Journal of Medicinal Chemistry p. 7936 - 7949 (2016)
Update date:2022-08-15
Topics:
McGowan, David
Herschke, Florence
Pauwels, Frederik
Stoops, Bart
Last, Stefaan
Pieters, Serge
Scholliers, Annick
Thoné, Tine
Van Schoubroeck, Bertrand
De Pooter, Dorien
Mostmans, Wendy
Khamlichi, Mourad Daoubi
Embrechts, Werner
Dhuyvetter, Deborah
Smyej, Ilham
Arnoult, Eric
Demin, Samu?l
Borghys, Herman
Fanning, Gregory
Vlach, Jaromir
Raboisson, Pierre
Toll-like receptor (TLR) 7 and 8 agonists can potentially be used in the treatment of viral infections and are particularly promising for chronic hepatitis B virus (HBV) infection. An internal screening effort identified a pyrimidine Toll-like receptor 7 and 8 dual agonist. This provided a novel alternative over the previously reported adenine and pteridone type of agonists. Structure-activity relationship, lead optimization, in silico docking, pharmacokinetics, and demonstration of ex vivo and in vivo cytokine production of the lead compound are presented.
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