TY  - CONF
AU  - Penjišević, Jelena
AU  - Andrić, Deana
AU  - Dukic-Stefanovic, Sladjana
AU  - Spalholz, Tina
AU  - Burst, Peter
AU  - Kostić-Rajačić, Slađana
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5833
AB  - Serotonin 5HT1a receptor belongs to a class of G-protein coupled receptors. It serves as a
potential target for neurological disorders such as depression, anxiety etc. It is a well-known
fact that N-arylpiperazine moiety is present in compounds with pronounced 5HT1a activity.
Taking into account previously published results1 novel structures of N-{4-[2-(4-
arylpiperazin-1-yl)ethyl]phenyl}arylamides (Figure 1.) were designed for target synthesis.
Proposed modifications include: different position of hydroxyl group in aryl amide part of
molecule and addition of methoxy and chloro substituents to the phenyl ring of parent
compounds, since their introduction in the molecule leads to increased receptor affinity.
New compounds were synthesized by acylation of N-arylpiperazines using 4-
nitrophenylacetic acid. Obtained amides were converted in 1-(4-nitrophenethyl)-4-
arylpiperazines using diborane in THF. Reduction of nitro compounds by Ra/Ni provided 1-
(4-aminophenethyl)-4-arylpiperazines. Target arylamides were obtained by condensation 1-
(4-aminophenethyl)-4-arylpiperazines with corresponding aryl acids in presence of
propylphosphoric acid anhydride (PPAA) in DMF.
All newly synthesized compounds were evaluated for their activity toward 5HT1a receptors
by in vitro competitive displacement assay of [3H] 8-OH-DPAT. HEK cell line were used as a
source of 5HT1a receptors.
Introduction of 2-methoxy and 2,3-dichloro groups,as well as meta and para hydroxyl group
in molecule resulted in increment of affinity toward 5HT1a receptors comparing to the parent
compounds.
PB  - European federation for medicinal chemistry (EFMC)
C3  - 11th Joint Meeting on Medicinal Chemistry, Final Programme, Јune 27-30, 2019,  Prague, Czech Republic
T1  - Synthesis and pharmacological evaluation of N-{4-[2-(4-arylpiperazin-1-      yl)ethyl]phenyl} arylamides
SP  - P-64
UR  - https://hdl.handle.net/21.15107/rcub_cer_5833
ER  - 

@conference{
author = "Penjišević, Jelena and Andrić, Deana and Dukic-Stefanovic, Sladjana and Spalholz, Tina and Burst, Peter and Kostić-Rajačić, Slađana",
year = "2019",
abstract = "Serotonin 5HT1a receptor belongs to a class of G-protein coupled receptors. It serves as a
potential target for neurological disorders such as depression, anxiety etc. It is a well-known
fact that N-arylpiperazine moiety is present in compounds with pronounced 5HT1a activity.
Taking into account previously published results1 novel structures of N-{4-[2-(4-
arylpiperazin-1-yl)ethyl]phenyl}arylamides (Figure 1.) were designed for target synthesis.
Proposed modifications include: different position of hydroxyl group in aryl amide part of
molecule and addition of methoxy and chloro substituents to the phenyl ring of parent
compounds, since their introduction in the molecule leads to increased receptor affinity.
New compounds were synthesized by acylation of N-arylpiperazines using 4-
nitrophenylacetic acid. Obtained amides were converted in 1-(4-nitrophenethyl)-4-
arylpiperazines using diborane in THF. Reduction of nitro compounds by Ra/Ni provided 1-
(4-aminophenethyl)-4-arylpiperazines. Target arylamides were obtained by condensation 1-
(4-aminophenethyl)-4-arylpiperazines with corresponding aryl acids in presence of
propylphosphoric acid anhydride (PPAA) in DMF.
All newly synthesized compounds were evaluated for their activity toward 5HT1a receptors
by in vitro competitive displacement assay of [3H] 8-OH-DPAT. HEK cell line were used as a
source of 5HT1a receptors.
Introduction of 2-methoxy and 2,3-dichloro groups,as well as meta and para hydroxyl group
in molecule resulted in increment of affinity toward 5HT1a receptors comparing to the parent
compounds.",
publisher = "European federation for medicinal chemistry (EFMC)",
journal = "11th Joint Meeting on Medicinal Chemistry, Final Programme, Јune 27-30, 2019,  Prague, Czech Republic",
title = "Synthesis and pharmacological evaluation of N-{4-[2-(4-arylpiperazin-1-      yl)ethyl]phenyl} arylamides",
pages = "P-64",
url = "https://hdl.handle.net/21.15107/rcub_cer_5833"
}

Penjišević, J., Andrić, D., Dukic-Stefanovic, S., Spalholz, T., Burst, P.,& Kostić-Rajačić, S.. (2019). Synthesis and pharmacological evaluation of N-{4-[2-(4-arylpiperazin-1-      yl)ethyl]phenyl} arylamides. in 11th Joint Meeting on Medicinal Chemistry, Final Programme, Јune 27-30, 2019,  Prague, Czech Republic
European federation for medicinal chemistry (EFMC)., P-64.
https://hdl.handle.net/21.15107/rcub_cer_5833

Penjišević J, Andrić D, Dukic-Stefanovic S, Spalholz T, Burst P, Kostić-Rajačić S. Synthesis and pharmacological evaluation of N-{4-[2-(4-arylpiperazin-1-      yl)ethyl]phenyl} arylamides. in 11th Joint Meeting on Medicinal Chemistry, Final Programme, Јune 27-30, 2019,  Prague, Czech Republic. 2019;:P-64.
https://hdl.handle.net/21.15107/rcub_cer_5833 .

Penjišević, Jelena, Andrić, Deana, Dukic-Stefanovic, Sladjana, Spalholz, Tina, Burst, Peter, Kostić-Rajačić, Slađana, "Synthesis and pharmacological evaluation of N-{4-[2-(4-arylpiperazin-1-      yl)ethyl]phenyl} arylamides" in 11th Joint Meeting on Medicinal Chemistry, Final Programme, Јune 27-30, 2019,  Prague, Czech Republic (2019):P-64,
https://hdl.handle.net/21.15107/rcub_cer_5833 .