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Preliminary Evaluation of a 3H Imidazoquinoline Library as Dual TLR7/TLR8 Antagonists
dc.contributor.author | Shukla, Nikunj M. | |
dc.contributor.author | Malladi, Subbalakshmi S. | |
dc.contributor.author | Day, Victor W. | |
dc.contributor.author | David, Sunil A. | |
dc.date.accessioned | 2017-05-04T19:20:48Z | |
dc.date.available | 2017-05-04T19:20:48Z | |
dc.date.issued | 2011-06-15 | |
dc.identifier.citation | Shukla, 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.2011.04.052 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/23896 | |
dc.description.abstract | Toll-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.publisher | Elsevier | en_US |
dc.rights | This 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.uri | https://creativecommons.org/licenses/by-nc-nd/3.0/us/ | en_US |
dc.subject | Toll-like receptor | en_US |
dc.subject | TLR7 | en_US |
dc.subject | TLR8 | en_US |
dc.subject | Imidazoquinoline | en_US |
dc.subject | NOESY | en_US |
dc.subject | HIV | en_US |
dc.subject | Autoimmune diseases | en_US |
dc.title | Preliminary Evaluation of a 3H Imidazoquinoline Library as Dual TLR7/TLR8 Antagonists | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Shukla, Nikunj M. | |
kusw.kuauthor | Malladi, Subbalakshmi S. | |
kusw.kuauthor | David, Sunil A. | |
kusw.kuauthor | Day, Victor | |
kusw.kudepartment | Medicinal Chemistry | en_US |
kusw.kudepartment | MSG-Xray Crystallography Lab | en_US |
dc.identifier.doi | 10.1016/j.bmc.2011.04.052 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC3114175 | en_US |
dc.rights.accessrights | openAccess |