Design and evaluation of naphthol- and carbazole- containing fluorescent sigma ligands as potential probes for receptor binding studies

Some 3,3-dimethyl-1-(3-naphthylpropyl)piperidine and 1-cyclohexyl-4-(3-naphthylpropyl)piperazine derivatives, structurally containing naphthol as a fluorescent moiety, were prepared for being potentially used as fluorescent  ligands. Structurally related analogs were also prepared, where the naphthalene nucleus was replaced by the fluorescent carbazole moiety and chain length was varied. For all compounds the in vitro affinities towards  receptors and 8–7 sterol isomerase site were measured and the fluorescent properties were determined. Compound 19 gave the best results both for  receptor affinities (1, Ki = 6.78 nM and 2, Ki = 26.4 nM) and fluorescence features, thus, it was chosen for in vitro saturation binding analysis at  receptors. The good results obtained in such assay suggested that the fluorescent compound 19 could be used instead of a radioligand in “green” binding assays.