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Molecules 2008, 13(5), 1081-1110; doi:10.3390/molecules13051081
Article

Identification of Terfenadine as an Inhibitor of Human CD81-Receptor HCV-E2 Interaction: Synthesis and Structure Optimization

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Received: 26 March 2008 / Revised: 2 May 2008 / Accepted: 7 May 2008 / Published: 7 May 2008
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Abstract

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 biologicalactivity, 63 terfenadine derivates were synthesized via microwave assisted nucleophilicsubstitution. The prepared compounds were tested for their inhibitory potency by means ofa fluorescence labeled antibody assay using HUH7.5 cells. Distinct structure-activityrelationships could be derived. Optimization was successful, leading to 3g, identfied as themost potent compound (69 % inhibition). Experiments with viral particles revealed thatthere might be additional HCV infection reducing mechanisms.
Keywords: Hepatitis C Virus; CD81-receptor; large extracellular loop; terfenadine derivatives; microwave assisted syntheses. Hepatitis C Virus; CD81-receptor; large extracellular loop; terfenadine derivatives; microwave assisted syntheses.
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Holzer, M.; Ziegler, S.; Albrecht, B.; Kronenberger, B.; Kaul, A.; Bartenschlager, R.; Kattner, L.; Klein, C.D.; Hartmann, R.W. Identification of Terfenadine as an Inhibitor of Human CD81-Receptor HCV-E2 Interaction: Synthesis and Structure Optimization. Molecules 2008, 13, 1081-1110.

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