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

Autor: McGowan D; Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium., Herschke F; Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium., Pauwels F; Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium., Stoops B; Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium., Last S; Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium., Pieters S; Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium., Scholliers A; Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium., Thoné T; Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium., Van Schoubroeck B; Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium., De Pooter D; Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium., Mostmans W; Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium., Khamlichi MD; 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., Embrechts W; Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium., Dhuyvetter D; Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium., Smyej I; Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium., Arnoult E; Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium., Demin S; Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium., Borghys H; Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium., Fanning G; Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium., Vlach J; Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium., Raboisson P; Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium.
Jazyk: angličtina
Zdroj: Journal of medicinal chemistry [J Med Chem] 2016 Sep 08; Vol. 59 (17), pp. 7936-49. Date of Electronic Publication: 2016 Aug 23.
DOI: 10.1021/acs.jmedchem.6b00747
Abstrakt: 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.
Databáze: MEDLINE
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