Identification and synthesis of potent and selective pyridyl-isoxazole based agonists of sphingosine-1-phosphate 1 (S1P1)
[Display omitted] The synthesis and structure–activity relationship (SAR) of a series of pyridyl-isoxazole based agonists of S1P1 are discussed. Compound 5b provided potent in vitro activity with selectivity, had an acceptable pharmacokinetic profile, and demonstrated efficacy in a dose dependent ma...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2016-05, Vol.26 (10), p.2470-2474 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Guo, Junqing Watterson, Scott H. Spergel, Steven H. Kempson, James Langevine, Charles M. Shen, Ding Ren Yarde, Melissa Cvijic, Mary Ellen Banas, Dana Liu, Richard Suchard, Suzanne J. Gillooly, Kathleen Taylor, Tracy Rex-Rabe, Sandra Shuster, David J. McIntyre, Kim W. Cornelius, Georgia D’Arienzo, Celia Marino, Anthony Balimane, Praveen Salter-Cid, Luisa McKinnon, Murray Barrish, Joel C. Carter, Percy H. Pitts, William J. Xie, Jenny Dyckman, Alaric J. |
| description | [Display omitted]
The synthesis and structure–activity relationship (SAR) of a series of pyridyl-isoxazole based agonists of S1P1 are discussed. Compound 5b provided potent in vitro activity with selectivity, had an acceptable pharmacokinetic profile, and demonstrated efficacy in a dose dependent manner when administered orally in a rodent model of arthritis. |
| doi_str_mv | 10.1016/j.bmcl.2016.03.105 |
| format | Article |
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The synthesis and structure–activity relationship (SAR) of a series of pyridyl-isoxazole based agonists of S1P1 are discussed. Compound 5b provided potent in vitro activity with selectivity, had an acceptable pharmacokinetic profile, and demonstrated efficacy in a dose dependent manner when administered orally in a rodent model of arthritis.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2016.03.105</identifier><identifier>PMID: 27055941</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Administration, Oral ; Animals ; Arthritis, Experimental - drug therapy ; Chemistry Techniques, Synthetic ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical - methods ; Fingolimod ; FTY720 ; Humans ; Isoxazole ; Isoxazoles - chemistry ; Isoxazoles - pharmacology ; Lymphocyte Count ; Lysophospholipids - agonists ; Male ; Rats, Inbred Lew ; Receptors, Lysosphingolipid - agonists ; S1P1 ; Sphingosine - agonists ; Sphingosine - analogs & derivatives ; Sphingosine-1-phosphate ; Sphingosine-1-phosphate 1 ; Structure-Activity Relationship</subject><ispartof>Bioorganic & medicinal chemistry letters, 2016-05, Vol.26 (10), p.2470-2474</ispartof><rights>2016 Elsevier Ltd</rights><rights>Copyright © 2016 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-73c715735b270b6a68d2826e9e63bc10e47fe39589fb31e48677bddba873d0e13</citedby><cites>FETCH-LOGICAL-c389t-73c715735b270b6a68d2826e9e63bc10e47fe39589fb31e48677bddba873d0e13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X16303353$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27055941$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Guo, Junqing</creatorcontrib><creatorcontrib>Watterson, Scott H.</creatorcontrib><creatorcontrib>Spergel, Steven H.</creatorcontrib><creatorcontrib>Kempson, James</creatorcontrib><creatorcontrib>Langevine, Charles M.</creatorcontrib><creatorcontrib>Shen, Ding Ren</creatorcontrib><creatorcontrib>Yarde, Melissa</creatorcontrib><creatorcontrib>Cvijic, Mary Ellen</creatorcontrib><creatorcontrib>Banas, Dana</creatorcontrib><creatorcontrib>Liu, Richard</creatorcontrib><creatorcontrib>Suchard, Suzanne J.</creatorcontrib><creatorcontrib>Gillooly, Kathleen</creatorcontrib><creatorcontrib>Taylor, Tracy</creatorcontrib><creatorcontrib>Rex-Rabe, Sandra</creatorcontrib><creatorcontrib>Shuster, David J.</creatorcontrib><creatorcontrib>McIntyre, Kim W.</creatorcontrib><creatorcontrib>Cornelius, Georgia</creatorcontrib><creatorcontrib>D’Arienzo, Celia</creatorcontrib><creatorcontrib>Marino, Anthony</creatorcontrib><creatorcontrib>Balimane, Praveen</creatorcontrib><creatorcontrib>Salter-Cid, Luisa</creatorcontrib><creatorcontrib>McKinnon, Murray</creatorcontrib><creatorcontrib>Barrish, Joel C.</creatorcontrib><creatorcontrib>Carter, Percy H.</creatorcontrib><creatorcontrib>Pitts, William J.</creatorcontrib><creatorcontrib>Xie, Jenny</creatorcontrib><creatorcontrib>Dyckman, Alaric J.</creatorcontrib><title>Identification and synthesis of potent and selective pyridyl-isoxazole based agonists of sphingosine-1-phosphate 1 (S1P1)</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>[Display omitted]
The synthesis and structure–activity relationship (SAR) of a series of pyridyl-isoxazole based agonists of S1P1 are discussed. Compound 5b provided potent in vitro activity with selectivity, had an acceptable pharmacokinetic profile, and demonstrated efficacy in a dose dependent manner when administered orally in a rodent model of arthritis.</description><subject>Administration, Oral</subject><subject>Animals</subject><subject>Arthritis, Experimental - drug therapy</subject><subject>Chemistry Techniques, Synthetic</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Evaluation, Preclinical - methods</subject><subject>Fingolimod</subject><subject>FTY720</subject><subject>Humans</subject><subject>Isoxazole</subject><subject>Isoxazoles - chemistry</subject><subject>Isoxazoles - pharmacology</subject><subject>Lymphocyte Count</subject><subject>Lysophospholipids - agonists</subject><subject>Male</subject><subject>Rats, Inbred Lew</subject><subject>Receptors, Lysosphingolipid - agonists</subject><subject>S1P1</subject><subject>Sphingosine - agonists</subject><subject>Sphingosine - analogs & derivatives</subject><subject>Sphingosine-1-phosphate</subject><subject>Sphingosine-1-phosphate 1</subject><subject>Structure-Activity Relationship</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkV9rFDEUxYModlv9Aj5IHuvDbJNJJsmAL1K0FgoVVPAt5M-dbpbZZJxki9NPb9atPtqnezn8zuFyD0JvKFlTQsXFdm13bly3dV8TVrXuGVpRLnjDOOmeoxXpBWlUz3-coNOct4RQTjh_iU5aSbqu53SFlmsPsYQhOFNCithEj_MSywZyyDgNeEqlAkcdRnAl3AOeljn4ZWxCTr_MQxoBW5PBY3OXYsjljzFPmxDvUg4RGtpMm1QFUwBTfP6VfqHvXqEXgxkzvH6cZ-j7p4_fLj83N7dX15cfbhrHVF8ayZyknWSdrUdbYYTyrWoF9CCYdZQAlwOwvlP9YBkFroSU1ntrlGSeAGVn6PyYO83p5x5y0buQHYyjiZD2WVNFqkcoKp9GZS-VUKrlFW2PqJtTzjMMeprDzsyLpkQf2tFbfWhHH9rRhFWtq6a3j_l7uwP_z_K3jgq8PwJQH3IfYNbZBYgOfJjr67VP4X_5vwFgp6EP</recordid><startdate>20160515</startdate><enddate>20160515</enddate><creator>Guo, Junqing</creator><creator>Watterson, Scott H.</creator><creator>Spergel, Steven H.</creator><creator>Kempson, James</creator><creator>Langevine, Charles M.</creator><creator>Shen, Ding Ren</creator><creator>Yarde, Melissa</creator><creator>Cvijic, Mary Ellen</creator><creator>Banas, Dana</creator><creator>Liu, Richard</creator><creator>Suchard, Suzanne J.</creator><creator>Gillooly, Kathleen</creator><creator>Taylor, Tracy</creator><creator>Rex-Rabe, Sandra</creator><creator>Shuster, David J.</creator><creator>McIntyre, Kim W.</creator><creator>Cornelius, Georgia</creator><creator>D’Arienzo, Celia</creator><creator>Marino, Anthony</creator><creator>Balimane, Praveen</creator><creator>Salter-Cid, Luisa</creator><creator>McKinnon, Murray</creator><creator>Barrish, Joel C.</creator><creator>Carter, Percy H.</creator><creator>Pitts, William J.</creator><creator>Xie, Jenny</creator><creator>Dyckman, Alaric J.</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>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20160515</creationdate><title>Identification and synthesis of potent and selective pyridyl-isoxazole based agonists of sphingosine-1-phosphate 1 (S1P1)</title><author>Guo, Junqing ; Watterson, Scott H. ; Spergel, Steven H. ; Kempson, James ; Langevine, Charles M. ; Shen, Ding Ren ; Yarde, Melissa ; Cvijic, Mary Ellen ; Banas, Dana ; Liu, Richard ; Suchard, Suzanne J. ; Gillooly, Kathleen ; Taylor, Tracy ; Rex-Rabe, Sandra ; Shuster, David J. ; McIntyre, Kim W. ; Cornelius, Georgia ; D’Arienzo, Celia ; Marino, Anthony ; Balimane, Praveen ; Salter-Cid, Luisa ; McKinnon, Murray ; Barrish, Joel C. ; Carter, Percy H. ; Pitts, William J. ; Xie, Jenny ; Dyckman, Alaric J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-73c715735b270b6a68d2826e9e63bc10e47fe39589fb31e48677bddba873d0e13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Administration, Oral</topic><topic>Animals</topic><topic>Arthritis, Experimental - drug therapy</topic><topic>Chemistry Techniques, Synthetic</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Evaluation, Preclinical - methods</topic><topic>Fingolimod</topic><topic>FTY720</topic><topic>Humans</topic><topic>Isoxazole</topic><topic>Isoxazoles - chemistry</topic><topic>Isoxazoles - pharmacology</topic><topic>Lymphocyte Count</topic><topic>Lysophospholipids - agonists</topic><topic>Male</topic><topic>Rats, Inbred Lew</topic><topic>Receptors, Lysosphingolipid - agonists</topic><topic>S1P1</topic><topic>Sphingosine - agonists</topic><topic>Sphingosine - analogs & derivatives</topic><topic>Sphingosine-1-phosphate</topic><topic>Sphingosine-1-phosphate 1</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guo, Junqing</creatorcontrib><creatorcontrib>Watterson, Scott H.</creatorcontrib><creatorcontrib>Spergel, Steven H.</creatorcontrib><creatorcontrib>Kempson, James</creatorcontrib><creatorcontrib>Langevine, Charles M.</creatorcontrib><creatorcontrib>Shen, Ding Ren</creatorcontrib><creatorcontrib>Yarde, Melissa</creatorcontrib><creatorcontrib>Cvijic, Mary Ellen</creatorcontrib><creatorcontrib>Banas, Dana</creatorcontrib><creatorcontrib>Liu, Richard</creatorcontrib><creatorcontrib>Suchard, Suzanne J.</creatorcontrib><creatorcontrib>Gillooly, Kathleen</creatorcontrib><creatorcontrib>Taylor, Tracy</creatorcontrib><creatorcontrib>Rex-Rabe, Sandra</creatorcontrib><creatorcontrib>Shuster, David J.</creatorcontrib><creatorcontrib>McIntyre, Kim W.</creatorcontrib><creatorcontrib>Cornelius, Georgia</creatorcontrib><creatorcontrib>D’Arienzo, Celia</creatorcontrib><creatorcontrib>Marino, Anthony</creatorcontrib><creatorcontrib>Balimane, Praveen</creatorcontrib><creatorcontrib>Salter-Cid, Luisa</creatorcontrib><creatorcontrib>McKinnon, Murray</creatorcontrib><creatorcontrib>Barrish, Joel C.</creatorcontrib><creatorcontrib>Carter, Percy H.</creatorcontrib><creatorcontrib>Pitts, William J.</creatorcontrib><creatorcontrib>Xie, Jenny</creatorcontrib><creatorcontrib>Dyckman, Alaric J.</creatorcontrib><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><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guo, Junqing</au><au>Watterson, Scott H.</au><au>Spergel, Steven H.</au><au>Kempson, James</au><au>Langevine, Charles M.</au><au>Shen, Ding Ren</au><au>Yarde, Melissa</au><au>Cvijic, Mary Ellen</au><au>Banas, Dana</au><au>Liu, Richard</au><au>Suchard, Suzanne J.</au><au>Gillooly, Kathleen</au><au>Taylor, Tracy</au><au>Rex-Rabe, Sandra</au><au>Shuster, David J.</au><au>McIntyre, Kim W.</au><au>Cornelius, Georgia</au><au>D’Arienzo, Celia</au><au>Marino, Anthony</au><au>Balimane, Praveen</au><au>Salter-Cid, Luisa</au><au>McKinnon, Murray</au><au>Barrish, Joel C.</au><au>Carter, Percy H.</au><au>Pitts, William J.</au><au>Xie, Jenny</au><au>Dyckman, Alaric J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification and synthesis of potent and selective pyridyl-isoxazole based agonists of sphingosine-1-phosphate 1 (S1P1)</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2016-05-15</date><risdate>2016</risdate><volume>26</volume><issue>10</issue><spage>2470</spage><epage>2474</epage><pages>2470-2474</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>[Display omitted]
The synthesis and structure–activity relationship (SAR) of a series of pyridyl-isoxazole based agonists of S1P1 are discussed. Compound 5b provided potent in vitro activity with selectivity, had an acceptable pharmacokinetic profile, and demonstrated efficacy in a dose dependent manner when administered orally in a rodent model of arthritis.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>27055941</pmid><doi>10.1016/j.bmcl.2016.03.105</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2016-05, Vol.26 (10), p.2470-2474 |
| issn | 0960-894X 1464-3405 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1808676817 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Administration, Oral Animals Arthritis, Experimental - drug therapy Chemistry Techniques, Synthetic Dose-Response Relationship, Drug Drug Evaluation, Preclinical - methods Fingolimod FTY720 Humans Isoxazole Isoxazoles - chemistry Isoxazoles - pharmacology Lymphocyte Count Lysophospholipids - agonists Male Rats, Inbred Lew Receptors, Lysosphingolipid - agonists S1P1 Sphingosine - agonists Sphingosine - analogs & derivatives Sphingosine-1-phosphate Sphingosine-1-phosphate 1 Structure-Activity Relationship |
| title | Identification and synthesis of potent and selective pyridyl-isoxazole based agonists of sphingosine-1-phosphate 1 (S1P1) |
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