Identification of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors
Tumor angiogenesis is mediated by KDR and other VEGFR and PDGFR kinases. Their inhibition presents an attractive approach for developing anticancer therapeutics. Here, we report a series of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors. A number of compounds have...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry 2008, Vol.18 (1), p.386-390 |
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| creator | Dai, Yujia Hartandi, Kresna Soni, Niru B. Pease, Lori J. Reuter, David R. Olson, Amanda M. Osterling, Donald J. Doktor, Stella Z. Albert, Daniel H. Bouska, Jennifer J. Glaser, Keith B. Marcotte, Patrick A. Stewart, Kent D. Davidsen, Steven K. Michaelides, Michael R. |
| description | Tumor angiogenesis is mediated by KDR and other VEGFR and PDGFR kinases. Their inhibition presents an attractive approach for developing anticancer therapeutics. Here, we report a series of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors. A number of compounds have been identified to be orally bioavailable and efficacious in the mouse edema model.
Tumor angiogenesis is mediated by KDR and other VEGFR and PDGFR kinases. Their inhibition presents an attractive approach for developing anticancer therapeutics. Here, we report a series of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors. A number of compounds have been identified to be orally bioavailable and efficacious in the mouse edema model. |
| doi_str_mv | 10.1016/j.bmcl.2007.10.018 |
| format | Article |
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Tumor angiogenesis is mediated by KDR and other VEGFR and PDGFR kinases. Their inhibition presents an attractive approach for developing anticancer therapeutics. Here, we report a series of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors. A number of compounds have been identified to be orally bioavailable and efficacious in the mouse edema model.</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.2007.10.018</identifier><identifier>PMID: 18023347</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Administration, Oral ; Aminopyridines - chemical synthesis ; Aminopyridines - chemistry ; Aminopyridines - pharmacokinetics ; Aminopyridines - pharmacology ; Animals ; Biological and medical sciences ; Biological Availability ; Edema - drug therapy ; Edema - metabolism ; Female ; Inhibitory Concentration 50 ; KDR ; Medical sciences ; Mice ; Miscellaneous ; Models, Molecular ; Pharmacology. Drug treatments ; Protein Kinase Inhibitors - chemical synthesis ; Protein Kinase Inhibitors - chemistry ; Protein Kinase Inhibitors - pharmacokinetics ; Protein Kinase Inhibitors - pharmacology ; Pyrazoles - chemical synthesis ; Pyrazoles - chemistry ; Pyrazoles - pharmacokinetics ; Pyrazoles - pharmacology ; Pyrazolopyridines ; Receptors, Platelet-Derived Growth Factor - antagonists & inhibitors ; Receptors, Vascular Endothelial Growth Factor - antagonists & inhibitors ; Structure-Activity Relationship ; Urea - analogs & derivatives ; Urea - chemical synthesis ; Urea - pharmacology ; Uterine Diseases - drug therapy ; Uterine Diseases - metabolism ; VEGFR/PDGFR kinase inhibitors</subject><ispartof>Bioorganic & medicinal chemistry, 2008, Vol.18 (1), p.386-390</ispartof><rights>2007 Elsevier Ltd</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c481t-d26252497650258a478cabe2e5ccc2813009dc1a51bf339e1cbe60f73653b3643</citedby><cites>FETCH-LOGICAL-c481t-d26252497650258a478cabe2e5ccc2813009dc1a51bf339e1cbe60f73653b3643</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X07011912$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,4010,27900,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20037453$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18023347$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dai, Yujia</creatorcontrib><creatorcontrib>Hartandi, Kresna</creatorcontrib><creatorcontrib>Soni, Niru B.</creatorcontrib><creatorcontrib>Pease, Lori J.</creatorcontrib><creatorcontrib>Reuter, David R.</creatorcontrib><creatorcontrib>Olson, Amanda M.</creatorcontrib><creatorcontrib>Osterling, Donald J.</creatorcontrib><creatorcontrib>Doktor, Stella Z.</creatorcontrib><creatorcontrib>Albert, Daniel H.</creatorcontrib><creatorcontrib>Bouska, Jennifer J.</creatorcontrib><creatorcontrib>Glaser, Keith B.</creatorcontrib><creatorcontrib>Marcotte, Patrick A.</creatorcontrib><creatorcontrib>Stewart, Kent D.</creatorcontrib><creatorcontrib>Davidsen, Steven K.</creatorcontrib><creatorcontrib>Michaelides, Michael R.</creatorcontrib><title>Identification of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem Lett</addtitle><description>Tumor angiogenesis is mediated by KDR and other VEGFR and PDGFR kinases. Their inhibition presents an attractive approach for developing anticancer therapeutics. Here, we report a series of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors. A number of compounds have been identified to be orally bioavailable and efficacious in the mouse edema model.
Tumor angiogenesis is mediated by KDR and other VEGFR and PDGFR kinases. Their inhibition presents an attractive approach for developing anticancer therapeutics. Here, we report a series of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors. A number of compounds have been identified to be orally bioavailable and efficacious in the mouse edema model.</description><subject>Administration, Oral</subject><subject>Aminopyridines - chemical synthesis</subject><subject>Aminopyridines - chemistry</subject><subject>Aminopyridines - pharmacokinetics</subject><subject>Aminopyridines - pharmacology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biological Availability</subject><subject>Edema - drug therapy</subject><subject>Edema - metabolism</subject><subject>Female</subject><subject>Inhibitory Concentration 50</subject><subject>KDR</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Miscellaneous</subject><subject>Models, Molecular</subject><subject>Pharmacology. 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Drug treatments</topic><topic>Protein Kinase Inhibitors - chemical synthesis</topic><topic>Protein Kinase Inhibitors - chemistry</topic><topic>Protein Kinase Inhibitors - pharmacokinetics</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Pyrazoles - chemical synthesis</topic><topic>Pyrazoles - chemistry</topic><topic>Pyrazoles - pharmacokinetics</topic><topic>Pyrazoles - pharmacology</topic><topic>Pyrazolopyridines</topic><topic>Receptors, Platelet-Derived Growth Factor - antagonists & inhibitors</topic><topic>Receptors, Vascular Endothelial Growth Factor - antagonists & inhibitors</topic><topic>Structure-Activity Relationship</topic><topic>Urea - analogs & derivatives</topic><topic>Urea - chemical synthesis</topic><topic>Urea - pharmacology</topic><topic>Uterine Diseases - drug therapy</topic><topic>Uterine Diseases - metabolism</topic><topic>VEGFR/PDGFR kinase inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dai, Yujia</creatorcontrib><creatorcontrib>Hartandi, Kresna</creatorcontrib><creatorcontrib>Soni, Niru B.</creatorcontrib><creatorcontrib>Pease, Lori J.</creatorcontrib><creatorcontrib>Reuter, David R.</creatorcontrib><creatorcontrib>Olson, Amanda M.</creatorcontrib><creatorcontrib>Osterling, Donald J.</creatorcontrib><creatorcontrib>Doktor, Stella Z.</creatorcontrib><creatorcontrib>Albert, Daniel H.</creatorcontrib><creatorcontrib>Bouska, Jennifer J.</creatorcontrib><creatorcontrib>Glaser, Keith B.</creatorcontrib><creatorcontrib>Marcotte, Patrick A.</creatorcontrib><creatorcontrib>Stewart, Kent D.</creatorcontrib><creatorcontrib>Davidsen, Steven K.</creatorcontrib><creatorcontrib>Michaelides, Michael R.</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>Dai, Yujia</au><au>Hartandi, Kresna</au><au>Soni, Niru B.</au><au>Pease, Lori J.</au><au>Reuter, David R.</au><au>Olson, Amanda M.</au><au>Osterling, Donald J.</au><au>Doktor, Stella Z.</au><au>Albert, Daniel H.</au><au>Bouska, Jennifer J.</au><au>Glaser, Keith B.</au><au>Marcotte, Patrick A.</au><au>Stewart, Kent D.</au><au>Davidsen, Steven K.</au><au>Michaelides, Michael R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2008</date><risdate>2008</risdate><volume>18</volume><issue>1</issue><spage>386</spage><epage>390</epage><pages>386-390</pages><issn>0960-894X</issn><issn>0968-0896</issn><eissn>1464-3405</eissn><eissn>1464-3391</eissn><abstract>Tumor angiogenesis is mediated by KDR and other VEGFR and PDGFR kinases. Their inhibition presents an attractive approach for developing anticancer therapeutics. Here, we report a series of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors. A number of compounds have been identified to be orally bioavailable and efficacious in the mouse edema model.
Tumor angiogenesis is mediated by KDR and other VEGFR and PDGFR kinases. Their inhibition presents an attractive approach for developing anticancer therapeutics. Here, we report a series of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors. A number of compounds have been identified to be orally bioavailable and efficacious in the mouse edema model.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>18023347</pmid><doi>10.1016/j.bmcl.2007.10.018</doi><tpages>5</tpages></addata></record> |
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| subjects | Administration, Oral Aminopyridines - chemical synthesis Aminopyridines - chemistry Aminopyridines - pharmacokinetics Aminopyridines - pharmacology Animals Biological and medical sciences Biological Availability Edema - drug therapy Edema - metabolism Female Inhibitory Concentration 50 KDR Medical sciences Mice Miscellaneous Models, Molecular Pharmacology. Drug treatments Protein Kinase Inhibitors - chemical synthesis Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - pharmacokinetics Protein Kinase Inhibitors - pharmacology Pyrazoles - chemical synthesis Pyrazoles - chemistry Pyrazoles - pharmacokinetics Pyrazoles - pharmacology Pyrazolopyridines Receptors, Platelet-Derived Growth Factor - antagonists & inhibitors Receptors, Vascular Endothelial Growth Factor - antagonists & inhibitors Structure-Activity Relationship Urea - analogs & derivatives Urea - chemical synthesis Urea - pharmacology Uterine Diseases - drug therapy Uterine Diseases - metabolism VEGFR/PDGFR kinase inhibitors |
| title | Identification of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors |
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