This article is cited in 12 papers

Communications

Positive and negative AMPA receptor modulators based on tricyclic bispidine derivative: Minor structural change inverts the type of activity

M. I. Lavrov^a, P. N. Veremeeva^a, E. A. Golubeva^a, E. V. Radchenko^a, V. L. Zamoyski^b, V. V. Grigoriev^ab, V. A. Palyulin<sup>a

a</sup> Department of Chemistry, M.V. Lomonosov Moscow State University, Moscow, Russian Federation
^b Institute of Physiologically Active Compounds, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Chernogolovka, Moscow Region, Russian Federation

Abstract: Two new potent AMPA receptor allosteric modulators, 6-(1,3-benzodioxol-5-yl)-1,11-dimethyl-3,6,9-triazatri-cyclo[7.3.1.1^3,11]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

Keywords: 3,7-diazabicyclo[3.3.1]nonane, bispidines, heterocyclization, AMPA receptors, allosteric modulators.

Language: English

DOI: 10.1016/j.mencom.2022.05.023

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