2-Aminothiazoles with improved pharmacotherapeutic properties for treatment of prion disease.

@article{Li20132AminothiazolesWI,
  title={2-Aminothiazoles with improved pharmacotherapeutic properties for treatment of prion disease.},
  author={Zhe Li and B. Michael Silber and Satish B. S. Rao and Joel R. Gever and Clifford M. Bryant and Alejandra Gallardo-Godoy and Elena Dolghih and Kartika Widjaja and Manuel L Elepano and Matthew P. Jacobson and Stanley B. Prusiner and Adam R. Renslo},
  journal={ChemMedChem},
  year={2013},
  volume={8 5},
  pages={
          847-57
        }
}
Recently, we described the aminothiazole lead (4-biphenyl-4-ylthiazol-2-yl)-(6-methylpyridin-2-yl)-amine (1), which exhibits many desirable properties, including excellent stability in liver microsomes, oral bioavailability of ∼40 %, and high exposure in the brains of mice. Despite its good pharmacokinetic properties, compound 1 exhibited only modest potency in mouse neuroblastoma cells overexpressing the disease-causing prion protein PrP(Sc) . Accordingly, we sought to identify analogues of 1… CONTINUE READING
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