Synthesis of para-alkyl aryl amide analogues of sphingosine-1-phosphate: Discovery of potent S1P receptor agonists
Sphingosine-1-phosphate (S1P) is a biologically active lysophospholipid with the capacity to induce a broad range of cellular responses via its interaction with the S1P family of G-protein coupled receptors. This report describes the synthesis of several potent S1P receptor agonists. For instance, c...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2003-10, Vol.13 (20), p.3401-3404 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | CLEMENS, Jeremy J DAVIS, Michael D LYNCH, Kevin R MACDONALD, Timothy L |
| description | Sphingosine-1-phosphate (S1P) is a biologically active lysophospholipid with the capacity to induce a broad range of cellular responses via its interaction with the S1P family of G-protein coupled receptors. This report describes the synthesis of several potent S1P receptor agonists. For instance, compound 9c displayed an EC(50)=8.6 nM at the S1P(1) receptor using a [gamma-35S]GTP binding assay as compared to an EC(50)=4.5 nM for the endogenous ligand. We also report the effects associated with introduction of a phenyl ring between the 'linker' and 'lipophilic tail' regions of the analogues, for example total loss of activity at S1P(2) and increased agonism at S1P(5). |
| doi_str_mv | 10.1016/S0960-894X(03)00812-6 |
| format | Article |
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Drug treatments</subject><subject>Receptors, G-Protein-Coupled - agonists</subject><subject>Receptors, Lysophospholipid</subject><subject>Sphingosine - analogs & derivatives</subject><subject>Sphingosine - chemical synthesis</subject><subject>Sphingosine - chemistry</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1LxDAQhoMouq7-BKUXRQ_RmeajjTdZP0FQWAVvIW3T3Wq3qUlX2H9vuy56mcDkmZmXh5AjhAsElJdTUBJoqvj7GbBzgBRjKrfICLnklHEQ22T0h-yR_RA-AJAD57tkD7kAIZkcET9dNd3chipEroxa4w019eeqjowfyqIqbGQaU7vZ0q6R0M6rZuZC1ViKtJ27vmE6exXdVCF339av1otcZ5sumuJL5G1u2875yMxcU4UuHJCd0tTBHm7eMXm7u32dPNCn5_vHyfUTzRkTHc1LlTKBGVPI-rSsKNIyjlVuMpkVGAslCikhxiThKSZYAGYKUij7zyJWaczG5PR3b-vdV5--04s-oq1r01i3DDoRUiUJyB4Uv2DuXQjelrr11aIXoBH0IFuvZevBpAam17L1MHe8ObDMFrb4n9rY7YGTDWBCburSmyavwj8nMFZKKPYDaImH_A</recordid><startdate>20031020</startdate><enddate>20031020</enddate><creator>CLEMENS, Jeremy J</creator><creator>DAVIS, Michael D</creator><creator>LYNCH, Kevin R</creator><creator>MACDONALD, Timothy L</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>20031020</creationdate><title>Synthesis of para-alkyl aryl amide analogues of sphingosine-1-phosphate: Discovery of potent S1P receptor agonists</title><author>CLEMENS, Jeremy J ; DAVIS, Michael D ; LYNCH, Kevin R ; MACDONALD, Timothy L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c335t-cf98351b39135053dd8f229cab6bd12595d660217748171d01b9080fbd1d29823</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Amides - chemistry</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>Humans</topic><topic>Immunomodulators</topic><topic>Lysophospholipids</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Receptors, G-Protein-Coupled - agonists</topic><topic>Receptors, Lysophospholipid</topic><topic>Sphingosine - analogs & derivatives</topic><topic>Sphingosine - chemical synthesis</topic><topic>Sphingosine - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CLEMENS, Jeremy J</creatorcontrib><creatorcontrib>DAVIS, Michael D</creatorcontrib><creatorcontrib>LYNCH, Kevin R</creatorcontrib><creatorcontrib>MACDONALD, Timothy L</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>CLEMENS, Jeremy J</au><au>DAVIS, Michael D</au><au>LYNCH, Kevin R</au><au>MACDONALD, Timothy L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis of para-alkyl aryl amide analogues of sphingosine-1-phosphate: Discovery of potent S1P receptor agonists</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2003-10-20</date><risdate>2003</risdate><volume>13</volume><issue>20</issue><spage>3401</spage><epage>3404</epage><pages>3401-3404</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>Sphingosine-1-phosphate (S1P) is a biologically active lysophospholipid with the capacity to induce a broad range of cellular responses via its interaction with the S1P family of G-protein coupled receptors. 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| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2003-10, Vol.13 (20), p.3401-3404 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Amides - chemistry Biological and medical sciences Cell Line Humans Immunomodulators Lysophospholipids Medical sciences Pharmacology. Drug treatments Receptors, G-Protein-Coupled - agonists Receptors, Lysophospholipid Sphingosine - analogs & derivatives Sphingosine - chemical synthesis Sphingosine - chemistry |
| title | Synthesis of para-alkyl aryl amide analogues of sphingosine-1-phosphate: Discovery of potent S1P receptor agonists |
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