1444302-67-3Relevant academic research and scientific papers
Design, synthesis and biological evaluation of novel aminothiazoles as antiviral compounds acting against human rhinovirus
Décor, Anne,Grand-Ma?tre, Chantal,Hucke, Oliver,O'Meara, Jeff,Kuhn, Cyrille,Forget, Léa Constantineau,Brochu, Christian,Malenfant, Eric,Bertrand-Laperle, Mégan,Bordeleau, Josée,Ghiro, Elise,Pesant, Marc,Fazal, Gulrez,Gorys, Vida,Little, Michael,Boucher, Colette,Bordeleau, Sylvain,Turcotte, Pascal,Guo, Tim,Garneau, Michel,Spickler, Catherine,Gauthier, Annick
, p. 3841 - 3847 (2013/07/27)
We describe here the design, synthesis and biological evaluation of antiviral compounds acting against human rhinovirus (HRV). A series of aminothiazoles demonstrated pan-activity against the HRV genotypes screened and productive structure-activity relationships. A comprehensive investigational library was designed and performed allowing the identification of potent compounds with lower molecular weight and improved ADME profile. 31d-1, 31d-2, 31f showed good exposures in CD-1 mice. The mechanism of action was discovered to be a host target: the lipid kinase phosphatidylinositol 4-kinase III beta (PI4KIII?). The identification of the pan-HRV active compound 31f combined with a structurally distinct literature compound T-00127-HEV1 allowed the assessment of target related tolerability of inhibiting this kinase for a short period of time in order to prevent HRV replication.
