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4-(3-Aryloxyaryl)quinoline sulfones are potent liver X receptor agonists
A series of 4-(3-aryloxyaryl)quinoline sulfones 7 was prepared as LXR agonists. A series of 4-(3-aryloxyaryl)quinolines with sulfone substituents on the terminal aryl ring ( 7) was prepared as LXR agonists. High affinity LXR ligands with excellent agonist potency and efficacy in functional assays of...
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| Published in: | Bioorganic & medicinal chemistry letters 2010, Vol.20 (1), p.209-212 |
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| Main Authors: | , , , , , , , , , , , , , |
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| cites | cdi_FETCH-LOGICAL-c416t-30c26c4ab3b1de20e5a4c0af1ac1f7ddc0fc9273caf88891c489c99aef46d11b3 |
| container_end_page | 212 |
| container_issue | 1 |
| container_start_page | 209 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 20 |
| creator | Bernotas, Ronald C. Singhaus, Robert R. Kaufman, David H. Travins, Jeremy M. Ullrich, John W. Unwalla, Rayomand Quinet, Elaine Evans, Mark Nambi, Ponnal Olland, Andrea Kauppi, Björn Wilhelmsson, Anna Goos-Nilsson, Annika Wrobel, Jay |
| description | A series of 4-(3-aryloxyaryl)quinoline sulfones
7 was prepared as LXR agonists.
A series of 4-(3-aryloxyaryl)quinolines with sulfone substituents on the terminal aryl ring (
7) was prepared as LXR agonists. High affinity LXR ligands with excellent agonist potency and efficacy in functional assays of LXR activity were identified. In general, these sulfone agonists were equal to or superior to previously described alcohol and amide analogs in terms of affinity, functional potency, and microsomal stability. Many of the sulfones had LXRβ binding IC
50 values |
| doi_str_mv | 10.1016/j.bmcl.2009.10.132 |
| format | article |
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7 was prepared as LXR agonists.
A series of 4-(3-aryloxyaryl)quinolines with sulfone substituents on the terminal aryl ring (
7) was prepared as LXR agonists. High affinity LXR ligands with excellent agonist potency and efficacy in functional assays of LXR activity were identified. In general, these sulfone agonists were equal to or superior to previously described alcohol and amide analogs in terms of affinity, functional potency, and microsomal stability. Many of the sulfones had LXRβ binding IC
50 values <10
nM while the most potent compounds in an ABCA1 mRNA induction assay in J774 mouse cells had EC
50 values <10
nM and were as efficacious as T0901317.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2009.10.132</identifier><identifier>PMID: 19932617</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>ABCA1 ; Animals ; Atherosclerosis ; ATP Binding Cassette Transporter 1 ; ATP-Binding Cassette Transporters - genetics ; ATP-Binding Cassette Transporters - metabolism ; Binding Sites ; Biological and medical sciences ; Cell Line ; Cholesterol ; Computer Simulation ; General and cellular metabolism. Vitamins ; Humans ; Hydrocarbons, Fluorinated - chemistry ; Hydrocarbons, Fluorinated - pharmacology ; Hydrogen Bonding ; Lipid ; Liver X receptor ; Liver X Receptors ; LXR ; Medical sciences ; Mice ; Microsomes, Liver - metabolism ; Orphan Nuclear Receptors - agonists ; Orphan Nuclear Receptors - metabolism ; Pharmacology. Drug treatments ; Quinoline ; Quinolines - chemical synthesis ; Quinolines - chemistry ; Quinolines - pharmacology ; Rats ; Structure-Activity Relationship ; Sulfonamides - chemistry ; Sulfonamides - pharmacology ; Sulfone ; Sulfones - chemical synthesis ; Sulfones - chemistry ; Sulfones - pharmacology</subject><ispartof>Bioorganic & medicinal chemistry letters, 2010, Vol.20 (1), p.209-212</ispartof><rights>2009 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright 2009 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c416t-30c26c4ab3b1de20e5a4c0af1ac1f7ddc0fc9273caf88891c489c99aef46d11b3</citedby><cites>FETCH-LOGICAL-c416t-30c26c4ab3b1de20e5a4c0af1ac1f7ddc0fc9273caf88891c489c99aef46d11b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,4024,27923,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22314223$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19932617$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bernotas, Ronald C.</creatorcontrib><creatorcontrib>Singhaus, Robert R.</creatorcontrib><creatorcontrib>Kaufman, David H.</creatorcontrib><creatorcontrib>Travins, Jeremy M.</creatorcontrib><creatorcontrib>Ullrich, John W.</creatorcontrib><creatorcontrib>Unwalla, Rayomand</creatorcontrib><creatorcontrib>Quinet, Elaine</creatorcontrib><creatorcontrib>Evans, Mark</creatorcontrib><creatorcontrib>Nambi, Ponnal</creatorcontrib><creatorcontrib>Olland, Andrea</creatorcontrib><creatorcontrib>Kauppi, Björn</creatorcontrib><creatorcontrib>Wilhelmsson, Anna</creatorcontrib><creatorcontrib>Goos-Nilsson, Annika</creatorcontrib><creatorcontrib>Wrobel, Jay</creatorcontrib><title>4-(3-Aryloxyaryl)quinoline sulfones are potent liver X receptor agonists</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>A series of 4-(3-aryloxyaryl)quinoline sulfones
7 was prepared as LXR agonists.
A series of 4-(3-aryloxyaryl)quinolines with sulfone substituents on the terminal aryl ring (
7) was prepared as LXR agonists. High affinity LXR ligands with excellent agonist potency and efficacy in functional assays of LXR activity were identified. In general, these sulfone agonists were equal to or superior to previously described alcohol and amide analogs in terms of affinity, functional potency, and microsomal stability. Many of the sulfones had LXRβ binding IC
50 values <10
nM while the most potent compounds in an ABCA1 mRNA induction assay in J774 mouse cells had EC
50 values <10
nM and were as efficacious as T0901317.</description><subject>ABCA1</subject><subject>Animals</subject><subject>Atherosclerosis</subject><subject>ATP Binding Cassette Transporter 1</subject><subject>ATP-Binding Cassette Transporters - genetics</subject><subject>ATP-Binding Cassette Transporters - metabolism</subject><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Cholesterol</subject><subject>Computer Simulation</subject><subject>General and cellular metabolism. Vitamins</subject><subject>Humans</subject><subject>Hydrocarbons, Fluorinated - chemistry</subject><subject>Hydrocarbons, Fluorinated - pharmacology</subject><subject>Hydrogen Bonding</subject><subject>Lipid</subject><subject>Liver X receptor</subject><subject>Liver X Receptors</subject><subject>LXR</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Microsomes, Liver - metabolism</subject><subject>Orphan Nuclear Receptors - agonists</subject><subject>Orphan Nuclear Receptors - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Quinoline</subject><subject>Quinolines - chemical synthesis</subject><subject>Quinolines - chemistry</subject><subject>Quinolines - pharmacology</subject><subject>Rats</subject><subject>Structure-Activity Relationship</subject><subject>Sulfonamides - chemistry</subject><subject>Sulfonamides - pharmacology</subject><subject>Sulfone</subject><subject>Sulfones - chemical synthesis</subject><subject>Sulfones - chemistry</subject><subject>Sulfones - pharmacology</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNp9kMFq3DAQhkVoSDZJX6CH4kub5uCtRpK9FuQSQtsUAr2kkJuQx6OiRWttJDs0b19td2lvuczAzzc_w8fYO-BL4NB-Xi_7DYal4Fwvd5kUR2wBqlW1VLx5wxZct7zutHo8ZWc5rzkHxZU6YaegtRQtrBbsTtWfZH2TXkL8_WLLunqa_RiDH6nKc3BxpFzZRNU2TjROVfDPlKrHKhHSdoqpsr_i6POUL9ixsyHT28M-Zz-_fnm4vavvf3z7fntzX6OCdqolR9Gisr3sYSDBqbEKuXVgEdxqGJA71GIl0bqu6zSg6jRqbcmpdgDo5Tm73PduU3yaKU9m4zNSCHakOGezklI3vGmaQn58lRQgpGoEFFDsQUwx50TObJPfFBkGuNmZNmuzM212pv9mUpSj94f2ud_Q8P_koLYAHw6AzWiDS3ZEn_9xQkhQZRTues9RsfbsKZmMnkakwRfJkxmif-2PP-SMnHU</recordid><startdate>2010</startdate><enddate>2010</enddate><creator>Bernotas, Ronald C.</creator><creator>Singhaus, Robert R.</creator><creator>Kaufman, David H.</creator><creator>Travins, Jeremy M.</creator><creator>Ullrich, John W.</creator><creator>Unwalla, Rayomand</creator><creator>Quinet, Elaine</creator><creator>Evans, Mark</creator><creator>Nambi, Ponnal</creator><creator>Olland, Andrea</creator><creator>Kauppi, Björn</creator><creator>Wilhelmsson, Anna</creator><creator>Goos-Nilsson, Annika</creator><creator>Wrobel, Jay</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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>2010</creationdate><title>4-(3-Aryloxyaryl)quinoline sulfones are potent liver X receptor agonists</title><author>Bernotas, Ronald C. ; Singhaus, Robert R. ; Kaufman, David H. ; Travins, Jeremy M. ; Ullrich, John W. ; Unwalla, Rayomand ; Quinet, Elaine ; Evans, Mark ; Nambi, Ponnal ; Olland, Andrea ; Kauppi, Björn ; Wilhelmsson, Anna ; Goos-Nilsson, Annika ; Wrobel, Jay</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-30c26c4ab3b1de20e5a4c0af1ac1f7ddc0fc9273caf88891c489c99aef46d11b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>ABCA1</topic><topic>Animals</topic><topic>Atherosclerosis</topic><topic>ATP Binding Cassette Transporter 1</topic><topic>ATP-Binding Cassette Transporters - genetics</topic><topic>ATP-Binding Cassette Transporters - metabolism</topic><topic>Binding Sites</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>Cholesterol</topic><topic>Computer Simulation</topic><topic>General and cellular metabolism. Vitamins</topic><topic>Humans</topic><topic>Hydrocarbons, Fluorinated - chemistry</topic><topic>Hydrocarbons, Fluorinated - pharmacology</topic><topic>Hydrogen Bonding</topic><topic>Lipid</topic><topic>Liver X receptor</topic><topic>Liver X Receptors</topic><topic>LXR</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Microsomes, Liver - metabolism</topic><topic>Orphan Nuclear Receptors - agonists</topic><topic>Orphan Nuclear Receptors - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Quinoline</topic><topic>Quinolines - chemical synthesis</topic><topic>Quinolines - chemistry</topic><topic>Quinolines - pharmacology</topic><topic>Rats</topic><topic>Structure-Activity Relationship</topic><topic>Sulfonamides - chemistry</topic><topic>Sulfonamides - pharmacology</topic><topic>Sulfone</topic><topic>Sulfones - chemical synthesis</topic><topic>Sulfones - chemistry</topic><topic>Sulfones - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bernotas, Ronald C.</creatorcontrib><creatorcontrib>Singhaus, Robert R.</creatorcontrib><creatorcontrib>Kaufman, David H.</creatorcontrib><creatorcontrib>Travins, Jeremy M.</creatorcontrib><creatorcontrib>Ullrich, John W.</creatorcontrib><creatorcontrib>Unwalla, Rayomand</creatorcontrib><creatorcontrib>Quinet, Elaine</creatorcontrib><creatorcontrib>Evans, Mark</creatorcontrib><creatorcontrib>Nambi, Ponnal</creatorcontrib><creatorcontrib>Olland, Andrea</creatorcontrib><creatorcontrib>Kauppi, Björn</creatorcontrib><creatorcontrib>Wilhelmsson, Anna</creatorcontrib><creatorcontrib>Goos-Nilsson, Annika</creatorcontrib><creatorcontrib>Wrobel, Jay</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>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>Bernotas, Ronald C.</au><au>Singhaus, Robert R.</au><au>Kaufman, David H.</au><au>Travins, Jeremy M.</au><au>Ullrich, John W.</au><au>Unwalla, Rayomand</au><au>Quinet, Elaine</au><au>Evans, Mark</au><au>Nambi, Ponnal</au><au>Olland, Andrea</au><au>Kauppi, Björn</au><au>Wilhelmsson, Anna</au><au>Goos-Nilsson, Annika</au><au>Wrobel, Jay</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>4-(3-Aryloxyaryl)quinoline sulfones are potent liver X receptor agonists</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2010</date><risdate>2010</risdate><volume>20</volume><issue>1</issue><spage>209</spage><epage>212</epage><pages>209-212</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>A series of 4-(3-aryloxyaryl)quinoline sulfones
7 was prepared as LXR agonists.
A series of 4-(3-aryloxyaryl)quinolines with sulfone substituents on the terminal aryl ring (
7) was prepared as LXR agonists. High affinity LXR ligands with excellent agonist potency and efficacy in functional assays of LXR activity were identified. In general, these sulfone agonists were equal to or superior to previously described alcohol and amide analogs in terms of affinity, functional potency, and microsomal stability. Many of the sulfones had LXRβ binding IC
50 values <10
nM while the most potent compounds in an ABCA1 mRNA induction assay in J774 mouse cells had EC
50 values <10
nM and were as efficacious as T0901317.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>19932617</pmid><doi>10.1016/j.bmcl.2009.10.132</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2010, Vol.20 (1), p.209-212 |
| issn | 0960-894X 1464-3405 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_733950555 |
| source | Elsevier |
| subjects | ABCA1 Animals Atherosclerosis ATP Binding Cassette Transporter 1 ATP-Binding Cassette Transporters - genetics ATP-Binding Cassette Transporters - metabolism Binding Sites Biological and medical sciences Cell Line Cholesterol Computer Simulation General and cellular metabolism. Vitamins Humans Hydrocarbons, Fluorinated - chemistry Hydrocarbons, Fluorinated - pharmacology Hydrogen Bonding Lipid Liver X receptor Liver X Receptors LXR Medical sciences Mice Microsomes, Liver - metabolism Orphan Nuclear Receptors - agonists Orphan Nuclear Receptors - metabolism Pharmacology. Drug treatments Quinoline Quinolines - chemical synthesis Quinolines - chemistry Quinolines - pharmacology Rats Structure-Activity Relationship Sulfonamides - chemistry Sulfonamides - pharmacology Sulfone Sulfones - chemical synthesis Sulfones - chemistry Sulfones - pharmacology |
| title | 4-(3-Aryloxyaryl)quinoline sulfones are potent liver X receptor agonists |
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