Keywords
2-amino-4-methoxybenzoic acid
3,7-diazabicyclo[3.3.1]nonanes
allosteric modulators
AMPA receptor
glutamatergic system
indane derivatives
PAMs
patch clamp
Abstract
A new tricyclic derivative of 1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonane was synthesized in three steps using 2-aminoindane-5-carbonitrile. A positive modulatory activity of this compound towards the glutamatergic system in a wide range of nanomolar and subnanomolar concentrations has been demonstrated in electrophysiological studies in vitro using patch clamp technique. A putative binding mode of this compound has been revealed by means of molecular docking and molecular dynamics simulations.
Funders
Russian Science Foundation
22-15-00041
References
1.
Huang J., MacKerell A.D.
Journal of Computational Chemistry,
2013
2.
Abraham M.J., Murtola T., Schulz R., Páll S., Smith J.C., Hess B., Lindahl E.
SoftwareX,
2015
3.
Vanommeslaeghe K., Hatcher E., Acharya C., Kundu S., Zhong S., Shim J., Darian E., Guvench O., Lopes P., Vorobyov I., Mackerell A.D.
Journal of Computational Chemistry,
2009
4.
Bickerton G.R., Paolini G.V., Besnard J., Muresan S., Hopkins A.L.
Nature Chemistry,
2012
5.
Sushko I., Novotarskyi S., Körner R., Pandey A.K., Rupp M., Teetz W., Brandmaier S., Abdelaziz A., Prokopenko V.V., Tanchuk V.Y., Todeschini R., Varnek A., Marcou G., Ertl P., Potemkin V., et. al.
Journal of Computer-Aided Molecular Design,
2011
6.
Trott O., Olson A.J.
Journal of Computational Chemistry,
2009
7.
Radchenko E.V., Rulev Y.A., Safanyaev A.Y., Palyulin V.A., Zefirov N.S.
Doklady Biochemistry and Biophysics,
2017
8.
Lavrov M.I., Veremeeva P.N., Karlov D.S., Zamoyski V.L., Grigoriev V.V., Palyulin V.A.
Mendeleev Communications,
2019
9.
Radchenko E.V., Dyabina A.S., Palyulin V.A., Zefirov N.S.
Russian Chemical Bulletin,
2016
10.
Radchenko E.V., Dyabina A.S., Palyulin V.A.
Molecules,
2020
11.
Lavrov M.I., Karlov D.S., Voronina T.A., Grigoriev V.V., Ustyugov A.A., Bachurin S.O., Palyulin V.A.
Molecular Neurobiology,
2019
12.
Grove S.J., Jamieson C., Maclean J.K., Morrow J.A., Rankovic Z.
Journal of Medicinal Chemistry,
2010
13.
Brogi S., Campiani G., Brindisi M., Butini S.
ACS Medicinal Chemistry Letters,
2019
14.
Mendez-David I., Guilloux J., Papp M., Tritschler L., Mocaer E., Gardier A.M., Bretin S., David D.J.
Frontiers in Pharmacology,
2017
15.
Gordillo-Salas M., Pascual-Antón R., Ren J., Greer J., Adell A.
Molecular Neurobiology,
2020
16.
Baranov M.S., Yampolsky I.V.
Chemistry of Heterocyclic Compounds,
2012
17.
Kew J.N., Kemp J.A.
Psychopharmacology,
2005
18.
Reuillon T., E. Ward S., Beswick P.
Current Topics in Medicinal Chemistry,
2016
19.
Partin K.M.
Current Opinion in Pharmacology,
2015
20.
Pirotte B., Francotte P., Goffin E., de Tullio P.
Expert Opinion on Therapeutic Patents,
2013
21.
Ward S.E., Bax B.D., Harries M.
British Journal of Pharmacology,
2010
22.
Golubeva E.A., Lavrov M.I., Radchenko E.V., Palyulin V.A.
Biomolecules,
2022
23.
Radin D.P., Johnson S., Purcell R., Lippa A.S.
Biomedicine and Pharmacotherapy,
2018
24.
Lavrov M.I., Veremeeva P.N., Golubeva E.A., Radchenko E.V., Zamoyski V.L., Grigoriev V.V., Palyulin V.A.
Mendeleev Communications,
2022
25.
Golubeva E.A., Lavrov M.I., Veremeeva P.N., Bovina E.M., Radchenko E.V., Topchiy M.A., Asachenko A.F., Zamoyski V.L., Grigoriev V.V., Palyulin V.A.
Mendeleev Communications,
2023
26.
Reuillon T., Ward S.E., Beswick P.
2017
27.
Golubeva E.A., Lavrov M.I., Veremeeva P.N., Vyunova T.V., Shevchenko K.V., Topchiy M.A., Asachenko A.F., Palyulin V.A.
International Journal of Molecular Sciences,
2023