Design, Synthesis and Pharmacological Evaluation of novel N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides
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2021
Autori
Andrić, Deana![](/themes/MirageCER/images/orcid.png)
Dukic-Stefanovic, Sladjana
Penjišević, Jelena
![](/themes/MirageCER/images/orcid.png)
Jevtić, Ivana
![](/themes/MirageCER/images/orcid.png)
Šukalović, Vladimir
![](/themes/MirageCER/images/orcid.png)
Suručić, Relja
![](/themes/MirageCER/images/orcid.png)
Kostić-Rajačić, Slađana
![](/themes/MirageCER/images/orcid.png)
Konferencijski prilog (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
5HT1A receptor targeting drugs have been used as the treatment for the many neuropsychiatric
disorders, such as schizophrenia and depression. As a part of ongoing research, we designed series of
new compounds that share arylpiperazine common structural motif with the 5HT1A receptor ligand
aripiprazole. Receptor-ligand interactions were determined by the molecular docking simulations,
revealing the positive impact of the phenyl substitution in the arylpiperazine part of the molecules. Nine
selected compounds were synthesized in four reaction steps in high overall yields (59-73%). In vitro
pharmacological evaluation of the synthesized compounds revealed three compounds (5b, 6b and 6c)
with high 5HT1A binding affinity, comparable with aripiprazole (Ki 12.0, 4.8, 12.8, 5.6 nM,
respectively). Compounds from b series, 5b and 6b, possess 2-methoxyphenyl substituents, while 6c
possess 2,3-dichlorophenyl substituent in the arylpiperazine part of the molecule. The pharmacological
resul...ts are therefore in accordance with the molecular docking simulations thus proving the rational
design. Compounds 5c, 6b and 6c can be considered as the candidates for further evaluation as new,
potential antidepressants.
Ključne reči:
5HT1A / Binding assay / arylpiperazineIzvor:
Book of proceedings - 1st International Conference on Chemo and Bioinformatics, October 26-27, 2021. Kragujevac, 2021, 355-358Izdavač:
- Kragujevac : Institute for Information Technologies
Finansiranje / projekti:
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200026 (Univerzitet u Beogradu, Institut za hemiju, tehnologiju i metalurgiju - IHTM) (RS-MESTD-inst-2020-200026)
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200168 (Univerzitet u Beogradu, Hemijski fakultet) (RS-MESTD-inst-2020-200168)
Institucija/grupa
IHTMTY - CONF AU - Andrić, Deana AU - Dukic-Stefanovic, Sladjana AU - Penjišević, Jelena AU - Jevtić, Ivana AU - Šukalović, Vladimir AU - Suručić, Relja AU - Kostić-Rajačić, Slađana PY - 2021 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/5849 AB - 5HT1A receptor targeting drugs have been used as the treatment for the many neuropsychiatric disorders, such as schizophrenia and depression. As a part of ongoing research, we designed series of new compounds that share arylpiperazine common structural motif with the 5HT1A receptor ligand aripiprazole. Receptor-ligand interactions were determined by the molecular docking simulations, revealing the positive impact of the phenyl substitution in the arylpiperazine part of the molecules. Nine selected compounds were synthesized in four reaction steps in high overall yields (59-73%). In vitro pharmacological evaluation of the synthesized compounds revealed three compounds (5b, 6b and 6c) with high 5HT1A binding affinity, comparable with aripiprazole (Ki 12.0, 4.8, 12.8, 5.6 nM, respectively). Compounds from b series, 5b and 6b, possess 2-methoxyphenyl substituents, while 6c possess 2,3-dichlorophenyl substituent in the arylpiperazine part of the molecule. The pharmacological results are therefore in accordance with the molecular docking simulations thus proving the rational design. Compounds 5c, 6b and 6c can be considered as the candidates for further evaluation as new, potential antidepressants. PB - Kragujevac : Institute for Information Technologies C3 - Book of proceedings - 1st International Conference on Chemo and Bioinformatics, October 26-27, 2021. Kragujevac T1 - Design, Synthesis and Pharmacological Evaluation of novel N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides SP - 355 EP - 358 DO - 10.46793/ICCBI21.355A ER -
@conference{ author = "Andrić, Deana and Dukic-Stefanovic, Sladjana and Penjišević, Jelena and Jevtić, Ivana and Šukalović, Vladimir and Suručić, Relja and Kostić-Rajačić, Slađana", year = "2021", abstract = "5HT1A receptor targeting drugs have been used as the treatment for the many neuropsychiatric disorders, such as schizophrenia and depression. As a part of ongoing research, we designed series of new compounds that share arylpiperazine common structural motif with the 5HT1A receptor ligand aripiprazole. Receptor-ligand interactions were determined by the molecular docking simulations, revealing the positive impact of the phenyl substitution in the arylpiperazine part of the molecules. Nine selected compounds were synthesized in four reaction steps in high overall yields (59-73%). In vitro pharmacological evaluation of the synthesized compounds revealed three compounds (5b, 6b and 6c) with high 5HT1A binding affinity, comparable with aripiprazole (Ki 12.0, 4.8, 12.8, 5.6 nM, respectively). Compounds from b series, 5b and 6b, possess 2-methoxyphenyl substituents, while 6c possess 2,3-dichlorophenyl substituent in the arylpiperazine part of the molecule. The pharmacological results are therefore in accordance with the molecular docking simulations thus proving the rational design. Compounds 5c, 6b and 6c can be considered as the candidates for further evaluation as new, potential antidepressants.", publisher = "Kragujevac : Institute for Information Technologies", journal = "Book of proceedings - 1st International Conference on Chemo and Bioinformatics, October 26-27, 2021. Kragujevac", title = "Design, Synthesis and Pharmacological Evaluation of novel N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides", pages = "355-358", doi = "10.46793/ICCBI21.355A" }
Andrić, D., Dukic-Stefanovic, S., Penjišević, J., Jevtić, I., Šukalović, V., Suručić, R.,& Kostić-Rajačić, S.. (2021). Design, Synthesis and Pharmacological Evaluation of novel N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides. in Book of proceedings - 1st International Conference on Chemo and Bioinformatics, October 26-27, 2021. Kragujevac Kragujevac : Institute for Information Technologies., 355-358. https://doi.org/10.46793/ICCBI21.355A
Andrić D, Dukic-Stefanovic S, Penjišević J, Jevtić I, Šukalović V, Suručić R, Kostić-Rajačić S. Design, Synthesis and Pharmacological Evaluation of novel N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides. in Book of proceedings - 1st International Conference on Chemo and Bioinformatics, October 26-27, 2021. Kragujevac. 2021;:355-358. doi:10.46793/ICCBI21.355A .
Andrić, Deana, Dukic-Stefanovic, Sladjana, Penjišević, Jelena, Jevtić, Ivana, Šukalović, Vladimir, Suručić, Relja, Kostić-Rajačić, Slađana, "Design, Synthesis and Pharmacological Evaluation of novel N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides" in Book of proceedings - 1st International Conference on Chemo and Bioinformatics, October 26-27, 2021. Kragujevac (2021):355-358, https://doi.org/10.46793/ICCBI21.355A . .