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...

Full description

Saved in:
Bibliographic Details
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
Format: Article
Language:English
Subjects:
Letter
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1948-5875
1948-5875
DOI:10.1021/acsmedchemlett.8b00540