Lead identification to generate 3-cyanoquinoline inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment
The strategies, synthesis, and SAR behind novel cyanoquinoline IGFR inhibitors ( 1) are reported. Insulin-like growth factor receptor (IGF-1R) is a growth factor receptor tyrosine kinase that acts as a critical mediator of cell proliferation and survival. Inhibitors of this receptor are believed to...
Gespeichert in:
| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2009, Vol.19 (1), p.62-66 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 66 |
|---|---|
| container_issue | 1 |
| container_start_page | 62 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 19 |
| creator | Miller, Lori M. Mayer, Scott C. Berger, Dan M. Boschelli, Diane H. Boschelli, Frank Di, Li Du, Xuemei Dutia, Minu Floyd, Middleton B. Johnson, Mark Kenny, Cynthia Hess Krishnamurthy, Girija Moy, Franklin Petusky, Susan Tkach, Diane Torres, Nancy Wu, Biqi Xu, Weixin |
| description | The strategies, synthesis, and SAR behind novel cyanoquinoline IGFR inhibitors (
1) are reported.
Insulin-like growth factor receptor (IGF-1R) is a growth factor receptor tyrosine kinase that acts as a critical mediator of cell proliferation and survival. Inhibitors of this receptor are believed to provide a new target in cancer therapy. We previously reported an isoquinolinedione series of IGF-1R inhibitors. Now we have identified a series of 3-cyanoquinoline compounds that are low nanomolar inhibitors of IGF-1R. The strategies, synthesis, and SAR behind the cyanoquinoline scaffold will be discussed. |
| doi_str_mv | 10.1016/j.bmcl.2008.11.037 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_66769900</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0960894X08013905</els_id><sourcerecordid>20258300</sourcerecordid><originalsourceid>FETCH-LOGICAL-c446t-7ddf3f2cd44bd895ab88898b5ba9f2b899f865d892bab72c0058f272802ad7703</originalsourceid><addsrcrecordid>eNqNkc9u1DAQxiMEokvhBTggX0DlkDB2nMSWekFVWyqthIRA4mb5b-sliRfbAfUxeGMcdgU3wBd7PL_5xp6vqp5jaDDg_s2uUZMeGwLAGowbaIcH1QbTntYthe5htQHeQ804_XxSPUlpB4ApUPq4OsEcKCYUNtWPrZUGeWPn7J3XMvswoxzQrZ1tlNmittb3cg5fFz-H0c8W-fnOK59DTCi4EqWlXNej_2LRbQzf8x1yUpc0ilbb_Xo4u7m-qvGH18iVYB_y2kuOaEmrGNJy1jaiHK3MU0k9rR45OSb77LifVp-uLj9evKu3769vLt5ua01pn-vBGNc6og2lyjDeScUY40x1SnJHFOPcsb4rGaKkGogG6JgjA2FApBkGaE-rVwfdfSy_symLySdtx1HONixJ9P3Qcw7_Bgm0ZTHyHyDpWPtLkRxAHUNK0Tqxj36S8V5gEKu1YidWa8VqrcBYFGtL0Yuj-qIma_6UHL0swMsjIJOWo4tlsD795giG0pvxwp0fOFum-83bKJL2tphgfLEsCxP8397xE0UYw28</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>20258300</pqid></control><display><type>article</type><title>Lead identification to generate 3-cyanoquinoline inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Miller, Lori M. ; Mayer, Scott C. ; Berger, Dan M. ; Boschelli, Diane H. ; Boschelli, Frank ; Di, Li ; Du, Xuemei ; Dutia, Minu ; Floyd, Middleton B. ; Johnson, Mark ; Kenny, Cynthia Hess ; Krishnamurthy, Girija ; Moy, Franklin ; Petusky, Susan ; Tkach, Diane ; Torres, Nancy ; Wu, Biqi ; Xu, Weixin</creator><creatorcontrib>Miller, Lori M. ; Mayer, Scott C. ; Berger, Dan M. ; Boschelli, Diane H. ; Boschelli, Frank ; Di, Li ; Du, Xuemei ; Dutia, Minu ; Floyd, Middleton B. ; Johnson, Mark ; Kenny, Cynthia Hess ; Krishnamurthy, Girija ; Moy, Franklin ; Petusky, Susan ; Tkach, Diane ; Torres, Nancy ; Wu, Biqi ; Xu, Weixin</creatorcontrib><description>The strategies, synthesis, and SAR behind novel cyanoquinoline IGFR inhibitors (
1) are reported.
Insulin-like growth factor receptor (IGF-1R) is a growth factor receptor tyrosine kinase that acts as a critical mediator of cell proliferation and survival. Inhibitors of this receptor are believed to provide a new target in cancer therapy. We previously reported an isoquinolinedione series of IGF-1R inhibitors. Now we have identified a series of 3-cyanoquinoline compounds that are low nanomolar inhibitors of IGF-1R. The strategies, synthesis, and SAR behind the cyanoquinoline scaffold will be discussed.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2008.11.037</identifier><identifier>PMID: 19041240</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>Antineoplastic agents ; Antineoplastic Agents - chemical synthesis ; Biological and medical sciences ; Cyanoquinoline ; General aspects ; Humans ; IGFR inhibitor ; Medical sciences ; Nitriles - chemical synthesis ; Nitriles - pharmacology ; Pharmacology. Drug treatments ; Quinolines - chemical synthesis ; Quinolines - pharmacology ; Receptor, IGF Type 1 - antagonists & inhibitors ; Structure-Activity Relationship ; ‘Hit to Lead’ investigations</subject><ispartof>Bioorganic & medicinal chemistry letters, 2009, Vol.19 (1), p.62-66</ispartof><rights>2008 Elsevier Ltd</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c446t-7ddf3f2cd44bd895ab88898b5ba9f2b899f865d892bab72c0058f272802ad7703</citedby><cites>FETCH-LOGICAL-c446t-7ddf3f2cd44bd895ab88898b5ba9f2b899f865d892bab72c0058f272802ad7703</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X08013905$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,4010,27900,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21030089$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19041240$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Miller, Lori M.</creatorcontrib><creatorcontrib>Mayer, Scott C.</creatorcontrib><creatorcontrib>Berger, Dan M.</creatorcontrib><creatorcontrib>Boschelli, Diane H.</creatorcontrib><creatorcontrib>Boschelli, Frank</creatorcontrib><creatorcontrib>Di, Li</creatorcontrib><creatorcontrib>Du, Xuemei</creatorcontrib><creatorcontrib>Dutia, Minu</creatorcontrib><creatorcontrib>Floyd, Middleton B.</creatorcontrib><creatorcontrib>Johnson, Mark</creatorcontrib><creatorcontrib>Kenny, Cynthia Hess</creatorcontrib><creatorcontrib>Krishnamurthy, Girija</creatorcontrib><creatorcontrib>Moy, Franklin</creatorcontrib><creatorcontrib>Petusky, Susan</creatorcontrib><creatorcontrib>Tkach, Diane</creatorcontrib><creatorcontrib>Torres, Nancy</creatorcontrib><creatorcontrib>Wu, Biqi</creatorcontrib><creatorcontrib>Xu, Weixin</creatorcontrib><title>Lead identification to generate 3-cyanoquinoline inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>The strategies, synthesis, and SAR behind novel cyanoquinoline IGFR inhibitors (
1) are reported.
Insulin-like growth factor receptor (IGF-1R) is a growth factor receptor tyrosine kinase that acts as a critical mediator of cell proliferation and survival. Inhibitors of this receptor are believed to provide a new target in cancer therapy. We previously reported an isoquinolinedione series of IGF-1R inhibitors. Now we have identified a series of 3-cyanoquinoline compounds that are low nanomolar inhibitors of IGF-1R. The strategies, synthesis, and SAR behind the cyanoquinoline scaffold will be discussed.</description><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Biological and medical sciences</subject><subject>Cyanoquinoline</subject><subject>General aspects</subject><subject>Humans</subject><subject>IGFR inhibitor</subject><subject>Medical sciences</subject><subject>Nitriles - chemical synthesis</subject><subject>Nitriles - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Quinolines - chemical synthesis</subject><subject>Quinolines - pharmacology</subject><subject>Receptor, IGF Type 1 - antagonists & inhibitors</subject><subject>Structure-Activity Relationship</subject><subject>‘Hit to Lead’ investigations</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc9u1DAQxiMEokvhBTggX0DlkDB2nMSWekFVWyqthIRA4mb5b-sliRfbAfUxeGMcdgU3wBd7PL_5xp6vqp5jaDDg_s2uUZMeGwLAGowbaIcH1QbTntYthe5htQHeQ804_XxSPUlpB4ApUPq4OsEcKCYUNtWPrZUGeWPn7J3XMvswoxzQrZ1tlNmittb3cg5fFz-H0c8W-fnOK59DTCi4EqWlXNej_2LRbQzf8x1yUpc0ilbb_Xo4u7m-qvGH18iVYB_y2kuOaEmrGNJy1jaiHK3MU0k9rR45OSb77LifVp-uLj9evKu3769vLt5ua01pn-vBGNc6og2lyjDeScUY40x1SnJHFOPcsb4rGaKkGogG6JgjA2FApBkGaE-rVwfdfSy_symLySdtx1HONixJ9P3Qcw7_Bgm0ZTHyHyDpWPtLkRxAHUNK0Tqxj36S8V5gEKu1YidWa8VqrcBYFGtL0Yuj-qIma_6UHL0swMsjIJOWo4tlsD795giG0pvxwp0fOFum-83bKJL2tphgfLEsCxP8397xE0UYw28</recordid><startdate>2009</startdate><enddate>2009</enddate><creator>Miller, Lori M.</creator><creator>Mayer, Scott C.</creator><creator>Berger, Dan M.</creator><creator>Boschelli, Diane H.</creator><creator>Boschelli, Frank</creator><creator>Di, Li</creator><creator>Du, Xuemei</creator><creator>Dutia, Minu</creator><creator>Floyd, Middleton B.</creator><creator>Johnson, Mark</creator><creator>Kenny, Cynthia Hess</creator><creator>Krishnamurthy, Girija</creator><creator>Moy, Franklin</creator><creator>Petusky, Susan</creator><creator>Tkach, Diane</creator><creator>Torres, Nancy</creator><creator>Wu, Biqi</creator><creator>Xu, Weixin</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>2009</creationdate><title>Lead identification to generate 3-cyanoquinoline inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment</title><author>Miller, Lori M. ; Mayer, Scott C. ; Berger, Dan M. ; Boschelli, Diane H. ; Boschelli, Frank ; Di, Li ; Du, Xuemei ; Dutia, Minu ; Floyd, Middleton B. ; Johnson, Mark ; Kenny, Cynthia Hess ; Krishnamurthy, Girija ; Moy, Franklin ; Petusky, Susan ; Tkach, Diane ; Torres, Nancy ; Wu, Biqi ; Xu, Weixin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c446t-7ddf3f2cd44bd895ab88898b5ba9f2b899f865d892bab72c0058f272802ad7703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Biological and medical sciences</topic><topic>Cyanoquinoline</topic><topic>General aspects</topic><topic>Humans</topic><topic>IGFR inhibitor</topic><topic>Medical sciences</topic><topic>Nitriles - chemical synthesis</topic><topic>Nitriles - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Quinolines - chemical synthesis</topic><topic>Quinolines - pharmacology</topic><topic>Receptor, IGF Type 1 - antagonists & inhibitors</topic><topic>Structure-Activity Relationship</topic><topic>‘Hit to Lead’ investigations</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miller, Lori M.</creatorcontrib><creatorcontrib>Mayer, Scott C.</creatorcontrib><creatorcontrib>Berger, Dan M.</creatorcontrib><creatorcontrib>Boschelli, Diane H.</creatorcontrib><creatorcontrib>Boschelli, Frank</creatorcontrib><creatorcontrib>Di, Li</creatorcontrib><creatorcontrib>Du, Xuemei</creatorcontrib><creatorcontrib>Dutia, Minu</creatorcontrib><creatorcontrib>Floyd, Middleton B.</creatorcontrib><creatorcontrib>Johnson, Mark</creatorcontrib><creatorcontrib>Kenny, Cynthia Hess</creatorcontrib><creatorcontrib>Krishnamurthy, Girija</creatorcontrib><creatorcontrib>Moy, Franklin</creatorcontrib><creatorcontrib>Petusky, Susan</creatorcontrib><creatorcontrib>Tkach, Diane</creatorcontrib><creatorcontrib>Torres, Nancy</creatorcontrib><creatorcontrib>Wu, Biqi</creatorcontrib><creatorcontrib>Xu, Weixin</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>Miller, Lori M.</au><au>Mayer, Scott C.</au><au>Berger, Dan M.</au><au>Boschelli, Diane H.</au><au>Boschelli, Frank</au><au>Di, Li</au><au>Du, Xuemei</au><au>Dutia, Minu</au><au>Floyd, Middleton B.</au><au>Johnson, Mark</au><au>Kenny, Cynthia Hess</au><au>Krishnamurthy, Girija</au><au>Moy, Franklin</au><au>Petusky, Susan</au><au>Tkach, Diane</au><au>Torres, Nancy</au><au>Wu, Biqi</au><au>Xu, Weixin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lead identification to generate 3-cyanoquinoline inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2009</date><risdate>2009</risdate><volume>19</volume><issue>1</issue><spage>62</spage><epage>66</epage><pages>62-66</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>The strategies, synthesis, and SAR behind novel cyanoquinoline IGFR inhibitors (
1) are reported.
Insulin-like growth factor receptor (IGF-1R) is a growth factor receptor tyrosine kinase that acts as a critical mediator of cell proliferation and survival. Inhibitors of this receptor are believed to provide a new target in cancer therapy. We previously reported an isoquinolinedione series of IGF-1R inhibitors. Now we have identified a series of 3-cyanoquinoline compounds that are low nanomolar inhibitors of IGF-1R. The strategies, synthesis, and SAR behind the cyanoquinoline scaffold will be discussed.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>19041240</pmid><doi>10.1016/j.bmcl.2008.11.037</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2009, Vol.19 (1), p.62-66 |
| issn | 0960-894X 1464-3405 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_66769900 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Antineoplastic agents Antineoplastic Agents - chemical synthesis Biological and medical sciences Cyanoquinoline General aspects Humans IGFR inhibitor Medical sciences Nitriles - chemical synthesis Nitriles - pharmacology Pharmacology. Drug treatments Quinolines - chemical synthesis Quinolines - pharmacology Receptor, IGF Type 1 - antagonists & inhibitors Structure-Activity Relationship ‘Hit to Lead’ investigations |
| title | Lead identification to generate 3-cyanoquinoline inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T05%3A26%3A41IST&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=Lead%20identification%20to%20generate%203-cyanoquinoline%20inhibitors%20of%20insulin-like%20growth%20factor%20receptor%20(IGF-1R)%20for%20potential%20use%20in%20cancer%20treatment&rft.jtitle=Bioorganic%20&%20medicinal%20chemistry%20letters&rft.au=Miller,%20Lori%20M.&rft.date=2009&rft.volume=19&rft.issue=1&rft.spage=62&rft.epage=66&rft.pages=62-66&rft.issn=0960-894X&rft.eissn=1464-3405&rft_id=info:doi/10.1016/j.bmcl.2008.11.037&rft_dat=%3Cproquest_cross%3E20258300%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=20258300&rft_id=info:pmid/19041240&rft_els_id=S0960894X08013905&rfr_iscdi=true |