An Uncharged Oxetanyl Sulfoxide as a Covalent Modifier for Improving Aqueous Solubility
Identifieur interne : 000285 ( Pmc/Corpus ); précédent : 000284; suivant : 000286An Uncharged Oxetanyl Sulfoxide as a Covalent Modifier for Improving Aqueous Solubility
Auteurs : Erin M. Skoda ; Joshua R. Sacher ; Mustafa Z. Kazancioglu ; Jaideep Saha ; Peter WipfSource :
- ACS Medicinal Chemistry Letters [ 1948-5875 ] ; 2014.
Abstract
Low aqueous solubility is a common challenge in drug discovery and development and can lead to inconclusive biological assay results. Attaching small, polar groups that do not interfere with the bioactivity of the pharmacophore often improves solubility, but there is a dearth of viable neutral moieties available for this purpose. We have modified several poorly soluble drugs or drug candidates with the oxetanyl sulfoxide moiety of the DMSO analog MMS-350 and noted in most cases a moderate to large improvement of aqueous solubility. Furthermore, the membrane permeability of a test sample was enhanced compared to the parent compound.
Url:
DOI: 10.1021/ml5001504
PubMed: 25147611
PubMed Central: 4137373
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Sulfoxide as a Covalent Modifier
for Improving Aqueous Solubility</title><author><name sortKey="Skoda, Erin M" sort="Skoda, Erin M" uniqKey="Skoda E" first="Erin M." last="Skoda">Erin M. Skoda</name></author><author><name sortKey="Sacher, Joshua R" sort="Sacher, Joshua R" uniqKey="Sacher J" first="Joshua R." last="Sacher">Joshua R. Sacher</name></author><author><name sortKey="Kazancioglu, Mustafa Z" sort="Kazancioglu, Mustafa Z" uniqKey="Kazancioglu M" first="Mustafa Z." last="Kazancioglu">Mustafa Z. Kazancioglu</name></author><author><name sortKey="Saha, Jaideep" sort="Saha, Jaideep" uniqKey="Saha J" first="Jaideep" last="Saha">Jaideep Saha</name></author><author><name sortKey="Wipf, Peter" sort="Wipf, Peter" uniqKey="Wipf P" first="Peter" last="Wipf">Peter Wipf</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25147611</idno><idno type="pmc">4137373</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137373</idno><idno type="RBID">PMC:4137373</idno><idno type="doi">10.1021/ml5001504</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000285</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000285</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">An Uncharged Oxetanyl
Sulfoxide as a Covalent Modifier
for Improving Aqueous Solubility</title><author><name sortKey="Skoda, Erin M" sort="Skoda, Erin M" uniqKey="Skoda E" first="Erin M." last="Skoda">Erin M. Skoda</name></author><author><name sortKey="Sacher, Joshua R" sort="Sacher, Joshua R" uniqKey="Sacher J" first="Joshua R." last="Sacher">Joshua R. Sacher</name></author><author><name sortKey="Kazancioglu, Mustafa Z" sort="Kazancioglu, Mustafa Z" uniqKey="Kazancioglu M" first="Mustafa Z." last="Kazancioglu">Mustafa Z. Kazancioglu</name></author><author><name sortKey="Saha, Jaideep" sort="Saha, Jaideep" uniqKey="Saha J" first="Jaideep" last="Saha">Jaideep Saha</name></author><author><name sortKey="Wipf, Peter" sort="Wipf, Peter" uniqKey="Wipf P" first="Peter" last="Wipf">Peter Wipf</name></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="2014">2014</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-2014-001504_0008" id="ab-d31e136"></graphic></p><p>Low
aqueous solubility is a common challenge in drug discovery
and development and can lead to inconclusive biological assay results.
Attaching small, polar groups that do not interfere with the bioactivity
of the pharmacophore often improves solubility, but there is a dearth
of viable neutral moieties available for this purpose. We have modified
several poorly soluble drugs or drug candidates with the oxetanyl
sulfoxide moiety of the DMSO analog MMS-350 and noted in most cases
a moderate to large improvement of aqueous solubility. Furthermore,
the membrane permeability of a test sample was enhanced compared to
the parent compound.</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">25147611</article-id><article-id pub-id-type="pmc">4137373</article-id><article-id pub-id-type="doi">10.1021/ml5001504</article-id><article-categories><subj-group><subject>Letter</subject></subj-group></article-categories><title-group><article-title>An Uncharged Oxetanyl
Sulfoxide as a Covalent Modifier
for Improving Aqueous Solubility</article-title></title-group><contrib-group><contrib contrib-type="author" id="ath1"><name><surname>Skoda</surname><given-names>Erin M.</given-names></name></contrib><contrib contrib-type="author" id="ath2"><name><surname>Sacher</surname><given-names>Joshua R.</given-names></name></contrib><contrib contrib-type="author" id="ath3"><name><surname>Kazancioglu</surname><given-names>Mustafa Z.</given-names></name><xref rid="notes-1" ref-type="notes">‡</xref></contrib><contrib contrib-type="author" id="ath4"><name><surname>Saha</surname><given-names>Jaideep</given-names></name><xref rid="notes-1" ref-type="notes">‡</xref></contrib><contrib contrib-type="author" corresp="yes" id="ath5"><name><surname>Wipf</surname><given-names>Peter</given-names></name><xref rid="cor1" ref-type="other">*</xref></contrib><aff id="aff1">Department of Chemistry,<institution>University of Pittsburgh</institution>, Pittsburgh, Pennsylvania 15260,<country>United States</country></aff></contrib-group><author-notes><corresp id="cor1"><label>*</label>E-mail: <email>pwipf@pitt.edu</email>.</corresp></author-notes><pub-date pub-type="epub"><day>27</day><month>06</month><year>2014</year></pub-date><pub-date pub-type="collection"><day>14</day><month>08</month><year>2014</year></pub-date><volume>5</volume><issue>8</issue><fpage>900</fpage><lpage>904</lpage><history><date date-type="received"><day>12</day><month>04</month><year>2014</year></date><date date-type="accepted"><day>27</day><month>06</month><year>2014</year></date></history><permissions><copyright-statement>Copyright © 2014 American Chemical Society</copyright-statement><copyright-year>2014</copyright-year><copyright-holder>American Chemical Society</copyright-holder></permissions><abstract><p content-type="toc-graphic"><graphic xlink:href="ml-2014-001504_0008" id="ab-d31e136"></graphic></p><p>Low
aqueous solubility is a common challenge in drug discovery
and development and can lead to inconclusive biological assay results.
Attaching small, polar groups that do not interfere with the bioactivity
of the pharmacophore often improves solubility, but there is a dearth
of viable neutral moieties available for this purpose. We have modified
several poorly soluble drugs or drug candidates with the oxetanyl
sulfoxide moiety of the DMSO analog MMS-350 and noted in most cases
a moderate to large improvement of aqueous solubility. Furthermore,
the membrane permeability of a test sample was enhanced compared to
the parent compound.</p></abstract><kwd-group><kwd>Aqueous solubility</kwd><kwd>MMS-350</kwd><kwd>oxetane</kwd><kwd>sulfoxide</kwd><kwd>JP4-039</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>ml5001504</meta-value></custom-meta><custom-meta><meta-name>document-id-new-14</meta-name><meta-value>ml-2014-001504</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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