3,4-Fused cyclohexyl sulfones as γ-secretase inhibitors
The identification of a potent γ-secretase inhibitor, for example (ED 50 = 0.06 nM), is reported. The 3,4-fused sulfamides, sulfonamides and sulfone have been identified as highly potent γ-secretase inhibitors. Evaluation of the SAR of substitution within these series has allowed the identification...
Gespeichert in:
| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2006-06, Vol.16 (11), p.3073-3077 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 3077 |
|---|---|
| container_issue | 11 |
| container_start_page | 3073 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 16 |
| creator | Shaw, Duncan Best, Jonathan Dinnell, Kevin Nadin, Alan Shearman, Mark Pattison, Christine Peachey, James Reilly, Michael Williams, Brian Wrigley, Jonathan Harrison, Timothy |
| description | The identification of a potent γ-secretase inhibitor, for example (ED
50
=
0.06
nM), is reported.
The 3,4-fused sulfamides, sulfonamides and sulfone have been identified as highly potent γ-secretase inhibitors. Evaluation of the SAR of substitution within these series has allowed the identification of a range of compounds which significantly reduce brain Aβ in transgenic mouse models and thus have potential as possible treatments for Alzheimer’s disease. |
| doi_str_mv | 10.1016/j.bmcl.2005.12.083 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67889427</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0960894X06000175</els_id><sourcerecordid>17147008</sourcerecordid><originalsourceid>FETCH-LOGICAL-c330t-9b07f1c914dd00c3692236a04afa99efbce097c6ce70e5d93d05071612644fe33</originalsourceid><addsrcrecordid>eNqFkMFq3DAQhkVJaTbbvkAOwZf0VLsjS5YsyCWEpi0EemkgNyGPx0SL1040dug-V9-jz1Qvu5Bbe5rL9__88wlxLqGQIM3nTdFssS9KgKqQZQG1eiNWUhudKw3ViViBM5DXTj-cijPmDYDUoPU7cSqNkXapWIlafdL57czUZrjDfnykX7s-47nvxoE4C5z9-Z0zYaIpMGVxeIxNnMbE78XbLvRMH453Le5vv_y8-Zbf_fj6_eb6LkelYMpdA7aT6KRuWwBUxpWlMgF06IJz1DVI4CwaJAtUtU61UIGVRpZG646UWouPh96nND7PxJPfRkbq-zDQOLM3tl4-LO1_QWmltrBIWovyAGIamRN1_inFbUg7L8HvxfqN34v1e7Feln7JLKGLY_vcbKl9jRxNLsDlEQiMoe9SGDDyK2ct1KaChbs6cLRIe4mUPGOkAamNiXDy7Rj_teMvYmmViA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17147008</pqid></control><display><type>article</type><title>3,4-Fused cyclohexyl sulfones as γ-secretase inhibitors</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Shaw, Duncan ; Best, Jonathan ; Dinnell, Kevin ; Nadin, Alan ; Shearman, Mark ; Pattison, Christine ; Peachey, James ; Reilly, Michael ; Williams, Brian ; Wrigley, Jonathan ; Harrison, Timothy</creator><creatorcontrib>Shaw, Duncan ; Best, Jonathan ; Dinnell, Kevin ; Nadin, Alan ; Shearman, Mark ; Pattison, Christine ; Peachey, James ; Reilly, Michael ; Williams, Brian ; Wrigley, Jonathan ; Harrison, Timothy</creatorcontrib><description>The identification of a potent γ-secretase inhibitor, for example (ED
50
=
0.06
nM), is reported.
The 3,4-fused sulfamides, sulfonamides and sulfone have been identified as highly potent γ-secretase inhibitors. Evaluation of the SAR of substitution within these series has allowed the identification of a range of compounds which significantly reduce brain Aβ in transgenic mouse models and thus have potential as possible treatments for Alzheimer’s disease.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2005.12.083</identifier><identifier>PMID: 16617016</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Alzheimer’s disease ; Amyloid Precursor Protein Secretases ; Animals ; Aspartic Acid Endopeptidases ; Biological and medical sciences ; Crystallography, X-Ray ; Cyclization ; Endopeptidases - metabolism ; Medical sciences ; Models, Molecular ; Molecular Structure ; Neuropharmacology ; Pharmacology. Drug treatments ; Protease Inhibitors - chemical synthesis ; Protease Inhibitors - chemistry ; Protease Inhibitors - pharmacology ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) ; Psychology. Psychoanalysis. Psychiatry ; Psychopharmacology ; Rats ; Structure-Activity Relationship ; Sulfones ; Sulfones - chemical synthesis ; Sulfones - chemistry ; Sulfones - pharmacology ; γ-Secretase inhibitors</subject><ispartof>Bioorganic & medicinal chemistry letters, 2006-06, Vol.16 (11), p.3073-3077</ispartof><rights>2006 Elsevier Ltd</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c330t-9b07f1c914dd00c3692236a04afa99efbce097c6ce70e5d93d05071612644fe33</citedby><cites>FETCH-LOGICAL-c330t-9b07f1c914dd00c3692236a04afa99efbce097c6ce70e5d93d05071612644fe33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmcl.2005.12.083$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17708650$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16617016$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shaw, Duncan</creatorcontrib><creatorcontrib>Best, Jonathan</creatorcontrib><creatorcontrib>Dinnell, Kevin</creatorcontrib><creatorcontrib>Nadin, Alan</creatorcontrib><creatorcontrib>Shearman, Mark</creatorcontrib><creatorcontrib>Pattison, Christine</creatorcontrib><creatorcontrib>Peachey, James</creatorcontrib><creatorcontrib>Reilly, Michael</creatorcontrib><creatorcontrib>Williams, Brian</creatorcontrib><creatorcontrib>Wrigley, Jonathan</creatorcontrib><creatorcontrib>Harrison, Timothy</creatorcontrib><title>3,4-Fused cyclohexyl sulfones as γ-secretase inhibitors</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>The identification of a potent γ-secretase inhibitor, for example (ED
50
=
0.06
nM), is reported.
The 3,4-fused sulfamides, sulfonamides and sulfone have been identified as highly potent γ-secretase inhibitors. Evaluation of the SAR of substitution within these series has allowed the identification of a range of compounds which significantly reduce brain Aβ in transgenic mouse models and thus have potential as possible treatments for Alzheimer’s disease.</description><subject>Alzheimer’s disease</subject><subject>Amyloid Precursor Protein Secretases</subject><subject>Animals</subject><subject>Aspartic Acid Endopeptidases</subject><subject>Biological and medical sciences</subject><subject>Crystallography, X-Ray</subject><subject>Cyclization</subject><subject>Endopeptidases - metabolism</subject><subject>Medical sciences</subject><subject>Models, Molecular</subject><subject>Molecular Structure</subject><subject>Neuropharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Protease Inhibitors - chemical synthesis</subject><subject>Protease Inhibitors - chemistry</subject><subject>Protease Inhibitors - pharmacology</subject><subject>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopharmacology</subject><subject>Rats</subject><subject>Structure-Activity Relationship</subject><subject>Sulfones</subject><subject>Sulfones - chemical synthesis</subject><subject>Sulfones - chemistry</subject><subject>Sulfones - pharmacology</subject><subject>γ-Secretase inhibitors</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMFq3DAQhkVJaTbbvkAOwZf0VLsjS5YsyCWEpi0EemkgNyGPx0SL1040dug-V9-jz1Qvu5Bbe5rL9__88wlxLqGQIM3nTdFssS9KgKqQZQG1eiNWUhudKw3ViViBM5DXTj-cijPmDYDUoPU7cSqNkXapWIlafdL57czUZrjDfnykX7s-47nvxoE4C5z9-Z0zYaIpMGVxeIxNnMbE78XbLvRMH453Le5vv_y8-Zbf_fj6_eb6LkelYMpdA7aT6KRuWwBUxpWlMgF06IJz1DVI4CwaJAtUtU61UIGVRpZG646UWouPh96nND7PxJPfRkbq-zDQOLM3tl4-LO1_QWmltrBIWovyAGIamRN1_inFbUg7L8HvxfqN34v1e7Feln7JLKGLY_vcbKl9jRxNLsDlEQiMoe9SGDDyK2ct1KaChbs6cLRIe4mUPGOkAamNiXDy7Rj_teMvYmmViA</recordid><startdate>20060601</startdate><enddate>20060601</enddate><creator>Shaw, Duncan</creator><creator>Best, Jonathan</creator><creator>Dinnell, Kevin</creator><creator>Nadin, Alan</creator><creator>Shearman, Mark</creator><creator>Pattison, Christine</creator><creator>Peachey, James</creator><creator>Reilly, Michael</creator><creator>Williams, Brian</creator><creator>Wrigley, Jonathan</creator><creator>Harrison, Timothy</creator><general>Elsevier Ltd</general><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>7QO</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20060601</creationdate><title>3,4-Fused cyclohexyl sulfones as γ-secretase inhibitors</title><author>Shaw, Duncan ; Best, Jonathan ; Dinnell, Kevin ; Nadin, Alan ; Shearman, Mark ; Pattison, Christine ; Peachey, James ; Reilly, Michael ; Williams, Brian ; Wrigley, Jonathan ; Harrison, Timothy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c330t-9b07f1c914dd00c3692236a04afa99efbce097c6ce70e5d93d05071612644fe33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Alzheimer’s disease</topic><topic>Amyloid Precursor Protein Secretases</topic><topic>Animals</topic><topic>Aspartic Acid Endopeptidases</topic><topic>Biological and medical sciences</topic><topic>Crystallography, X-Ray</topic><topic>Cyclization</topic><topic>Endopeptidases - metabolism</topic><topic>Medical sciences</topic><topic>Models, Molecular</topic><topic>Molecular Structure</topic><topic>Neuropharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Protease Inhibitors - chemical synthesis</topic><topic>Protease Inhibitors - chemistry</topic><topic>Protease Inhibitors - pharmacology</topic><topic>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopharmacology</topic><topic>Rats</topic><topic>Structure-Activity Relationship</topic><topic>Sulfones</topic><topic>Sulfones - chemical synthesis</topic><topic>Sulfones - chemistry</topic><topic>Sulfones - pharmacology</topic><topic>γ-Secretase inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shaw, Duncan</creatorcontrib><creatorcontrib>Best, Jonathan</creatorcontrib><creatorcontrib>Dinnell, Kevin</creatorcontrib><creatorcontrib>Nadin, Alan</creatorcontrib><creatorcontrib>Shearman, Mark</creatorcontrib><creatorcontrib>Pattison, Christine</creatorcontrib><creatorcontrib>Peachey, James</creatorcontrib><creatorcontrib>Reilly, Michael</creatorcontrib><creatorcontrib>Williams, Brian</creatorcontrib><creatorcontrib>Wrigley, Jonathan</creatorcontrib><creatorcontrib>Harrison, Timothy</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>Biotechnology Research Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shaw, Duncan</au><au>Best, Jonathan</au><au>Dinnell, Kevin</au><au>Nadin, Alan</au><au>Shearman, Mark</au><au>Pattison, Christine</au><au>Peachey, James</au><au>Reilly, Michael</au><au>Williams, Brian</au><au>Wrigley, Jonathan</au><au>Harrison, Timothy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>3,4-Fused cyclohexyl sulfones as γ-secretase inhibitors</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2006-06-01</date><risdate>2006</risdate><volume>16</volume><issue>11</issue><spage>3073</spage><epage>3077</epage><pages>3073-3077</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>The identification of a potent γ-secretase inhibitor, for example (ED
50
=
0.06
nM), is reported.
The 3,4-fused sulfamides, sulfonamides and sulfone have been identified as highly potent γ-secretase inhibitors. Evaluation of the SAR of substitution within these series has allowed the identification of a range of compounds which significantly reduce brain Aβ in transgenic mouse models and thus have potential as possible treatments for Alzheimer’s disease.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>16617016</pmid><doi>10.1016/j.bmcl.2005.12.083</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2006-06, Vol.16 (11), p.3073-3077 |
| issn | 0960-894X 1464-3405 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_67889427 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Alzheimer’s disease Amyloid Precursor Protein Secretases Animals Aspartic Acid Endopeptidases Biological and medical sciences Crystallography, X-Ray Cyclization Endopeptidases - metabolism Medical sciences Models, Molecular Molecular Structure Neuropharmacology Pharmacology. Drug treatments Protease Inhibitors - chemical synthesis Protease Inhibitors - chemistry Protease Inhibitors - pharmacology Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychopharmacology Rats Structure-Activity Relationship Sulfones Sulfones - chemical synthesis Sulfones - chemistry Sulfones - pharmacology γ-Secretase inhibitors |
| title | 3,4-Fused cyclohexyl sulfones as γ-secretase inhibitors |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-03T15%3A15%3A32IST&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=3,4-Fused%20cyclohexyl%20sulfones%20as%20%CE%B3-secretase%20inhibitors&rft.jtitle=Bioorganic%20&%20medicinal%20chemistry%20letters&rft.au=Shaw,%20Duncan&rft.date=2006-06-01&rft.volume=16&rft.issue=11&rft.spage=3073&rft.epage=3077&rft.pages=3073-3077&rft.issn=0960-894X&rft.eissn=1464-3405&rft_id=info:doi/10.1016/j.bmcl.2005.12.083&rft_dat=%3Cproquest_cross%3E17147008%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=17147008&rft_id=info:pmid/16617016&rft_els_id=S0960894X06000175&rfr_iscdi=true |