Tricyclic azepine derivatives as selective brain penetrant 5-HT6 receptor antagonists
Starting from a benzazepine sulfonamide 5-HT(6) receptor antagonist lead with limited brain penetration, application of a strategy of conformational constraint and reduction of hydrogen bond donor count led to a novel series of tricyclic derivatives with high 5-HT(6) receptor affinity and excellent...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2008-10, Vol.18 (20), p.5698-5700 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | TRANI, Giancarlo BADDELEY, Stuart M QUINN, Leann P RAY, Alison M RIVERS, Dean A STEAN, Tania O STEMP, Geoffrey TRAIL, Brenda K WITTY, David R BRIGGS, Michael A CHUANG, Tsu T DEEKS, Nigel J JOHNSON, Christopher N KHAZRAGI, Abir A MEAD, Tania L MEDHURST, Andrew D MILNER, Peter H |
| description | Starting from a benzazepine sulfonamide 5-HT(6) receptor antagonist lead with limited brain penetration, application of a strategy of conformational constraint and reduction of hydrogen bond donor count led to a novel series of tricyclic derivatives with high 5-HT(6) receptor affinity and excellent brain:blood ratios. |
| doi_str_mv | 10.1016/j.bmcl.2008.08.010 |
| format | Article |
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Neurotransmission. Receptors</subject><subject>Pharmacology. Drug treatments</subject><subject>Protein Isoforms</subject><subject>Rats</subject><subject>Receptors, Serotonin - chemistry</subject><subject>Serotonin Antagonists - chemical synthesis</subject><subject>Serotonin Antagonists - pharmacology</subject><subject>Serotoninergic system</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1LxDAQhoMo7rr6BzxILnprnTRp2hxF1BUWvOyCt5CmU8nSL5PuwvrrbdlFYWCYmWfew0PILYOYAZOP27hobB0nAHk8FYMzMmdCiogLSM_JHJSEKFfic0auQtgCMAFCXJIZyzPFc5HPyWbtnT3Y2llqfrB3LdISvdubwe0xUBNowBrtNNHCG9fSHlscvGkHmkbLtaQeLfZD5-m4Ml9d68IQrslFZeqAN6e-IJvXl_XzMlp9vL0_P60imwg5RFZlMi8zzk0OsjQVFwjKCKZ4oRJkRalEhcyUAhC4QpmVIG0KwqbjpUw4X5CHY27vu-8dhkE3Llisa9NitwtaKpllo4URTI6g9V0IHivde9cYf9AM9CRTb_UkU08y9VQMxqe7U_quaLD8fznZG4H7E2CCNXU1WrEu_HEJZCpngvNfOzh-xw</recordid><startdate>20081015</startdate><enddate>20081015</enddate><creator>TRANI, Giancarlo</creator><creator>BADDELEY, Stuart M</creator><creator>QUINN, Leann P</creator><creator>RAY, Alison M</creator><creator>RIVERS, Dean A</creator><creator>STEAN, Tania O</creator><creator>STEMP, Geoffrey</creator><creator>TRAIL, Brenda K</creator><creator>WITTY, David R</creator><creator>BRIGGS, Michael A</creator><creator>CHUANG, Tsu T</creator><creator>DEEKS, Nigel J</creator><creator>JOHNSON, Christopher N</creator><creator>KHAZRAGI, Abir A</creator><creator>MEAD, Tania L</creator><creator>MEDHURST, Andrew D</creator><creator>MILNER, Peter H</creator><general>Elsevier</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>20081015</creationdate><title>Tricyclic azepine derivatives as selective brain penetrant 5-HT6 receptor antagonists</title><author>TRANI, Giancarlo ; BADDELEY, Stuart M ; QUINN, Leann P ; RAY, Alison M ; RIVERS, Dean A ; STEAN, Tania O ; STEMP, Geoffrey ; TRAIL, Brenda K ; WITTY, David R ; BRIGGS, Michael A ; CHUANG, Tsu T ; DEEKS, Nigel J ; JOHNSON, Christopher N ; KHAZRAGI, Abir A ; MEAD, Tania L ; MEDHURST, Andrew D ; MILNER, Peter H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c246t-c9768d733a806daf34e09a4193b92e1bd94fe1ad40e039e67d06c504c5d94d233</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Antidepressive Agents, Tricyclic - chemical synthesis</topic><topic>Antidepressive Agents, Tricyclic - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Blood-Brain Barrier - drug effects</topic><topic>Brain - drug effects</topic><topic>Chemistry, Pharmaceutical - methods</topic><topic>Cytochrome P-450 CYP3A</topic><topic>Cytochrome P-450 Enzyme System - chemistry</topic><topic>Humans</topic><topic>Hydrogen Bonding</topic><topic>Medical sciences</topic><topic>Microsomes - drug effects</topic><topic>Models, Chemical</topic><topic>Molecular Conformation</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>Pharmacology. 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| subjects | Animals Antidepressive Agents, Tricyclic - chemical synthesis Antidepressive Agents, Tricyclic - pharmacology Biological and medical sciences Blood-Brain Barrier - drug effects Brain - drug effects Chemistry, Pharmaceutical - methods Cytochrome P-450 CYP3A Cytochrome P-450 Enzyme System - chemistry Humans Hydrogen Bonding Medical sciences Microsomes - drug effects Models, Chemical Molecular Conformation Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Pharmacology. Drug treatments Protein Isoforms Rats Receptors, Serotonin - chemistry Serotonin Antagonists - chemical synthesis Serotonin Antagonists - pharmacology Serotoninergic system |
| title | Tricyclic azepine derivatives as selective brain penetrant 5-HT6 receptor antagonists |
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