Synthesis and study of cyclic pronucleotides of 5-fluoro-2′-deoxyuridine
A one-step method for the synthesis of cyclic pronucleotide (cProTide) derivatives of 5-fluoro-2′-deoxyuridine (FdUrd), utilizing a novel phosphoramidating reagent, is described. Stereochemistry at phosphorus was established by NMR studies and modeling. Cytotoxicity data of representative cProTide d...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2012-07, Vol.22 (14), p.4497-4501 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Jain, Harsh V. Kalman, Thomas I. |
| description | A one-step method for the synthesis of cyclic pronucleotide (cProTide) derivatives of 5-fluoro-2′-deoxyuridine (FdUrd), utilizing a novel phosphoramidating reagent, is described. Stereochemistry at phosphorus was established by NMR studies and modeling. Cytotoxicity data of representative cProTide derivatives of FdUrd are presented. The observed cell-to-cell variations in activity suggests that it is feasible to screen for structural variations in the cProTide moiety favoring metabolic activation in cancer cells, which may lead to an increase in the therapeutic effectiveness of FdUrd. The method described is applicable to all anticancer and antiviral nucleoside analogs having both the 5′- and the 3′-OH groups available for modification, forming cProTide derivatives capable of delivering the 5′-monophosphates to cells. |
| doi_str_mv | 10.1016/j.bmcl.2012.06.011 |
| format | Article |
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Stereochemistry at phosphorus was established by NMR studies and modeling. Cytotoxicity data of representative cProTide derivatives of FdUrd are presented. The observed cell-to-cell variations in activity suggests that it is feasible to screen for structural variations in the cProTide moiety favoring metabolic activation in cancer cells, which may lead to an increase in the therapeutic effectiveness of FdUrd. 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All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c410t-8591bccc51099f1b8d4de864279042ba51cfcf4d6e9fdb361ec5e34440c05a6c3</citedby><cites>FETCH-LOGICAL-c410t-8591bccc51099f1b8d4de864279042ba51cfcf4d6e9fdb361ec5e34440c05a6c3</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.2012.06.011$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26151439$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22738636$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jain, Harsh V.</creatorcontrib><creatorcontrib>Kalman, Thomas I.</creatorcontrib><title>Synthesis and study of cyclic pronucleotides of 5-fluoro-2′-deoxyuridine</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>A one-step method for the synthesis of cyclic pronucleotide (cProTide) derivatives of 5-fluoro-2′-deoxyuridine (FdUrd), utilizing a novel phosphoramidating reagent, is described. Stereochemistry at phosphorus was established by NMR studies and modeling. Cytotoxicity data of representative cProTide derivatives of FdUrd are presented. The observed cell-to-cell variations in activity suggests that it is feasible to screen for structural variations in the cProTide moiety favoring metabolic activation in cancer cells, which may lead to an increase in the therapeutic effectiveness of FdUrd. The method described is applicable to all anticancer and antiviral nucleoside analogs having both the 5′- and the 3′-OH groups available for modification, forming cProTide derivatives capable of delivering the 5′-monophosphates to cells.</description><subject>Anticancer</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Cell Proliferation - drug effects</subject><subject>Cyclization</subject><subject>cytotoxicity</subject><subject>Deoxyuridine - analogs & derivatives</subject><subject>Deoxyuridine - chemical synthesis</subject><subject>Deoxyuridine - pharmacology</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Models, Molecular</subject><subject>Molecular Structure</subject><subject>nuclear magnetic resonance spectroscopy</subject><subject>Nucleoside</subject><subject>nucleosides</subject><subject>Nucleotides - chemical synthesis</subject><subject>Pharmacology. Drug treatments</subject><subject>phosphorus</subject><subject>Prodrug</subject><subject>Pronucleotide</subject><subject>stereochemistry</subject><subject>Stereoisomerism</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc9u1DAQhy0EokvhBThALkhcEsaO400kLlXFv6oSh1KJm-WMx-BVNi52gsitz8Qj9UlwtAvceprDfL-Z0TeMPedQceDqza7q9zhUArioQFXA-QO24VLJspbQPGQb6BSUbSe_nrAnKe0AuAQpH7MTIbZ1q2q1YRdXyzh9p-RTYUZbpGm2SxFcgQsOHoubGMYZBwqTt5TWRlO6YQ4xlOLu9ndpKfxa5uitH-kpe-TMkOjZsZ6y6_fvvpx_LC8_f_h0fnZZouQwlW3T8R4RGw5d53jfWmmpVVJsO5CiNw1Hh05aRZ2zfa04YUO1lBIQGqOwPmWvD3PzcT9mSpPe-4Q0DGakMCfNQdSi26q2y6g4oBhDSpGcvol-b-KSIb061Du9OtSrQw1KZ4c59OI4f-73ZP9F_krLwKsjYBKawUUzok__OcUbLut1-8sD50zQ5lvMzPVV3tTkR9TQyjYTbw8EZV8_PUWd0NOIZH0knLQN_r5L_wCMFpmR</recordid><startdate>20120715</startdate><enddate>20120715</enddate><creator>Jain, Harsh V.</creator><creator>Kalman, Thomas I.</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>FBQ</scope><scope>IQODW</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></search><sort><creationdate>20120715</creationdate><title>Synthesis and study of cyclic pronucleotides of 5-fluoro-2′-deoxyuridine</title><author>Jain, Harsh V. ; Kalman, Thomas I.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c410t-8591bccc51099f1b8d4de864279042ba51cfcf4d6e9fdb361ec5e34440c05a6c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Anticancer</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>Cell Proliferation - drug effects</topic><topic>Cyclization</topic><topic>cytotoxicity</topic><topic>Deoxyuridine - analogs & derivatives</topic><topic>Deoxyuridine - chemical synthesis</topic><topic>Deoxyuridine - pharmacology</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Models, Molecular</topic><topic>Molecular Structure</topic><topic>nuclear magnetic resonance spectroscopy</topic><topic>Nucleoside</topic><topic>nucleosides</topic><topic>Nucleotides - chemical synthesis</topic><topic>Pharmacology. Drug treatments</topic><topic>phosphorus</topic><topic>Prodrug</topic><topic>Pronucleotide</topic><topic>stereochemistry</topic><topic>Stereoisomerism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jain, Harsh V.</creatorcontrib><creatorcontrib>Kalman, Thomas I.</creatorcontrib><collection>AGRIS</collection><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>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jain, Harsh V.</au><au>Kalman, Thomas I.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and study of cyclic pronucleotides of 5-fluoro-2′-deoxyuridine</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2012-07-15</date><risdate>2012</risdate><volume>22</volume><issue>14</issue><spage>4497</spage><epage>4501</epage><pages>4497-4501</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>A one-step method for the synthesis of cyclic pronucleotide (cProTide) derivatives of 5-fluoro-2′-deoxyuridine (FdUrd), utilizing a novel phosphoramidating reagent, is described. Stereochemistry at phosphorus was established by NMR studies and modeling. Cytotoxicity data of representative cProTide derivatives of FdUrd are presented. The observed cell-to-cell variations in activity suggests that it is feasible to screen for structural variations in the cProTide moiety favoring metabolic activation in cancer cells, which may lead to an increase in the therapeutic effectiveness of FdUrd. The method described is applicable to all anticancer and antiviral nucleoside analogs having both the 5′- and the 3′-OH groups available for modification, forming cProTide derivatives capable of delivering the 5′-monophosphates to cells.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>22738636</pmid><doi>10.1016/j.bmcl.2012.06.011</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Bioorganic & medicinal chemistry letters, 2012-07, Vol.22 (14), p.4497-4501 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Anticancer Biological and medical sciences Cell Line Cell Proliferation - drug effects Cyclization cytotoxicity Deoxyuridine - analogs & derivatives Deoxyuridine - chemical synthesis Deoxyuridine - pharmacology Humans Medical sciences Models, Molecular Molecular Structure nuclear magnetic resonance spectroscopy Nucleoside nucleosides Nucleotides - chemical synthesis Pharmacology. Drug treatments phosphorus Prodrug Pronucleotide stereochemistry Stereoisomerism |
| title | Synthesis and study of cyclic pronucleotides of 5-fluoro-2′-deoxyuridine |
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