title: Novel Pyrimidine Toll-like Receptor 7 and 8 Dual Agonists to Treat Hepatitis B Virus.
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.
authors: Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium.
authors: David
authors: D
authors: McGowan
authors: Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium.
authors: Florence
authors: F
authors: Herschke
authors: Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium.
authors: Frederik
authors: F
authors: Pauwels
authors: Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium.
authors: Bart
authors: B
authors: Stoops
authors: Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium.
authors: Stefaan
authors: S
authors: Last
authors: Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium.
authors: Serge
authors: S
authors: Pieters
authors: Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium.
authors: Annick
authors: A
authors: Scholliers
authors: Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium.
authors: Tine
authors: T
authors: Thoné
authors: Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium.
authors: Bertrand
authors: B
authors: Van Schoubroeck
authors: Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium.
authors: Dorien
authors: D
authors: De Pooter
authors: Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium.
authors: Wendy
authors: W
authors: Mostmans
authors: 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.
authors: Mourad Daoubi
authors: MD
authors: Khamlichi
authors: Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium.
authors: Werner
authors: W
authors: Embrechts
authors: Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium.
authors: Deborah
authors: D
authors: Dhuyvetter
authors: Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium.
authors: Ilham
authors: I
authors: Smyej
authors: Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium.
authors: Eric
authors: E
authors: Arnoult
authors: Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium.
authors: Samuël
authors: S
authors: Demin
authors: Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium.
authors: Herman
authors: H
authors: Borghys
authors: Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium.
authors: Gregory
authors: G
authors: Fanning
authors: Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium.
authors: Jaromir
authors: J
authors: Vlach
authors: Janssen Infectious Diseases Diagnostics BVBA , Turnhoutseweg 30, 2340 Beerse, Belgium.
authors: Pierre
authors: P
authors: Raboisson
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D003198:Computer Simulation; D016207:Cytokines / Q000096:biosynthesis; D004285:Dogs; D006509:Hepatitis B / Q000188:drug therapy / Q000821:virology; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology; D057166:High-Throughput Screening Assays; D006801:Humans; D008252:Macaca fascicularis; D051379:Mice; D008810:Mice, Inbred C57BL; D062105:Molecular Docking Simulation; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D051199:Toll-Like Receptor 7 / Q000819:agonists*; D051200:Toll-Like Receptor 8 / Q000819:agonists*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D011743:Pyrimidines; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8