Pyridyl-pyrimidine benzimidazole derivatives as potent, selective, and orally bioavailable inhibitors of Tie-2 kinase
The optimization of a nonselective scaffold into 15, a potent inhibitor of Tie-2 kinase with selectivity against VEGFR2 kinase, is reported. Selective small molecule inhibitors of Tie-2 kinase are important tools for the validation of Tie-2 signaling in pathological angiogenesis. Reported herein is...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2009-01, Vol.19 (2), p.424-427 |
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| creator | Cee, Victor J. Cheng, Alan C. Romero, Karina Bellon, Steve Mohr, Christopher Whittington, Douglas A. Bak, Annette Bready, James Caenepeel, Sean Coxon, Angela Deak, Holly L. Fretland, Jenne Gu, Yan Hodous, Brian L. Huang, Xin Kim, Joseph L. Lin, Jasmine Long, Alexander M. Nguyen, Hanh Olivieri, Philip R. Patel, Vinod F. Wang, Ling Zhou, Yihong Hughes, Paul Geuns-Meyer, Stephanie |
| description | The optimization of a nonselective scaffold into
15, a potent inhibitor of Tie-2 kinase with selectivity against VEGFR2 kinase, is reported.
Selective small molecule inhibitors of Tie-2 kinase are important tools for the validation of Tie-2 signaling in pathological angiogenesis. Reported herein is the optimization of a nonselective scaffold into a potent and highly selective inhibitor of Tie-2 kinase. |
| doi_str_mv | 10.1016/j.bmcl.2008.11.056 |
| format | Article |
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15, a potent inhibitor of Tie-2 kinase with selectivity against VEGFR2 kinase, is reported.
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15, a potent inhibitor of Tie-2 kinase with selectivity against VEGFR2 kinase, is reported.
Selective small molecule inhibitors of Tie-2 kinase are important tools for the validation of Tie-2 signaling in pathological angiogenesis. Reported herein is the optimization of a nonselective scaffold into a potent and highly selective inhibitor of Tie-2 kinase.</description><subject>Administration, Oral</subject><subject>Angiogenesis</subject><subject>Benzimidazole</subject><subject>Benzimidazoles - administration & dosage</subject><subject>Benzimidazoles - chemistry</subject><subject>Benzimidazoles - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Biological Availability</subject><subject>Crystallography, X-Ray</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Kinase inhibitor</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Models, Molecular</subject><subject>Pharmacology. Drug treatments</subject><subject>Protein Kinase Inhibitors - administration & dosage</subject><subject>Protein Kinase Inhibitors - chemistry</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Receptor, TIE-2 - antagonists & inhibitors</subject><subject>Tie-2 kinase</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>eNqFkcGKFDEQhoMo7rj6Ah4kFz1tt5V0kkmDl2XRVVjQwwreQjqpxoyZzpj0DMw-vWlmcG96qqL4_qKoj5DXDFoGTL3ftMPWxZYD6JaxFqR6QlZMKNF0AuRTsoJeQaN78eOCvChlA8AECPGcXLAeFOdruSL7b8cc_DE2u1q3wYcJ6YDTw9LbhxSReszhYOdwwEJtobs04zRf0YIR3TK9onbyNGUb45EOIdmDDdEONRmmn2EIc8qFppHeB2w4_RUmW_AleTbaWPDVuV6S758-3t98bu6-3n65ub5rnGBybno3apBaci6g59wpKaT23GsxoGdocQ0AHLRltpP9CHY9qkEMvewlMt-x7pK8O-3d5fR7j2U221AcxmgnTPtilFqrXmr1X5BDJxiTuoL8BLqcSsk4ml39m81Hw8AsVszGLFbMYsUwZqqVGnpz3r4ftugfI2cNFXh7BmxxNo7ZTi6Uvxxn0IHQXeU-nDisTzsEzKa4gJNDH3K1YXwK_7rjD-B5q84</recordid><startdate>20090115</startdate><enddate>20090115</enddate><creator>Cee, Victor J.</creator><creator>Cheng, Alan C.</creator><creator>Romero, Karina</creator><creator>Bellon, Steve</creator><creator>Mohr, Christopher</creator><creator>Whittington, Douglas A.</creator><creator>Bak, Annette</creator><creator>Bready, James</creator><creator>Caenepeel, Sean</creator><creator>Coxon, Angela</creator><creator>Deak, Holly L.</creator><creator>Fretland, Jenne</creator><creator>Gu, Yan</creator><creator>Hodous, Brian L.</creator><creator>Huang, Xin</creator><creator>Kim, Joseph L.</creator><creator>Lin, Jasmine</creator><creator>Long, Alexander M.</creator><creator>Nguyen, Hanh</creator><creator>Olivieri, Philip R.</creator><creator>Patel, Vinod F.</creator><creator>Wang, Ling</creator><creator>Zhou, Yihong</creator><creator>Hughes, Paul</creator><creator>Geuns-Meyer, Stephanie</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>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20090115</creationdate><title>Pyridyl-pyrimidine benzimidazole derivatives as potent, selective, and orally bioavailable inhibitors of Tie-2 kinase</title><author>Cee, Victor J. ; Cheng, Alan C. ; Romero, Karina ; Bellon, Steve ; Mohr, Christopher ; Whittington, Douglas A. ; Bak, Annette ; Bready, James ; Caenepeel, Sean ; Coxon, Angela ; Deak, Holly L. ; Fretland, Jenne ; Gu, Yan ; Hodous, Brian L. ; Huang, Xin ; Kim, Joseph L. ; Lin, Jasmine ; Long, Alexander M. ; Nguyen, Hanh ; Olivieri, Philip R. ; Patel, Vinod F. ; Wang, Ling ; Zhou, Yihong ; Hughes, Paul ; Geuns-Meyer, Stephanie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-9cf805852240922c65458d2d84bed1eae7000208a1a359f0a7f6b4b9595e1d313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Administration, Oral</topic><topic>Angiogenesis</topic><topic>Benzimidazole</topic><topic>Benzimidazoles - administration & dosage</topic><topic>Benzimidazoles - chemistry</topic><topic>Benzimidazoles - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Biological Availability</topic><topic>Crystallography, X-Ray</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Kinase inhibitor</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Models, Molecular</topic><topic>Pharmacology. Drug treatments</topic><topic>Protein Kinase Inhibitors - administration & dosage</topic><topic>Protein Kinase Inhibitors - chemistry</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Receptor, TIE-2 - antagonists & inhibitors</topic><topic>Tie-2 kinase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cee, Victor J.</creatorcontrib><creatorcontrib>Cheng, Alan C.</creatorcontrib><creatorcontrib>Romero, Karina</creatorcontrib><creatorcontrib>Bellon, Steve</creatorcontrib><creatorcontrib>Mohr, Christopher</creatorcontrib><creatorcontrib>Whittington, Douglas A.</creatorcontrib><creatorcontrib>Bak, Annette</creatorcontrib><creatorcontrib>Bready, James</creatorcontrib><creatorcontrib>Caenepeel, Sean</creatorcontrib><creatorcontrib>Coxon, Angela</creatorcontrib><creatorcontrib>Deak, Holly L.</creatorcontrib><creatorcontrib>Fretland, Jenne</creatorcontrib><creatorcontrib>Gu, Yan</creatorcontrib><creatorcontrib>Hodous, Brian L.</creatorcontrib><creatorcontrib>Huang, Xin</creatorcontrib><creatorcontrib>Kim, Joseph L.</creatorcontrib><creatorcontrib>Lin, Jasmine</creatorcontrib><creatorcontrib>Long, Alexander M.</creatorcontrib><creatorcontrib>Nguyen, Hanh</creatorcontrib><creatorcontrib>Olivieri, Philip R.</creatorcontrib><creatorcontrib>Patel, Vinod F.</creatorcontrib><creatorcontrib>Wang, Ling</creatorcontrib><creatorcontrib>Zhou, Yihong</creatorcontrib><creatorcontrib>Hughes, Paul</creatorcontrib><creatorcontrib>Geuns-Meyer, Stephanie</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>Nucleic Acids 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>Cee, Victor J.</au><au>Cheng, Alan C.</au><au>Romero, Karina</au><au>Bellon, Steve</au><au>Mohr, Christopher</au><au>Whittington, Douglas A.</au><au>Bak, Annette</au><au>Bready, James</au><au>Caenepeel, Sean</au><au>Coxon, Angela</au><au>Deak, Holly L.</au><au>Fretland, Jenne</au><au>Gu, Yan</au><au>Hodous, Brian L.</au><au>Huang, Xin</au><au>Kim, Joseph L.</au><au>Lin, Jasmine</au><au>Long, Alexander M.</au><au>Nguyen, Hanh</au><au>Olivieri, Philip R.</au><au>Patel, Vinod F.</au><au>Wang, Ling</au><au>Zhou, Yihong</au><au>Hughes, Paul</au><au>Geuns-Meyer, Stephanie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pyridyl-pyrimidine benzimidazole derivatives as potent, selective, and orally bioavailable inhibitors of Tie-2 kinase</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2009-01-15</date><risdate>2009</risdate><volume>19</volume><issue>2</issue><spage>424</spage><epage>427</epage><pages>424-427</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>The optimization of a nonselective scaffold into
15, a potent inhibitor of Tie-2 kinase with selectivity against VEGFR2 kinase, is reported.
Selective small molecule inhibitors of Tie-2 kinase are important tools for the validation of Tie-2 signaling in pathological angiogenesis. Reported herein is the optimization of a nonselective scaffold into a potent and highly selective inhibitor of Tie-2 kinase.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>19062275</pmid><doi>10.1016/j.bmcl.2008.11.056</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2009-01, Vol.19 (2), p.424-427 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Administration, Oral Angiogenesis Benzimidazole Benzimidazoles - administration & dosage Benzimidazoles - chemistry Benzimidazoles - pharmacology Biological and medical sciences Biological Availability Crystallography, X-Ray HeLa Cells Humans Kinase inhibitor Medical sciences Miscellaneous Models, Molecular Pharmacology. Drug treatments Protein Kinase Inhibitors - administration & dosage Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - pharmacology Receptor, TIE-2 - antagonists & inhibitors Tie-2 kinase |
| title | Pyridyl-pyrimidine benzimidazole derivatives as potent, selective, and orally bioavailable inhibitors of Tie-2 kinase |
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