Lactam and oxazolidinone derived potent 5-hydroxytryptamine 6 receptor antagonists
Lactam and oxazolidinone derived potent 5-hydroxytryptamine 6 (5-HT6) receptor antagonists have been disclosed. One potent member from the lactam series, racemic compound 14 (Ki of 2.6nM in binding assay, IC50 of 15nM in functional cAMP antagonism assay) was separated into corresponding enantiomers...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2014-05, Vol.24 (9), p.2094-2097 |
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| container_end_page | 2097 |
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| container_issue | 9 |
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| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 24 |
| creator | Hostetler, Greg Dunn, Derek McKenna, Beth Ann Kopec, Karla Chatterjee, Sankar |
| description | Lactam and oxazolidinone derived potent 5-hydroxytryptamine 6 (5-HT6) receptor antagonists have been disclosed. One potent member from the lactam series, racemic compound 14 (Ki of 2.6nM in binding assay, IC50 of 15nM in functional cAMP antagonism assay) was separated into corresponding enantiomers that displayed the effect of chirality on binding potency (Ki of 1.6nM and 3000nM, respectively). The potent enantiomer displayed an IC50 of 8nM in cAMP antagonism assay, selectivity against a number of family members as well as brain permeability in rats after 6h post oral administration. |
| doi_str_mv | 10.1016/j.bmcl.2014.03.049 |
| format | Article |
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The potent enantiomer displayed an IC50 of 8nM in cAMP antagonism assay, selectivity against a number of family members as well as brain permeability in rats after 6h post oral administration.</description><subject>5-Hydroxytryptamine</subject><subject>Animals</subject><subject>Antagonist</subject><subject>Brain - metabolism</subject><subject>CNS</subject><subject>Humans</subject><subject>Lactam</subject><subject>Lactams - chemistry</subject><subject>Lactams - pharmacokinetics</subject><subject>Lactams - pharmacology</subject><subject>Oxazolidinone</subject><subject>Oxazolidinones - chemistry</subject><subject>Oxazolidinones - pharmacokinetics</subject><subject>Oxazolidinones - pharmacology</subject><subject>Rats</subject><subject>Receptors, Serotonin - metabolism</subject><subject>Serotonin Antagonists - chemistry</subject><subject>Serotonin Antagonists - pharmacokinetics</subject><subject>Serotonin Antagonists - pharmacology</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkM1q3DAYRUVJSSZpXiCL4GU2dj_9-QeyKSFtCgOFkkB3QpY-NRpsy5E0IdOnr6eTdFm6uptz7uIQckGhokDrj5uqH81QMaCiAl6B6N6RFRW1KLkAeURW0NVQtp34cUJOU9rAAoIQx-SEiQYEsGZFvq-1yXos9GSL8KJ_hcFbP4UJC4vRP6Mt5pBxyoUsH3c2hpddjrt5MfyC1EVEg3MOcfGz_hkmn3L6QN47PSQ8f90z8vD59v7mrlx_-_L15tO6NLztctk7RnvpJKMAlrqOd7WQPW8t19IZR7npG9bWzjbMatZKzR3TouGuRyOQMX5Grg6_cwxPW0xZjT4ZHAY9YdgmRSUXrZS86f4DpS0TnIs9yg6oiSGliE7N0Y867hQFtc-uNmqfXe2zK-AK_kiXr__bfkT7V3nrvADXBwCXIM8eo0rG42TQ-iVhVjb4f_3_BiuLlFo</recordid><startdate>20140501</startdate><enddate>20140501</enddate><creator>Hostetler, Greg</creator><creator>Dunn, Derek</creator><creator>McKenna, Beth Ann</creator><creator>Kopec, Karla</creator><creator>Chatterjee, Sankar</creator><general>Elsevier Ltd</general><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>20140501</creationdate><title>Lactam and oxazolidinone derived potent 5-hydroxytryptamine 6 receptor antagonists</title><author>Hostetler, Greg ; Dunn, Derek ; McKenna, Beth Ann ; Kopec, Karla ; Chatterjee, Sankar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-bf21b5f52100d1f939645b38d3a5fcf13cb7286fd72da285a3f2a473fbec4e223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>5-Hydroxytryptamine</topic><topic>Animals</topic><topic>Antagonist</topic><topic>Brain - metabolism</topic><topic>CNS</topic><topic>Humans</topic><topic>Lactam</topic><topic>Lactams - chemistry</topic><topic>Lactams - pharmacokinetics</topic><topic>Lactams - pharmacology</topic><topic>Oxazolidinone</topic><topic>Oxazolidinones - chemistry</topic><topic>Oxazolidinones - pharmacokinetics</topic><topic>Oxazolidinones - pharmacology</topic><topic>Rats</topic><topic>Receptors, Serotonin - metabolism</topic><topic>Serotonin Antagonists - chemistry</topic><topic>Serotonin Antagonists - pharmacokinetics</topic><topic>Serotonin Antagonists - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hostetler, Greg</creatorcontrib><creatorcontrib>Dunn, Derek</creatorcontrib><creatorcontrib>McKenna, Beth Ann</creatorcontrib><creatorcontrib>Kopec, Karla</creatorcontrib><creatorcontrib>Chatterjee, Sankar</creatorcontrib><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>Hostetler, Greg</au><au>Dunn, Derek</au><au>McKenna, Beth Ann</au><au>Kopec, Karla</au><au>Chatterjee, Sankar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lactam and oxazolidinone derived potent 5-hydroxytryptamine 6 receptor antagonists</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2014-05-01</date><risdate>2014</risdate><volume>24</volume><issue>9</issue><spage>2094</spage><epage>2097</epage><pages>2094-2097</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>Lactam and oxazolidinone derived potent 5-hydroxytryptamine 6 (5-HT6) receptor antagonists have been disclosed. One potent member from the lactam series, racemic compound 14 (Ki of 2.6nM in binding assay, IC50 of 15nM in functional cAMP antagonism assay) was separated into corresponding enantiomers that displayed the effect of chirality on binding potency (Ki of 1.6nM and 3000nM, respectively). The potent enantiomer displayed an IC50 of 8nM in cAMP antagonism assay, selectivity against a number of family members as well as brain permeability in rats after 6h post oral administration.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>24704027</pmid><doi>10.1016/j.bmcl.2014.03.049</doi><tpages>4</tpages></addata></record> |
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| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2014-05, Vol.24 (9), p.2094-2097 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | 5-Hydroxytryptamine Animals Antagonist Brain - metabolism CNS Humans Lactam Lactams - chemistry Lactams - pharmacokinetics Lactams - pharmacology Oxazolidinone Oxazolidinones - chemistry Oxazolidinones - pharmacokinetics Oxazolidinones - pharmacology Rats Receptors, Serotonin - metabolism Serotonin Antagonists - chemistry Serotonin Antagonists - pharmacokinetics Serotonin Antagonists - pharmacology |
| title | Lactam and oxazolidinone derived potent 5-hydroxytryptamine 6 receptor antagonists |
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