Synthesis of 4′-Ethynyl-2′-deoxy-4′-thioribonucleosides and Discovery of a Highly Potent and Less Toxic NRTI
Identifieur interne : 000057 ( Pmc/Curation ); précédent : 000056; suivant : 000058Synthesis of 4′-Ethynyl-2′-deoxy-4′-thioribonucleosides and Discovery of a Highly Potent and Less Toxic NRTI
Auteurs : Kazuhiro Haraguchi [Japon] ; Hisashi Shimada [Japon] ; Keigo Kimura [Japon] ; Genta Akutsu [Japon] ; Hiromichi Tanaka [Japon] ; Hiroshi Abe [Japon] ; Takayuki Hamasaki [Japon] ; Masanori Baba [Japon] ; Elizabeth A. Gullen [États-Unis] ; Ginger E. Dutschman [États-Unis] ; Yung-Chi Cheng [États-Unis] ; Jan Balzarini [Belgique]Source :
- ACS Medicinal Chemistry Letters [ 1948-5875 ] ; 2011.
Abstract
The synthesis of 4′-ethynyl-2′-deoxy-4′-thioribonucleosides was carried out utilizing an electrophilic glycosidation in which 4-ethynyl-4-thiofuranoid glycal
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DOI: 10.1021/ml2001054
PubMed: 23795238
PubMed Central: 3686520
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Synthesis of 4′-Ethynyl-2′-deoxy-4′-thioribonucleosides and Discovery of a Highly Potent and Less Toxic NRTI</title><author><name sortKey="Haraguchi, Kazuhiro" sort="Haraguchi, Kazuhiro" uniqKey="Haraguchi K" first="Kazuhiro" last="Haraguchi">Kazuhiro Haraguchi</name><affiliation wicri:level="1"><nlm:aff id="aff1">School of Pharmacy,<institution>Showa University</institution>, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555</wicri:regionArea></affiliation></author><author><name sortKey="Shimada, Hisashi" sort="Shimada, Hisashi" uniqKey="Shimada H" first="Hisashi" last="Shimada">Hisashi Shimada</name><affiliation wicri:level="1"><nlm:aff id="aff1">School of Pharmacy,<institution>Showa University</institution>, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555</wicri:regionArea></affiliation></author><author><name sortKey="Kimura, Keigo" sort="Kimura, Keigo" uniqKey="Kimura K" first="Keigo" last="Kimura">Keigo Kimura</name><affiliation wicri:level="1"><nlm:aff id="aff1">School of Pharmacy,<institution>Showa University</institution>, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555</wicri:regionArea></affiliation></author><author><name sortKey="Akutsu, Genta" sort="Akutsu, Genta" uniqKey="Akutsu G" first="Genta" last="Akutsu">Genta Akutsu</name><affiliation wicri:level="1"><nlm:aff id="aff1">School of Pharmacy,<institution>Showa University</institution>, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555</wicri:regionArea></affiliation></author><author><name sortKey="Tanaka, Hiromichi" sort="Tanaka, Hiromichi" uniqKey="Tanaka H" first="Hiromichi" last="Tanaka">Hiromichi Tanaka</name><affiliation wicri:level="1"><nlm:aff id="aff1">School of Pharmacy,<institution>Showa University</institution>, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555</wicri:regionArea></affiliation></author><author><name sortKey="Abe, Hiroshi" sort="Abe, Hiroshi" uniqKey="Abe H" first="Hiroshi" last="Abe">Hiroshi Abe</name><affiliation wicri:level="1"><nlm:aff id="aff2">RIKEN Advanced Science Institute,<institution>Nanomedical Engineering Laboratory</institution>, 2-1, Hirosawa, Wako-shi, Saitama 351-0198, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>, 2-1, Hirosawa, Wako-shi, Saitama 351-0198</wicri:regionArea></affiliation></author><author><name sortKey="Hamasaki, Takayuki" sort="Hamasaki, Takayuki" uniqKey="Hamasaki T" first="Takayuki" last="Hamasaki">Takayuki Hamasaki</name><affiliation wicri:level="1"><nlm:aff id="aff3">Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences,<institution>Kagoshima University</institution>, Kagoshima 89-8544, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>, Kagoshima 89-8544</wicri:regionArea></affiliation></author><author><name sortKey="Baba, Masanori" sort="Baba, Masanori" uniqKey="Baba M" first="Masanori" last="Baba">Masanori Baba</name><affiliation wicri:level="1"><nlm:aff id="aff3">Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences,<institution>Kagoshima University</institution>, Kagoshima 89-8544, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>, Kagoshima 89-8544</wicri:regionArea></affiliation></author><author><name sortKey="Gullen, Elizabeth A" sort="Gullen, Elizabeth A" uniqKey="Gullen E" first="Elizabeth A." last="Gullen">Elizabeth A. Gullen</name><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Pharmacology, School of Medicine,<institution>Yale University</institution>, New Haven, Connecticut 06520, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>, New Haven, Connecticut 06520</wicri:regionArea></affiliation></author><author><name sortKey="Dutschman, Ginger E" sort="Dutschman, Ginger E" uniqKey="Dutschman G" first="Ginger E." last="Dutschman">Ginger E. Dutschman</name><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Pharmacology, School of Medicine,<institution>Yale University</institution>, New Haven, Connecticut 06520, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>, New Haven, Connecticut 06520</wicri:regionArea></affiliation></author><author><name sortKey="Cheng, Yung Chi" sort="Cheng, Yung Chi" uniqKey="Cheng Y" first="Yung-Chi" last="Cheng">Yung-Chi Cheng</name><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Pharmacology, School of Medicine,<institution>Yale University</institution>, New Haven, Connecticut 06520, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>, New Haven, Connecticut 06520</wicri:regionArea></affiliation></author><author><name sortKey="Balzarini, Jan" sort="Balzarini, Jan" uniqKey="Balzarini J" first="Jan" last="Balzarini">Jan Balzarini</name><affiliation wicri:level="1"><nlm:aff id="aff5">Rega Institute for Medical Research,<institution>Katholieke Universiteit Leuven</institution>, B-3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>, B-3000 Leuven</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23795238</idno><idno type="pmc">3686520</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3686520</idno><idno type="RBID">PMC:3686520</idno><idno type="doi">10.1021/ml2001054</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">000057</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000057</idno><idno type="wicri:Area/Pmc/Curation">000057</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000057</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Synthesis of 4′-Ethynyl-2′-deoxy-4′-thioribonucleosides and Discovery of a Highly Potent and Less Toxic NRTI</title><author><name sortKey="Haraguchi, Kazuhiro" sort="Haraguchi, Kazuhiro" uniqKey="Haraguchi K" first="Kazuhiro" last="Haraguchi">Kazuhiro Haraguchi</name><affiliation wicri:level="1"><nlm:aff id="aff1">School of Pharmacy,<institution>Showa University</institution>, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555</wicri:regionArea></affiliation></author><author><name sortKey="Shimada, Hisashi" sort="Shimada, Hisashi" uniqKey="Shimada H" first="Hisashi" last="Shimada">Hisashi Shimada</name><affiliation wicri:level="1"><nlm:aff id="aff1">School of Pharmacy,<institution>Showa University</institution>, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555</wicri:regionArea></affiliation></author><author><name sortKey="Kimura, Keigo" sort="Kimura, Keigo" uniqKey="Kimura K" first="Keigo" last="Kimura">Keigo Kimura</name><affiliation wicri:level="1"><nlm:aff id="aff1">School of Pharmacy,<institution>Showa University</institution>, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555</wicri:regionArea></affiliation></author><author><name sortKey="Akutsu, Genta" sort="Akutsu, Genta" uniqKey="Akutsu G" first="Genta" last="Akutsu">Genta Akutsu</name><affiliation wicri:level="1"><nlm:aff id="aff1">School of Pharmacy,<institution>Showa University</institution>, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555</wicri:regionArea></affiliation></author><author><name sortKey="Tanaka, Hiromichi" sort="Tanaka, Hiromichi" uniqKey="Tanaka H" first="Hiromichi" last="Tanaka">Hiromichi Tanaka</name><affiliation wicri:level="1"><nlm:aff id="aff1">School of Pharmacy,<institution>Showa University</institution>, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555</wicri:regionArea></affiliation></author><author><name sortKey="Abe, Hiroshi" sort="Abe, Hiroshi" uniqKey="Abe H" first="Hiroshi" last="Abe">Hiroshi Abe</name><affiliation wicri:level="1"><nlm:aff id="aff2">RIKEN Advanced Science Institute,<institution>Nanomedical Engineering Laboratory</institution>, 2-1, Hirosawa, Wako-shi, Saitama 351-0198, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>, 2-1, Hirosawa, Wako-shi, Saitama 351-0198</wicri:regionArea></affiliation></author><author><name sortKey="Hamasaki, Takayuki" sort="Hamasaki, Takayuki" uniqKey="Hamasaki T" first="Takayuki" last="Hamasaki">Takayuki Hamasaki</name><affiliation wicri:level="1"><nlm:aff id="aff3">Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences,<institution>Kagoshima University</institution>, Kagoshima 89-8544, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>, Kagoshima 89-8544</wicri:regionArea></affiliation></author><author><name sortKey="Baba, Masanori" sort="Baba, Masanori" uniqKey="Baba M" first="Masanori" last="Baba">Masanori Baba</name><affiliation wicri:level="1"><nlm:aff id="aff3">Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences,<institution>Kagoshima University</institution>, Kagoshima 89-8544, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>, Kagoshima 89-8544</wicri:regionArea></affiliation></author><author><name sortKey="Gullen, Elizabeth A" sort="Gullen, Elizabeth A" uniqKey="Gullen E" first="Elizabeth A." last="Gullen">Elizabeth A. Gullen</name><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Pharmacology, School of Medicine,<institution>Yale University</institution>, New Haven, Connecticut 06520, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>, New Haven, Connecticut 06520</wicri:regionArea></affiliation></author><author><name sortKey="Dutschman, Ginger E" sort="Dutschman, Ginger E" uniqKey="Dutschman G" first="Ginger E." last="Dutschman">Ginger E. Dutschman</name><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Pharmacology, School of Medicine,<institution>Yale University</institution>, New Haven, Connecticut 06520, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>, New Haven, Connecticut 06520</wicri:regionArea></affiliation></author><author><name sortKey="Cheng, Yung Chi" sort="Cheng, Yung Chi" uniqKey="Cheng Y" first="Yung-Chi" last="Cheng">Yung-Chi Cheng</name><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Pharmacology, School of Medicine,<institution>Yale University</institution>, New Haven, Connecticut 06520, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>, New Haven, Connecticut 06520</wicri:regionArea></affiliation></author><author><name sortKey="Balzarini, Jan" sort="Balzarini, Jan" uniqKey="Balzarini J" first="Jan" last="Balzarini">Jan Balzarini</name><affiliation wicri:level="1"><nlm:aff id="aff5">Rega Institute for Medical Research,<institution>Katholieke Universiteit Leuven</institution>, B-3000 Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>, B-3000 Leuven</wicri:regionArea></affiliation></author></analytic><series><title level="j">ACS Medicinal Chemistry Letters</title><idno type="ISSN">1948-5875</idno><idno type="eISSN">1948-5875</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p content-type="toc-graphic"><graphic xlink:href="ml-2011-001054_0014" id="ab-tgr1"></graphic></p><p>The synthesis of 4′-ethynyl-2′-deoxy-4′-thioribonucleosides was carried out utilizing an electrophilic glycosidation in which 4-ethynyl-4-thiofuranoid glycal <bold>16</bold> served as a glycosyl donor. Electrophilic glycosidation between <bold>16</bold> and the silylated nucleobases (<italic>N</italic><sup>4</sup>-acetylcytosine, <italic>N</italic><sup>6</sup>-benzoyladenine, and <italic>N</italic><sup>2</sup>-acetyl-<italic>O</italic><sup>6</sup>-diphenylcarbamoylguanine) was carried out in the presence of <italic>N</italic>-iodosuccinimide (NIS), leading to the exclusive formation of the desired β-anomers <bold>29</bold>, <bold>33</bold>, and <bold>36</bold>. Anti-HIV studies demonstrated that these 4′-thio nucleosides were less cytotoxic to T-lymphocyte (i.e., MT-4 cells) than the corresponding 4′-ethynyl derivatives of 2′-deoxycytidine (<bold>44</bold>), 2′-deoxyadenosine (<bold>45</bold>), and 2′-deoxyguanosine (<bold>46</bold>). Comparison of the selectivity indices (SI) was made between 4′-thionucleosides (<bold>32</bold>, <bold>41</bold>, and <bold>43</bold>) and the corresponding 4′-oxygen analogues <bold>44</bold>-<bold>46</bold> by using the reported CC<sub>50</sub> and EC<sub>50</sub> values. In the case of cytosine and adenine nucleosides, comparable SI values were obtained as follows: <bold>32</bold> (545) and <bold>44</bold> (458); <bold>41</bold> (>230) and <bold>45</bold> (1630). In contrast, 4′-ethynyl-2′-deoxy-4′-thioguanosine <bold>43</bold> was found to possess a SI value of >18200, which is 20 times better than that of <bold>46</bold> (933).</p></div></front></TEI><pmc article-type="rapid-communication" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">ACS Med Chem Lett</journal-id><journal-id journal-id-type="iso-abbrev">ACS Med Chem Lett</journal-id><journal-id journal-id-type="publisher-id">ml</journal-id><journal-id journal-id-type="coden">amclct</journal-id><journal-title-group><journal-title>ACS Medicinal Chemistry Letters</journal-title></journal-title-group><issn pub-type="ppub">1948-5875</issn><issn pub-type="epub">1948-5875</issn><publisher><publisher-name>American Chemical Society</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23795238</article-id><article-id pub-id-type="pmc">3686520</article-id><article-id pub-id-type="doi">10.1021/ml2001054</article-id><article-categories><subj-group><subject>Letter</subject></subj-group></article-categories><title-group><article-title>Synthesis of 4′-Ethynyl-2′-deoxy-4′-thioribonucleosides and Discovery of a Highly Potent and Less Toxic NRTI</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes" id="ath1"><name><surname>Haraguchi</surname><given-names>Kazuhiro</given-names></name><xref rid="cor1" ref-type="other">*</xref><xref rid="aff1" ref-type="aff">†</xref></contrib><contrib contrib-type="author" id="ath2"><name><surname>Shimada</surname><given-names>Hisashi</given-names></name><xref rid="aff1" ref-type="aff">†</xref></contrib><contrib contrib-type="author" id="ath3"><name><surname>Kimura</surname><given-names>Keigo</given-names></name><xref rid="aff1" ref-type="aff">†</xref></contrib><contrib contrib-type="author" id="ath4"><name><surname>Akutsu</surname><given-names>Genta</given-names></name><xref rid="aff1" ref-type="aff">†</xref></contrib><contrib contrib-type="author" id="ath5"><name><surname>Tanaka</surname><given-names>Hiromichi</given-names></name><xref rid="aff1" ref-type="aff">†</xref></contrib><contrib contrib-type="author" id="ath6"><name><surname>Abe</surname><given-names>Hiroshi</given-names></name><xref rid="aff2" ref-type="aff">‡</xref></contrib><contrib contrib-type="author" id="ath7"><name><surname>Hamasaki</surname><given-names>Takayuki</given-names></name><xref rid="aff3" ref-type="aff">§</xref></contrib><contrib contrib-type="author" id="ath8"><name><surname>Baba</surname><given-names>Masanori</given-names></name><xref rid="aff3" ref-type="aff">§</xref></contrib><contrib contrib-type="author" id="ath9"><name><surname>Gullen</surname><given-names>Elizabeth A.</given-names></name><xref rid="aff4" ref-type="aff">∥</xref></contrib><contrib contrib-type="author" id="ath10"><name><surname>Dutschman</surname><given-names>Ginger E.</given-names></name><xref rid="aff4" ref-type="aff">∥</xref></contrib><contrib contrib-type="author" id="ath11"><name><surname>Cheng</surname><given-names>Yung-Chi</given-names></name><xref rid="aff4" ref-type="aff">∥</xref></contrib><contrib contrib-type="author" id="ath12"><name><surname>Balzarini</surname><given-names>Jan</given-names></name><xref rid="aff5" ref-type="aff">⊥</xref></contrib><aff id="aff1"><label>†</label>School of Pharmacy,<institution>Showa University</institution>, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan</aff><aff id="aff2"><label>‡</label>RIKEN Advanced Science Institute,<institution>Nanomedical Engineering Laboratory</institution>, 2-1, Hirosawa, Wako-shi, Saitama 351-0198, Japan</aff><aff id="aff3"><label>§</label>Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences,<institution>Kagoshima University</institution>, Kagoshima 89-8544, Japan</aff><aff id="aff4"><label>∥</label>Department of Pharmacology, School of Medicine,<institution>Yale University</institution>, New Haven, Connecticut 06520, United States</aff><aff id="aff5"><label>⊥</label>Rega Institute for Medical Research,<institution>Katholieke Universiteit Leuven</institution>, B-3000 Leuven, Belgium</aff></contrib-group><author-notes><corresp id="cor1"><label>*</label>Tel: <phone>81-3-3784-8187</phone>. Fax: <fax>81-3-3784-8252</fax>. E-mail: <email>harakazu@pharm.showa-u.acjp</email>.</corresp></author-notes><pub-date pub-type="epub"><day>20</day><month>07</month><year>2011</year></pub-date><pub-date pub-type="collection"><day>08</day><month>09</month><year>2011</year></pub-date><volume>2</volume><issue>9</issue><fpage>692</fpage><lpage>697</lpage><history><date date-type="received"><day>22</day><month>04</month><year>2011</year></date><date date-type="accepted"><day>10</day><month>07</month><year>2011</year></date></history><permissions><copyright-statement>Copyright © 2011 American Chemical Society</copyright-statement><copyright-year>2011</copyright-year><copyright-holder>American Chemical Society</copyright-holder></permissions><abstract><p content-type="toc-graphic"><graphic xlink:href="ml-2011-001054_0014" id="ab-tgr1"></graphic></p><p>The synthesis of 4′-ethynyl-2′-deoxy-4′-thioribonucleosides was carried out utilizing an electrophilic glycosidation in which 4-ethynyl-4-thiofuranoid glycal <bold>16</bold> served as a glycosyl donor. Electrophilic glycosidation between <bold>16</bold> and the silylated nucleobases (<italic>N</italic><sup>4</sup>-acetylcytosine, <italic>N</italic><sup>6</sup>-benzoyladenine, and <italic>N</italic><sup>2</sup>-acetyl-<italic>O</italic><sup>6</sup>-diphenylcarbamoylguanine) was carried out in the presence of <italic>N</italic>-iodosuccinimide (NIS), leading to the exclusive formation of the desired β-anomers <bold>29</bold>, <bold>33</bold>, and <bold>36</bold>. Anti-HIV studies demonstrated that these 4′-thio nucleosides were less cytotoxic to T-lymphocyte (i.e., MT-4 cells) than the corresponding 4′-ethynyl derivatives of 2′-deoxycytidine (<bold>44</bold>), 2′-deoxyadenosine (<bold>45</bold>), and 2′-deoxyguanosine (<bold>46</bold>). Comparison of the selectivity indices (SI) was made between 4′-thionucleosides (<bold>32</bold>, <bold>41</bold>, and <bold>43</bold>) and the corresponding 4′-oxygen analogues <bold>44</bold>-<bold>46</bold> by using the reported CC<sub>50</sub> and EC<sub>50</sub> values. In the case of cytosine and adenine nucleosides, comparable SI values were obtained as follows: <bold>32</bold> (545) and <bold>44</bold> (458); <bold>41</bold> (>230) and <bold>45</bold> (1630). In contrast, 4′-ethynyl-2′-deoxy-4′-thioguanosine <bold>43</bold> was found to possess a SI value of >18200, which is 20 times better than that of <bold>46</bold> (933).</p></abstract><kwd-group><kwd>4′-Thionucleosides</kwd><kwd>glycal</kwd><kwd>electrophilic glycosidation</kwd><kwd>anti-HIV-1 activity</kwd><kwd>nucleoside reverse transcriptase inhibitors</kwd></kwd-group><funding-group><funding-statement><funding-source>National Institutes of Health, United States</funding-source></funding-statement></funding-group><custom-meta-group><custom-meta><meta-name>document-id-old-9</meta-name><meta-value>ml2001054</meta-value></custom-meta><custom-meta><meta-name>document-id-new-14</meta-name><meta-value>ml-2011-001054</meta-value></custom-meta><custom-meta><meta-name>ccc-price</meta-name><meta-value></meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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