Novel morpholin-3-one fused quinazoline derivatives as EGFR tyrosine kinase inhibitors
[Display omitted] A series of novel morpholin-3-one-fused quinazoline derivatives were designed, synthesized and evaluated as EGFR tyrosine kinase inhibitors. Nineteen compounds showed significant inhibitory activities against EGFRwt kinase (IC50
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2016-03, Vol.26 (6), p.1571-1575 |
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| container_end_page | 1575 |
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| container_issue | 6 |
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| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 26 |
| creator | Qin, Xuemei Lv, Yongjuan Liu, Peng Li, Zhipeng Hu, Liming Zeng, Chengchu Yang, Leifu |
| description | [Display omitted]
A series of novel morpholin-3-one-fused quinazoline derivatives were designed, synthesized and evaluated as EGFR tyrosine kinase inhibitors. Nineteen compounds showed significant inhibitory activities against EGFRwt kinase (IC50 |
| doi_str_mv | 10.1016/j.bmcl.2016.02.009 |
| format | Article |
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A series of novel morpholin-3-one-fused quinazoline derivatives were designed, synthesized and evaluated as EGFR tyrosine kinase inhibitors. Nineteen compounds showed significant inhibitory activities against EGFRwt kinase (IC50<1μM). Compound a8 demonstrated the most potent inhibitory activity toward EGFRwt (IC50=53.1nM). Compound a7 and a8 showed excellent inhibitory activities against mutant EGFRT790M/L858R and strong antiproliferative activity against H358 and A549 cell lines. Finally, molecular docking studies were performed to predict the possible binding mode of the target compounds. It is believed that this work would be very useful for designing a new series of tyrosine kinase inhibitors targeting EGFR.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2016.02.009</identifier><identifier>PMID: 26879314</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Anti-cancer ; Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; EGFR inhibitors ; Humans ; Molecular docking ; Molecular Docking Simulation ; Molecular Structure ; Morpholines - chemistry ; Morpholines - pharmacology ; NSCLC ; Protein Kinase Inhibitors - chemical synthesis ; Protein Kinase Inhibitors - chemistry ; Protein Kinase Inhibitors - pharmacology ; Quinazoline ; Quinazolines - chemistry ; Quinazolines - pharmacology ; Receptor, Epidermal Growth Factor - antagonists & inhibitors ; Receptor, Epidermal Growth Factor - metabolism ; Structure-Activity Relationship</subject><ispartof>Bioorganic & medicinal chemistry letters, 2016-03, Vol.26 (6), p.1571-1575</ispartof><rights>2016</rights><rights>Copyright © 2016. Published by Elsevier Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c503t-885f6b18a2e5ad41af7bdad28f95b21a36930974db30ea7ed9f323d7cace5bf93</citedby><cites>FETCH-LOGICAL-c503t-885f6b18a2e5ad41af7bdad28f95b21a36930974db30ea7ed9f323d7cace5bf93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmcl.2016.02.009$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26879314$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qin, Xuemei</creatorcontrib><creatorcontrib>Lv, Yongjuan</creatorcontrib><creatorcontrib>Liu, Peng</creatorcontrib><creatorcontrib>Li, Zhipeng</creatorcontrib><creatorcontrib>Hu, Liming</creatorcontrib><creatorcontrib>Zeng, Chengchu</creatorcontrib><creatorcontrib>Yang, Leifu</creatorcontrib><title>Novel morpholin-3-one fused quinazoline derivatives as EGFR tyrosine kinase inhibitors</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>[Display omitted]
A series of novel morpholin-3-one-fused quinazoline derivatives were designed, synthesized and evaluated as EGFR tyrosine kinase inhibitors. Nineteen compounds showed significant inhibitory activities against EGFRwt kinase (IC50<1μM). Compound a8 demonstrated the most potent inhibitory activity toward EGFRwt (IC50=53.1nM). Compound a7 and a8 showed excellent inhibitory activities against mutant EGFRT790M/L858R and strong antiproliferative activity against H358 and A549 cell lines. Finally, molecular docking studies were performed to predict the possible binding mode of the target compounds. It is believed that this work would be very useful for designing a new series of tyrosine kinase inhibitors targeting EGFR.</description><subject>Anti-cancer</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Screening Assays, Antitumor</subject><subject>EGFR inhibitors</subject><subject>Humans</subject><subject>Molecular docking</subject><subject>Molecular Docking Simulation</subject><subject>Molecular Structure</subject><subject>Morpholines - chemistry</subject><subject>Morpholines - pharmacology</subject><subject>NSCLC</subject><subject>Protein Kinase Inhibitors - chemical synthesis</subject><subject>Protein Kinase Inhibitors - chemistry</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Quinazoline</subject><subject>Quinazolines - chemistry</subject><subject>Quinazolines - pharmacology</subject><subject>Receptor, Epidermal Growth Factor - antagonists & inhibitors</subject><subject>Receptor, Epidermal Growth Factor - metabolism</subject><subject>Structure-Activity Relationship</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkE1L5EAQhhtZ0XH0D3hYctxLstUf-WjYyyKjLoiCqHhrOt0V7NkkPdOdDIy_3oRx97jsqYqqp16oh5BLChkFWnxfZ3Vn2oxNfQYsA5BHZEFFIVIuIP9CFiALSCspXk_JWYxrACpAiBNyyoqqlJyKBXm59ztsk86HzZtvXZ_y1PeYNGNEm2xH1-v3eYyJxeB2enA7jImOyerm-jEZ9sHHefl74iImrn9ztRt8iOfkuNFtxIvPuiTP16unq9v07uHm19XPu9TkwIe0qvKmqGmlGebaCqqbsrbasqqRec2o5oXkIEthaw6oS7Sy4Yzb0miDed1IviTfDrmb4LcjxkF1LhpsW92jH6OipQSZy7IS_4EWUlYUinJC2QE1038xYKM2wXU67BUFNatXazWrV7N6BUxN6qejr5_5Y92h_Xvyx_UE_DgAOAnZOQwqGoe9QesCmkFZ7_6V_wGudpXz</recordid><startdate>20160315</startdate><enddate>20160315</enddate><creator>Qin, Xuemei</creator><creator>Lv, Yongjuan</creator><creator>Liu, Peng</creator><creator>Li, Zhipeng</creator><creator>Hu, Liming</creator><creator>Zeng, Chengchu</creator><creator>Yang, Leifu</creator><general>Elsevier Ltd</general><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>20160315</creationdate><title>Novel morpholin-3-one fused quinazoline derivatives as EGFR tyrosine kinase inhibitors</title><author>Qin, Xuemei ; 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A series of novel morpholin-3-one-fused quinazoline derivatives were designed, synthesized and evaluated as EGFR tyrosine kinase inhibitors. Nineteen compounds showed significant inhibitory activities against EGFRwt kinase (IC50<1μM). Compound a8 demonstrated the most potent inhibitory activity toward EGFRwt (IC50=53.1nM). Compound a7 and a8 showed excellent inhibitory activities against mutant EGFRT790M/L858R and strong antiproliferative activity against H358 and A549 cell lines. Finally, molecular docking studies were performed to predict the possible binding mode of the target compounds. It is believed that this work would be very useful for designing a new series of tyrosine kinase inhibitors targeting EGFR.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>26879314</pmid><doi>10.1016/j.bmcl.2016.02.009</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Anti-cancer Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Cell Line, Tumor Cell Proliferation - drug effects Dose-Response Relationship, Drug Drug Screening Assays, Antitumor EGFR inhibitors Humans Molecular docking Molecular Docking Simulation Molecular Structure Morpholines - chemistry Morpholines - pharmacology NSCLC Protein Kinase Inhibitors - chemical synthesis Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - pharmacology Quinazoline Quinazolines - chemistry Quinazolines - pharmacology Receptor, Epidermal Growth Factor - antagonists & inhibitors Receptor, Epidermal Growth Factor - metabolism Structure-Activity Relationship |
| title | Novel morpholin-3-one fused quinazoline derivatives as EGFR tyrosine kinase inhibitors |
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