Discovery of selective 2, 4-diaminoquinazoline toll-like receptor 7 (TLR 7) agonists. Issue 4 (15th February 2018)

• Record Type: Journal Article
• Authors: Pieters, Serge; McGowan, David; Herschke, Florence; Pauwels, Frederik; Stoops, Bart; Last, Stefaan; Embrechts, Werner; Scholliers, Annick; Mostmans, Wendy; Van Dijck, Kris; Van Schoubroeck, Bertrand; Thoné, Tine; De Pooter, Dorien; Fanning, Gregory; Rosauro, Mari Luz; Khamlichi, Mourad Daoubi; Houpis, Ioannis; Arnoult, Eric; Jonckers, Tim H.M.; Raboisson, Pierre
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 4(2018)
• Page Start: 711
• Page End: 719
• Publication Date: 2018-02-15
• Subjects: HBV -- TLR7 -- Quinazoline; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.01.014
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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 agonist48 . Pharmacokinetic and pharmacodynamic studies highlighted48 as an orally available endogenous interferon (IFN-α) inducer in mice.