Synthesis and molecular modeling study of new trimeric quinoline derivatives

Di- and trimeric quinoline derivatives have been recently described as potential modulators of Bcl-2 family protein interactions. However, only a few trimeric compounds have been described so far and an enlargement of the number of analogs of this class is needed to expand the structure–activity relationship study. Therefore, the synthesis of six new trimeric quinoline derivatives is reported. Moreover molecular modeling experiments were performed to study the conformational arrangement of compound 36 in Bak binding site of Bcl-xL, showing that these compounds could be potential ligands for Bcl-xL.

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► We synthesized six new trimeric quinoline derivatives by Suzuki cross coupling.
► Synthetic intermediates are useful building blocks for biologically active compounds.
► Molecular modeling experiments showed that reported compounds could be Bcl-xL ligands.