μ-opioid/D2 dopamine receptor pharmacophore containing ligands: Synthesis and pharmacological evaluation
Herein, the synthesis and pharmacological evaluation of 13 novel compounds, designed as potential heterobivalent ligands for μ-opioid receptor (MOR) and dopamine D2 receptors (D2DAR), are reported. The compounds consisted of anilido piperidine and N-aryl piperazine moieties, joined by a variable-len...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Serbian Chemical Society
2020-01-01
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| Series: | Journal of the Serbian Chemical Society |
| Subjects: | |
| Online Access: | http://www.doiserbia.nb.rs/img/doi/0352-5139/2020/0352-51391900118J.pdf |
| Summary: | Herein, the synthesis and pharmacological evaluation of 13 novel compounds, designed as potential heterobivalent ligands for μ-opioid receptor (MOR) and dopamine D2 receptors (D2DAR), are reported. The compounds consisted 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, the compounds of the general structure prepared in this research are unlikely to be useful as opioid–dopamine receptor heterobivalent ligands. [Project of
the Serbian Ministry of Education, Science and Technological Development,
Grant no. 172032] |
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| ISSN: | 0352-5139 1820-7421 |