Discovery of novel FMS kinase inhibitors as anti-inflammatory agents
Discovery of a series of novel 2,4-disubstituted arylamides as potential anti-inflammatory agents is described. Compound 8 was utilized in an in vivo CIA model to evaluate the therapeutic potential of FMS inhibition. The optimization of the arylamide lead 2 resulted in identification of a highly pot...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry 2008-03, Vol.18 (5), p.1642-1648 |
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| container_title | Bioorganic & medicinal chemistry |
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| creator | Illig, Carl R. Chen, Jinsheng Wall, Mark J. Wilson, Kenneth J. Ballentine, Shelley K. Rudolph, M. Jonathan DesJarlais, Renee L. Chen, Yanmin Schubert, Carsten Petrounia, Ioanna Crysler, Carl S. Molloy, Christopher J. Chaikin, Margery A. Manthey, Carl L. Player, Mark R. Tomczuk, Bruce E. Meegalla, Sanath K. |
| description | Discovery of a series of novel 2,4-disubstituted arylamides as potential anti-inflammatory agents is described. Compound
8 was utilized in an in vivo CIA model to evaluate the therapeutic potential of FMS inhibition.
The optimization of the arylamide lead
2 resulted in identification of a highly potent series of 2,4-disubstituted arylamides. Compound
8 (FMS kinase IC
50
=
0.0008
μM) served as a proof-of-concept candidate in a collagen-induced model of arthritis in mice. |
| doi_str_mv | 10.1016/j.bmcl.2008.01.059 |
| format | Article |
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8 was utilized in an in vivo CIA model to evaluate the therapeutic potential of FMS inhibition.
The optimization of the arylamide lead
2 resulted in identification of a highly potent series of 2,4-disubstituted arylamides. Compound
8 (FMS kinase IC
50
=
0.0008
μM) served as a proof-of-concept candidate in a collagen-induced model of arthritis in mice.</description><identifier>ISSN: 0960-894X</identifier><identifier>ISSN: 0968-0896</identifier><identifier>EISSN: 1464-3405</identifier><identifier>EISSN: 1464-3391</identifier><identifier>DOI: 10.1016/j.bmcl.2008.01.059</identifier><identifier>PMID: 18242992</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Animals ; Anti-inflammatory activity ; Anti-Inflammatory Agents - chemistry ; Anti-Inflammatory Agents - pharmacology ; Arthritis - chemically induced ; Arthritis - drug therapy ; Biological and medical sciences ; Bones, joints and connective tissue. Antiinflammatory agents ; Collagen ; Colony stimulating factor-1 ; CSF-1R ; Dose-Response Relationship, Drug ; FMS ; M-CSF ; Macrophages ; Medical sciences ; Mice ; Models, Molecular ; Molecular Structure ; Pharmacology. Drug treatments ; Receptor, Macrophage Colony-Stimulating Factor - antagonists & inhibitors ; Structure-Activity Relationship ; Time Factors</subject><ispartof>Bioorganic & medicinal chemistry, 2008-03, Vol.18 (5), p.1642-1648</ispartof><rights>2008 Elsevier Ltd</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-cc56ac22ad155e019ba5253882e6d53032e88fdcddfd149033f189df8c45027c3</citedby><cites>FETCH-LOGICAL-c415t-cc56ac22ad155e019ba5253882e6d53032e88fdcddfd149033f189df8c45027c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X08000760$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20167636$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18242992$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Illig, Carl R.</creatorcontrib><creatorcontrib>Chen, Jinsheng</creatorcontrib><creatorcontrib>Wall, Mark J.</creatorcontrib><creatorcontrib>Wilson, Kenneth J.</creatorcontrib><creatorcontrib>Ballentine, Shelley K.</creatorcontrib><creatorcontrib>Rudolph, M. Jonathan</creatorcontrib><creatorcontrib>DesJarlais, Renee L.</creatorcontrib><creatorcontrib>Chen, Yanmin</creatorcontrib><creatorcontrib>Schubert, Carsten</creatorcontrib><creatorcontrib>Petrounia, Ioanna</creatorcontrib><creatorcontrib>Crysler, Carl S.</creatorcontrib><creatorcontrib>Molloy, Christopher J.</creatorcontrib><creatorcontrib>Chaikin, Margery A.</creatorcontrib><creatorcontrib>Manthey, Carl L.</creatorcontrib><creatorcontrib>Player, Mark R.</creatorcontrib><creatorcontrib>Tomczuk, Bruce E.</creatorcontrib><creatorcontrib>Meegalla, Sanath K.</creatorcontrib><title>Discovery of novel FMS kinase inhibitors as anti-inflammatory agents</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem Lett</addtitle><description>Discovery of a series of novel 2,4-disubstituted arylamides as potential anti-inflammatory agents is described. Compound
8 was utilized in an in vivo CIA model to evaluate the therapeutic potential of FMS inhibition.
The optimization of the arylamide lead
2 resulted in identification of a highly potent series of 2,4-disubstituted arylamides. Compound
8 (FMS kinase IC
50
=
0.0008
μM) served as a proof-of-concept candidate in a collagen-induced model of arthritis in mice.</description><subject>Animals</subject><subject>Anti-inflammatory activity</subject><subject>Anti-Inflammatory Agents - chemistry</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Arthritis - chemically induced</subject><subject>Arthritis - drug therapy</subject><subject>Biological and medical sciences</subject><subject>Bones, joints and connective tissue. Antiinflammatory agents</subject><subject>Collagen</subject><subject>Colony stimulating factor-1</subject><subject>CSF-1R</subject><subject>Dose-Response Relationship, Drug</subject><subject>FMS</subject><subject>M-CSF</subject><subject>Macrophages</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Models, Molecular</subject><subject>Molecular Structure</subject><subject>Pharmacology. Drug treatments</subject><subject>Receptor, Macrophage Colony-Stimulating Factor - antagonists & inhibitors</subject><subject>Structure-Activity Relationship</subject><subject>Time Factors</subject><issn>0960-894X</issn><issn>0968-0896</issn><issn>1464-3405</issn><issn>1464-3391</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtqHDEQRYWJiSdOfsAL05tk1-3Sqy1BNsGOH2DjhRPITmikUqJxt9qRegzz99Ewg7MzFKgQ516KQ8gJhY4C7c9W3XJ0Q8cAVAe0A6kPyIKKXrRcgHxHFqB7aJUWv47Ih1JWAFSAEO_JEVVMMK3ZglxexuKmF8ybZgpNqtvQXN0_Nk8x2YJNTH_iMs5TLo2tk-bYxhQGO462fm4a-xvTXD6Sw2CHgp_27zH5efX9x8VNe_dwfXvx7a51gsq5dU721jFmPZUSgeqllUxypRj2XnLgDJUK3nkfPBUaOA9UaR-UExLYuePH5Muu9zlPf9dYZjPW63EYbMJpXQzVnNccqyDbgS5PpWQM5jnH0eaNoWC27szKbN2ZrTsD1FR3NXS6b18vR_T_I3tZFfi8B2xxdgjZJhfLK8dq73nP-8p93XFYXbxEzKa4iMmhjxndbPwU37rjH4ZojI4</recordid><startdate>20080301</startdate><enddate>20080301</enddate><creator>Illig, Carl R.</creator><creator>Chen, Jinsheng</creator><creator>Wall, Mark J.</creator><creator>Wilson, Kenneth J.</creator><creator>Ballentine, Shelley K.</creator><creator>Rudolph, M. Jonathan</creator><creator>DesJarlais, Renee L.</creator><creator>Chen, Yanmin</creator><creator>Schubert, Carsten</creator><creator>Petrounia, Ioanna</creator><creator>Crysler, Carl S.</creator><creator>Molloy, Christopher J.</creator><creator>Chaikin, Margery A.</creator><creator>Manthey, Carl L.</creator><creator>Player, Mark R.</creator><creator>Tomczuk, Bruce E.</creator><creator>Meegalla, Sanath K.</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></search><sort><creationdate>20080301</creationdate><title>Discovery of novel FMS kinase inhibitors as anti-inflammatory agents</title><author>Illig, Carl R. ; Chen, Jinsheng ; Wall, Mark J. ; Wilson, Kenneth J. ; Ballentine, Shelley K. ; Rudolph, M. Jonathan ; DesJarlais, Renee L. ; Chen, Yanmin ; Schubert, Carsten ; Petrounia, Ioanna ; Crysler, Carl S. ; Molloy, Christopher J. ; Chaikin, Margery A. ; Manthey, Carl L. ; Player, Mark R. ; Tomczuk, Bruce E. ; Meegalla, Sanath K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-cc56ac22ad155e019ba5253882e6d53032e88fdcddfd149033f189df8c45027c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Anti-inflammatory activity</topic><topic>Anti-Inflammatory Agents - chemistry</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Arthritis - chemically induced</topic><topic>Arthritis - drug therapy</topic><topic>Biological and medical sciences</topic><topic>Bones, joints and connective tissue. Antiinflammatory agents</topic><topic>Collagen</topic><topic>Colony stimulating factor-1</topic><topic>CSF-1R</topic><topic>Dose-Response Relationship, Drug</topic><topic>FMS</topic><topic>M-CSF</topic><topic>Macrophages</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Models, Molecular</topic><topic>Molecular Structure</topic><topic>Pharmacology. Drug treatments</topic><topic>Receptor, Macrophage Colony-Stimulating Factor - antagonists & inhibitors</topic><topic>Structure-Activity Relationship</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Illig, Carl R.</creatorcontrib><creatorcontrib>Chen, Jinsheng</creatorcontrib><creatorcontrib>Wall, Mark J.</creatorcontrib><creatorcontrib>Wilson, Kenneth J.</creatorcontrib><creatorcontrib>Ballentine, Shelley K.</creatorcontrib><creatorcontrib>Rudolph, M. Jonathan</creatorcontrib><creatorcontrib>DesJarlais, Renee L.</creatorcontrib><creatorcontrib>Chen, Yanmin</creatorcontrib><creatorcontrib>Schubert, Carsten</creatorcontrib><creatorcontrib>Petrounia, Ioanna</creatorcontrib><creatorcontrib>Crysler, Carl S.</creatorcontrib><creatorcontrib>Molloy, Christopher J.</creatorcontrib><creatorcontrib>Chaikin, Margery A.</creatorcontrib><creatorcontrib>Manthey, Carl L.</creatorcontrib><creatorcontrib>Player, Mark R.</creatorcontrib><creatorcontrib>Tomczuk, Bruce E.</creatorcontrib><creatorcontrib>Meegalla, Sanath K.</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><jtitle>Bioorganic & medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Illig, Carl R.</au><au>Chen, Jinsheng</au><au>Wall, Mark J.</au><au>Wilson, Kenneth J.</au><au>Ballentine, Shelley K.</au><au>Rudolph, M. Jonathan</au><au>DesJarlais, Renee L.</au><au>Chen, Yanmin</au><au>Schubert, Carsten</au><au>Petrounia, Ioanna</au><au>Crysler, Carl S.</au><au>Molloy, Christopher J.</au><au>Chaikin, Margery A.</au><au>Manthey, Carl L.</au><au>Player, Mark R.</au><au>Tomczuk, Bruce E.</au><au>Meegalla, Sanath K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discovery of novel FMS kinase inhibitors as anti-inflammatory agents</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2008-03-01</date><risdate>2008</risdate><volume>18</volume><issue>5</issue><spage>1642</spage><epage>1648</epage><pages>1642-1648</pages><issn>0960-894X</issn><issn>0968-0896</issn><eissn>1464-3405</eissn><eissn>1464-3391</eissn><abstract>Discovery of a series of novel 2,4-disubstituted arylamides as potential anti-inflammatory agents is described. Compound
8 was utilized in an in vivo CIA model to evaluate the therapeutic potential of FMS inhibition.
The optimization of the arylamide lead
2 resulted in identification of a highly potent series of 2,4-disubstituted arylamides. Compound
8 (FMS kinase IC
50
=
0.0008
μM) served as a proof-of-concept candidate in a collagen-induced model of arthritis in mice.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>18242992</pmid><doi>10.1016/j.bmcl.2008.01.059</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry, 2008-03, Vol.18 (5), p.1642-1648 |
| issn | 0960-894X 0968-0896 1464-3405 1464-3391 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_19334902 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Animals Anti-inflammatory activity Anti-Inflammatory Agents - chemistry Anti-Inflammatory Agents - pharmacology Arthritis - chemically induced Arthritis - drug therapy Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Collagen Colony stimulating factor-1 CSF-1R Dose-Response Relationship, Drug FMS M-CSF Macrophages Medical sciences Mice Models, Molecular Molecular Structure Pharmacology. Drug treatments Receptor, Macrophage Colony-Stimulating Factor - antagonists & inhibitors Structure-Activity Relationship Time Factors |
| title | Discovery of novel FMS kinase inhibitors as anti-inflammatory agents |
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