Discovery of novel pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety as c-Met kinase inhibitors
A series of pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety (18–45) were designed, synthesized and evaluated for their activity against c-Met kinase and cancer cell lines. The most promising compound 34 showed excellent in vitro activity. [Display omitted] A series of novel pyrrolo[...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2016-04, Vol.26 (7), p.1680-1684 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Tang, Qidong Wang, Linxiao Tu, Yayi Zhu, Wufu Luo, Rong Tu, Qidong Wang, Ping Wu, Chunjiang Gong, Ping Zheng, Pengwu |
| description | A series of pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety (18–45) were designed, synthesized and evaluated for their activity against c-Met kinase and cancer cell lines. The most promising compound 34 showed excellent in vitro activity. [Display omitted]
A series of novel pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety were designed, synthesized, and evaluated for their c-Met kinase inhibitory activities and antiproliferative activities against 4 cancer cell lines (HT-29, A549, MCF-7, and PC-3) in vitro. Most compounds showed moderate to excellent potency, with the most promising analog 34 showing a c-Met IC50 value of 1.68nM. Structure–activity relationship studies indicated that electron-withdrawing groups (X=CF3, R1=F, R2=4-F) were required to decrease the higher electron density on the 5-atom linker to a proper degree to improve the inhibitory activity. |
| doi_str_mv | 10.1016/j.bmcl.2016.02.059 |
| format | Article |
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A series of novel pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety were designed, synthesized, and evaluated for their c-Met kinase inhibitory activities and antiproliferative activities against 4 cancer cell lines (HT-29, A549, MCF-7, and PC-3) in vitro. Most compounds showed moderate to excellent potency, with the most promising analog 34 showing a c-Met IC50 value of 1.68nM. Structure–activity relationship studies indicated that electron-withdrawing groups (X=CF3, R1=F, R2=4-F) were required to decrease the higher electron density on the 5-atom linker to a proper degree to improve the inhibitory activity.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2016.02.059</identifier><identifier>PMID: 26923692</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>1,2,3-Triazole ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Antiproliferative activity ; c-Met ; Cell Line, Tumor ; Drug Design ; Drug Screening Assays, Antitumor ; Humans ; Models, Molecular ; Molecular Docking Simulation ; Neoplasms - drug therapy ; Neoplasms - metabolism ; Protein Kinase Inhibitors - chemistry ; Protein Kinase Inhibitors - pharmacology ; Proto-Oncogene Proteins c-met - antagonists & inhibitors ; Proto-Oncogene Proteins c-met - metabolism ; Pyridines - chemistry ; Pyridines - pharmacology ; Pyrroles - chemistry ; Pyrroles - pharmacology ; Pyrrolo[2,3-b]pyridine derivatives ; Structure-Activity Relationship ; Synthesis ; Triazoles - chemistry ; Triazoles - pharmacology</subject><ispartof>Bioorganic & medicinal chemistry letters, 2016-04, Vol.26 (7), p.1680-1684</ispartof><rights>2016 Elsevier Ltd</rights><rights>Copyright © 2016 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-9ec556eb70d09a35190fdfdc1db53d45bbe2e63e39a4bbf34352c89121ce45c53</citedby><cites>FETCH-LOGICAL-c459t-9ec556eb70d09a35190fdfdc1db53d45bbe2e63e39a4bbf34352c89121ce45c53</cites><orcidid>0000-0002-2045-4646</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X1630172X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26923692$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tang, Qidong</creatorcontrib><creatorcontrib>Wang, Linxiao</creatorcontrib><creatorcontrib>Tu, Yayi</creatorcontrib><creatorcontrib>Zhu, Wufu</creatorcontrib><creatorcontrib>Luo, Rong</creatorcontrib><creatorcontrib>Tu, Qidong</creatorcontrib><creatorcontrib>Wang, Ping</creatorcontrib><creatorcontrib>Wu, Chunjiang</creatorcontrib><creatorcontrib>Gong, Ping</creatorcontrib><creatorcontrib>Zheng, Pengwu</creatorcontrib><title>Discovery of novel pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety as c-Met kinase inhibitors</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>A series of pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety (18–45) were designed, synthesized and evaluated for their activity against c-Met kinase and cancer cell lines. The most promising compound 34 showed excellent in vitro activity. [Display omitted]
A series of novel pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety were designed, synthesized, and evaluated for their c-Met kinase inhibitory activities and antiproliferative activities against 4 cancer cell lines (HT-29, A549, MCF-7, and PC-3) in vitro. Most compounds showed moderate to excellent potency, with the most promising analog 34 showing a c-Met IC50 value of 1.68nM. Structure–activity relationship studies indicated that electron-withdrawing groups (X=CF3, R1=F, R2=4-F) were required to decrease the higher electron density on the 5-atom linker to a proper degree to improve the inhibitory activity.</description><subject>1,2,3-Triazole</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antiproliferative activity</subject><subject>c-Met</subject><subject>Cell Line, Tumor</subject><subject>Drug Design</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Humans</subject><subject>Models, Molecular</subject><subject>Molecular Docking Simulation</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - metabolism</subject><subject>Protein Kinase Inhibitors - chemistry</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Proto-Oncogene Proteins c-met - antagonists & inhibitors</subject><subject>Proto-Oncogene Proteins c-met - metabolism</subject><subject>Pyridines - chemistry</subject><subject>Pyridines - pharmacology</subject><subject>Pyrroles - chemistry</subject><subject>Pyrroles - pharmacology</subject><subject>Pyrrolo[2,3-b]pyridine derivatives</subject><subject>Structure-Activity Relationship</subject><subject>Synthesis</subject><subject>Triazoles - chemistry</subject><subject>Triazoles - pharmacology</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>eNqNkV1rFDEUhkNR2u3HH-hFyaUXnTGfsw14I9WqUPHGgiAS8nFGzzozWZPZhfXXm2VbL8WLkBN4zgt5H0IuOWs5493LVevHMLSizi0TLdPmiCy46lQjFdPPyIKZjjU3Rn05IaelrBjjiil1TE5EZ4SsZ0GmN1hC2kLe0dTTqU4DXe9yTkP6Kq5l47_VF0acgEbIuHUzbqFQDy7j9J3y6z00Z3S_0wB0TAjzjrpCQ_MRZvoTJ1eA4vQDPc4pl3PyvHdDgYvH-4w83L39fPu-uf_07sPt6_smKG3mxkDQugO_ZJEZJzU3rI99DDx6LaPS3oOAToI0TnnfSyW1CDeGCx5A6aDlGXlxyF3n9GsDZbZj_ScMg5sgbYrlS1PL6ZZC_Ae6FLVUw1VFxQENOZWSobfrjKPLO8uZ3SuxK7tXYvdKLBO2KqlLV4_5Gz9C_Lvy5KACrw4A1EK2CNmWgDAFiJghzDYm_Ff-H5dOnXk</recordid><startdate>20160401</startdate><enddate>20160401</enddate><creator>Tang, Qidong</creator><creator>Wang, Linxiao</creator><creator>Tu, Yayi</creator><creator>Zhu, Wufu</creator><creator>Luo, Rong</creator><creator>Tu, Qidong</creator><creator>Wang, Ping</creator><creator>Wu, Chunjiang</creator><creator>Gong, Ping</creator><creator>Zheng, Pengwu</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><orcidid>https://orcid.org/0000-0002-2045-4646</orcidid></search><sort><creationdate>20160401</creationdate><title>Discovery of novel pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety as c-Met kinase inhibitors</title><author>Tang, Qidong ; Wang, Linxiao ; Tu, Yayi ; Zhu, Wufu ; Luo, Rong ; Tu, Qidong ; Wang, Ping ; Wu, Chunjiang ; Gong, Ping ; Zheng, Pengwu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-9ec556eb70d09a35190fdfdc1db53d45bbe2e63e39a4bbf34352c89121ce45c53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>1,2,3-Triazole</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antiproliferative activity</topic><topic>c-Met</topic><topic>Cell Line, Tumor</topic><topic>Drug Design</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Humans</topic><topic>Models, Molecular</topic><topic>Molecular Docking Simulation</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - metabolism</topic><topic>Protein Kinase Inhibitors - chemistry</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Proto-Oncogene Proteins c-met - antagonists & inhibitors</topic><topic>Proto-Oncogene Proteins c-met - metabolism</topic><topic>Pyridines - chemistry</topic><topic>Pyridines - pharmacology</topic><topic>Pyrroles - chemistry</topic><topic>Pyrroles - pharmacology</topic><topic>Pyrrolo[2,3-b]pyridine derivatives</topic><topic>Structure-Activity Relationship</topic><topic>Synthesis</topic><topic>Triazoles - chemistry</topic><topic>Triazoles - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tang, Qidong</creatorcontrib><creatorcontrib>Wang, Linxiao</creatorcontrib><creatorcontrib>Tu, Yayi</creatorcontrib><creatorcontrib>Zhu, Wufu</creatorcontrib><creatorcontrib>Luo, Rong</creatorcontrib><creatorcontrib>Tu, Qidong</creatorcontrib><creatorcontrib>Wang, Ping</creatorcontrib><creatorcontrib>Wu, Chunjiang</creatorcontrib><creatorcontrib>Gong, Ping</creatorcontrib><creatorcontrib>Zheng, Pengwu</creatorcontrib><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>Tang, Qidong</au><au>Wang, Linxiao</au><au>Tu, Yayi</au><au>Zhu, Wufu</au><au>Luo, Rong</au><au>Tu, Qidong</au><au>Wang, Ping</au><au>Wu, Chunjiang</au><au>Gong, Ping</au><au>Zheng, Pengwu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discovery of novel pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety as c-Met kinase inhibitors</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2016-04-01</date><risdate>2016</risdate><volume>26</volume><issue>7</issue><spage>1680</spage><epage>1684</epage><pages>1680-1684</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>A series of pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety (18–45) were designed, synthesized and evaluated for their activity against c-Met kinase and cancer cell lines. The most promising compound 34 showed excellent in vitro activity. [Display omitted]
A series of novel pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety were designed, synthesized, and evaluated for their c-Met kinase inhibitory activities and antiproliferative activities against 4 cancer cell lines (HT-29, A549, MCF-7, and PC-3) in vitro. Most compounds showed moderate to excellent potency, with the most promising analog 34 showing a c-Met IC50 value of 1.68nM. Structure–activity relationship studies indicated that electron-withdrawing groups (X=CF3, R1=F, R2=4-F) were required to decrease the higher electron density on the 5-atom linker to a proper degree to improve the inhibitory activity.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>26923692</pmid><doi>10.1016/j.bmcl.2016.02.059</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0002-2045-4646</orcidid></addata></record> |
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| ispartof | Bioorganic & medicinal chemistry letters, 2016-04, Vol.26 (7), p.1680-1684 |
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| subjects | 1,2,3-Triazole Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Antiproliferative activity c-Met Cell Line, Tumor Drug Design Drug Screening Assays, Antitumor Humans Models, Molecular Molecular Docking Simulation Neoplasms - drug therapy Neoplasms - metabolism Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - pharmacology Proto-Oncogene Proteins c-met - antagonists & inhibitors Proto-Oncogene Proteins c-met - metabolism Pyridines - chemistry Pyridines - pharmacology Pyrroles - chemistry Pyrroles - pharmacology Pyrrolo[2,3-b]pyridine derivatives Structure-Activity Relationship Synthesis Triazoles - chemistry Triazoles - pharmacology |
| title | Discovery of novel pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety as c-Met kinase inhibitors |
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