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

Autor:	Serge Pieters, David McGowan, Florence Herschke, Frederik Pauwels, Bart Stoops, Stefaan Last, Werner Embrechts, Annick Scholliers, Wendy Mostmans, Kris Van Dijck, Bertrand Van Schoubroeck, Tine Thoné, Dorien De Pooter, Gregory Fanning, Mari Luz Rosauro, Mourad Daoubi Khamlichi, Ioannis Houpis, Eric Arnoult, Tim H.M. Jonckers, Pierre Raboisson
Rok vydání:	2018
Předmět:	Male 0301 basic medicine Agonist medicine.drug_class Clinical Biochemistry Pharmaceutical Science Alpha interferon Endogeny Pharmacology 01 natural sciences Biochemistry Rats Sprague-Dawley Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Interferon Drug Discovery medicine Quinazoline Animals Cytochrome P-450 Enzyme Inhibitors Humans Structure–activity relationship Molecular Biology Toll-like receptor Membrane Glycoproteins Molecular Structure 010405 organic chemistry Organic Chemistry Interferon-alpha TLR7 0104 chemical sciences Mice Inbred C57BL Molecular Docking Simulation HEK293 Cells 030104 developmental biology Toll-Like Receptor 7 chemistry Toll-Like Receptor 8 Microsomes Liver Quinazolines Molecular Medicine Half-Life medicine.drug
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 28:711-719
ISSN:	0960-894X
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ecb247545d952c5e2d61547d1061dea6 https://doi.org/10.1016/j.bmcl.2018.01.014 Zobrazit plný text záznamu Full Text from ScienceDirect