New substituted 2-methylthiomethyl- and 2-methylsulphinylmethylenebenz- imidazoles with D 2 /5-HT(1A) activity
Апстракт
Several 2-methylthiomethylbenzimidazoles (3a-e) and the corresponding sulphinyl derivatives 4a-e were synthesized and evaluated measuring their in vitro binding affinity at the D 1 and D 2 dopamine (source: synaptosomal membranes of the bovine nucleus caudatus) and 5-HT(1A) serotonin (source: synaptosomal membranes of the bovine hippocampus) receptors. [ 3 H]SCH 23390, [ 3 H]spiperone, and [ 3 H]-8-OH-DPAT were employed as specific radioligands for the D 1 , D 2 and 5-HT(1A) receptors, respectively. None of the compounds except for 3b acting as a moderate [ 3 H]SCH 23390, competitor, expressed binding affinity at the D 1 receptor. Compounds 4a and 4e were inactive displacers of both [ 3 H]spiperone and [ 3 H]-8-OH-DPAT. Ligands 4b, 3d and 4d acted as weak to moderate [ 3 H]spiperone competitors and 3a was a weak [ 3 H]- 8-OH-DPAT displacer. The remaining ligands expressed binding affinity at the corresponding receptors in a nanomolar concentration range. Among them, compound 3b with K(...i) of 14.2 nM and 8.4 nM in [ 3 H]spiperone and [ 3 H]-8- OH-DPAT binding assay, respectively, was the most potent mixed dopaminergic/serotonergic ligand. Although sterically similar, the two classes of ligands differ with regard to electronic properties of substituents in position 2 of the benzimidazole ring. Oxidation of 2- (methylthiomethyl)benzimidazoles afforded ligands devoid of binding affinity at the 5-HT(1A) receptor and significantly reduced binding affinity at the D 2 receptor. This points to the importance of electronic properties of substituents in position 2 of benzimidazole ring for the D 2 /5-HT(1A) affinity ratio of this type of ligands.
Кључне речи:
Antipsychotic Agents / Receptors / atypical antipsychotic / Dopamine D2Извор:
Pharmazie, 1998, 53, 7, 438-441Издавач:
- Govi-Verlag Pharmazeutischer Verlag GmbH
Институција/група
IHTMTY - JOUR AU - Kostić Rajačić, Slađana AU - Šoškić, Vukić AU - Joksimović, J PY - 1998 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/2828 AB - Several 2-methylthiomethylbenzimidazoles (3a-e) and the corresponding sulphinyl derivatives 4a-e were synthesized and evaluated measuring their in vitro binding affinity at the D 1 and D 2 dopamine (source: synaptosomal membranes of the bovine nucleus caudatus) and 5-HT(1A) serotonin (source: synaptosomal membranes of the bovine hippocampus) receptors. [ 3 H]SCH 23390, [ 3 H]spiperone, and [ 3 H]-8-OH-DPAT were employed as specific radioligands for the D 1 , D 2 and 5-HT(1A) receptors, respectively. None of the compounds except for 3b acting as a moderate [ 3 H]SCH 23390, competitor, expressed binding affinity at the D 1 receptor. Compounds 4a and 4e were inactive displacers of both [ 3 H]spiperone and [ 3 H]-8-OH-DPAT. Ligands 4b, 3d and 4d acted as weak to moderate [ 3 H]spiperone competitors and 3a was a weak [ 3 H]- 8-OH-DPAT displacer. The remaining ligands expressed binding affinity at the corresponding receptors in a nanomolar concentration range. Among them, compound 3b with K(i) of 14.2 nM and 8.4 nM in [ 3 H]spiperone and [ 3 H]-8- OH-DPAT binding assay, respectively, was the most potent mixed dopaminergic/serotonergic ligand. Although sterically similar, the two classes of ligands differ with regard to electronic properties of substituents in position 2 of the benzimidazole ring. Oxidation of 2- (methylthiomethyl)benzimidazoles afforded ligands devoid of binding affinity at the 5-HT(1A) receptor and significantly reduced binding affinity at the D 2 receptor. This points to the importance of electronic properties of substituents in position 2 of benzimidazole ring for the D 2 /5-HT(1A) affinity ratio of this type of ligands. PB - Govi-Verlag Pharmazeutischer Verlag GmbH T2 - Pharmazie T1 - New substituted 2-methylthiomethyl- and 2-methylsulphinylmethylenebenz- imidazoles with D 2 /5-HT(1A) activity VL - 53 IS - 7 SP - 438 EP - 441 UR - https://hdl.handle.net/21.15107/rcub_cer_2828 ER -
@article{ author = "Kostić Rajačić, Slađana and Šoškić, Vukić and Joksimović, J", year = "1998", abstract = "Several 2-methylthiomethylbenzimidazoles (3a-e) and the corresponding sulphinyl derivatives 4a-e were synthesized and evaluated measuring their in vitro binding affinity at the D 1 and D 2 dopamine (source: synaptosomal membranes of the bovine nucleus caudatus) and 5-HT(1A) serotonin (source: synaptosomal membranes of the bovine hippocampus) receptors. [ 3 H]SCH 23390, [ 3 H]spiperone, and [ 3 H]-8-OH-DPAT were employed as specific radioligands for the D 1 , D 2 and 5-HT(1A) receptors, respectively. None of the compounds except for 3b acting as a moderate [ 3 H]SCH 23390, competitor, expressed binding affinity at the D 1 receptor. Compounds 4a and 4e were inactive displacers of both [ 3 H]spiperone and [ 3 H]-8-OH-DPAT. Ligands 4b, 3d and 4d acted as weak to moderate [ 3 H]spiperone competitors and 3a was a weak [ 3 H]- 8-OH-DPAT displacer. The remaining ligands expressed binding affinity at the corresponding receptors in a nanomolar concentration range. Among them, compound 3b with K(i) of 14.2 nM and 8.4 nM in [ 3 H]spiperone and [ 3 H]-8- OH-DPAT binding assay, respectively, was the most potent mixed dopaminergic/serotonergic ligand. Although sterically similar, the two classes of ligands differ with regard to electronic properties of substituents in position 2 of the benzimidazole ring. Oxidation of 2- (methylthiomethyl)benzimidazoles afforded ligands devoid of binding affinity at the 5-HT(1A) receptor and significantly reduced binding affinity at the D 2 receptor. This points to the importance of electronic properties of substituents in position 2 of benzimidazole ring for the D 2 /5-HT(1A) affinity ratio of this type of ligands.", publisher = "Govi-Verlag Pharmazeutischer Verlag GmbH", journal = "Pharmazie", title = "New substituted 2-methylthiomethyl- and 2-methylsulphinylmethylenebenz- imidazoles with D 2 /5-HT(1A) activity", volume = "53", number = "7", pages = "438-441", url = "https://hdl.handle.net/21.15107/rcub_cer_2828" }
Kostić Rajačić, S., Šoškić, V.,& Joksimović, J.. (1998). New substituted 2-methylthiomethyl- and 2-methylsulphinylmethylenebenz- imidazoles with D 2 /5-HT(1A) activity. in Pharmazie Govi-Verlag Pharmazeutischer Verlag GmbH., 53(7), 438-441. https://hdl.handle.net/21.15107/rcub_cer_2828
Kostić Rajačić S, Šoškić V, Joksimović J. New substituted 2-methylthiomethyl- and 2-methylsulphinylmethylenebenz- imidazoles with D 2 /5-HT(1A) activity. in Pharmazie. 1998;53(7):438-441. https://hdl.handle.net/21.15107/rcub_cer_2828 .
Kostić Rajačić, Slađana, Šoškić, Vukić, Joksimović, J, "New substituted 2-methylthiomethyl- and 2-methylsulphinylmethylenebenz- imidazoles with D 2 /5-HT(1A) activity" in Pharmazie, 53, no. 7 (1998):438-441, https://hdl.handle.net/21.15107/rcub_cer_2828 .