title: Syntheses of Human TLR8-Specific Small-Molecule Agonists.
abstract: Human toll-like receptor (hTLR)-8 is expressed in myeloid dendritic cells, monocytes, and monocyte-derived dendritic cells. Engagement by TLR8 agonists evokes a distinct cytokine profile which favors the development of type 1 helper T cells. Focused exploration of structure-activity relationships in the imidazoquinolines has led to the identification of several novel human TLR8-specific agonists. The synthetic procedures for best-in-class analogues encompassing four chemotypes are described.
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, 2-132, Cancer & Cardiovascular Research Building, 2231 6th Street SE, Minneapolis, MN, 55455, USA.
authors.forename: Mallesh
authors.initials: M
authors.lastname: Beesu
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, 2-132, Cancer & Cardiovascular Research Building, 2231 6th Street SE, Minneapolis, MN, 55455, USA.
authors.forename: Hari Prasad
authors.initials: HP
authors.lastname: Kokatla
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, 2-132, Cancer & Cardiovascular Research Building, 2231 6th Street SE, Minneapolis, MN, 55455, USA. sdavid@umn.edu.
authors.forename: Sunil A
authors.initials: SA
authors.lastname: David
mesh_terms: D000276:Adjuvants, Immunologic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D057809:HEK293 Cells; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D051200:Toll-Like Receptor 8 / Q000819:agonists* / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D006575:Heterocyclic Compounds, 3-Ring; C495349:TLR8 protein, human; D051200:Toll-Like Receptor 8
keywords: Innate immunity; TLR8; TLR8 agonists; Vaccine adjuvants