Identification of Human Toll-like Receptor 2‑Agonistic Activity in Dihydropyridine–Quinolone Carboxamides

Using a multiplexed, reporter gene-based, high-throughput screen, we identified 9-fluoro-7-hydroxy-3-methyl-5-oxo-N-(pyridin-3-ylmethyl)-2,3-dihydro-1H,5H-pyrido­[3,2,1-ij]­quinoline-6-carboxamide as a TLR2 agonist. Preliminary structure–activity relationship studies on the carboxamide moiety led to...

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Published in:ACS medicinal chemistry letters 2019-01, Vol.10 (1), p.132-136
Main Authors: Hu, Ziwei, Banothu, Janardhan, Beesu, Mallesh, Gustafson, Collin J, Brush, Michael J. H, Trautman, Kathryn L, Salyer, Alex C. D, Pathakumari, Balaji, David, Sunil A
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cited_by cdi_FETCH-LOGICAL-a457t-283e7ae223534672ef6a19597f1ce5264859323fe17b78556a8b642eaf29808a3
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container_title ACS medicinal chemistry letters
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creator Hu, Ziwei
Banothu, Janardhan
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David, Sunil A
description Using a multiplexed, reporter gene-based, high-throughput screen, we identified 9-fluoro-7-hydroxy-3-methyl-5-oxo-N-(pyridin-3-ylmethyl)-2,3-dihydro-1H,5H-pyrido­[3,2,1-ij]­quinoline-6-carboxamide as a TLR2 agonist. Preliminary structure–activity relationship studies on the carboxamide moiety led to the identification of analogues that induce chemokines and cytokines in a TLR2-dependent manner. These results represent new leads for the development of vaccine adjuvants.
doi_str_mv 10.1021/acsmedchemlett.8b00540
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subjects Letter
title Identification of Human Toll-like Receptor 2‑Agonistic Activity in Dihydropyridine–Quinolone Carboxamides
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