6-[2-(4-arylpiperazin-1-yl)ethyl]-4-halo-1,3-dihydro-2h-benzimidazole-2-thiones: Synthesis and pharmacological evaluation
6-[2-(4-arilpiperazin-1-il)etil]-4-halo-1,3-dihidro-2h-benzimidazol-2-tioni - sinteza i farmakološko ispitivanje
2007
Аутори
Andrić, DeanaTovilović, Gordana
Roglić, Goran
Šoškić, Vukić
Tomić, Mirko
Kostić Rajačić, Slađana
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Eight new compounds with halogen atom introduced into the benzimidazole- 2-thione dopaminergic pharmacophore of 5-[2-(4-arylpiperazin-1-yl)ethyl]-1,3-dihydro- 2H-benzimidazole-2-thiones with the arylpiperazine part of the molecule being selected according to known structure-affinity requirements, have been synthesized. All the new compounds were evaluated for the in vitro binding affinity at the dopamine (DA) D1 and D2 and serotonin 5-HT1A receptors by the competitive radioassays, performed on synaptosomal membranes prepared from fresh bovine caudate nuclei and hippocampi. All the new compounds were strong competitors for the binding of the radioligands to the D2 and 5-HT1A receptors, with the most active of them having 34 and 170 time higher affinity than non-halogenated congeners in the D2 DA receptor radioassays (compounds 9.1b and 9.2b, respectively). Divergently, these compounds were without significant affinities for the D1 DA receptors. .
Sintetisano je osam novih jedinjenja kod kojih je atom halogena uveden u benzimidazol-2-tionsku dopaminergičku farmakoforu 5-[2-(4-arilpiperazin-1-il)etil]-1,3-dihidro-2N-benzimidazol-2-tiona sa arilpiperazinskim delom molekula izabranim shodno pozna- tim zahtevima o odnosu strukture i reaktivnosti. Za sva novosintetisana jedinjenja je određen afinitet vezivanja za dopaminske (D1 i D2) i 5-NT1A receptore u in vitro eksperimentima kompeticije sa radioligandima. Kao izvor dopaminskih i 5-NT1A receptora su korištene sinaptozomalne membrane izolovane iz goveđeg nukleusa kaudatusa i hipokampusa. Sva novosintetisana jedinjenja pokazala su se kao jaki kompetitori [3H]spiperona i [3H]8-OH-DPAT, od kojih najaktivnija (9.1b i 9.2b) poseduju 34 i 170 puta veći afinitet ka D2 DA receptorima od polaznih, nehalogenovanih jedinjenja. Sa druge strane, ova jedinjenja ne poseduju značajan afinitet ka D1 dopaminskim receptorima. .
Кључне речи:
arylpiperazines / benzimidazole-2-thiones / dopamine receptors / serotonin receptorsИзвор:
Journal of the Serbian Chemical Society, 2007, 72, 8-9, 747-755Издавач:
- Serbian Chemical Society
Финансирање / пројекти:
- Биомедицинска испитивања и развој неких нових психотропних супстанци (RS-MESTD-MPN2006-2010-143032)
- Синтеза и карактеризација биолошки активних супстанци и компјутерска симулација биолошких система (RS-MESTD-MPN2006-2010-142009)
Институција/група
IHTMTY - JOUR AU - Andrić, Deana AU - Tovilović, Gordana AU - Roglić, Goran AU - Šoškić, Vukić AU - Tomić, Mirko AU - Kostić Rajačić, Slađana PY - 2007 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/323 AB - Eight new compounds with halogen atom introduced into the benzimidazole- 2-thione dopaminergic pharmacophore of 5-[2-(4-arylpiperazin-1-yl)ethyl]-1,3-dihydro- 2H-benzimidazole-2-thiones with the arylpiperazine part of the molecule being selected according to known structure-affinity requirements, have been synthesized. All the new compounds were evaluated for the in vitro binding affinity at the dopamine (DA) D1 and D2 and serotonin 5-HT1A receptors by the competitive radioassays, performed on synaptosomal membranes prepared from fresh bovine caudate nuclei and hippocampi. All the new compounds were strong competitors for the binding of the radioligands to the D2 and 5-HT1A receptors, with the most active of them having 34 and 170 time higher affinity than non-halogenated congeners in the D2 DA receptor radioassays (compounds 9.1b and 9.2b, respectively). Divergently, these compounds were without significant affinities for the D1 DA receptors. . AB - Sintetisano je osam novih jedinjenja kod kojih je atom halogena uveden u benzimidazol-2-tionsku dopaminergičku farmakoforu 5-[2-(4-arilpiperazin-1-il)etil]-1,3-dihidro-2N-benzimidazol-2-tiona sa arilpiperazinskim delom molekula izabranim shodno pozna- tim zahtevima o odnosu strukture i reaktivnosti. Za sva novosintetisana jedinjenja je određen afinitet vezivanja za dopaminske (D1 i D2) i 5-NT1A receptore u in vitro eksperimentima kompeticije sa radioligandima. Kao izvor dopaminskih i 5-NT1A receptora su korištene sinaptozomalne membrane izolovane iz goveđeg nukleusa kaudatusa i hipokampusa. Sva novosintetisana jedinjenja pokazala su se kao jaki kompetitori [3H]spiperona i [3H]8-OH-DPAT, od kojih najaktivnija (9.1b i 9.2b) poseduju 34 i 170 puta veći afinitet ka D2 DA receptorima od polaznih, nehalogenovanih jedinjenja. Sa druge strane, ova jedinjenja ne poseduju značajan afinitet ka D1 dopaminskim receptorima. . PB - Serbian Chemical Society T2 - Journal of the Serbian Chemical Society T1 - 6-[2-(4-arylpiperazin-1-yl)ethyl]-4-halo-1,3-dihydro-2h-benzimidazole-2-thiones: Synthesis and pharmacological evaluation T1 - 6-[2-(4-arilpiperazin-1-il)etil]-4-halo-1,3-dihidro-2h-benzimidazol-2-tioni - sinteza i farmakološko ispitivanje VL - 72 IS - 8-9 SP - 747 EP - 755 DO - 10.2298/JSC0709747A ER -
@article{ author = "Andrić, Deana and Tovilović, Gordana and Roglić, Goran and Šoškić, Vukić and Tomić, Mirko and Kostić Rajačić, Slađana", year = "2007", abstract = "Eight new compounds with halogen atom introduced into the benzimidazole- 2-thione dopaminergic pharmacophore of 5-[2-(4-arylpiperazin-1-yl)ethyl]-1,3-dihydro- 2H-benzimidazole-2-thiones with the arylpiperazine part of the molecule being selected according to known structure-affinity requirements, have been synthesized. All the new compounds were evaluated for the in vitro binding affinity at the dopamine (DA) D1 and D2 and serotonin 5-HT1A receptors by the competitive radioassays, performed on synaptosomal membranes prepared from fresh bovine caudate nuclei and hippocampi. All the new compounds were strong competitors for the binding of the radioligands to the D2 and 5-HT1A receptors, with the most active of them having 34 and 170 time higher affinity than non-halogenated congeners in the D2 DA receptor radioassays (compounds 9.1b and 9.2b, respectively). Divergently, these compounds were without significant affinities for the D1 DA receptors. ., Sintetisano je osam novih jedinjenja kod kojih je atom halogena uveden u benzimidazol-2-tionsku dopaminergičku farmakoforu 5-[2-(4-arilpiperazin-1-il)etil]-1,3-dihidro-2N-benzimidazol-2-tiona sa arilpiperazinskim delom molekula izabranim shodno pozna- tim zahtevima o odnosu strukture i reaktivnosti. Za sva novosintetisana jedinjenja je određen afinitet vezivanja za dopaminske (D1 i D2) i 5-NT1A receptore u in vitro eksperimentima kompeticije sa radioligandima. Kao izvor dopaminskih i 5-NT1A receptora su korištene sinaptozomalne membrane izolovane iz goveđeg nukleusa kaudatusa i hipokampusa. Sva novosintetisana jedinjenja pokazala su se kao jaki kompetitori [3H]spiperona i [3H]8-OH-DPAT, od kojih najaktivnija (9.1b i 9.2b) poseduju 34 i 170 puta veći afinitet ka D2 DA receptorima od polaznih, nehalogenovanih jedinjenja. Sa druge strane, ova jedinjenja ne poseduju značajan afinitet ka D1 dopaminskim receptorima. .", publisher = "Serbian Chemical Society", journal = "Journal of the Serbian Chemical Society", title = "6-[2-(4-arylpiperazin-1-yl)ethyl]-4-halo-1,3-dihydro-2h-benzimidazole-2-thiones: Synthesis and pharmacological evaluation, 6-[2-(4-arilpiperazin-1-il)etil]-4-halo-1,3-dihidro-2h-benzimidazol-2-tioni - sinteza i farmakološko ispitivanje", volume = "72", number = "8-9", pages = "747-755", doi = "10.2298/JSC0709747A" }
Andrić, D., Tovilović, G., Roglić, G., Šoškić, V., Tomić, M.,& Kostić Rajačić, S.. (2007). 6-[2-(4-arylpiperazin-1-yl)ethyl]-4-halo-1,3-dihydro-2h-benzimidazole-2-thiones: Synthesis and pharmacological evaluation. in Journal of the Serbian Chemical Society Serbian Chemical Society., 72(8-9), 747-755. https://doi.org/10.2298/JSC0709747A
Andrić D, Tovilović G, Roglić G, Šoškić V, Tomić M, Kostić Rajačić S. 6-[2-(4-arylpiperazin-1-yl)ethyl]-4-halo-1,3-dihydro-2h-benzimidazole-2-thiones: Synthesis and pharmacological evaluation. in Journal of the Serbian Chemical Society. 2007;72(8-9):747-755. doi:10.2298/JSC0709747A .
Andrić, Deana, Tovilović, Gordana, Roglić, Goran, Šoškić, Vukić, Tomić, Mirko, Kostić Rajačić, Slađana, "6-[2-(4-arylpiperazin-1-yl)ethyl]-4-halo-1,3-dihydro-2h-benzimidazole-2-thiones: Synthesis and pharmacological evaluation" in Journal of the Serbian Chemical Society, 72, no. 8-9 (2007):747-755, https://doi.org/10.2298/JSC0709747A . .