2. Academic Validation
  3. Novel Pyrimidine Toll-like Receptor 7 and 8 Dual Agonists to Treat Hepatitis B Virus

Novel Pyrimidine Toll-like Receptor 7 and 8 Dual Agonists to Treat Hepatitis B Virus

  • J Med Chem. 2016 Sep 8;59(17):7936-49. doi: 10.1021/acs.jmedchem.6b00747.
David McGowan 1,  Florence Herschke 1,  Frederik Pauwels 1,  Bart Stoops 1,  Stefaan Last 1,  Serge Pieters 1,  Annick Scholliers 1,  Tine Thoné 1,  Bertrand Van Schoubroeck 1,  Dorien De Pooter 1,  Wendy Mostmans 1,  Mourad Daoubi Khamlichi 2,  Werner Embrechts 1,  Deborah Dhuyvetter 1,  Ilham Smyej 1,  Eric Arnoult 1,  Samuël Demin 1,  Herman Borghys 1,  Gregory Fanning 1,  Jaromir Vlach 1,  Pierre Raboisson 1
Affiliations

Affiliations

  • 1 Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium.
  • 2 Villapharma Research S.L. , Parque Tecnológico de Fuente Álamo. Ctra. El Estrecho-Lobosillo, Km. 2.5, Av. Azul 30320 Fuente Álamo de Murcia, Murcia, Spain.
PMID: 27513093 DOI: 10.1021/acs.jmedchem.6b00747
Abstract

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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