Abstract:
Two new potent AMPA receptor allosteric modulators, 6-(1,3-benzodioxol-5-yl)-1,11-dimethyl-3,6,9-triazatri-cyclo[7.3.1.13,11]tetradecane-4,8,12-trione and -4,8-dione were synthesized from 1,3-benzodioxol-5-amine and the corresponding 3,7-dichloroacetyl-3,7-diazabicyclo[3.3.1]-nonanes. In a wide concentration range (10−12–10−7 m), the 12-oxo derivative acts as a positive modulator causing the potentiation of the kainate-induced AMPA receptor currents with maximum potentiation at 1 nm (62%) while its analogue without a ketone group has significant (up to 40%) negative modulator effect. Their tentative mechanisms of action were analyzed by means of molecular modelling
Citation:
M. I. Lavrov, P. N. Veremeeva, E. A. Golubeva, E. V. Radchenko, V. L. Zamoyski, V. V. Grigoriev, V. A. Palyulin, “Positive and negative AMPA receptor modulators based on tricyclic bispidine derivative: Minor structural change inverts the type of activity”, Mendeleev Commun., 32:3 (2022), 360–363
Linking options:
https://www.mathnet.ru/eng/mendc664
https://www.mathnet.ru/eng/mendc/v32/i3/p360
This publication is cited in the following 10 articles:
James Matthews, Polina N. Veremeeva, Elena A. Golubeva, Mstislav I. Lavrov, Eugene V. Radchenko, Vladimir L. Zamoyski, Vladimir V. Grigoriev, Vladimir A. Palyulin, “Synthesis and modulatory activity of 3-acetyl-7-(benzofuran-5-carbonyl)-1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonan-9-one on AMPA receptors”, Chem Heterocycl Comp, 2025
E. A. Golubeva, M. I. Lavrov, P. N. Veremeeva, J. Matthews, E. V. Radchenko, V. L. Zamoyski, V. V. Grigoriev, V. A. Palyulin, Mendeleev Commun., 35:2 (2025), 142–144
I. V. Svitanko, T. S. Pivina, “Molecular modeling in synthesis: from statistical methods to quantum chemistry and practical applications”, Russ Chem Bull, 73:5 (2024), 1093
K. N. Sedenkova, S. V. Kositov, D. V. Zverev, E. V. Radchenko, Yu. K. Grishin, A. V. Gabrel'yan, V. L. Zamoyski, V. V. Grigoriev, E. B. Averina, V. A. Palyulin, “Novel AMPA receptor allosteric modulators of bis(pyrimidine) series: synthesis and SAR evaluation”, Mendeleev Commun., 34:1 (2024), 8–10
N. S. Li-Zhulanov, K. Yu. Ponomarev, S. Sari, D. Gülmez, S. Arikan-Akdagli, V. I. Krasnov, E. V. Suslov, K. P. Volcho, N. F. Salakhutdinov, “Myrtenyl-bispidine containing azole: synthesis and antifungal activity”, Mendeleev Commun., 34:1 (2024), 119–121
J. Matthews, P. N. Veremeeva, E. A. Golubeva, M. I. Lavrov, E. V. Radchenko, M. A. Topchiy, V. L. Zamoyski, V. V. Grigoriev, V. A. Palyulin, “7-Benzyl-1,5-dimethyl-3-piperonyloyl-3,7-diazabicyclo[3.3.1]nonan-9-one as an allosteric modulator of glutamatergic system”, Mendeleev Commun., 34:3 (2024), 354–356
Dmitry A. Vasilenko, Nadezhda S. Temnyakova, Sevastian E. Dronov, Eugene V. Radchenko, Yuri K. Grishin, Alexey V. Gabrel'yan, Vladimir L. Zamoyski, Vladimir V. Grigoriev, Elena B. Averina, Vladimir A. Palyulin, “5-Nitroisoxazoles in SNAr Reactions: A Novel Chemo- and Regioselective Approach to Isoxazole-Based Bivalent Ligands of AMPA Receptors”, IJMS, 24:22 (2023), 16135
E. A. Golubeva, M. I. Lavrov, P. N. Veremeeva, E. M. Bovina, E. V. Radchenko, M. A. Topchiy, A. F. Asachenko, V. L. Zamoyski, V. V. Grigoriev, V. A. Palyulin, “New 1,11-dimethyl-3,6,9-triazatricyclo[7.3.1.13,11]tetradecane-4,8,12-trione derivative as an allosteric modulator of the glutamatergic system”, Mendeleev Commun., 33:1 (2023), 70–72
Kseniya N. Sedenkova, Denis V. Zverev, Anna A. Nazarova, Mstislav I. Lavrov, Eugene V. Radchenko, Yuri K. Grishin, Alexey V. Gabrel'yan, Vladimir L. Zamoyski, Vladimir V. Grigoriev, Elena B. Averina, Vladimir A. Palyulin, “Novel Nanomolar Allosteric Modulators of AMPA Receptor of Bis(pyrimidine) Series: Synthesis, Biotesting and SAR Analysis”, Molecules, 27:23 (2022), 8252
Elena A. Golubeva, Mstislav I. Lavrov, Eugene V. Radchenko, Vladimir A. Palyulin, “Diversity of AMPA Receptor Ligands: Chemotypes, Binding Modes, Mechanisms of Action, and Therapeutic Effects”, Biomolecules, 13:1 (2022), 56
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