Optimisation of a series of potent, selective and orally bioavailable GlyT1 inhibitors
A series of heterocyclic sulfonamides have been developed which are potent and selective inhibitors of hGlyT1. SAR studies to optimise the in vitro and in vivo properties are described. Optimisation of the central scaffold resulted in cyclohexane sulfones 28 and 29, which have good PK properties and...
Gespeichert in:
| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2009-04, Vol.19 (8), p.2235-2239 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2239 |
|---|---|
| container_issue | 8 |
| container_start_page | 2235 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 19 |
| creator | Thomson, Joanne L. Blackaby, Wesley P. Jennings, Andrew S.R. Goodacre, Simon C. Pike, Andrew Thomas, Steve Brown, Terry A. Smith, Alison Pillai, Gopalan Street, Leslie J. Lewis, Richard T. |
| description | A series of heterocyclic sulfonamides have been developed which are potent and selective inhibitors of hGlyT1. SAR studies to optimise the in vitro and in vivo properties are described. Optimisation of the central scaffold resulted in cyclohexane sulfones
28 and
29, which have good PK properties and show promise for further development.
A series of heterocyclic sulfonamides have been developed which are potent and selective inhibitors of hGlyT1. SAR studies to optimise the in vitro and in vivo properties are described. Optimisation of the central scaffold resulted in cyclohexane sulfones
28 and
29, which have good PK properties and show promise for further development. |
| doi_str_mv | 10.1016/j.bmcl.2009.02.102 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67111373</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0960894X09002479</els_id><sourcerecordid>67111373</sourcerecordid><originalsourceid>FETCH-LOGICAL-c385t-e8c158916aa86b92023539678ef647e7cbfbbf2f9ac72eccfcf44067dff8d743</originalsourceid><addsrcrecordid>eNqFkE1LAzEQhoMotn78AQ-yJ09uTbLZJAteRLQKgpci3kKSnWBKuqnJttB_7y4teNPTDC_PvDAPQlcEzwgm_G45MysbZhTjZobpkNEjNCWMs7JiuD5GU9xwXMqGfU7QWc5LjAnDjJ2iCWkqIimTU_Txvu79ymfd-9gV0RW6yJA85HFfxx66_nZIAtjeb6HQXVvEpEPYFcZHvdU-aBOgmIfdghS--_LG9zHlC3TidMhweZjnaPH8tHh8Kd_e56-PD2-lrWTdlyAtqWVDuNaSm4ZiWtVVw4UEx5kAYY0zxlHXaCsoWOusYwxz0TonW8Gqc3Szr12n-L2B3KvhFQsh6A7iJisuCCGVqP4FKa4pE3xspHvQpphzAqfWya902imC1WhdLdVoXY3WFaZDRoej60P7xqyg_T05aB6A-z0Ag4uth6Sy9dBZaH0azKo2-r_6fwA_UZQi</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>20524764</pqid></control><display><type>article</type><title>Optimisation of a series of potent, selective and orally bioavailable GlyT1 inhibitors</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Thomson, Joanne L. ; Blackaby, Wesley P. ; Jennings, Andrew S.R. ; Goodacre, Simon C. ; Pike, Andrew ; Thomas, Steve ; Brown, Terry A. ; Smith, Alison ; Pillai, Gopalan ; Street, Leslie J. ; Lewis, Richard T.</creator><creatorcontrib>Thomson, Joanne L. ; Blackaby, Wesley P. ; Jennings, Andrew S.R. ; Goodacre, Simon C. ; Pike, Andrew ; Thomas, Steve ; Brown, Terry A. ; Smith, Alison ; Pillai, Gopalan ; Street, Leslie J. ; Lewis, Richard T.</creatorcontrib><description>A series of heterocyclic sulfonamides have been developed which are potent and selective inhibitors of hGlyT1. SAR studies to optimise the in vitro and in vivo properties are described. Optimisation of the central scaffold resulted in cyclohexane sulfones
28 and
29, which have good PK properties and show promise for further development.
A series of heterocyclic sulfonamides have been developed which are potent and selective inhibitors of hGlyT1. SAR studies to optimise the in vitro and in vivo properties are described. Optimisation of the central scaffold resulted in cyclohexane sulfones
28 and
29, which have good PK properties and show promise for further development.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2009.02.102</identifier><identifier>PMID: 19318248</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Administration, Oral ; Animals ; Bioavailable ; Biological Availability ; Glycine Plasma Membrane Transport Proteins - antagonists & inhibitors ; Glycine Plasma Membrane Transport Proteins - metabolism ; Glycine transporter ; GLYT1 ; Humans ; Inhibitor ; Male ; Microsomes, Liver - chemistry ; Microsomes, Liver - metabolism ; NMDA ; Pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Schizophrenia ; Sulfonamides - administration & dosage ; Sulfonamides - chemistry ; Sulfonamides - metabolism ; Triazoles - administration & dosage ; Triazoles - chemical synthesis</subject><ispartof>Bioorganic & medicinal chemistry letters, 2009-04, Vol.19 (8), p.2235-2239</ispartof><rights>2009 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c385t-e8c158916aa86b92023539678ef647e7cbfbbf2f9ac72eccfcf44067dff8d743</citedby><cites>FETCH-LOGICAL-c385t-e8c158916aa86b92023539678ef647e7cbfbbf2f9ac72eccfcf44067dff8d743</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X09002479$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19318248$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Thomson, Joanne L.</creatorcontrib><creatorcontrib>Blackaby, Wesley P.</creatorcontrib><creatorcontrib>Jennings, Andrew S.R.</creatorcontrib><creatorcontrib>Goodacre, Simon C.</creatorcontrib><creatorcontrib>Pike, Andrew</creatorcontrib><creatorcontrib>Thomas, Steve</creatorcontrib><creatorcontrib>Brown, Terry A.</creatorcontrib><creatorcontrib>Smith, Alison</creatorcontrib><creatorcontrib>Pillai, Gopalan</creatorcontrib><creatorcontrib>Street, Leslie J.</creatorcontrib><creatorcontrib>Lewis, Richard T.</creatorcontrib><title>Optimisation of a series of potent, selective and orally bioavailable GlyT1 inhibitors</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>A series of heterocyclic sulfonamides have been developed which are potent and selective inhibitors of hGlyT1. SAR studies to optimise the in vitro and in vivo properties are described. Optimisation of the central scaffold resulted in cyclohexane sulfones
28 and
29, which have good PK properties and show promise for further development.
A series of heterocyclic sulfonamides have been developed which are potent and selective inhibitors of hGlyT1. SAR studies to optimise the in vitro and in vivo properties are described. Optimisation of the central scaffold resulted in cyclohexane sulfones
28 and
29, which have good PK properties and show promise for further development.</description><subject>Administration, Oral</subject><subject>Animals</subject><subject>Bioavailable</subject><subject>Biological Availability</subject><subject>Glycine Plasma Membrane Transport Proteins - antagonists & inhibitors</subject><subject>Glycine Plasma Membrane Transport Proteins - metabolism</subject><subject>Glycine transporter</subject><subject>GLYT1</subject><subject>Humans</subject><subject>Inhibitor</subject><subject>Male</subject><subject>Microsomes, Liver - chemistry</subject><subject>Microsomes, Liver - metabolism</subject><subject>NMDA</subject><subject>Pharmacokinetics</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Schizophrenia</subject><subject>Sulfonamides - administration & dosage</subject><subject>Sulfonamides - chemistry</subject><subject>Sulfonamides - metabolism</subject><subject>Triazoles - administration & dosage</subject><subject>Triazoles - chemical synthesis</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1LAzEQhoMotn78AQ-yJ09uTbLZJAteRLQKgpci3kKSnWBKuqnJttB_7y4teNPTDC_PvDAPQlcEzwgm_G45MysbZhTjZobpkNEjNCWMs7JiuD5GU9xwXMqGfU7QWc5LjAnDjJ2iCWkqIimTU_Txvu79ymfd-9gV0RW6yJA85HFfxx66_nZIAtjeb6HQXVvEpEPYFcZHvdU-aBOgmIfdghS--_LG9zHlC3TidMhweZjnaPH8tHh8Kd_e56-PD2-lrWTdlyAtqWVDuNaSm4ZiWtVVw4UEx5kAYY0zxlHXaCsoWOusYwxz0TonW8Gqc3Szr12n-L2B3KvhFQsh6A7iJisuCCGVqP4FKa4pE3xspHvQpphzAqfWya902imC1WhdLdVoXY3WFaZDRoej60P7xqyg_T05aB6A-z0Ag4uth6Sy9dBZaH0azKo2-r_6fwA_UZQi</recordid><startdate>20090415</startdate><enddate>20090415</enddate><creator>Thomson, Joanne L.</creator><creator>Blackaby, Wesley P.</creator><creator>Jennings, Andrew S.R.</creator><creator>Goodacre, Simon C.</creator><creator>Pike, Andrew</creator><creator>Thomas, Steve</creator><creator>Brown, Terry A.</creator><creator>Smith, Alison</creator><creator>Pillai, Gopalan</creator><creator>Street, Leslie J.</creator><creator>Lewis, Richard T.</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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20090415</creationdate><title>Optimisation of a series of potent, selective and orally bioavailable GlyT1 inhibitors</title><author>Thomson, Joanne L. ; Blackaby, Wesley P. ; Jennings, Andrew S.R. ; Goodacre, Simon C. ; Pike, Andrew ; Thomas, Steve ; Brown, Terry A. ; Smith, Alison ; Pillai, Gopalan ; Street, Leslie J. ; Lewis, Richard T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c385t-e8c158916aa86b92023539678ef647e7cbfbbf2f9ac72eccfcf44067dff8d743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Administration, Oral</topic><topic>Animals</topic><topic>Bioavailable</topic><topic>Biological Availability</topic><topic>Glycine Plasma Membrane Transport Proteins - antagonists & inhibitors</topic><topic>Glycine Plasma Membrane Transport Proteins - metabolism</topic><topic>Glycine transporter</topic><topic>GLYT1</topic><topic>Humans</topic><topic>Inhibitor</topic><topic>Male</topic><topic>Microsomes, Liver - chemistry</topic><topic>Microsomes, Liver - metabolism</topic><topic>NMDA</topic><topic>Pharmacokinetics</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Schizophrenia</topic><topic>Sulfonamides - administration & dosage</topic><topic>Sulfonamides - chemistry</topic><topic>Sulfonamides - metabolism</topic><topic>Triazoles - administration & dosage</topic><topic>Triazoles - chemical synthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Thomson, Joanne L.</creatorcontrib><creatorcontrib>Blackaby, Wesley P.</creatorcontrib><creatorcontrib>Jennings, Andrew S.R.</creatorcontrib><creatorcontrib>Goodacre, Simon C.</creatorcontrib><creatorcontrib>Pike, Andrew</creatorcontrib><creatorcontrib>Thomas, Steve</creatorcontrib><creatorcontrib>Brown, Terry A.</creatorcontrib><creatorcontrib>Smith, Alison</creatorcontrib><creatorcontrib>Pillai, Gopalan</creatorcontrib><creatorcontrib>Street, Leslie J.</creatorcontrib><creatorcontrib>Lewis, Richard T.</creatorcontrib><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>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>Thomson, Joanne L.</au><au>Blackaby, Wesley P.</au><au>Jennings, Andrew S.R.</au><au>Goodacre, Simon C.</au><au>Pike, Andrew</au><au>Thomas, Steve</au><au>Brown, Terry A.</au><au>Smith, Alison</au><au>Pillai, Gopalan</au><au>Street, Leslie J.</au><au>Lewis, Richard T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Optimisation of a series of potent, selective and orally bioavailable GlyT1 inhibitors</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2009-04-15</date><risdate>2009</risdate><volume>19</volume><issue>8</issue><spage>2235</spage><epage>2239</epage><pages>2235-2239</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>A series of heterocyclic sulfonamides have been developed which are potent and selective inhibitors of hGlyT1. SAR studies to optimise the in vitro and in vivo properties are described. Optimisation of the central scaffold resulted in cyclohexane sulfones
28 and
29, which have good PK properties and show promise for further development.
A series of heterocyclic sulfonamides have been developed which are potent and selective inhibitors of hGlyT1. SAR studies to optimise the in vitro and in vivo properties are described. Optimisation of the central scaffold resulted in cyclohexane sulfones
28 and
29, which have good PK properties and show promise for further development.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>19318248</pmid><doi>10.1016/j.bmcl.2009.02.102</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2009-04, Vol.19 (8), p.2235-2239 |
| issn | 0960-894X 1464-3405 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_67111373 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Administration, Oral Animals Bioavailable Biological Availability Glycine Plasma Membrane Transport Proteins - antagonists & inhibitors Glycine Plasma Membrane Transport Proteins - metabolism Glycine transporter GLYT1 Humans Inhibitor Male Microsomes, Liver - chemistry Microsomes, Liver - metabolism NMDA Pharmacokinetics Rats Rats, Sprague-Dawley Schizophrenia Sulfonamides - administration & dosage Sulfonamides - chemistry Sulfonamides - metabolism Triazoles - administration & dosage Triazoles - chemical synthesis |
| title | Optimisation of a series of potent, selective and orally bioavailable GlyT1 inhibitors |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T04%3A20%3A24IST&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=Optimisation%20of%20a%20series%20of%20potent,%20selective%20and%20orally%20bioavailable%20GlyT1%20inhibitors&rft.jtitle=Bioorganic%20&%20medicinal%20chemistry%20letters&rft.au=Thomson,%20Joanne%20L.&rft.date=2009-04-15&rft.volume=19&rft.issue=8&rft.spage=2235&rft.epage=2239&rft.pages=2235-2239&rft.issn=0960-894X&rft.eissn=1464-3405&rft_id=info:doi/10.1016/j.bmcl.2009.02.102&rft_dat=%3Cproquest_cross%3E67111373%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=20524764&rft_id=info:pmid/19318248&rft_els_id=S0960894X09002479&rfr_iscdi=true |