M. I. Lavrov, D. S. Karlov, V. A. Palyulin, V. V. Grigoriev, V. L. Zamoyski, G. E. Brkich, N. V. Pyatigorskaya, M. E. Zapolskiy, “Novel positive allosteric modulator of AMPA-receptors based on tricyclic scaffold”, Mendeleev Commun., 28:3 (2018), 311

Эта публикация цитируется в 16 статьях

Communications

Novel positive allosteric modulator of AMPA-receptors based on tricyclic scaffold

M. I. Lavrov^ab, D. S. Karlov^ab, V. A. Palyulin^ab, V. V. Grigoriev^b, V. L. Zamoyski^b, G. E. Brkich^c, N. V. Pyatigorskaya^c, M. E. Zapolskiy^d

^a 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
^c I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
^d QM Pharma LLC, Skolkovo Innovation Center, Moscow, Russian Federation

Аннотация: Molecular modeling, synthesis, and activity evaluation of a novel positive allosteric modulator of the AMPA receptor, 6-[4-methoxy-3-(1H-pyrazol-1-ylmethyl)benzyl]-1,11-dimethyl-3,6,9-triazatricyclo[7.3.1.1^3,11]tetradecane-4,8,12-trione, are presented. The main point of the design was to fill the interdomain cavity of GluA2 ligand binding domains based on the cyclothiazide binding mode. Electrophysiological studies showed high potentiation of the kainate-induced currents (pECmax∼12).

Язык публикации: английский

DOI: 10.1016/j.mencom.2018.05.028