mi-Opioid/D2 dopamine receptor pharmacophore containing ligands: Synthesis and pharmacological evaluation

Ivana Jevtić, Jelena Penjišević, Katarina Savić-Vujović, Dragana Srebro, Sonja Vučković, Milovan Ivanović, Slađana Kostić-Rajačić

Abstract


Here, we report the synthesis and pharmacological evaluation of 13 novel compounds, designed as potential heterobivalent ligands for m-opioid receptor (MOR) and dopamine D2 receptors (D2DAR). The compounds consist of anilido piperidine and N-aryl piperazine moieties, joined by a variable-length methylene linker. The two moieties represent MOR and D2DAR pharmacophores respectively. The synthesis encompassed four steps, securing the final products in 28-42 % overall yields. The approach has a considerable synthetic potential, providing access to various related structures. Pharmacological tests involved in vitro competitive assay for D2DAR using [3H] spiperon, as a standard radio­ligand, and in vivo antinociceptive tests for MOR. The measured dopamine affinities were modest to low, while antinociceptive activity was completely absent. Therefore, compounds of the general structure prepared in this research are unlikely to be useful as opioid-dopamine receptor heterobivalent ligands.


Keywords


piperidine; piperazine; heterobivalent; opioids; analgesics; dopaminergic

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DOI: https://doi.org/10.2298/10.2298/JSC190912118J

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