Identification of terfenadine as an inhibitor of human CD81-receptor HCV-E2 interaction: Synthesis and structure optimization
Terfenadine (4-[4-(hydroxydiphenylmethyl)-1-piperidyl]-1-(4-tert- butylphenyl)-butan-1-ol) was identified in a biological screening to be a moderate inhibitor (27 % inhibition) of the CD81-LEL-HCV-E2 interaction. To increase the observed biological activity, 63 terfenadine derivates were synthesized via microwave assisted nucleophilic substitution. The prepared compounds were tested for their inhibitory potency by means of a fluorescence labeled antibody assay using HUH7.5 cells. Distinct structure-activity relationships could be derived. Optimization was successful, leading to 3g, identfied as the most potent compound (69 % inhibition). Experiments with viral particles revealed that there might be additional HCV infection reducing mechanisms.
Holzer, Marcel,Ziegler, Sigrid,Albrecht, Beatrice,Kronenberger, Bernd,Kaul, Artur,Bartenschlager, Ralf,Kattner, Lars,Klein, Christian D.,Hartmann, Rolf W.
p. 1081 - 1110
(2008/09/21)
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