Design and synthesis of tetrahydropyridopyrimidine based Toll-Like Receptor (TLR) 7/8 dual agonists.
Basic Information
ID: ALA4265889
Journal: Bioorg Med Chem Lett
Title: Design and synthesis of tetrahydropyridopyrimidine based Toll-Like Receptor (TLR) 7/8 dual agonists.
Authors: McGowan DC, Herschke F, Khamlichi MD, Rosauro ML, Benedicto SMP, Pauwels F, Stoops B, Pande V, Scholliers A, Van Schoubroeck B, Mostmans W, Van Dijck K, Thoné T, Horton H, Fanning G, Jonckers THM, Raboisson P.
Abstract: In a continuing effort to discover novel TLR agonists, herein we report on the discovery and structure-activity relationship of novel tetrahydropyridopyrimidine TLR 7/8 agonists. Optimization of this series towards dual agonist activity and a high clearance profile resulted in the identification of compound 52a1. Evaluation in vivo revealed an interferon stimulated response (ISG) in mice with limited systemic exposure and demonstrated the potential in antiviral treatment or as a vaccine adjuvant.
CiteXplore: 30143425
DOI: 10.1016/j.bmcl.2018.08.015
Patent ID: ┄