940911-00-2Relevant academic research and scientific papers
Library synthesis and screening: 2,4-Diphenylthiazoles and 2,4-diphenyloxazoles as potential novel prion disease therapeutics
Heal, William,Thompson, Mark J.,Mutter, Roger,Cope, Hannah,Louth, Jenny C.,Chen, Beining
, p. 1347 - 1353 (2007)
Transmissible spongiform encephalopathies (TSEs) are a family of invariably fatal neurodegenerative disorders for which no effective therapeutics are currently available. In this paper, we report on the synthesis and screening of a small library of 2,4-diphenylthiazol-5-ylamine and 2,4-diphenyloxazol-5- ylamine derivatives as potential novel prion disease therapeutics. Various synthetic strategies were investigated, including a novel phosgene-mediated cyclization of 2-N-benzoylphenylglycinonitrile, and a total of 45 compounds were synthesized. Library members were tested for both binding to prion protein (PrPC) using the surface plasmon resonance technique and for inhibition of PrPSc formation in persistently infected SMB cells. Of the compounds prepared, 15 were found to bind to human PrPC and six showed inhibition of PrPSc formation, displaying EC50s between 1.5 and 20 μM.
THIAZOLE AND OXAZOLE DERIVATIVES FOR USE IN THE TREATMENT OF PRION DISEASES, CANCER AND CONDITIONS OF THE CENTRAL NERVOUS SYSTEM AS WELL AS IN THE REGULATION OF STEM CELLS
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Page/Page column 45, (2008/12/07)
Compounds of the formula (I) are provided: Fomula (I) wherein X, Y, R1, R2 and R3 are as defined in the specification. The compounds may be useful in the treatment of various diseases and conditions, in particular prion diseases.
