Discovery of pyrazolopyrimidine derivatives as novel inhibitors of ataxia telangiectasia and rad3 related protein (ATR)
[Display omitted] The ATR pathway is a critical mediator of the replication stress response in cells. In aberrantly proliferating cancer cells, this pathway can help maintain sufficient genomic integrity for cancer cell progression. Herein we describe the discovery of 19, a pyrazolopyrimidine-contai...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2017-02, Vol.27 (4), p.750-754 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Ramachandran, Sreekanth A. Jadhavar, Pradeep S. Singh, Manvendra P. Sharma, Ankesh Bagle, Gaurav N. Quinn, Kevin P. Wong, Po-yin Protter, Andrew A. Rai, Roopa Pham, Son M. Lindquist, Jeffrey N. |
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The ATR pathway is a critical mediator of the replication stress response in cells. In aberrantly proliferating cancer cells, this pathway can help maintain sufficient genomic integrity for cancer cell progression. Herein we describe the discovery of 19, a pyrazolopyrimidine-containing inhibitor of ATR via a strategic repurposing of compounds targeting PI3K. |
| doi_str_mv | 10.1016/j.bmcl.2017.01.045 |
| format | Article |
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The ATR pathway is a critical mediator of the replication stress response in cells. In aberrantly proliferating cancer cells, this pathway can help maintain sufficient genomic integrity for cancer cell progression. Herein we describe the discovery of 19, a pyrazolopyrimidine-containing inhibitor of ATR via a strategic repurposing of compounds targeting PI3K.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2017.01.045</identifier><identifier>PMID: 28131712</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Ataxia Telangiectasia Mutated Proteins - antagonists & inhibitors ; Ataxia Telangiectasia Mutated Proteins - metabolism ; ATR ; DNA damage ; Drug Evaluation, Preclinical ; HTS ; Humans ; Inhibitory Concentration 50 ; Phosphatidylinositol 3-Kinases - chemistry ; Phosphatidylinositol 3-Kinases - metabolism ; PI3K ; Protein Binding ; Protein Kinase Inhibitors - chemistry ; Protein Kinase Inhibitors - metabolism ; Protein-Serine-Threonine Kinases - antagonists & inhibitors ; Protein-Serine-Threonine Kinases - metabolism ; Pyrazoles - chemistry ; Pyrazoles - metabolism ; Pyrazolopyrimidine ; Pyridines - chemistry ; Pyridines - metabolism ; Pyrimidines - chemistry ; Pyrimidines - metabolism</subject><ispartof>Bioorganic & medicinal chemistry letters, 2017-02, Vol.27 (4), p.750-754</ispartof><rights>2017 Elsevier Ltd</rights><rights>Copyright © 2017 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-f0c6446c4ce316db7af5a87abbb4a5d499d755b02dc462cb41ab568474e4c7133</citedby><cites>FETCH-LOGICAL-c356t-f0c6446c4ce316db7af5a87abbb4a5d499d755b02dc462cb41ab568474e4c7133</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.2017.01.045$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28131712$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ramachandran, Sreekanth A.</creatorcontrib><creatorcontrib>Jadhavar, Pradeep S.</creatorcontrib><creatorcontrib>Singh, Manvendra P.</creatorcontrib><creatorcontrib>Sharma, Ankesh</creatorcontrib><creatorcontrib>Bagle, Gaurav N.</creatorcontrib><creatorcontrib>Quinn, Kevin P.</creatorcontrib><creatorcontrib>Wong, Po-yin</creatorcontrib><creatorcontrib>Protter, Andrew A.</creatorcontrib><creatorcontrib>Rai, Roopa</creatorcontrib><creatorcontrib>Pham, Son M.</creatorcontrib><creatorcontrib>Lindquist, Jeffrey N.</creatorcontrib><title>Discovery of pyrazolopyrimidine derivatives as novel inhibitors of ataxia telangiectasia and rad3 related protein (ATR)</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>[Display omitted]
The ATR pathway is a critical mediator of the replication stress response in cells. In aberrantly proliferating cancer cells, this pathway can help maintain sufficient genomic integrity for cancer cell progression. Herein we describe the discovery of 19, a pyrazolopyrimidine-containing inhibitor of ATR via a strategic repurposing of compounds targeting PI3K.</description><subject>Ataxia Telangiectasia Mutated Proteins - antagonists & inhibitors</subject><subject>Ataxia Telangiectasia Mutated Proteins - metabolism</subject><subject>ATR</subject><subject>DNA damage</subject><subject>Drug Evaluation, Preclinical</subject><subject>HTS</subject><subject>Humans</subject><subject>Inhibitory Concentration 50</subject><subject>Phosphatidylinositol 3-Kinases - chemistry</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>PI3K</subject><subject>Protein Binding</subject><subject>Protein Kinase Inhibitors - chemistry</subject><subject>Protein Kinase Inhibitors - metabolism</subject><subject>Protein-Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Pyrazoles - chemistry</subject><subject>Pyrazoles - metabolism</subject><subject>Pyrazolopyrimidine</subject><subject>Pyridines - chemistry</subject><subject>Pyridines - metabolism</subject><subject>Pyrimidines - chemistry</subject><subject>Pyrimidines - metabolism</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEGP0zAQhS0EYruFP8AB-bgcEuxk4iQSl9XCAtJKSGiRuFljewKu0rjYbqH8elx14chlRmO998bzMfZCiloKqV5varO1c90I2ddC1gK6R2wlQUHVguges5UYlaiGEb5esMuUNkJIEABP2UUzyFb2slmxn299suFA8cjDxHfHiL_DHEr3W-_8QtxR9AfM_kCJY-JL0c7cL9-98TnEdHJhxl8eeaYZl2-ebMZURlwcj-haHst7Jsd3MWTyC7-6vv_86hl7MuGc6PlDX7Mvt-_ubz5Ud5_ef7y5vqts26lcTcIqAGXBUiuVMz1OHQ49GmMAOwfj6PquM6JxFlRjDUg0nRqgBwLby7Zds6tzbtn-Y08p6205mObyVQr7pOWgmrEdm1LWrDlLbQwpRZr0rlDAeNRS6BNwvdEn4PoEXAupC_BievmQvzdbcv8sfwkXwZuzgMqVB09RJ-tpseR8LKi0C_5_-X8AeYqTzA</recordid><startdate>20170215</startdate><enddate>20170215</enddate><creator>Ramachandran, Sreekanth A.</creator><creator>Jadhavar, Pradeep S.</creator><creator>Singh, Manvendra P.</creator><creator>Sharma, Ankesh</creator><creator>Bagle, Gaurav N.</creator><creator>Quinn, Kevin P.</creator><creator>Wong, Po-yin</creator><creator>Protter, Andrew A.</creator><creator>Rai, Roopa</creator><creator>Pham, Son M.</creator><creator>Lindquist, Jeffrey N.</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></search><sort><creationdate>20170215</creationdate><title>Discovery of pyrazolopyrimidine derivatives as novel inhibitors of ataxia telangiectasia and rad3 related protein (ATR)</title><author>Ramachandran, Sreekanth A. ; Jadhavar, Pradeep S. ; Singh, Manvendra P. ; Sharma, Ankesh ; Bagle, Gaurav N. ; Quinn, Kevin P. ; Wong, Po-yin ; Protter, Andrew A. ; Rai, Roopa ; Pham, Son M. ; Lindquist, Jeffrey N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-f0c6446c4ce316db7af5a87abbb4a5d499d755b02dc462cb41ab568474e4c7133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Ataxia Telangiectasia Mutated Proteins - antagonists & inhibitors</topic><topic>Ataxia Telangiectasia Mutated Proteins - metabolism</topic><topic>ATR</topic><topic>DNA damage</topic><topic>Drug Evaluation, Preclinical</topic><topic>HTS</topic><topic>Humans</topic><topic>Inhibitory Concentration 50</topic><topic>Phosphatidylinositol 3-Kinases - chemistry</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>PI3K</topic><topic>Protein Binding</topic><topic>Protein Kinase Inhibitors - chemistry</topic><topic>Protein Kinase Inhibitors - metabolism</topic><topic>Protein-Serine-Threonine Kinases - antagonists & inhibitors</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Pyrazoles - chemistry</topic><topic>Pyrazoles - metabolism</topic><topic>Pyrazolopyrimidine</topic><topic>Pyridines - chemistry</topic><topic>Pyridines - metabolism</topic><topic>Pyrimidines - chemistry</topic><topic>Pyrimidines - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ramachandran, Sreekanth A.</creatorcontrib><creatorcontrib>Jadhavar, Pradeep S.</creatorcontrib><creatorcontrib>Singh, Manvendra P.</creatorcontrib><creatorcontrib>Sharma, Ankesh</creatorcontrib><creatorcontrib>Bagle, Gaurav N.</creatorcontrib><creatorcontrib>Quinn, Kevin P.</creatorcontrib><creatorcontrib>Wong, Po-yin</creatorcontrib><creatorcontrib>Protter, Andrew A.</creatorcontrib><creatorcontrib>Rai, Roopa</creatorcontrib><creatorcontrib>Pham, Son M.</creatorcontrib><creatorcontrib>Lindquist, Jeffrey N.</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><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ramachandran, Sreekanth A.</au><au>Jadhavar, Pradeep S.</au><au>Singh, Manvendra P.</au><au>Sharma, Ankesh</au><au>Bagle, Gaurav N.</au><au>Quinn, Kevin P.</au><au>Wong, Po-yin</au><au>Protter, Andrew A.</au><au>Rai, Roopa</au><au>Pham, Son M.</au><au>Lindquist, Jeffrey N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discovery of pyrazolopyrimidine derivatives as novel inhibitors of ataxia telangiectasia and rad3 related protein (ATR)</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2017-02-15</date><risdate>2017</risdate><volume>27</volume><issue>4</issue><spage>750</spage><epage>754</epage><pages>750-754</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>[Display omitted]
The ATR pathway is a critical mediator of the replication stress response in cells. In aberrantly proliferating cancer cells, this pathway can help maintain sufficient genomic integrity for cancer cell progression. Herein we describe the discovery of 19, a pyrazolopyrimidine-containing inhibitor of ATR via a strategic repurposing of compounds targeting PI3K.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>28131712</pmid><doi>10.1016/j.bmcl.2017.01.045</doi><tpages>5</tpages></addata></record> |
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| subjects | Ataxia Telangiectasia Mutated Proteins - antagonists & inhibitors Ataxia Telangiectasia Mutated Proteins - metabolism ATR DNA damage Drug Evaluation, Preclinical HTS Humans Inhibitory Concentration 50 Phosphatidylinositol 3-Kinases - chemistry Phosphatidylinositol 3-Kinases - metabolism PI3K Protein Binding Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - metabolism Protein-Serine-Threonine Kinases - antagonists & inhibitors Protein-Serine-Threonine Kinases - metabolism Pyrazoles - chemistry Pyrazoles - metabolism Pyrazolopyrimidine Pyridines - chemistry Pyridines - metabolism Pyrimidines - chemistry Pyrimidines - metabolism |
| title | Discovery of pyrazolopyrimidine derivatives as novel inhibitors of ataxia telangiectasia and rad3 related protein (ATR) |
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