3nLelc69hFwyuGXA2d2mLQAKId6PyJhlHJI0h_SYjAE4T7jkYkTOQtgAgGBcnJIRK6QUIp-OyWa2Vl7piN5-q2g7RztDn7otNvQFG9TRbpEuWHLvol3bEFVrHQZqOk9njXVWq4bOt6rpf5-to3GN9NWjii26uEtbutC1zqpzcmJUE_Bifyfk7WH-Olskq-fH5ex-lSieQUwQtDZTUee1qWsuDRS8Bp1myIHnlZhmaYWmYjJTg5jMc4EGWSVSSDPNNdNiQm5-cz9899ljiGVrg8amUQ67PpRyKrmUaTaAV3uwr1qsyw9vW-W_yr92BuB6D6gwiBqvnLbhwHEORc6y4p9TOpSbrvdu8CsZlLt1ysM64gegnX-D</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>67626645</pqid></control><display><type>article</type><title>Characterization of Novel Selective H1-Antihistamines for Clinical Evaluation in the Treatment of Insomnia</title><source>ACS Publications</source><source>MEDLINE</source><creator>Moree, Wilna J ; Li, Bin-Feng ; Jovic, Florence ; Coon, Timothy ; Yu, Jinghua ; Gross, Raymond S ; Tucci, Fabio ; Marinkovic, Dragan ; Zamani-Kord, Said ; Malany, Siobhan ; Bradbury, Margaret J ; Hernandez, Lisa M ; O’Brien, Zhihong ; Wen, Jianyun ; Wang, Hua ; Hoare, Samuel R. J ; Petroski, Robert E ; Sacaan, Aida ; Madan, Ajay ; Crowe, Paul D ; Beaton, Graham</creator><creatorcontrib>Moree, Wilna J ; Li, Bin-Feng ; Jovic, Florence ; Coon, Timothy ; Yu, Jinghua ; Gross, Raymond S ; Tucci, Fabio ; Marinkovic, Dragan ; Zamani-Kord, Said ; Malany, Siobhan ; Bradbury, Margaret J ; Hernandez, Lisa M ; O’Brien, Zhihong ; Wen, Jianyun ; Wang, Hua ; Hoare, Samuel R. J ; Petroski, Robert E ; Sacaan, Aida ; Madan, Ajay ; Crowe, Paul D ; Beaton, Graham</creatorcontrib><description>Analogues of the known H1-antihistamine R-dimethindene were profiled as potential agents for the treatment of insomnia. Several highly selective compounds were efficacious in rodent sleep models. On the basis of overall profile, indene 1d and benzothiophene 2a had pharmacokinetic properties suitable for evaluation in night time dosing. Compound 2a did not show an in vivo cardiovascular effect from weak hERG channel inhibition.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm900933k</identifier><identifier>PMID: 19663387</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Columbus, OH: American Chemical Society</publisher><subject>Animals ; Biological and medical sciences ; Brain - metabolism ; Dimethindene - metabolism ; Dimethindene - pharmacokinetics ; Dimethindene - pharmacology ; Dimethindene - therapeutic use ; Electroencephalography - drug effects ; Ether-A-Go-Go Potassium Channels - antagonists & inhibitors ; Histamine H1 Antagonists - metabolism ; Histamine H1 Antagonists - pharmacokinetics ; Histamine H1 Antagonists - pharmacology ; Histamine H1 Antagonists - therapeutic use ; Humans ; Medical sciences ; Miscellaneous ; Neuropharmacology ; Neurotransmitters. Neurotransmission. Receptors ; Pharmacology. Drug treatments ; Rats ; Receptors, Muscarinic - metabolism ; Sleep - drug effects ; Sleep Initiation and Maintenance Disorders - drug therapy ; Substrate Specificity</subject><ispartof>Journal of medicinal chemistry, 2009-09, Vol.52 (17), p.5307-5310</ispartof><rights>Copyright © 2009 American Chemical Society</rights><rights>2015 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/jm900933k$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm900933k$$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=22098159$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19663387$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moree, Wilna J</creatorcontrib><creatorcontrib>Li, Bin-Feng</creatorcontrib><creatorcontrib>Jovic, Florence</creatorcontrib><creatorcontrib>Coon, Timothy</creatorcontrib><creatorcontrib>Yu, Jinghua</creatorcontrib><creatorcontrib>Gross, Raymond S</creatorcontrib><creatorcontrib>Tucci, Fabio</creatorcontrib><creatorcontrib>Marinkovic, Dragan</creatorcontrib><creatorcontrib>Zamani-Kord, Said</creatorcontrib><creatorcontrib>Malany, Siobhan</creatorcontrib><creatorcontrib>Bradbury, Margaret J</creatorcontrib><creatorcontrib>Hernandez, Lisa M</creatorcontrib><creatorcontrib>O’Brien, Zhihong</creatorcontrib><creatorcontrib>Wen, Jianyun</creatorcontrib><creatorcontrib>Wang, Hua</creatorcontrib><creatorcontrib>Hoare, Samuel R. J</creatorcontrib><creatorcontrib>Petroski, Robert E</creatorcontrib><creatorcontrib>Sacaan, Aida</creatorcontrib><creatorcontrib>Madan, Ajay</creatorcontrib><creatorcontrib>Crowe, Paul D</creatorcontrib><creatorcontrib>Beaton, Graham</creatorcontrib><title>Characterization of Novel Selective H1-Antihistamines for Clinical Evaluation in the Treatment of Insomnia</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>Analogues of the known H1-antihistamine R-dimethindene were profiled as potential agents for the treatment of insomnia. Several highly selective compounds were efficacious in rodent sleep models. On the basis of overall profile, indene 1d and benzothiophene 2a had pharmacokinetic properties suitable for evaluation in night time dosing. Compound 2a did not show an in vivo cardiovascular effect from weak hERG channel inhibition.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Brain - metabolism</subject><subject>Dimethindene - metabolism</subject><subject>Dimethindene - pharmacokinetics</subject><subject>Dimethindene - pharmacology</subject><subject>Dimethindene - therapeutic use</subject><subject>Electroencephalography - drug effects</subject><subject>Ether-A-Go-Go Potassium Channels - antagonists & inhibitors</subject><subject>Histamine H1 Antagonists - metabolism</subject><subject>Histamine H1 Antagonists - pharmacokinetics</subject><subject>Histamine H1 Antagonists - pharmacology</subject><subject>Histamine H1 Antagonists - therapeutic use</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Receptors, Muscarinic - metabolism</subject><subject>Sleep - drug effects</subject><subject>Sleep Initiation and Maintenance Disorders - drug therapy</subject><subject>Substrate Specificity</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>eNpFkbFOwzAURS0EoqUw8APIC2yBZztxkxFVhVaqYADmyHGeVZfEAdupBF9PKkqZ3nLelc69hFwyuGXA2d2mLQAKId6PyJhlHJI0h_SYjAE4T7jkYkTOQtgAgGBcnJIRK6QUIp-OyWa2Vl7piN5-q2g7RztDn7otNvQFG9TRbpEuWHLvol3bEFVrHQZqOk9njXVWq4bOt6rpf5-to3GN9NWjii26uEtbutC1zqpzcmJUE_Bifyfk7WH-Olskq-fH5ex-lSieQUwQtDZTUee1qWsuDRS8Bp1myIHnlZhmaYWmYjJTg5jMc4EGWSVSSDPNNdNiQm5-cz9899ljiGVrg8amUQ67PpRyKrmUaTaAV3uwr1qsyw9vW-W_yr92BuB6D6gwiBqvnLbhwHEORc6y4p9TOpSbrvdu8CsZlLt1ysM64gegnX-D</recordid><startdate>20090910</startdate><enddate>20090910</enddate><creator>Moree, Wilna J</creator><creator>Li, Bin-Feng</creator><creator>Jovic, Florence</creator><creator>Coon, Timothy</creator><creator>Yu, Jinghua</creator><creator>Gross, Raymond S</creator><creator>Tucci, Fabio</creator><creator>Marinkovic, Dragan</creator><creator>Zamani-Kord, Said</creator><creator>Malany, Siobhan</creator><creator>Bradbury, Margaret J</creator><creator>Hernandez, Lisa M</creator><creator>O’Brien, Zhihong</creator><creator>Wen, Jianyun</creator><creator>Wang, Hua</creator><creator>Hoare, Samuel R. J</creator><creator>Petroski, Robert E</creator><creator>Sacaan, Aida</creator><creator>Madan, Ajay</creator><creator>Crowe, Paul D</creator><creator>Beaton, Graham</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>7X8</scope></search><sort><creationdate>20090910</creationdate><title>Characterization of Novel Selective H1-Antihistamines for Clinical Evaluation in the Treatment of Insomnia</title><author>Moree, Wilna J ; Li, Bin-Feng ; Jovic, Florence ; Coon, Timothy ; Yu, Jinghua ; Gross, Raymond S ; Tucci, Fabio ; Marinkovic, Dragan ; Zamani-Kord, Said ; Malany, Siobhan ; Bradbury, Margaret J ; Hernandez, Lisa M ; O’Brien, Zhihong ; Wen, Jianyun ; Wang, Hua ; Hoare, Samuel R. J ; Petroski, Robert E ; Sacaan, Aida ; Madan, Ajay ; Crowe, Paul D ; Beaton, Graham</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a250t-e0ccf73d8dfdd26f092d0c45e2028b3754befb165a6236883efe1b34045c2c1c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Brain - metabolism</topic><topic>Dimethindene - metabolism</topic><topic>Dimethindene - pharmacokinetics</topic><topic>Dimethindene - pharmacology</topic><topic>Dimethindene - therapeutic use</topic><topic>Electroencephalography - drug effects</topic><topic>Ether-A-Go-Go Potassium Channels - antagonists & inhibitors</topic><topic>Histamine H1 Antagonists - metabolism</topic><topic>Histamine H1 Antagonists - pharmacokinetics</topic><topic>Histamine H1 Antagonists - pharmacology</topic><topic>Histamine H1 Antagonists - therapeutic use</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Receptors, Muscarinic - metabolism</topic><topic>Sleep - drug effects</topic><topic>Sleep Initiation and Maintenance Disorders - drug therapy</topic><topic>Substrate Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moree, Wilna J</creatorcontrib><creatorcontrib>Li, Bin-Feng</creatorcontrib><creatorcontrib>Jovic, Florence</creatorcontrib><creatorcontrib>Coon, Timothy</creatorcontrib><creatorcontrib>Yu, Jinghua</creatorcontrib><creatorcontrib>Gross, Raymond S</creatorcontrib><creatorcontrib>Tucci, Fabio</creatorcontrib><creatorcontrib>Marinkovic, Dragan</creatorcontrib><creatorcontrib>Zamani-Kord, Said</creatorcontrib><creatorcontrib>Malany, Siobhan</creatorcontrib><creatorcontrib>Bradbury, Margaret J</creatorcontrib><creatorcontrib>Hernandez, Lisa M</creatorcontrib><creatorcontrib>O’Brien, Zhihong</creatorcontrib><creatorcontrib>Wen, Jianyun</creatorcontrib><creatorcontrib>Wang, Hua</creatorcontrib><creatorcontrib>Hoare, Samuel R. J</creatorcontrib><creatorcontrib>Petroski, Robert E</creatorcontrib><creatorcontrib>Sacaan, Aida</creatorcontrib><creatorcontrib>Madan, Ajay</creatorcontrib><creatorcontrib>Crowe, Paul D</creatorcontrib><creatorcontrib>Beaton, Graham</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>MEDLINE - Academic</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moree, Wilna J</au><au>Li, Bin-Feng</au><au>Jovic, Florence</au><au>Coon, Timothy</au><au>Yu, Jinghua</au><au>Gross, Raymond S</au><au>Tucci, Fabio</au><au>Marinkovic, Dragan</au><au>Zamani-Kord, Said</au><au>Malany, Siobhan</au><au>Bradbury, Margaret J</au><au>Hernandez, Lisa M</au><au>O’Brien, Zhihong</au><au>Wen, Jianyun</au><au>Wang, Hua</au><au>Hoare, Samuel R. J</au><au>Petroski, Robert E</au><au>Sacaan, Aida</au><au>Madan, Ajay</au><au>Crowe, Paul D</au><au>Beaton, Graham</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of Novel Selective H1-Antihistamines for Clinical Evaluation in the Treatment of Insomnia</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>5307</spage><epage>5310</epage><pages>5307-5310</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>Analogues of the known H1-antihistamine R-dimethindene were profiled as potential agents for the treatment of insomnia. Several highly selective compounds were efficacious in rodent sleep models. On the basis of overall profile, indene 1d and benzothiophene 2a had pharmacokinetic properties suitable for evaluation in night time dosing. Compound 2a did not show an in vivo cardiovascular effect from weak hERG channel inhibition.</abstract><cop>Columbus, OH</cop><pub>American Chemical Society</pub><pmid>19663387</pmid><doi>10.1021/jm900933k</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 2009-09, Vol.52 (17), p.5307-5310 |
| issn | 0022-2623 1520-4804 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_67626645 |
| source | ACS Publications; MEDLINE |
| subjects | Animals Biological and medical sciences Brain - metabolism Dimethindene - metabolism Dimethindene - pharmacokinetics Dimethindene - pharmacology Dimethindene - therapeutic use Electroencephalography - drug effects Ether-A-Go-Go Potassium Channels - antagonists & inhibitors Histamine H1 Antagonists - metabolism Histamine H1 Antagonists - pharmacokinetics Histamine H1 Antagonists - pharmacology Histamine H1 Antagonists - therapeutic use Humans Medical sciences Miscellaneous Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Pharmacology. Drug treatments Rats Receptors, Muscarinic - metabolism Sleep - drug effects Sleep Initiation and Maintenance Disorders - drug therapy Substrate Specificity |
| title | Characterization of Novel Selective H1-Antihistamines for Clinical Evaluation in the Treatment of Insomnia |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T10%3A42%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Characterization%20of%20Novel%20Selective%20H1-Antihistamines%20for%20Clinical%20Evaluation%20in%20the%20Treatment%20of%20Insomnia&rft.jtitle=Journal%20of%20medicinal%20chemistry&rft.au=Moree,%20Wilna%20J&rft.date=2009-09-10&rft.volume=52&rft.issue=17&rft.spage=5307&rft.epage=5310&rft.pages=5307-5310&rft.issn=0022-2623&rft.eissn=1520-4804&rft.coden=JMCMAR&rft_id=info:doi/10.1021/jm900933k&rft_dat=%3Cproquest_pubme%3E67626645%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=67626645&rft_id=info:pmid/19663387&rfr_iscdi=true |