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

Ziwei Hu; Janardhan Banothu; Mallesh Beesu; Collin J. Gustafson; Michael J.H. Brush; Kathryn L. Trautman; Alex C.D. Salyer; Balaji Pathakumari; Sunil A. David

doi:10.1021/acsmedchemlett.8b00540

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

Ziwei Hu, Janardhan Banothu, Mallesh Beesu, Collin J. Gustafson, Michael J.H. Brush, Kathryn L. Trautman, Alex C.D. Salyer, Balaji Pathakumari, Sunil A. David

Medicinal Chemistry

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Abstract

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.

Original language	English (US)
Pages (from-to)	132-136
Number of pages	5
Journal	ACS Medicinal Chemistry Letters
Volume	10
Issue number	1
DOIs	https://doi.org/10.1021/acsmedchemlett.8b00540
State	Published - Oct 1 2019

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Publisher Copyright:
© 2018 American Chemical Society.

Keywords

Toll-like receptor 2
Vaccine adjuvants
chemokines
cytokines
dihydropyridine-quinolones

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10.1021/acsmedchemlett.8b00540

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331173

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AU - Beesu, Mallesh

AU - Gustafson, Collin J.

AU - Brush, Michael J.H.

AU - Trautman, Kathryn L.

AU - Salyer, Alex C.D.

AU - Pathakumari, Balaji

AU - David, Sunil A.

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

Abstract

Bibliographical note

Keywords

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