TY  - JOUR
AU  - Penjišević, Jelena
AU  - Šukalović, Vladimir
AU  - Dukić-Stefanović, Sladjana
AU  - Deuther-Conrad, Winnie
AU  - Andrić, Deana
AU  - Kostić-Rajačić, Slađana
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5830
AB  - Serotonin receptors modulate numerous behavioral and neuropsychological processes.
Therefore, they are the target for the action of many drugs, such as antipsychotics, antidepressants,
antiemetics, migraine remedies, and many others. The 5-HT1A receptors have been involved in the
pathogenesis and treatment of anxiety and depression and represent a promising target for new
drugs with reduced extrapyramidal side effects. In most antidepressants, a piperazine-based structural
motif can be identified as a common moiety. Here we describe the synthesis, pharmacological,
and in silico characterization of a novel arylpiperazines series with excellent 5-HT1A affinity. The
final compounds, 4a, 8a, and 8b, were selected according to predictions of in silico pharmacokinetics,
docking analysis, and molecular dynamics in conjunction with physical properties, and metabolic
stability. The accentuated molecules could serve as a lead compound for developing 5-
HT1A drug-like molecules for depression treatment.
PB  - Elsevier
T2  - Arabian Journal of Chemistry
T1  - Synthesis of novel 5-HT1A arylpiperazine ligands: Binding data and computer-aided analysis of pharmacological potency
VL  - 16
IS  - 4
SP  - 104636
DO  - 10.1016/j.arabjc.2023.104636
ER  - 

@article{
author = "Penjišević, Jelena and Šukalović, Vladimir and Dukić-Stefanović, Sladjana and Deuther-Conrad, Winnie and Andrić, Deana and Kostić-Rajačić, Slađana",
year = "2023",
abstract = "Serotonin receptors modulate numerous behavioral and neuropsychological processes.
Therefore, they are the target for the action of many drugs, such as antipsychotics, antidepressants,
antiemetics, migraine remedies, and many others. The 5-HT1A receptors have been involved in the
pathogenesis and treatment of anxiety and depression and represent a promising target for new
drugs with reduced extrapyramidal side effects. In most antidepressants, a piperazine-based structural
motif can be identified as a common moiety. Here we describe the synthesis, pharmacological,
and in silico characterization of a novel arylpiperazines series with excellent 5-HT1A affinity. The
final compounds, 4a, 8a, and 8b, were selected according to predictions of in silico pharmacokinetics,
docking analysis, and molecular dynamics in conjunction with physical properties, and metabolic
stability. The accentuated molecules could serve as a lead compound for developing 5-
HT1A drug-like molecules for depression treatment.",
publisher = "Elsevier",
journal = "Arabian Journal of Chemistry",
title = "Synthesis of novel 5-HT1A arylpiperazine ligands: Binding data and computer-aided analysis of pharmacological potency",
volume = "16",
number = "4",
pages = "104636",
doi = "10.1016/j.arabjc.2023.104636"
}

Penjišević, J., Šukalović, V., Dukić-Stefanović, S., Deuther-Conrad, W., Andrić, D.,& Kostić-Rajačić, S.. (2023). Synthesis of novel 5-HT1A arylpiperazine ligands: Binding data and computer-aided analysis of pharmacological potency. in Arabian Journal of Chemistry
Elsevier., 16(4), 104636.
https://doi.org/10.1016/j.arabjc.2023.104636

Penjišević J, Šukalović V, Dukić-Stefanović S, Deuther-Conrad W, Andrić D, Kostić-Rajačić S. Synthesis of novel 5-HT1A arylpiperazine ligands: Binding data and computer-aided analysis of pharmacological potency. in Arabian Journal of Chemistry. 2023;16(4):104636.
doi:10.1016/j.arabjc.2023.104636 .

Penjišević, Jelena, Šukalović, Vladimir, Dukić-Stefanović, Sladjana, Deuther-Conrad, Winnie, Andrić, Deana, Kostić-Rajačić, Slađana, "Synthesis of novel 5-HT1A arylpiperazine ligands: Binding data and computer-aided analysis of pharmacological potency" in Arabian Journal of Chemistry, 16, no. 4 (2023):104636,
https://doi.org/10.1016/j.arabjc.2023.104636 . .

TY  - JOUR
AU  - Dukić-Stefanović, Sladjana
AU  - Lai, Thu Hang
AU  - Toussaint, Magali
AU  - Clauß, Oliver
AU  - Jevtić, Ivana
AU  - Penjišević, Jelena
AU  - Andrić, Deana
AU  - Ludwig, Friedrich-Alexander
AU  - Gündel, Daniel
AU  - Deuther-Conrad, Winnie
AU  - Kostić Rajačić, Slađana
AU  - Brust, Peter
AU  - Teodoro, Rodrigo
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4756
AB  - Monoamine oxidases (MAOs) play a key role in the metabolism of major monoamine neurotransmitters. In particular, the upregulation of MAO-B in Parkinson's disease, Alzheimer's disease and cancer augmented the development of selective MAO-B inhibitors for diagnostic and therapeutic purposes, such as the anti-parkinsonian MAO-B irreversible binder L-deprenyl (Selegiline®). Herein we report on the synthesis of novel fluorinated indanone derivatives for PET imaging of MAO-B in the brain. Out of our series, the derivatives 6, 8, 9 and 13 are amongst the most affine and selective ligands for MAO-B reported so far. For the derivative 6-((3-fluorobenzyl)oxy)-2,3-dihydro-1H-inden-1-one (6) exhibiting an outstanding affinity (Ki MAO-B = 6 nM), an automated copper-mediated radiofluorination starting from the pinacol boronic ester 17 is described. An in vitro screening in different species revealed a MAO-B region-specific accumulation of [18F]6 in rats and piglets in comparison to L-[3H]deprenyl. The pre-clinical in vivo assessment of [18F]6 in mice demonstrated the potential of indanones to readily cross the blood–brain barrier. Nonetheless, parallel in vivo metabolism studies indicated the presence of blood–brain barrier metabolites, thus arguing for further structural modifications. With the matching analytical profiles of the radiometabolite analysis from the in vitro liver microsome studies and the in vivo evaluation, the structure's elucidation of the blood–brain barrier penetrant radiometabolites is possible and will serve as basis for the development of new indanone derivatives suitable for the PET imaging of MAO-B.
PB  - Elsevier
T2  - Bioorganic and Medicinal Chemistry Letters
T1  - In vitro and in vivo evaluation of fluorinated indanone derivatives as potential positron emission tomography agents for the imaging of monoamine oxidase B in the brain
VL  - 48
SP  - 128254
DO  - 10.1016/j.bmcl.2021.128254
ER  - 

@article{
author = "Dukić-Stefanović, Sladjana and Lai, Thu Hang and Toussaint, Magali and Clauß, Oliver and Jevtić, Ivana and Penjišević, Jelena and Andrić, Deana and Ludwig, Friedrich-Alexander and Gündel, Daniel and Deuther-Conrad, Winnie and Kostić Rajačić, Slađana and Brust, Peter and Teodoro, Rodrigo",
year = "2021",
abstract = "Monoamine oxidases (MAOs) play a key role in the metabolism of major monoamine neurotransmitters. In particular, the upregulation of MAO-B in Parkinson's disease, Alzheimer's disease and cancer augmented the development of selective MAO-B inhibitors for diagnostic and therapeutic purposes, such as the anti-parkinsonian MAO-B irreversible binder L-deprenyl (Selegiline®). Herein we report on the synthesis of novel fluorinated indanone derivatives for PET imaging of MAO-B in the brain. Out of our series, the derivatives 6, 8, 9 and 13 are amongst the most affine and selective ligands for MAO-B reported so far. For the derivative 6-((3-fluorobenzyl)oxy)-2,3-dihydro-1H-inden-1-one (6) exhibiting an outstanding affinity (Ki MAO-B = 6 nM), an automated copper-mediated radiofluorination starting from the pinacol boronic ester 17 is described. An in vitro screening in different species revealed a MAO-B region-specific accumulation of [18F]6 in rats and piglets in comparison to L-[3H]deprenyl. The pre-clinical in vivo assessment of [18F]6 in mice demonstrated the potential of indanones to readily cross the blood–brain barrier. Nonetheless, parallel in vivo metabolism studies indicated the presence of blood–brain barrier metabolites, thus arguing for further structural modifications. With the matching analytical profiles of the radiometabolite analysis from the in vitro liver microsome studies and the in vivo evaluation, the structure's elucidation of the blood–brain barrier penetrant radiometabolites is possible and will serve as basis for the development of new indanone derivatives suitable for the PET imaging of MAO-B.",
publisher = "Elsevier",
journal = "Bioorganic and Medicinal Chemistry Letters",
title = "In vitro and in vivo evaluation of fluorinated indanone derivatives as potential positron emission tomography agents for the imaging of monoamine oxidase B in the brain",
volume = "48",
pages = "128254",
doi = "10.1016/j.bmcl.2021.128254"
}

Dukić-Stefanović, S., Lai, T. H., Toussaint, M., Clauß, O., Jevtić, I., Penjišević, J., Andrić, D., Ludwig, F., Gündel, D., Deuther-Conrad, W., Kostić Rajačić, S., Brust, P.,& Teodoro, R.. (2021). In vitro and in vivo evaluation of fluorinated indanone derivatives as potential positron emission tomography agents for the imaging of monoamine oxidase B in the brain. in Bioorganic and Medicinal Chemistry Letters
Elsevier., 48, 128254.
https://doi.org/10.1016/j.bmcl.2021.128254

Dukić-Stefanović S, Lai TH, Toussaint M, Clauß O, Jevtić I, Penjišević J, Andrić D, Ludwig F, Gündel D, Deuther-Conrad W, Kostić Rajačić S, Brust P, Teodoro R. In vitro and in vivo evaluation of fluorinated indanone derivatives as potential positron emission tomography agents for the imaging of monoamine oxidase B in the brain. in Bioorganic and Medicinal Chemistry Letters. 2021;48:128254.
doi:10.1016/j.bmcl.2021.128254 .

Dukić-Stefanović, Sladjana, Lai, Thu Hang, Toussaint, Magali, Clauß, Oliver, Jevtić, Ivana, Penjišević, Jelena, Andrić, Deana, Ludwig, Friedrich-Alexander, Gündel, Daniel, Deuther-Conrad, Winnie, Kostić Rajačić, Slađana, Brust, Peter, Teodoro, Rodrigo, "In vitro and in vivo evaluation of fluorinated indanone derivatives as potential positron emission tomography agents for the imaging of monoamine oxidase B in the brain" in Bioorganic and Medicinal Chemistry Letters, 48 (2021):128254,
https://doi.org/10.1016/j.bmcl.2021.128254 . .

TY  - JOUR
AU  - Jevtić, Ivana
AU  - Lai, Thu Hang
AU  - Penjišević, Jelena
AU  - Dukić-Stefanović, Sladjana
AU  - Andrić, Deana
AU  - Brust, Peter
AU  - Kostić Rajačić, Slađana
AU  - Teodoro, Rodrigo
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4040
AB  - Herein, we report on the synthesis and pharmacological evaluation of ten novel fluorinated cinnamylpiperazines as potential monoamine oxidase B (MAO-B) ligands. The designed derivatives consist of either cinnamyl or 2-fluorocinnamyl moieties connected to 2-fluoropyridylpiperazines. The three-step synthesis starting from commercially available piperazine afforded the final products in overall yields between 9% and 29%. An in vitro competitive binding assay using l-[3H]Deprenyl as radioligand was developed and the MAO-B binding affinities of the synthesized derivatives were assessed. Docking studies revealed that the compounds 8–17 were stabilized in both MAO-B entrance and substrate cavities, thus resembling the binding pose of l-Deprenyl. Although our results revealed that the novel fluorinated cinnamylpiperazines 8–17 do not possess sufficient MAO-B binding affinity to be eligible as positron emission tomography (PET) agents, the herein developed binding assay and the insights gained within our docking studies will certainly pave the way for further development of MAO-B ligands.
PB  - MDPI
T2  - Molecules
T1  - Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding
VL  - 25
IS  - 21
SP  - 4941
DO  - 10.3390/molecules25214941
ER  - 

@article{
author = "Jevtić, Ivana and Lai, Thu Hang and Penjišević, Jelena and Dukić-Stefanović, Sladjana and Andrić, Deana and Brust, Peter and Kostić Rajačić, Slađana and Teodoro, Rodrigo",
year = "2020",
abstract = "Herein, we report on the synthesis and pharmacological evaluation of ten novel fluorinated cinnamylpiperazines as potential monoamine oxidase B (MAO-B) ligands. The designed derivatives consist of either cinnamyl or 2-fluorocinnamyl moieties connected to 2-fluoropyridylpiperazines. The three-step synthesis starting from commercially available piperazine afforded the final products in overall yields between 9% and 29%. An in vitro competitive binding assay using l-[3H]Deprenyl as radioligand was developed and the MAO-B binding affinities of the synthesized derivatives were assessed. Docking studies revealed that the compounds 8–17 were stabilized in both MAO-B entrance and substrate cavities, thus resembling the binding pose of l-Deprenyl. Although our results revealed that the novel fluorinated cinnamylpiperazines 8–17 do not possess sufficient MAO-B binding affinity to be eligible as positron emission tomography (PET) agents, the herein developed binding assay and the insights gained within our docking studies will certainly pave the way for further development of MAO-B ligands.",
publisher = "MDPI",
journal = "Molecules",
title = "Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding",
volume = "25",
number = "21",
pages = "4941",
doi = "10.3390/molecules25214941"
}

Jevtić, I., Lai, T. H., Penjišević, J., Dukić-Stefanović, S., Andrić, D., Brust, P., Kostić Rajačić, S.,& Teodoro, R.. (2020). Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding. in Molecules
MDPI., 25(21), 4941.
https://doi.org/10.3390/molecules25214941

Jevtić I, Lai TH, Penjišević J, Dukić-Stefanović S, Andrić D, Brust P, Kostić Rajačić S, Teodoro R. Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding. in Molecules. 2020;25(21):4941.
doi:10.3390/molecules25214941 .

Jevtić, Ivana, Lai, Thu Hang, Penjišević, Jelena, Dukić-Stefanović, Sladjana, Andrić, Deana, Brust, Peter, Kostić Rajačić, Slađana, Teodoro, Rodrigo, "Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding" in Molecules, 25, no. 21 (2020):4941,
https://doi.org/10.3390/molecules25214941 . .

TY  - JOUR
AU  - Roglić, Goran
AU  - Andrić, Deana
AU  - Kostić Rajačić, Slađana
AU  - Dukić, Slađana
AU  - Šoškić, Vukić
PY  - 2001
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2824
AB  - 1-(2-Heteroarylalkyl)-4-phenylpiperazines containing methyl group in either the alpha- or the beta-position of the side alkyl chain were synthesized as racemic mixtures. They were evaluated for in vitro binding affinity at the D-1 and D-2 dopamine and 5-HT1A serotonin receptors using synaptosomal membranes of the bovine caudate nucleus and hippocampus, respectively, as a source of the corresponding receptors. Tritiated SCH 23390 (D-1 receptor-selective), spiperone (D-2 receptor-selective), and 8-OH-DPAT (5-HT1A receptor-selective) were employed as the radioligands. None of the new compounds expressed significant affinity for the D-1 receptor. Introduction of the methyl group into the beta-position of the parent molecules increased the affinity for the D-2 receptor (10b-13b), and decreased the affinity for the 5-HT1A receptor with the exception of imidazole (11b) which was a rather efficient displacer of 8-OH-DPAT. Most potent of the newly synthesized compounds in [H-3]spiperone assay were compounds (+/-)6-[1-methyl-2-(4-phenylpiperazin-n-1-yl)-ethyl]-1, 4-dihydroquinoxaline-2,3-dione (10b), K-d = 6.0 nM and (+/-)5-[1-methyl-2-(4-phenylpiperazin-1-yl)-ethyl]-1,3-dihydrobenzoirnidazol-2-thione (13b), K-d = 5.3 nM. However, compounds containing methyl group in alpha-position (10a-13a) of the parent molecules expressed a decreased affinity for the D-2 receptor, while the affinity for the 5-HT1A receptor remained in the same range of concentrations as that of closely related achiral parent compounds (14-17) run in the same binding assays as references.
PB  - Wiley-VCH Verlag Gmbh, Weinheim
T2  - Archiv der Pharmazie
T1  - Introduction of a methyl group in alpha- or beta-position of 1-heteroarylethyl-4-phenyl-piperazines affects their dopaminergic/serotonergic properties
VL  - 334
IS  - 12
SP  - 375
EP  - 380
DO  - 10.1002/1521-4184(200112)334:12<375::AID-ARDP375>3.0.CO;2-P
ER  - 

@article{
author = "Roglić, Goran and Andrić, Deana and Kostić Rajačić, Slađana and Dukić, Slađana and Šoškić, Vukić",
year = "2001",
abstract = "1-(2-Heteroarylalkyl)-4-phenylpiperazines containing methyl group in either the alpha- or the beta-position of the side alkyl chain were synthesized as racemic mixtures. They were evaluated for in vitro binding affinity at the D-1 and D-2 dopamine and 5-HT1A serotonin receptors using synaptosomal membranes of the bovine caudate nucleus and hippocampus, respectively, as a source of the corresponding receptors. Tritiated SCH 23390 (D-1 receptor-selective), spiperone (D-2 receptor-selective), and 8-OH-DPAT (5-HT1A receptor-selective) were employed as the radioligands. None of the new compounds expressed significant affinity for the D-1 receptor. Introduction of the methyl group into the beta-position of the parent molecules increased the affinity for the D-2 receptor (10b-13b), and decreased the affinity for the 5-HT1A receptor with the exception of imidazole (11b) which was a rather efficient displacer of 8-OH-DPAT. Most potent of the newly synthesized compounds in [H-3]spiperone assay were compounds (+/-)6-[1-methyl-2-(4-phenylpiperazin-n-1-yl)-ethyl]-1, 4-dihydroquinoxaline-2,3-dione (10b), K-d = 6.0 nM and (+/-)5-[1-methyl-2-(4-phenylpiperazin-1-yl)-ethyl]-1,3-dihydrobenzoirnidazol-2-thione (13b), K-d = 5.3 nM. However, compounds containing methyl group in alpha-position (10a-13a) of the parent molecules expressed a decreased affinity for the D-2 receptor, while the affinity for the 5-HT1A receptor remained in the same range of concentrations as that of closely related achiral parent compounds (14-17) run in the same binding assays as references.",
publisher = "Wiley-VCH Verlag Gmbh, Weinheim",
journal = "Archiv der Pharmazie",
title = "Introduction of a methyl group in alpha- or beta-position of 1-heteroarylethyl-4-phenyl-piperazines affects their dopaminergic/serotonergic properties",
volume = "334",
number = "12",
pages = "375-380",
doi = "10.1002/1521-4184(200112)334:12<375::AID-ARDP375>3.0.CO;2-P"
}

Roglić, G., Andrić, D., Kostić Rajačić, S., Dukić, S.,& Šoškić, V.. (2001). Introduction of a methyl group in alpha- or beta-position of 1-heteroarylethyl-4-phenyl-piperazines affects their dopaminergic/serotonergic properties. in Archiv der Pharmazie
Wiley-VCH Verlag Gmbh, Weinheim., 334(12), 375-380.
https://doi.org/10.1002/1521-4184(200112)334:12<375::AID-ARDP375>3.0.CO;2-P

Roglić G, Andrić D, Kostić Rajačić S, Dukić S, Šoškić V. Introduction of a methyl group in alpha- or beta-position of 1-heteroarylethyl-4-phenyl-piperazines affects their dopaminergic/serotonergic properties. in Archiv der Pharmazie. 2001;334(12):375-380.
doi:10.1002/1521-4184(200112)334:12<375::AID-ARDP375>3.0.CO;2-P .

Roglić, Goran, Andrić, Deana, Kostić Rajačić, Slađana, Dukić, Slađana, Šoškić, Vukić, "Introduction of a methyl group in alpha- or beta-position of 1-heteroarylethyl-4-phenyl-piperazines affects their dopaminergic/serotonergic properties" in Archiv der Pharmazie, 334, no. 12 (2001):375-380,
https://doi.org/10.1002/1521-4184(200112)334:12<375::AID-ARDP375>3.0.CO;2-P . .

TY  - JOUR
AU  - Roglić, Goran
AU  - Dukić-Stefanović, Sladjana
AU  - Andrić, Deana
AU  - Kostić Rajačić, Slađana
AU  - Šoškić, Vukić
PY  - 2001
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2825
AB  - Eight novel N-heteroarylalkyl-N-phenylpiperazines have been synthesized, chemically characterized and evaluated for in vitro binding affinity at the dopamine and serotonin receptors. Synaptosomal membranes of fresh bovine caudate nuclei (D(1) and D(2)), the membranes of COS-7 cells (D(4.4)) and those prepared from fresh bovine hippocampi (5-HT(1A)) were used as a source of the corresponding receptor subtypes. [(3)H]SCH 23390 (D(1)-selective), [(3)H]spiperone (D(2)- and D(4.4)- selective) and [(3)H]-8-OH-DPAT (5-HT(1A)-selective) served as radioligands. None of the compounds expressed the affinity for the binding at the D(1) subtype receptor. Compounds 7-9 containing a single methylene group serving as a bridge between heteroaryl and N-phenylpiperazine part of the molecule were inactive [(3)H]spiperone and [(3)H]-8-OH-DPAT competitors. Ligands 15-19 (three methylene groups connecting heteroaryl- and N-phenylpiperazine part of the molecule) acted as moderate competitors of [(3)H]spiperone binding at the D(2) receptor subtype, with the exception of 15 (a thione) which expressed a high binding affinity at the D(2) receptor subtype. Compounds 15-19 behaved as moderate displacers of 8-OH-[(3)H]DPAT. Among all eight novel ligands only compound 15 expressed a moderate binding affinity at the D(4.4) receptor subtype.
PB  - Govi-Verlag  Pharmazeutischer Verlag Gmbh, Eschborn
T2  - Pharmazie
T1  - Investigation of mixed D(2)/5-HT(1A) activity of N-heteroarylmethyl-N-phenylpiperazines, N-heteroarylethyl-N-phenylpiperazines and N-heteroarylpropyl-N-phenylpiperazines
VL  - 56
IS  - 10
SP  - 803
EP  - 807
UR  - https://hdl.handle.net/21.15107/rcub_cherry_475
ER  - 

@article{
author = "Roglić, Goran and Dukić-Stefanović, Sladjana and Andrić, Deana and Kostić Rajačić, Slađana and Šoškić, Vukić",
year = "2001",
abstract = "Eight novel N-heteroarylalkyl-N-phenylpiperazines have been synthesized, chemically characterized and evaluated for in vitro binding affinity at the dopamine and serotonin receptors. Synaptosomal membranes of fresh bovine caudate nuclei (D(1) and D(2)), the membranes of COS-7 cells (D(4.4)) and those prepared from fresh bovine hippocampi (5-HT(1A)) were used as a source of the corresponding receptor subtypes. [(3)H]SCH 23390 (D(1)-selective), [(3)H]spiperone (D(2)- and D(4.4)- selective) and [(3)H]-8-OH-DPAT (5-HT(1A)-selective) served as radioligands. None of the compounds expressed the affinity for the binding at the D(1) subtype receptor. Compounds 7-9 containing a single methylene group serving as a bridge between heteroaryl and N-phenylpiperazine part of the molecule were inactive [(3)H]spiperone and [(3)H]-8-OH-DPAT competitors. Ligands 15-19 (three methylene groups connecting heteroaryl- and N-phenylpiperazine part of the molecule) acted as moderate competitors of [(3)H]spiperone binding at the D(2) receptor subtype, with the exception of 15 (a thione) which expressed a high binding affinity at the D(2) receptor subtype. Compounds 15-19 behaved as moderate displacers of 8-OH-[(3)H]DPAT. Among all eight novel ligands only compound 15 expressed a moderate binding affinity at the D(4.4) receptor subtype.",
publisher = "Govi-Verlag  Pharmazeutischer Verlag Gmbh, Eschborn",
journal = "Pharmazie",
title = "Investigation of mixed D(2)/5-HT(1A) activity of N-heteroarylmethyl-N-phenylpiperazines, N-heteroarylethyl-N-phenylpiperazines and N-heteroarylpropyl-N-phenylpiperazines",
volume = "56",
number = "10",
pages = "803-807",
url = "https://hdl.handle.net/21.15107/rcub_cherry_475"
}

Roglić, G., Dukić-Stefanović, S., Andrić, D., Kostić Rajačić, S.,& Šoškić, V.. (2001). Investigation of mixed D(2)/5-HT(1A) activity of N-heteroarylmethyl-N-phenylpiperazines, N-heteroarylethyl-N-phenylpiperazines and N-heteroarylpropyl-N-phenylpiperazines. in Pharmazie
Govi-Verlag  Pharmazeutischer Verlag Gmbh, Eschborn., 56(10), 803-807.
https://hdl.handle.net/21.15107/rcub_cherry_475

Roglić G, Dukić-Stefanović S, Andrić D, Kostić Rajačić S, Šoškić V. Investigation of mixed D(2)/5-HT(1A) activity of N-heteroarylmethyl-N-phenylpiperazines, N-heteroarylethyl-N-phenylpiperazines and N-heteroarylpropyl-N-phenylpiperazines. in Pharmazie. 2001;56(10):803-807.
https://hdl.handle.net/21.15107/rcub_cherry_475 .

Roglić, Goran, Dukić-Stefanović, Sladjana, Andrić, Deana, Kostić Rajačić, Slađana, Šoškić, Vukić, "Investigation of mixed D(2)/5-HT(1A) activity of N-heteroarylmethyl-N-phenylpiperazines, N-heteroarylethyl-N-phenylpiperazines and N-heteroarylpropyl-N-phenylpiperazines" in Pharmazie, 56, no. 10 (2001):803-807,
https://hdl.handle.net/21.15107/rcub_cherry_475 .

TY  - JOUR
AU  - Dukić, Slađana
AU  - Kostić Rajačić, Slađana
AU  - Šoškić, Vukić
AU  - Joksimovic, J
PY  - 1997
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2830
AB  - With an aim of creating new, high affinity dopaminergic ligands, six different 3- and 4-substituted 1-{2-[5-(1H-benzimidazole-2-thione)]ethyl}piperidines and nine related heterocyclic congeners were synthesized and evaluated for in vitro binding affinity at D 1 and D 2 dopamine receptors. Synaptosomal membranes prepared from fresh bovine caudate nuclei were used as a source of the dopamine receptors. Only 4-[bis-(4-fluorophenyl)methylene]-piperidines, compounds 9e, 10d, and 11d, expressed moderate affinity for the D 1 receptors, while all other compounds were inactive competitors of [ 3H]SCH 23390. Compounds 9c, 9d, 10c, 11a, and 11c were inactive in the D 2 receptor binding assay, as well. Derivatives of 4-phenylpiperidine (9-11b) and 3-phenyl-piperidine (10a) expressed a moderate to low affinity for the D 2 receptors. However, racemic (±)-1-{2-[5-(1H-benzimidazole-2-thione)]ethyl}-3-phenylpiperidine 9a and its enantiomer (+)-9a behaved as selective, high affinity D 2 receptor ligands, the latter being some four times more active than the racemate.
PB  - Wiley
T2  - Archiv der Pharmazie
T1  - Synthesis and dopaminergic properteis of 3- and 4-substituted 1-{-[5-(1H-benzimidazole-2-thione)]ethyl}piperidines and related compounds
VL  - 330
IS  - 1-2
SP  - 25
EP  - 28
DO  - 10.1002/ardp.19973300107
ER  - 

@article{
author = "Dukić, Slađana and Kostić Rajačić, Slađana and Šoškić, Vukić and Joksimovic, J",
year = "1997",
abstract = "With an aim of creating new, high affinity dopaminergic ligands, six different 3- and 4-substituted 1-{2-[5-(1H-benzimidazole-2-thione)]ethyl}piperidines and nine related heterocyclic congeners were synthesized and evaluated for in vitro binding affinity at D 1 and D 2 dopamine receptors. Synaptosomal membranes prepared from fresh bovine caudate nuclei were used as a source of the dopamine receptors. Only 4-[bis-(4-fluorophenyl)methylene]-piperidines, compounds 9e, 10d, and 11d, expressed moderate affinity for the D 1 receptors, while all other compounds were inactive competitors of [ 3H]SCH 23390. Compounds 9c, 9d, 10c, 11a, and 11c were inactive in the D 2 receptor binding assay, as well. Derivatives of 4-phenylpiperidine (9-11b) and 3-phenyl-piperidine (10a) expressed a moderate to low affinity for the D 2 receptors. However, racemic (±)-1-{2-[5-(1H-benzimidazole-2-thione)]ethyl}-3-phenylpiperidine 9a and its enantiomer (+)-9a behaved as selective, high affinity D 2 receptor ligands, the latter being some four times more active than the racemate.",
publisher = "Wiley",
journal = "Archiv der Pharmazie",
title = "Synthesis and dopaminergic properteis of 3- and 4-substituted 1-{-[5-(1H-benzimidazole-2-thione)]ethyl}piperidines and related compounds",
volume = "330",
number = "1-2",
pages = "25-28",
doi = "10.1002/ardp.19973300107"
}

Dukić, S., Kostić Rajačić, S., Šoškić, V.,& Joksimovic, J.. (1997). Synthesis and dopaminergic properteis of 3- and 4-substituted 1-{-[5-(1H-benzimidazole-2-thione)]ethyl}piperidines and related compounds. in Archiv der Pharmazie
Wiley., 330(1-2), 25-28.
https://doi.org/10.1002/ardp.19973300107

Dukić S, Kostić Rajačić S, Šoškić V, Joksimovic J. Synthesis and dopaminergic properteis of 3- and 4-substituted 1-{-[5-(1H-benzimidazole-2-thione)]ethyl}piperidines and related compounds. in Archiv der Pharmazie. 1997;330(1-2):25-28.
doi:10.1002/ardp.19973300107 .

Dukić, Slađana, Kostić Rajačić, Slađana, Šoškić, Vukić, Joksimovic, J, "Synthesis and dopaminergic properteis of 3- and 4-substituted 1-{-[5-(1H-benzimidazole-2-thione)]ethyl}piperidines and related compounds" in Archiv der Pharmazie, 330, no. 1-2 (1997):25-28,
https://doi.org/10.1002/ardp.19973300107 . .

TY  - JOUR
AU  - Dukić, Slađana
AU  - Kostić Rajačić, Slađana
AU  - Dragović, D
AU  - Šoškić, Vukić
AU  - Joksimović, J
PY  - 1997
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2831
AB  - Twenty-two different compounds have been synthesized with the aim of creating new, mixed D2/5HT(1A) ligands. For this purpose l-substituted phenylpiperazines attached by the N-4 nitrogen to dopaminergic pharmacophores of the 2-(5-benzimidazole)ethyl-, 2-(5-benztriazole)ethyl-, 2-[5-(benzimidazole-2thione)]ethyl- and 2-[6-(1,4-dihydroquinoxaline-2,3-dione)]ethyl-type were selected according to known structure affinity requirements of l-arylpiperazines. All the new compounds were evaluated for in-vitro binding affinity at the dopamine (D1 and D2) and 5-HT(1A) receptors. Synaptosomal membranes prepared from fresh bovine caudate nuclei and hippocampi were used as a source of dopamine and 5-hydroxytryptamine receptors, respectively. [3H]SCH 23390 (D1 selective), [3H]spiperone (D2 selective) and 8-OH-[3H]DPAT (5-HT(1A) selective) were employed as the radio-ligands. None of the compounds expressed affinity for binding at D1 dopamine receptors. Compounds 3b and 4b were inactive 8-OH-[3H]DPAT competitors whereas 1b, 2b and 4b were inactive in the [3H] spiperone-binding assay. The other compounds tested showed fair (1c, 1e, 1f, 2c, 2f, 3b, 3c and 4c) to high (1a, 1d, 2a, 1d, 3a, 3d-3f, 4a, and 4d) affinity in the [3H]spiperone-binding assay, the most potent representative being 4-[2-(5-benzimidazole-2-thione)ethyl]1-(2-methoxyphenyl)piperazine, 3a (K(i)=1.7 nM). In the 8-OH-[3H]DPAT-displacement assay compounds 1b, 1d, 1f, 2b, 2f and 3f behaved as moderate competitors and 1a, 1c, 1e, 2a, 2c, 2d, 3a, 3c-3e, 4a, 4c, 4d and 4f as rather strong competitors; 4-[2-(5-benztriazole)ethyl]-1-(2-methoxyphenyl)piperazine, 2a had the highest binding affinity at the 5-HT(1A) receptors (K(i) = 2.6 nM). Because many antipsychotic and anxiolytic agents behave as mixed dopaminergic and serotonergic ligands, the high affinity of several of these new ligands for binding at both D2 and 5-HT(1A) receptors make them promising candidates deserving further pharmacological evaluation as antipsychotic or anxiolytic pharmaceuticals.
PB  - Blackwell Publishing Ltd
T2  - Journal of Pharmacy and Pharmacology
T1  - Synthesis of several substituted phenylpiperazines behaving as mixed D2/5HT(1A) ligands
VL  - 49
IS  - 10
SP  - 1036
EP  - 1041
DO  - 10.1111/j.2042-7158.1997.tb06037.x
ER  - 

@article{
author = "Dukić, Slađana and Kostić Rajačić, Slađana and Dragović, D and Šoškić, Vukić and Joksimović, J",
year = "1997",
abstract = "Twenty-two different compounds have been synthesized with the aim of creating new, mixed D2/5HT(1A) ligands. For this purpose l-substituted phenylpiperazines attached by the N-4 nitrogen to dopaminergic pharmacophores of the 2-(5-benzimidazole)ethyl-, 2-(5-benztriazole)ethyl-, 2-[5-(benzimidazole-2thione)]ethyl- and 2-[6-(1,4-dihydroquinoxaline-2,3-dione)]ethyl-type were selected according to known structure affinity requirements of l-arylpiperazines. All the new compounds were evaluated for in-vitro binding affinity at the dopamine (D1 and D2) and 5-HT(1A) receptors. Synaptosomal membranes prepared from fresh bovine caudate nuclei and hippocampi were used as a source of dopamine and 5-hydroxytryptamine receptors, respectively. [3H]SCH 23390 (D1 selective), [3H]spiperone (D2 selective) and 8-OH-[3H]DPAT (5-HT(1A) selective) were employed as the radio-ligands. None of the compounds expressed affinity for binding at D1 dopamine receptors. Compounds 3b and 4b were inactive 8-OH-[3H]DPAT competitors whereas 1b, 2b and 4b were inactive in the [3H] spiperone-binding assay. The other compounds tested showed fair (1c, 1e, 1f, 2c, 2f, 3b, 3c and 4c) to high (1a, 1d, 2a, 1d, 3a, 3d-3f, 4a, and 4d) affinity in the [3H]spiperone-binding assay, the most potent representative being 4-[2-(5-benzimidazole-2-thione)ethyl]1-(2-methoxyphenyl)piperazine, 3a (K(i)=1.7 nM). In the 8-OH-[3H]DPAT-displacement assay compounds 1b, 1d, 1f, 2b, 2f and 3f behaved as moderate competitors and 1a, 1c, 1e, 2a, 2c, 2d, 3a, 3c-3e, 4a, 4c, 4d and 4f as rather strong competitors; 4-[2-(5-benztriazole)ethyl]-1-(2-methoxyphenyl)piperazine, 2a had the highest binding affinity at the 5-HT(1A) receptors (K(i) = 2.6 nM). Because many antipsychotic and anxiolytic agents behave as mixed dopaminergic and serotonergic ligands, the high affinity of several of these new ligands for binding at both D2 and 5-HT(1A) receptors make them promising candidates deserving further pharmacological evaluation as antipsychotic or anxiolytic pharmaceuticals.",
publisher = "Blackwell Publishing Ltd",
journal = "Journal of Pharmacy and Pharmacology",
title = "Synthesis of several substituted phenylpiperazines behaving as mixed D2/5HT(1A) ligands",
volume = "49",
number = "10",
pages = "1036-1041",
doi = "10.1111/j.2042-7158.1997.tb06037.x"
}

Dukić, S., Kostić Rajačić, S., Dragović, D., Šoškić, V.,& Joksimović, J.. (1997). Synthesis of several substituted phenylpiperazines behaving as mixed D2/5HT(1A) ligands. in Journal of Pharmacy and Pharmacology
Blackwell Publishing Ltd., 49(10), 1036-1041.
https://doi.org/10.1111/j.2042-7158.1997.tb06037.x

Dukić S, Kostić Rajačić S, Dragović D, Šoškić V, Joksimović J. Synthesis of several substituted phenylpiperazines behaving as mixed D2/5HT(1A) ligands. in Journal of Pharmacy and Pharmacology. 1997;49(10):1036-1041.
doi:10.1111/j.2042-7158.1997.tb06037.x .

Dukić, Slađana, Kostić Rajačić, Slađana, Dragović, D, Šoškić, Vukić, Joksimović, J, "Synthesis of several substituted phenylpiperazines behaving as mixed D2/5HT(1A) ligands" in Journal of Pharmacy and Pharmacology, 49, no. 10 (1997):1036-1041,
https://doi.org/10.1111/j.2042-7158.1997.tb06037.x . .