Novel pyrrolo[2,1- f][1,2,4]triazin-4-amines: Dual inhibitors of EGFR and HER2 protein tyrosine kinases
A novel series of 5-((4-aminopiperidin-1-yl)methyl)-pyrrolo[2,1- f][1,2,4]triazin-4-amines with small aniline substituents at the C4 position were optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. Compound 8l exhibited promising oral efficacy in both EGFR and HER2-driven human tum...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2011-01, Vol.21 (2), p.781-785 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Fink, Brian E. Norris, Derek Mastalerz, Harold Chen, Ping Goyal, Bindu Zhao, Yufen Kim, Soong-Hoon Vite, Gregory D. Lee, Francis Y. Zhang, Hongjian Oppenheimer, Simone Tokarski, John S. Wong, Tai W. Gavai, Ashvinikumar V. |
| description | A novel series of 5-((4-aminopiperidin-1-yl)methyl)-pyrrolo[2,1-
f][1,2,4]triazin-4-amines with small aniline substituents at the C4 position were optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. Compound
8l exhibited promising oral efficacy in both EGFR and HER2-driven human tumor xenograft models.
A novel series of 5-((4-aminopiperidin-1-yl)methyl)-pyrrolo[2,1-
f][1,2,4]triazin-4-amines with small aniline substituents at the C4 position were optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. Compound
8l exhibited promising oral efficacy in both EGFR and HER2-driven human tumor xenograft models. |
| doi_str_mv | 10.1016/j.bmcl.2010.11.100 |
| format | Article |
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f][1,2,4]triazin-4-amines with small aniline substituents at the C4 position were optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. Compound
8l exhibited promising oral efficacy in both EGFR and HER2-driven human tumor xenograft models.
A novel series of 5-((4-aminopiperidin-1-yl)methyl)-pyrrolo[2,1-
f][1,2,4]triazin-4-amines with small aniline substituents at the C4 position were optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. Compound
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f][1,2,4]triazin-4-amines with small aniline substituents at the C4 position were optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. Compound
8l exhibited promising oral efficacy in both EGFR and HER2-driven human tumor xenograft models.
A novel series of 5-((4-aminopiperidin-1-yl)methyl)-pyrrolo[2,1-
f][1,2,4]triazin-4-amines with small aniline substituents at the C4 position were optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. Compound
8l exhibited promising oral efficacy in both EGFR and HER2-driven human tumor xenograft models.</description><subject>aniline</subject><subject>Animals</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacokinetics</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Cell Line, Tumor</subject><subject>Colonic Neoplasms - drug therapy</subject><subject>EGFR</subject><subject>HER2</subject><subject>Humans</subject><subject>Kinase inhibitor</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Models, Molecular</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - enzymology</subject><subject>protein-tyrosine kinases</subject><subject>Protein-Tyrosine Kinases - chemistry</subject><subject>Protein-Tyrosine Kinases - pharmacokinetics</subject><subject>Protein-Tyrosine Kinases - pharmacology</subject><subject>Protein-Tyrosine Kinases - therapeutic use</subject><subject>Pyrroles - chemistry</subject><subject>Pyrroles - pharmacokinetics</subject><subject>Pyrroles - pharmacology</subject><subject>Pyrroles - therapeutic use</subject><subject>Receptor, Epidermal Growth Factor - antagonists & inhibitors</subject><subject>Receptor, Epidermal Growth Factor - metabolism</subject><subject>Receptor, ErbB-2 - antagonists & inhibitors</subject><subject>Receptor, ErbB-2 - metabolism</subject><subject>Stomach Neoplasms - drug therapy</subject><subject>Triazines - chemistry</subject><subject>Triazines - pharmacokinetics</subject><subject>Triazines - pharmacology</subject><subject>Triazines - therapeutic use</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFv1DAQhS0EokvhD3AA37hslpnY3jioF1S2LVIFUqESUlVZTjIuXpJ4sbOVll-PV1s4wsn20_eexvMYe4mwQMDl2_WiGdp-UcJewKzBIzZDuZSFkKAesxnUSyh0Lb8dsWcprQFQgpRP2VGJWFUIasbuPoV76vlmF2Pow005x4K72xucl3N5O0Vvf_mxkIUd_EjpHf-wtT3343ff-CnExIPjq_OzK27Hjl-srkq-iWEiP_JpF0PKHv7DjzZRes6eONsnevFwHrPrs9XX04vi8vP5x9P3l0UrEaei0ZVw1tqGHFTgtKtrp3UpGmgb10gBVisEmW9VDTVQ1epaVR05VVN-KXHM3hxy8yA_t5QmM_jUUt_bkcI2Ga0FoADQ_ydFJZVQS8xkeSDb_KcUyZlN9IONO4Ng9k2Ytdk3YfZNGMSsQTa9eojfNgN1fy1_Vp-B1wfA2WDsXfTJXH_JCSrXJKQoq0ycHAjKC7v3FE1qPY0tdT5SO5ku-H9N8BsRI6DK</recordid><startdate>20110115</startdate><enddate>20110115</enddate><creator>Fink, Brian E.</creator><creator>Norris, Derek</creator><creator>Mastalerz, Harold</creator><creator>Chen, Ping</creator><creator>Goyal, Bindu</creator><creator>Zhao, Yufen</creator><creator>Kim, Soong-Hoon</creator><creator>Vite, Gregory D.</creator><creator>Lee, Francis Y.</creator><creator>Zhang, Hongjian</creator><creator>Oppenheimer, Simone</creator><creator>Tokarski, John S.</creator><creator>Wong, Tai W.</creator><creator>Gavai, Ashvinikumar V.</creator><general>Elsevier Ltd</general><scope>FBQ</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>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20110115</creationdate><title>Novel pyrrolo[2,1- f][1,2,4]triazin-4-amines: Dual inhibitors of EGFR and HER2 protein tyrosine kinases</title><author>Fink, Brian E. ; Norris, Derek ; Mastalerz, Harold ; Chen, Ping ; Goyal, Bindu ; Zhao, Yufen ; Kim, Soong-Hoon ; Vite, Gregory D. ; Lee, Francis Y. ; Zhang, Hongjian ; Oppenheimer, Simone ; Tokarski, John S. ; Wong, Tai W. ; Gavai, Ashvinikumar V.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c411t-b873faaabef070f8f99f8823b0cbfb430a85104b4379090e7c8957def59e0e753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>aniline</topic><topic>Animals</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacokinetics</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Cell Line, Tumor</topic><topic>Colonic Neoplasms - drug therapy</topic><topic>EGFR</topic><topic>HER2</topic><topic>Humans</topic><topic>Kinase inhibitor</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Models, Molecular</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - enzymology</topic><topic>protein-tyrosine kinases</topic><topic>Protein-Tyrosine Kinases - chemistry</topic><topic>Protein-Tyrosine Kinases - pharmacokinetics</topic><topic>Protein-Tyrosine Kinases - pharmacology</topic><topic>Protein-Tyrosine Kinases - therapeutic use</topic><topic>Pyrroles - chemistry</topic><topic>Pyrroles - pharmacokinetics</topic><topic>Pyrroles - pharmacology</topic><topic>Pyrroles - therapeutic use</topic><topic>Receptor, Epidermal Growth Factor - antagonists & inhibitors</topic><topic>Receptor, Epidermal Growth Factor - metabolism</topic><topic>Receptor, ErbB-2 - antagonists & inhibitors</topic><topic>Receptor, ErbB-2 - metabolism</topic><topic>Stomach Neoplasms - drug therapy</topic><topic>Triazines - chemistry</topic><topic>Triazines - pharmacokinetics</topic><topic>Triazines - pharmacology</topic><topic>Triazines - therapeutic use</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fink, Brian E.</creatorcontrib><creatorcontrib>Norris, Derek</creatorcontrib><creatorcontrib>Mastalerz, Harold</creatorcontrib><creatorcontrib>Chen, Ping</creatorcontrib><creatorcontrib>Goyal, Bindu</creatorcontrib><creatorcontrib>Zhao, Yufen</creatorcontrib><creatorcontrib>Kim, Soong-Hoon</creatorcontrib><creatorcontrib>Vite, Gregory D.</creatorcontrib><creatorcontrib>Lee, Francis Y.</creatorcontrib><creatorcontrib>Zhang, Hongjian</creatorcontrib><creatorcontrib>Oppenheimer, Simone</creatorcontrib><creatorcontrib>Tokarski, John S.</creatorcontrib><creatorcontrib>Wong, Tai W.</creatorcontrib><creatorcontrib>Gavai, Ashvinikumar V.</creatorcontrib><collection>AGRIS</collection><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>Fink, Brian E.</au><au>Norris, Derek</au><au>Mastalerz, Harold</au><au>Chen, Ping</au><au>Goyal, Bindu</au><au>Zhao, Yufen</au><au>Kim, Soong-Hoon</au><au>Vite, Gregory D.</au><au>Lee, Francis Y.</au><au>Zhang, Hongjian</au><au>Oppenheimer, Simone</au><au>Tokarski, John S.</au><au>Wong, Tai W.</au><au>Gavai, Ashvinikumar V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel pyrrolo[2,1- f][1,2,4]triazin-4-amines: Dual inhibitors of EGFR and HER2 protein tyrosine kinases</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2011-01-15</date><risdate>2011</risdate><volume>21</volume><issue>2</issue><spage>781</spage><epage>785</epage><pages>781-785</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>A novel series of 5-((4-aminopiperidin-1-yl)methyl)-pyrrolo[2,1-
f][1,2,4]triazin-4-amines with small aniline substituents at the C4 position were optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. Compound
8l exhibited promising oral efficacy in both EGFR and HER2-driven human tumor xenograft models.
A novel series of 5-((4-aminopiperidin-1-yl)methyl)-pyrrolo[2,1-
f][1,2,4]triazin-4-amines with small aniline substituents at the C4 position were optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. Compound
8l exhibited promising oral efficacy in both EGFR and HER2-driven human tumor xenograft models.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>21177105</pmid><doi>10.1016/j.bmcl.2010.11.100</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2011-01, Vol.21 (2), p.781-785 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | aniline Animals Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacokinetics Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Cell Line, Tumor Colonic Neoplasms - drug therapy EGFR HER2 Humans Kinase inhibitor Male Mice Mice, Inbred BALB C Models, Molecular Neoplasms - drug therapy Neoplasms - enzymology protein-tyrosine kinases Protein-Tyrosine Kinases - chemistry Protein-Tyrosine Kinases - pharmacokinetics Protein-Tyrosine Kinases - pharmacology Protein-Tyrosine Kinases - therapeutic use Pyrroles - chemistry Pyrroles - pharmacokinetics Pyrroles - pharmacology Pyrroles - therapeutic use Receptor, Epidermal Growth Factor - antagonists & inhibitors Receptor, Epidermal Growth Factor - metabolism Receptor, ErbB-2 - antagonists & inhibitors Receptor, ErbB-2 - metabolism Stomach Neoplasms - drug therapy Triazines - chemistry Triazines - pharmacokinetics Triazines - pharmacology Triazines - therapeutic use Xenograft Model Antitumor Assays |
| title | Novel pyrrolo[2,1- f][1,2,4]triazin-4-amines: Dual inhibitors of EGFR and HER2 protein tyrosine kinases |
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