TY  - JOUR
AU  - Jevtić, Ivana
AU  - Savić Vujović, Katarina
AU  - Srebro, Dragana
AU  - Vučković, Sonja
AU  - Ivanović, Milovan D.
AU  - Kostić Rajačić, Slađana
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3591
AB  - Background 4-Anilidopiperidine class of synthetic opioid analgesics, with it’s representative fentanyl, are by far the most potent and clinically significant for the treatment of the severe chronic and surgical pain. However, side effects of μ-opioids are often quite serious. In order to improve the pharmacological profile of this class of opioid analgesics, a novel fentanyl analogs were designed, synthesized and evaluated in vivo for their antinociceptive activity.
Methods The title compounds were prepared using known synthetic transformations, including N-bromoacetamide mediated Hofmann rearrangement, highly selective carbamate cleavage with trimethylsilyl iodide and dehydration of carboxamide group to nitrile in the presence of SOCl2. The antinociceptive activity of the synthesized compounds was determined by tail-immersion and formalin test.
Results The scalable synthetic route towards novel fentanyl analogs bearing nitrogen groups in position C3 of piperidine ring is designed. In addition, Hofmann rearrangement was substantially improved for the more efficient synthesis of previously published 3-substituted fentanyl analogs. The series of ten fentanyl analogs was tested in vivo for their antinociceptive activity. The most potent compound of the series was found to be cis-4, based on the determined ED50 values in tail-immersion test.
Conclusion Of ten compounds tested for their antinociceptive activity, compound cis-4 is characterized by high potency, rapid beginning and short duration of action and due to this might be incorporated in different pharmaceutical forms.
PB  - Springer Nature
T2  - Pharmacological Reports
T1  - Synthesis and pharmacological evaluation of novel cis and trans 3‑substituted anilidopiperidines
VL  - 72
IS  - 4
SP  - 1069
EP  - 1075
DO  - 10.1007/s43440-020-00121-2
ER  - 

@article{
author = "Jevtić, Ivana and Savić Vujović, Katarina and Srebro, Dragana and Vučković, Sonja and Ivanović, Milovan D. and Kostić Rajačić, Slađana",
year = "2020",
abstract = "Background 4-Anilidopiperidine class of synthetic opioid analgesics, with it’s representative fentanyl, are by far the most potent and clinically significant for the treatment of the severe chronic and surgical pain. However, side effects of μ-opioids are often quite serious. In order to improve the pharmacological profile of this class of opioid analgesics, a novel fentanyl analogs were designed, synthesized and evaluated in vivo for their antinociceptive activity.
Methods The title compounds were prepared using known synthetic transformations, including N-bromoacetamide mediated Hofmann rearrangement, highly selective carbamate cleavage with trimethylsilyl iodide and dehydration of carboxamide group to nitrile in the presence of SOCl2. The antinociceptive activity of the synthesized compounds was determined by tail-immersion and formalin test.
Results The scalable synthetic route towards novel fentanyl analogs bearing nitrogen groups in position C3 of piperidine ring is designed. In addition, Hofmann rearrangement was substantially improved for the more efficient synthesis of previously published 3-substituted fentanyl analogs. The series of ten fentanyl analogs was tested in vivo for their antinociceptive activity. The most potent compound of the series was found to be cis-4, based on the determined ED50 values in tail-immersion test.
Conclusion Of ten compounds tested for their antinociceptive activity, compound cis-4 is characterized by high potency, rapid beginning and short duration of action and due to this might be incorporated in different pharmaceutical forms.",
publisher = "Springer Nature",
journal = "Pharmacological Reports",
title = "Synthesis and pharmacological evaluation of novel cis and trans 3‑substituted anilidopiperidines",
volume = "72",
number = "4",
pages = "1069-1075",
doi = "10.1007/s43440-020-00121-2"
}

Jevtić, I., Savić Vujović, K., Srebro, D., Vučković, S., Ivanović, M. D.,& Kostić Rajačić, S.. (2020). Synthesis and pharmacological evaluation of novel cis and trans 3‑substituted anilidopiperidines. in Pharmacological Reports
Springer Nature., 72(4), 1069-1075.
https://doi.org/10.1007/s43440-020-00121-2

Jevtić I, Savić Vujović K, Srebro D, Vučković S, Ivanović MD, Kostić Rajačić S. Synthesis and pharmacological evaluation of novel cis and trans 3‑substituted anilidopiperidines. in Pharmacological Reports. 2020;72(4):1069-1075.
doi:10.1007/s43440-020-00121-2 .

Jevtić, Ivana, Savić Vujović, Katarina, Srebro, Dragana, Vučković, Sonja, Ivanović, Milovan D., Kostić Rajačić, Slađana, "Synthesis and pharmacological evaluation of novel cis and trans 3‑substituted anilidopiperidines" in Pharmacological Reports, 72, no. 4 (2020):1069-1075,
https://doi.org/10.1007/s43440-020-00121-2 . .

TY  - JOUR
AU  - Jevtić, Ivana
AU  - Savić Vujović, Katarina
AU  - Srebro, Dragana
AU  - Vučković, Sonja
AU  - Ivanović, Milovan D.
AU  - Kostić Rajačić, Slađana
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3591
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3592
AB  - Background 4-Anilidopiperidine class of synthetic opioid analgesics, with it’s representative fentanyl, are by far the most potent and clinically significant for the treatment of the severe chronic and surgical pain. However, side effects of μ-opioids are often quite serious. In order to improve the pharmacological profile of this class of opioid analgesics, a novel fentanyl analogs were designed, synthesized and evaluated in vivo for their antinociceptive activity.Methods The title compounds were prepared using known synthetic transformations, including N-bromoacetamide mediated Hofmann rearrangement, highly selective carbamate cleavage with trimethylsilyl iodide and dehydration of carboxamide group to nitrile in the presence of SOCl2. The antinociceptive activity of the synthesized compounds was determined by tail-immersion and formalin test.Results The scalable synthetic route towards novel fentanyl analogs bearing nitrogen groups in position C3 of piperidine ring is designed. In addition, Hofmann rearrangement was substantially improved for the more efficient synthesis of previously published 3-substituted fentanyl analogs. The series of ten fentanyl analogs was tested in vivo for their antinociceptive activity. The most potent compound of the series was found to be cis-4, based on the determined ED50 values in tail-immersion test.Conclusion Of ten compounds tested for their antinociceptive activity, compound cis-4 is characterized by high potency, rapid beginning and short duration of action and due to this might be incorporated in different pharmaceutical forms.
PB  - Springer Nature
T2  - Pharmacological Reports
T1  - Synthesis and pharmacological evaluation of novel cis and trans 3‑substituted anilidopiperidines
DO  - 10.1007/s43440-020-00121-2
ER  - 

@article{
author = "Jevtić, Ivana and Savić Vujović, Katarina and Srebro, Dragana and Vučković, Sonja and Ivanović, Milovan D. and Kostić Rajačić, Slađana",
year = "2020",
abstract = "Background 4-Anilidopiperidine class of synthetic opioid analgesics, with it’s representative fentanyl, are by far the most potent and clinically significant for the treatment of the severe chronic and surgical pain. However, side effects of μ-opioids are often quite serious. In order to improve the pharmacological profile of this class of opioid analgesics, a novel fentanyl analogs were designed, synthesized and evaluated in vivo for their antinociceptive activity.Methods The title compounds were prepared using known synthetic transformations, including N-bromoacetamide mediated Hofmann rearrangement, highly selective carbamate cleavage with trimethylsilyl iodide and dehydration of carboxamide group to nitrile in the presence of SOCl2. The antinociceptive activity of the synthesized compounds was determined by tail-immersion and formalin test.Results The scalable synthetic route towards novel fentanyl analogs bearing nitrogen groups in position C3 of piperidine ring is designed. In addition, Hofmann rearrangement was substantially improved for the more efficient synthesis of previously published 3-substituted fentanyl analogs. The series of ten fentanyl analogs was tested in vivo for their antinociceptive activity. The most potent compound of the series was found to be cis-4, based on the determined ED50 values in tail-immersion test.Conclusion Of ten compounds tested for their antinociceptive activity, compound cis-4 is characterized by high potency, rapid beginning and short duration of action and due to this might be incorporated in different pharmaceutical forms.",
publisher = "Springer Nature",
journal = "Pharmacological Reports",
title = "Synthesis and pharmacological evaluation of novel cis and trans 3‑substituted anilidopiperidines",
doi = "10.1007/s43440-020-00121-2"
}

Jevtić, I., Savić Vujović, K., Srebro, D., Vučković, S., Ivanović, M. D.,& Kostić Rajačić, S.. (2020). Synthesis and pharmacological evaluation of novel cis and trans 3‑substituted anilidopiperidines. in Pharmacological Reports
Springer Nature..
https://doi.org/10.1007/s43440-020-00121-2

Jevtić I, Savić Vujović K, Srebro D, Vučković S, Ivanović MD, Kostić Rajačić S. Synthesis and pharmacological evaluation of novel cis and trans 3‑substituted anilidopiperidines. in Pharmacological Reports. 2020;.
doi:10.1007/s43440-020-00121-2 .

Jevtić, Ivana, Savić Vujović, Katarina, Srebro, Dragana, Vučković, Sonja, Ivanović, Milovan D., Kostić Rajačić, Slađana, "Synthesis and pharmacological evaluation of novel cis and trans 3‑substituted anilidopiperidines" in Pharmacological Reports (2020),
https://doi.org/10.1007/s43440-020-00121-2 . .

TY  - JOUR
AU  - Jevtić, Ivana
AU  - Penjišević, Jelena
AU  - Savić-Vujović, Katarina
AU  - Srebro, Dragana
AU  - Vučković, Sonja
AU  - Ivanović, Milovan
AU  - Kostić Rajačić, Slađana
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3999
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.
AB  - У овом раду је приказана синтеза и фармаколошко испитивање 13 нових једињења, дизајнираних са циљем да буду потенцијални бивалентни лиганди за μ-опиоидни рецептор (MOR) и допамински D2 рецептор (D2DAR). Једињења се састоје од анилидо-пиперидинских (МОR фармакофора) и N-арилпиперазинских остатака (D2DAR фармакофора), повезаних метиленским ланцем променљиве дужине. Синтеза је обухватала четири корака, обезбеђујући крајње производе у укупним приносима од 28 до 42 %. Афинитет везивања за D2DAR одређен је in vitro тестом компетиције користећи [3H] спиперон као стандардни радиолиганд док је антиноцицептивна (опиоидна) активност испитана in vivo
антиноцицептивним тестом. Активности новосинтетисаних једињења ка D2DAR биле су умерене до ниске, док је антиноцицептивна активност у потпуности изостала.
PB  - Belgrade : Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - μ-opioid/D2 dopamine receptor pharmacophore containing ligands: Synthesis and pharmacological evaluation
T1  - Ligandi koji sadrže farmakofore za μ-opioidne i D2 dopaminske receptore: Sinteza i farmakološko ispitivanje
VL  - 85
IS  - 6
SP  - 711
EP  - 720
DO  - 10.2298/JSC190912118J
ER  - 

@article{
author = "Jevtić, Ivana and Penjišević, Jelena and Savić-Vujović, Katarina and Srebro, Dragana and Vučković, Sonja 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., У овом раду је приказана синтеза и фармаколошко испитивање 13 нових једињења, дизајнираних са циљем да буду потенцијални бивалентни лиганди за μ-опиоидни рецептор (MOR) и допамински D2 рецептор (D2DAR). Једињења се састоје од анилидо-пиперидинских (МОR фармакофора) и N-арилпиперазинских остатака (D2DAR фармакофора), повезаних метиленским ланцем променљиве дужине. Синтеза је обухватала четири корака, обезбеђујући крајње производе у укупним приносима од 28 до 42 %. Афинитет везивања за D2DAR одређен је in vitro тестом компетиције користећи [3H] спиперон као стандардни радиолиганд док је антиноцицептивна (опиоидна) активност испитана in vivo
антиноцицептивним тестом. Активности новосинтетисаних једињења ка D2DAR биле су умерене до ниске, док је антиноцицептивна активност у потпуности изостала.",
publisher = "Belgrade : Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "μ-opioid/D2 dopamine receptor pharmacophore containing ligands: Synthesis and pharmacological evaluation, Ligandi koji sadrže farmakofore za μ-opioidne i D2 dopaminske receptore: Sinteza i farmakološko ispitivanje",
volume = "85",
number = "6",
pages = "711-720",
doi = "10.2298/JSC190912118J"
}

Jevtić, I., Penjišević, J., Savić-Vujović, K., Srebro, D., Vučković, S., 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
Belgrade : Serbian Chemical Society., 85(6), 711-720.
https://doi.org/10.2298/JSC190912118J

Jevtić I, Penjišević J, Savić-Vujović K, Srebro D, Vučković S, 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, Penjišević, Jelena, Savić-Vujović, Katarina, Srebro, Dragana, Vučković, Sonja, 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 . .