2. Academic Validation
  3. Design, synthesis and biological evaluation of novel aminothiazoles as antiviral compounds acting against human rhinovirus

Design, synthesis and biological evaluation of novel aminothiazoles as antiviral compounds acting against human rhinovirus

  • Bioorg Med Chem Lett. 2013 Jul 1;23(13):3841-7. doi: 10.1016/j.bmcl.2013.04.077.
Anne Décor 1,  Chantal Grand-Maître,  Oliver Hucke,  Jeff O'Meara,  Cyrille Kuhn,  Léa Constantineau-Forget,  Christian Brochu,  Eric Malenfant,  Mégan Bertrand-Laperle,  Josée Bordeleau,  Elise Ghiro,  Marc Pesant,  Gulrez Fazal,  Vida Gorys,  Michael Little,  Colette Boucher,  Sylvain Bordeleau,  Pascal Turcotte,  Tim Guo,  Michel Garneau,  Catherine Spickler,  Annick Gauthier
Affiliations

Affiliation

  • 1 Boehringer Ingelheim (Canada) Ltd., Research and Development, 2100 Cunard Street, Laval, Québec, Canada H7S 2G5.
PMID: 23726345 DOI: 10.1016/j.bmcl.2013.04.077
Abstract

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 (PI4KIIIß). 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.

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