μ-opioid/D2 dopamine receptor pharmacophore containing ligands: Synthesis and pharmacological evaluation
Authors
Jevtić, Ivana I.Penjišević, Jelena
Savić-Vujović, Katarina
Srebro, Dragana
Vučković, Sonja M.
Ivanović, Milovan
Kostić-Rajačić, Slađana
Article (Published version)
Metadata
Show full item recordAbstract
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 li...gands.
Keywords:
piperidine / piperazine / heterobivalent / opioids / analgesics / dopaminergicSource:
Journal of the Serbian Chemical Society, 2020, 85, 6, 711-720Publisher:
- Serbian Chemical Society
Funding / projects:
- Structure-activity relationship of newly synthesized biological active compound (RS-MESTD-Basic Research (BR or ON)-172032)
DOI: 10.2298/JSC190912118J
ISSN: 0352-5139
WoS: 000548146900002
Scopus: 2-s2.0-85090445912
Collections
Institution/Community
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Jevtić, Ivana I. AU - Penjišević, Jelena AU - Savić-Vujović, Katarina AU - Srebro, Dragana AU - Vučković, Sonja M. AU - Ivanović, Milovan AU - Kostić-Rajačić, Slađana PY - 2020 UR - https://cherry.chem.bg.ac.rs/handle/123456789/4243 AB - 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. PB - Serbian Chemical Society T2 - Journal of the Serbian Chemical Society T1 - μ-opioid/D2 dopamine receptor pharmacophore containing ligands: Synthesis and pharmacological evaluation VL - 85 IS - 6 SP - 711 EP - 720 DO - 10.2298/JSC190912118J ER -
@article{ author = "Jevtić, Ivana I. and Penjišević, Jelena and Savić-Vujović, Katarina and Srebro, Dragana and Vučković, Sonja M. and Ivanović, Milovan and Kostić-Rajačić, Slađana", year = "2020", abstract = "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.", publisher = "Serbian Chemical Society", journal = "Journal of the Serbian Chemical Society", title = "μ-opioid/D2 dopamine receptor pharmacophore containing ligands: Synthesis and pharmacological evaluation", volume = "85", number = "6", pages = "711-720", doi = "10.2298/JSC190912118J" }
Jevtić, I. I., Penjišević, J., Savić-Vujović, K., Srebro, D., Vučković, S. M., Ivanović, M.,& Kostić-Rajačić, S.. (2020). μ-opioid/D2 dopamine receptor pharmacophore containing ligands: Synthesis and pharmacological evaluation. in Journal of the Serbian Chemical Society Serbian Chemical Society., 85(6), 711-720. https://doi.org/10.2298/JSC190912118J
Jevtić II, Penjišević J, Savić-Vujović K, Srebro D, Vučković SM, Ivanović M, Kostić-Rajačić S. μ-opioid/D2 dopamine receptor pharmacophore containing ligands: Synthesis and pharmacological evaluation. in Journal of the Serbian Chemical Society. 2020;85(6):711-720. doi:10.2298/JSC190912118J .
Jevtić, Ivana I., Penjišević, Jelena, Savić-Vujović, Katarina, Srebro, Dragana, Vučković, Sonja M., Ivanović, Milovan, Kostić-Rajačić, Slađana, "μ-opioid/D2 dopamine receptor pharmacophore containing ligands: Synthesis and pharmacological evaluation" in Journal of the Serbian Chemical Society, 85, no. 6 (2020):711-720, https://doi.org/10.2298/JSC190912118J . .