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Article: Discovery and Optimization of 2,4-Diaminoquinazoline Derivatives As a New Class of Potent Dengue Virus Inhibitors
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TitleDiscovery and Optimization of 2,4-Diaminoquinazoline Derivatives As a New Class of Potent Dengue Virus Inhibitors
 
AuthorsChao, B1
Tong, XK1
Tang, W1
Li, DW1
He, PL1
Garcia, JM2
Zeng, LM1
Gao, AH1
Yang, L1
Li, J1
Nan, FJ1
Jacobs, M3
Altmeyer, RM
Zuo, JP1
Hu, YH1
 
Issue Date2012
 
PublisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/jmc
 
CitationJournal of Medicinal Chemistry, 2012, v. 55 n. 7, p. 3135-3143 [How to Cite?]
DOI: http://dx.doi.org/10.1021/jm2015952
 
AbstractThe results of a high-throughput screening assay using the DENV-2 replicon showed that the 2,4-diaminoquinazoline derivative 4a has a high dengue virus inhibitory activity (EC(50) = 0.15 muM). A series of 2,4-diaminoquinazoline derivatives based on 4a as a lead compound were synthesized and subjected to structure-antidengue activity relationship studies. Among the series of 2,4-diaminoquinazoline derivative probed, 4o was observed to display both the highest antiviral potency (EC(50) = 2.8 nM, SI > 1000) and an excellent pharmacokinetic profile.
 
ISSN0022-2623
2012 Impact Factor: 5.614
2012 SCImago Journal Rankings: 1.950
 
DOIhttp://dx.doi.org/10.1021/jm2015952
 
DC FieldValue
dc.contributor.authorChao, B
 
dc.contributor.authorTong, XK
 
dc.contributor.authorTang, W
 
dc.contributor.authorLi, DW
 
dc.contributor.authorHe, PL
 
dc.contributor.authorGarcia, JM
 
dc.contributor.authorZeng, LM
 
dc.contributor.authorGao, AH
 
dc.contributor.authorYang, L
 
dc.contributor.authorLi, J
 
dc.contributor.authorNan, FJ
 
dc.contributor.authorJacobs, M
 
dc.contributor.authorAltmeyer, RM
 
dc.contributor.authorZuo, JP
 
dc.contributor.authorHu, YH
 
dc.date.accessioned2012-09-20T08:08:31Z
 
dc.date.available2012-09-20T08:08:31Z
 
dc.date.issued2012
 
dc.description.abstractThe results of a high-throughput screening assay using the DENV-2 replicon showed that the 2,4-diaminoquinazoline derivative 4a has a high dengue virus inhibitory activity (EC(50) = 0.15 muM). A series of 2,4-diaminoquinazoline derivatives based on 4a as a lead compound were synthesized and subjected to structure-antidengue activity relationship studies. Among the series of 2,4-diaminoquinazoline derivative probed, 4o was observed to display both the highest antiviral potency (EC(50) = 2.8 nM, SI > 1000) and an excellent pharmacokinetic profile.
 
dc.identifier.citationJournal of Medicinal Chemistry, 2012, v. 55 n. 7, p. 3135-3143 [How to Cite?]
DOI: http://dx.doi.org/10.1021/jm2015952
 
dc.identifier.doihttp://dx.doi.org/10.1021/jm2015952
 
dc.identifier.epage3143
 
dc.identifier.hkuros205828
 
dc.identifier.issn0022-2623
2012 Impact Factor: 5.614
2012 SCImago Journal Rankings: 1.950
 
dc.identifier.issue7
 
dc.identifier.pmid22448770
 
dc.identifier.scopuseid_2-s2.0-84859791780
 
dc.identifier.spage3135
 
dc.identifier.urihttp://hdl.handle.net/10722/164714
 
dc.identifier.volume55
 
dc.languageeng
 
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/jmc
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of Medicinal Chemistry
 
dc.subject.meshAntiviral Agents - chemical synthesis - pharmacokinetics - pharmacology
 
dc.subject.meshDengue Virus - drug effects - genetics
 
dc.subject.meshQuinazolines - chemical synthesis - pharmacokinetics - pharmacology
 
dc.subject.meshReplicon - drug effects
 
dc.subject.meshStructure-Activity Relationship
 
dc.titleDiscovery and Optimization of 2,4-Diaminoquinazoline Derivatives As a New Class of Potent Dengue Virus Inhibitors
 
dc.typeArticle
 
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<item><contributor.author>Chao, B</contributor.author>
<contributor.author>Tong, XK</contributor.author>
<contributor.author>Tang, W</contributor.author>
<contributor.author>Li, DW</contributor.author>
<contributor.author>He, PL</contributor.author>
<contributor.author>Garcia, JM</contributor.author>
<contributor.author>Zeng, LM</contributor.author>
<contributor.author>Gao, AH</contributor.author>
<contributor.author>Yang, L</contributor.author>
<contributor.author>Li, J</contributor.author>
<contributor.author>Nan, FJ</contributor.author>
<contributor.author>Jacobs, M</contributor.author>
<contributor.author>Altmeyer, RM</contributor.author>
<contributor.author>Zuo, JP</contributor.author>
<contributor.author>Hu, YH</contributor.author>
<date.accessioned>2012-09-20T08:08:31Z</date.accessioned>
<date.available>2012-09-20T08:08:31Z</date.available>
<date.issued>2012</date.issued>
<identifier.citation>Journal of Medicinal Chemistry, 2012, v. 55 n. 7, p. 3135-3143</identifier.citation>
<identifier.issn>0022-2623</identifier.issn>
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<description.abstract>The results of a high-throughput screening assay using the DENV-2 replicon showed that the 2,4-diaminoquinazoline derivative 4a has a high dengue virus inhibitory activity (EC(50) = 0.15 muM). A series of 2,4-diaminoquinazoline derivatives based on 4a as a lead compound were synthesized and subjected to structure-antidengue activity relationship studies. Among the series of 2,4-diaminoquinazoline derivative probed, 4o was observed to display both the highest antiviral potency (EC(50) = 2.8 nM, SI &gt; 1000) and an excellent pharmacokinetic profile.</description.abstract>
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<publisher>American Chemical Society. The Journal&apos;s web site is located at http://pubs.acs.org/jmc</publisher>
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<subject.mesh>Antiviral Agents - chemical synthesis - pharmacokinetics - pharmacology</subject.mesh>
<subject.mesh>Dengue Virus - drug effects - genetics</subject.mesh>
<subject.mesh>Quinazolines - chemical synthesis - pharmacokinetics - pharmacology</subject.mesh>
<subject.mesh>Replicon - drug effects</subject.mesh>
<subject.mesh>Structure-Activity Relationship</subject.mesh>
<title>Discovery and Optimization of 2,4-Diaminoquinazoline Derivatives As a New Class of Potent Dengue Virus Inhibitors</title>
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Author Affiliations
  1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences
  2. HKU-Pasteur Research Centre
  3. UCL Medical School