2. Academic Validation
  3. Discovery of selective 2,4-diaminoquinazoline toll-like receptor 7 (TLR 7) agonists

Discovery of selective 2,4-diaminoquinazoline toll-like receptor 7 (TLR 7) agonists

  • Bioorg Med Chem Lett. 2018 Feb 15;28(4):711-719. doi: 10.1016/j.bmcl.2018.01.014.
Serge Pieters 1,  David McGowan 2,  Florence Herschke 2,  Frederik Pauwels 2,  Bart Stoops 2,  Stefaan Last 2,  Werner Embrechts 2,  Annick Scholliers 2,  Wendy Mostmans 2,  Kris Van Dijck 2,  Bertrand Van Schoubroeck 2,  Tine Thoné 2,  Dorien De Pooter 2,  Gregory Fanning 2,  Mari Luz Rosauro 3,  Mourad Daoubi Khamlichi 3,  Ioannis Houpis 2,  Eric Arnoult 4,  Tim H M Jonckers 2,  Pierre Raboisson 2
Affiliations

Affiliations

  • 1 Janssen Infectious Diseases Diagnostics BVBA, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address: spieters@its.jnj.com.
  • 2 Janssen Infectious Diseases Diagnostics BVBA, Turnhoutseweg 30, 2340 Beerse, Belgium.
  • 3 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.
  • 4 Janssen Research & Development L.L.C., 1400 McKean Rd, Spring House, PA 19454, United States.
PMID: 29366653 DOI: 10.1016/j.bmcl.2018.01.014
Abstract

The discovery of a novel series of highly potent quinazoline TLR 7/8 agonists is described. The synthesis and structure-activity relationship is presented. Structural requirements and optimization of this series toward TLR 7 selectivity afforded the potent agonist 48. Pharmacokinetic and pharmacodynamic studies highlighted 48 as an orally available endogenous interferon (IFN-α) inducer in mice.

Keywords

HBV; Quinazoline; TLR7.

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