In a first aspect, the present invention relates to new compounds based on diphenylpiperazine and diphenylpiperidine structures. In particular, the present invention provides new flunarizine derivatives having improved hepaci
virus infection inhibitory activity. In a further aspect, the present invention relates to a pharmaceutical composition containing said compound as well as the use of said pharmaceutical composition and the compounds according to the present invention in preventing or treating hepaci
virus infection, in particular, HCV
virus infection, like HCV of
genotype 2. Moreover, a method for determining effectiveness of prophylactic or
therapeutic treatment of hepaci virus, like HCV infection as well as a method for determining the therapy
regimen of an individual afflicted with hepaci vims infection including HCV infection is provided. Said method is based on determining the sequence or interfacial hydrophobicity of the hepaci virus E1
protein. This may include determining the presence of mutations at predetermined positions of the E1 sequence. Based on determining the interfacial hydrophobicity of the E1
protein, the sensitivity to a diphenylpiperazine or diphenylpiperidine based hepaci virus inhibitor as well as a
phenothiazine and cycloheptenepiperidine based hepaci virus inhibitor can be determined. When the central hydrophobicity region is disrupted or the hydrophobicity is below zero applying the Wimley-White hydropathy plot, or the mutations at positions 290, 299, 301 and 310 of SEQ ID No. 1 are present, it is submitted that the sensitivity against said compounds is reduced. Hence, it is possible to determine the therapy
regimen of an individual afflicted with hepaci virus infection or being a risk of being afflicted with hepaci vims infection, in particular HCV infection like HCV
genotype 2 infection.