Synthetic route towards potential bivalent ligands possessing opioid and D2/D3 pharmacophores

Ivana Jevtić, Jelena Penjišević, Milovan Ivanović, Slađana Kostić-Rajačić

Abstract


The scalable, cost-efficient and simple synthetic pathway towards potential bivalent opioid/dopamine receptor ligands was developed and optimized. Three novel compounds, that contain both opioid and dopamine pharmacophores linked by the four methylene group chain, were synthesized in 33 %, 35 % and 39 % overall yield after four steps synthetic route starting from three commercially available N-aryl piperazines. The anilino piperidine precursor was easily prepared in three steps, as previously published, starting from 4-piperidone. Synthesis presented in this paper can be of interest for heterocyclic and general organic chemistry. The newly designed compounds, possessing two pharmacophores, opioid and D2/D3, are potentially useful pharmacological probes. Of particular interest would be the simultaneous binding to both opioid and D2/D3 receptors, and the resulting pharmacological responses may be useful for further understanding оf tolerance and dependence phenomena in opioid clinical use and/or abuse.


Keywords


piperidine; piperazine; heterocycles; N-alkylation; analgesics; dopaminergic

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DOI: https://doi.org/10.2298/JSC181002105J

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