Discovery of N-(2-hydroxy-2-aryl-cyclohexyl) substituted spiropiperidines as GlyT1 antagonists with improved pharmacological profile
During SAR exploration of N-(2-aryl-cyclohexyl) substituted spiropiperidine as GlyT1 inhibitors, it was found that introduction of a hydroxy group in position 2 of the cyclohexyl residue considerably improves the pharmacological profile. In particular, reduction of the binding affinity at the nocice...
Gespeichert in:
| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2006-01, Vol.16 (2), p.354-357 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 357 |
|---|---|
| container_issue | 2 |
| container_start_page | 354 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 16 |
| creator | Ceccarelli, Simona M. Pinard, Emmanuel Stalder, Henri Alberati, Daniela |
| description | During SAR exploration of
N-(2-aryl-cyclohexyl) substituted spiropiperidine as GlyT1 inhibitors, it was found that introduction of a hydroxy group in position 2 of the cyclohexyl residue considerably improves the pharmacological profile. In particular, reduction of the binding affinity at the nociceptin/orphanin FQ peptide and the μ opioid receptors was achieved.
During SAR exploration of
N-(2-aryl-cyclohexyl) substituted spiropiperidine as GlyT1 inhibitors, it was found that introduction of an hydroxy group in position 2 of the cyclohexyl residue considerably improves the pharmacological profile. In particular, reduction of the binding affinity at the nociceptin/orphanin FQ peptide and the μ opioid receptors was achieved. |
| doi_str_mv | 10.1016/j.bmcl.2005.09.067 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_70190218</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0960894X05012473</els_id><sourcerecordid>70190218</sourcerecordid><originalsourceid>FETCH-LOGICAL-c409t-32f4eb6c996bc8da35ce4671df5534a2f813ea7b4a1baedb5079cd0806c350273</originalsourceid><addsrcrecordid>eNp9kE1v1DAQhiMEotvCH-CAfAHBIWHs2M5G4oJKKUgVXIrEzXLsSdcrJw52Upo7PxyvdqXeOI00et75eIriFYWKApUf9lU3GF8xAFFBW4FsnhQbyiUvaw7iabGBVkK5bfmvs-I8pT0A5cD58-KMSsalkHRT_P3skgn3GFcSevK9fMfK3WpjeFhLVuq4-tKsxocdPqz-PUlLl2Y3LzNakiYXw-QmjM66ERPRiVz79ZYSPc76LowuzYn8cfOOuGGKeYcl007HQZvgw50z2pPc7p3HF8WzXvuEL0_1ovj55er28mt58-P62-Wnm9JwaOeyZj3HTpq2lZ3ZWl0Lg1w21PZC1Fyzfktr1E3HNe002k5A0xoLW5CmFsCa-qJ4e5yb9_5eMM1qyN-j93rEsCTVAG2B0W0G2RE0MaQUsVdTdEPWoSiog3u1Vwf36uBeQauy-xx6fZq-dAPax8hJdgbenACd8vd91KNx6ZFrWFsLJjL38chhdnHvMKpkHI4GrYtoZmWD-98d_wAPI6Vy</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>70190218</pqid></control><display><type>article</type><title>Discovery of N-(2-hydroxy-2-aryl-cyclohexyl) substituted spiropiperidines as GlyT1 antagonists with improved pharmacological profile</title><source>ScienceDirect</source><source>MEDLINE</source><creator>Ceccarelli, Simona M. ; Pinard, Emmanuel ; Stalder, Henri ; Alberati, Daniela</creator><creatorcontrib>Ceccarelli, Simona M. ; Pinard, Emmanuel ; Stalder, Henri ; Alberati, Daniela</creatorcontrib><description>During SAR exploration of
N-(2-aryl-cyclohexyl) substituted spiropiperidine as GlyT1 inhibitors, it was found that introduction of a hydroxy group in position 2 of the cyclohexyl residue considerably improves the pharmacological profile. In particular, reduction of the binding affinity at the nociceptin/orphanin FQ peptide and the μ opioid receptors was achieved.
During SAR exploration of
N-(2-aryl-cyclohexyl) substituted spiropiperidine as GlyT1 inhibitors, it was found that introduction of an hydroxy group in position 2 of the cyclohexyl residue considerably improves the pharmacological profile. In particular, reduction of the binding affinity at the nociceptin/orphanin FQ peptide and the μ opioid receptors was achieved.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2005.09.067</identifier><identifier>PMID: 16246561</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Binding Sites ; Biological and medical sciences ; Drug Evaluation, Preclinical ; Glutamatergic system (aspartate and other excitatory aminoacids) ; Glycine Plasma Membrane Transport Proteins - antagonists & inhibitors ; GlyT1 ; GlyT2 ; Humans ; In Vitro Techniques ; Medical sciences ; Molecular Conformation ; Narcotic Antagonists ; Neuropharmacology ; Neurotransmitters. Neurotransmission. Receptors ; NMDA ; Pharmacology. Drug treatments ; Piperidines - chemistry ; Piperidines - classification ; Piperidines - pharmacology ; Receptors, Opioid ; Receptors, Opioid, mu - antagonists & inhibitors ; Schizophrenia ; Spiro Compounds - chemistry ; Spiro Compounds - classification ; Spiro Compounds - pharmacology ; Spiropiperidine ; Structure-Activity Relationship ; Transporter</subject><ispartof>Bioorganic & medicinal chemistry letters, 2006-01, Vol.16 (2), p.354-357</ispartof><rights>2005 Elsevier Ltd</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c409t-32f4eb6c996bc8da35ce4671df5534a2f813ea7b4a1baedb5079cd0806c350273</citedby><cites>FETCH-LOGICAL-c409t-32f4eb6c996bc8da35ce4671df5534a2f813ea7b4a1baedb5079cd0806c350273</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X05012473$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17293525$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16246561$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ceccarelli, Simona M.</creatorcontrib><creatorcontrib>Pinard, Emmanuel</creatorcontrib><creatorcontrib>Stalder, Henri</creatorcontrib><creatorcontrib>Alberati, Daniela</creatorcontrib><title>Discovery of N-(2-hydroxy-2-aryl-cyclohexyl) substituted spiropiperidines as GlyT1 antagonists with improved pharmacological profile</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>During SAR exploration of
N-(2-aryl-cyclohexyl) substituted spiropiperidine as GlyT1 inhibitors, it was found that introduction of a hydroxy group in position 2 of the cyclohexyl residue considerably improves the pharmacological profile. In particular, reduction of the binding affinity at the nociceptin/orphanin FQ peptide and the μ opioid receptors was achieved.
During SAR exploration of
N-(2-aryl-cyclohexyl) substituted spiropiperidine as GlyT1 inhibitors, it was found that introduction of an hydroxy group in position 2 of the cyclohexyl residue considerably improves the pharmacological profile. In particular, reduction of the binding affinity at the nociceptin/orphanin FQ peptide and the μ opioid receptors was achieved.</description><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Drug Evaluation, Preclinical</subject><subject>Glutamatergic system (aspartate and other excitatory aminoacids)</subject><subject>Glycine Plasma Membrane Transport Proteins - antagonists & inhibitors</subject><subject>GlyT1</subject><subject>GlyT2</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Medical sciences</subject><subject>Molecular Conformation</subject><subject>Narcotic Antagonists</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>NMDA</subject><subject>Pharmacology. Drug treatments</subject><subject>Piperidines - chemistry</subject><subject>Piperidines - classification</subject><subject>Piperidines - pharmacology</subject><subject>Receptors, Opioid</subject><subject>Receptors, Opioid, mu - antagonists & inhibitors</subject><subject>Schizophrenia</subject><subject>Spiro Compounds - chemistry</subject><subject>Spiro Compounds - classification</subject><subject>Spiro Compounds - pharmacology</subject><subject>Spiropiperidine</subject><subject>Structure-Activity Relationship</subject><subject>Transporter</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>eNp9kE1v1DAQhiMEotvCH-CAfAHBIWHs2M5G4oJKKUgVXIrEzXLsSdcrJw52Upo7PxyvdqXeOI00et75eIriFYWKApUf9lU3GF8xAFFBW4FsnhQbyiUvaw7iabGBVkK5bfmvs-I8pT0A5cD58-KMSsalkHRT_P3skgn3GFcSevK9fMfK3WpjeFhLVuq4-tKsxocdPqz-PUlLl2Y3LzNakiYXw-QmjM66ERPRiVz79ZYSPc76LowuzYn8cfOOuGGKeYcl007HQZvgw50z2pPc7p3HF8WzXvuEL0_1ovj55er28mt58-P62-Wnm9JwaOeyZj3HTpq2lZ3ZWl0Lg1w21PZC1Fyzfktr1E3HNe002k5A0xoLW5CmFsCa-qJ4e5yb9_5eMM1qyN-j93rEsCTVAG2B0W0G2RE0MaQUsVdTdEPWoSiog3u1Vwf36uBeQauy-xx6fZq-dAPax8hJdgbenACd8vd91KNx6ZFrWFsLJjL38chhdnHvMKpkHI4GrYtoZmWD-98d_wAPI6Vy</recordid><startdate>20060115</startdate><enddate>20060115</enddate><creator>Ceccarelli, Simona M.</creator><creator>Pinard, Emmanuel</creator><creator>Stalder, Henri</creator><creator>Alberati, Daniela</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>7X8</scope></search><sort><creationdate>20060115</creationdate><title>Discovery of N-(2-hydroxy-2-aryl-cyclohexyl) substituted spiropiperidines as GlyT1 antagonists with improved pharmacological profile</title><author>Ceccarelli, Simona M. ; Pinard, Emmanuel ; Stalder, Henri ; Alberati, Daniela</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c409t-32f4eb6c996bc8da35ce4671df5534a2f813ea7b4a1baedb5079cd0806c350273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Binding Sites</topic><topic>Biological and medical sciences</topic><topic>Drug Evaluation, Preclinical</topic><topic>Glutamatergic system (aspartate and other excitatory aminoacids)</topic><topic>Glycine Plasma Membrane Transport Proteins - antagonists & inhibitors</topic><topic>GlyT1</topic><topic>GlyT2</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Medical sciences</topic><topic>Molecular Conformation</topic><topic>Narcotic Antagonists</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>NMDA</topic><topic>Pharmacology. Drug treatments</topic><topic>Piperidines - chemistry</topic><topic>Piperidines - classification</topic><topic>Piperidines - pharmacology</topic><topic>Receptors, Opioid</topic><topic>Receptors, Opioid, mu - antagonists & inhibitors</topic><topic>Schizophrenia</topic><topic>Spiro Compounds - chemistry</topic><topic>Spiro Compounds - classification</topic><topic>Spiro Compounds - pharmacology</topic><topic>Spiropiperidine</topic><topic>Structure-Activity Relationship</topic><topic>Transporter</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ceccarelli, Simona M.</creatorcontrib><creatorcontrib>Pinard, Emmanuel</creatorcontrib><creatorcontrib>Stalder, Henri</creatorcontrib><creatorcontrib>Alberati, Daniela</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>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ceccarelli, Simona M.</au><au>Pinard, Emmanuel</au><au>Stalder, Henri</au><au>Alberati, Daniela</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discovery of N-(2-hydroxy-2-aryl-cyclohexyl) substituted spiropiperidines as GlyT1 antagonists with improved pharmacological profile</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2006-01-15</date><risdate>2006</risdate><volume>16</volume><issue>2</issue><spage>354</spage><epage>357</epage><pages>354-357</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>During SAR exploration of
N-(2-aryl-cyclohexyl) substituted spiropiperidine as GlyT1 inhibitors, it was found that introduction of a hydroxy group in position 2 of the cyclohexyl residue considerably improves the pharmacological profile. In particular, reduction of the binding affinity at the nociceptin/orphanin FQ peptide and the μ opioid receptors was achieved.
During SAR exploration of
N-(2-aryl-cyclohexyl) substituted spiropiperidine as GlyT1 inhibitors, it was found that introduction of an hydroxy group in position 2 of the cyclohexyl residue considerably improves the pharmacological profile. In particular, reduction of the binding affinity at the nociceptin/orphanin FQ peptide and the μ opioid receptors was achieved.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>16246561</pmid><doi>10.1016/j.bmcl.2005.09.067</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2006-01, Vol.16 (2), p.354-357 |
| issn | 0960-894X 1464-3405 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_70190218 |
| source | ScienceDirect; MEDLINE |
| subjects | Binding Sites Biological and medical sciences Drug Evaluation, Preclinical Glutamatergic system (aspartate and other excitatory aminoacids) Glycine Plasma Membrane Transport Proteins - antagonists & inhibitors GlyT1 GlyT2 Humans In Vitro Techniques Medical sciences Molecular Conformation Narcotic Antagonists Neuropharmacology Neurotransmitters. Neurotransmission. Receptors NMDA Pharmacology. Drug treatments Piperidines - chemistry Piperidines - classification Piperidines - pharmacology Receptors, Opioid Receptors, Opioid, mu - antagonists & inhibitors Schizophrenia Spiro Compounds - chemistry Spiro Compounds - classification Spiro Compounds - pharmacology Spiropiperidine Structure-Activity Relationship Transporter |
| title | Discovery of N-(2-hydroxy-2-aryl-cyclohexyl) substituted spiropiperidines as GlyT1 antagonists with improved pharmacological profile |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T17%3A08%3A05IST&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=Discovery%20of%20N-(2-hydroxy-2-aryl-cyclohexyl)%20substituted%20spiropiperidines%20as%20GlyT1%20antagonists%20with%20improved%20pharmacological%20profile&rft.jtitle=Bioorganic%20&%20medicinal%20chemistry%20letters&rft.au=Ceccarelli,%20Simona%20M.&rft.date=2006-01-15&rft.volume=16&rft.issue=2&rft.spage=354&rft.epage=357&rft.pages=354-357&rft.issn=0960-894X&rft.eissn=1464-3405&rft_id=info:doi/10.1016/j.bmcl.2005.09.067&rft_dat=%3Cproquest_cross%3E70190218%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=70190218&rft_id=info:pmid/16246561&rft_els_id=S0960894X05012473&rfr_iscdi=true |