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dc.contributor.authorShukla, Nikunj M.
dc.contributor.authorMalladi, Subbalakshmi S.
dc.contributor.authorDay, Victor W.
dc.contributor.authorDavid, Sunil A.
dc.date.accessioned2017-05-04T19:20:48Z
dc.date.available2017-05-04T19:20:48Z
dc.date.issued2011-06-15
dc.identifier.citationShukla, N. M., Malladi, S. S., Day, V., & David, S. A. (2011). Preliminary Evaluation of a 3H Imidazoquinoline Library as Dual TLR7/TLR8 Antagonists. Bioorganic & Medicinal Chemistry, 19(12), 3801–3811. http://doi.org/10.1016/j.bmc.2011.04.052en_US
dc.identifier.urihttp://hdl.handle.net/1808/23896
dc.description.abstractToll-like receptors (TLR) -7 and -8 are thought to play an important role in immune activation processes underlying the pathophysiology of HIV and several clinically important autoimmune diseases. Based on our earlier findings of TLR7-antagonistic activity in a 3H imidazoquinoline, we sought to examine a pilot library of 3H imidazoquinolines for dual TLR7/8 antagonists, since they remain a poorly explored chemotype. Two-dimensional NOE experiments were employed to unequivocally characterize the compounds. A quinolinium compound 12, bearing p-methoxybenzyl substituents on N3 and N5 positions was identified as a lead. Compound 12 was found to inhibit both TLR7 and TLR8 at low micromolar concentrations. Our preliminary results suggest that alkylation with electron-rich substituents on the quinoline N5, or conversely, elimination of the fixed charge of the resultant quaternary amine on the quinolinium may yield more active compounds.en_US
dc.publisherElsevieren_US
dc.rightsThis article is made available under an Attribution-NonCommercial-NoDerivs 3.0 United States (CC BY-NC-ND 3.0 US) License.en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/3.0/us/en_US
dc.subjectToll-like receptoren_US
dc.subjectTLR7en_US
dc.subjectTLR8en_US
dc.subjectImidazoquinolineen_US
dc.subjectNOESYen_US
dc.subjectHIVen_US
dc.subjectAutoimmune diseasesen_US
dc.titlePreliminary Evaluation of a 3H Imidazoquinoline Library as Dual TLR7/TLR8 Antagonistsen_US
dc.typeArticleen_US
kusw.kuauthorShukla, Nikunj M.
kusw.kuauthorMalladi, Subbalakshmi S.
kusw.kuauthorDavid, Sunil A.
kusw.kuauthorDay, Victor
kusw.kudepartmentMedicinal Chemistryen_US
kusw.kudepartmentMSG-Xray Crystallography Laben_US
dc.identifier.doi10.1016/j.bmc.2011.04.052en_US
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.identifier.pmidPMC3114175en_US
dc.rights.accessrightsopenAccess


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This article is made available under an Attribution-NonCommercial-NoDerivs 3.0 United States (CC BY-NC-ND 3.0 US) License.
Except where otherwise noted, this item's license is described as: This article is made available under an Attribution-NonCommercial-NoDerivs 3.0 United States (CC BY-NC-ND 3.0 US) License.