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, B
Tong, XK
Tang, W
Li, DW
He, PL
Garcia, JM
Zeng, LM
Gao, AH
Yang, L
Li, J
Nan, FJ
Jacobs, M
Altmeyer, RM
Zuo, JP
Hu, YH
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
2011 Impact Factor: 5.248
2011 SCImago Journal Rankings: 0.451
DOIhttp://dx.doi.org/10.1021/jm2015952
DC Field
Value
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
2011 Impact Factor: 5.248
2011 SCImago Journal Rankings: 0.451
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
Author Affiliations
  1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences
  2. HKU-Pasteur Research Centre
  3. UCL Medical School