Design, synthesis and pharmacological evaluation of N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides
Autori
Andrić, DeanaDukić-Stefanović, Sladjana
Penjišević, Jelena
Jevtić, Ivana I.
Šukalović, Vladimir
Suručić, Relja
Kostić-Rajačić, Sladjana V.
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 / aripiprazole / arylpiperazines / molecular docking / binding assayIzvor:
1st International Conference on Chemo and BioInformatics (ICCBIKG 2021), Kragujevac, Serbia, 26-27th October 2021, 2021Finansiranje / projekti:
Kolekcije
Institucija/grupa
Hemijski fakultet / Faculty of ChemistryTY - CONF AU - Andrić, Deana AU - Dukić-Stefanović, Sladjana AU - Penjišević, Jelena AU - Jevtić, Ivana I. AU - Šukalović, Vladimir AU - Suručić, Relja AU - Kostić-Rajačić, Sladjana V. PY - 2021 UR - http://cherry.chem.bg.ac.rs/handle/123456789/5282 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. C3 - 1st International Conference on Chemo and BioInformatics (ICCBIKG 2021), Kragujevac, Serbia, 26-27th October 2021 T1 - Design, synthesis and pharmacological evaluation of N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides DO - 10.46793/ICCBI21.355A ER -
@conference{ author = "Andrić, Deana and Dukić-Stefanović, Sladjana and Penjišević, Jelena and Jevtić, Ivana I. and Šukalović, Vladimir and Suručić, Relja and Kostić-Rajačić, Sladjana V.", 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.", journal = "1st International Conference on Chemo and BioInformatics (ICCBIKG 2021), Kragujevac, Serbia, 26-27th October 2021", title = "Design, synthesis and pharmacological evaluation of N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides", doi = "10.46793/ICCBI21.355A" }
Andrić, D., Dukić-Stefanović, S., Penjišević, J., Jevtić, I. I., Šukalović, V., Suručić, R.,& Kostić-Rajačić, S. V.. (2021). Design, synthesis and pharmacological evaluation of N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides. in 1st International Conference on Chemo and BioInformatics (ICCBIKG 2021), Kragujevac, Serbia, 26-27th October 2021. https://doi.org/10.46793/ICCBI21.355A
Andrić D, Dukić-Stefanović S, Penjišević J, Jevtić II, Šukalović V, Suručić R, Kostić-Rajačić SV. Design, synthesis and pharmacological evaluation of N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides. in 1st International Conference on Chemo and BioInformatics (ICCBIKG 2021), Kragujevac, Serbia, 26-27th October 2021. 2021;. doi:10.46793/ICCBI21.355A .
Andrić, Deana, Dukić-Stefanović, Sladjana, Penjišević, Jelena , Jevtić, Ivana I., Šukalović, Vladimir , Suručić, Relja, Kostić-Rajačić, Sladjana V., "Design, synthesis and pharmacological evaluation of N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides" in 1st International Conference on Chemo and BioInformatics (ICCBIKG 2021), Kragujevac, Serbia, 26-27th October 2021 (2021), https://doi.org/10.46793/ICCBI21.355A . .