Design, Synthesis, and Study of the Anxiolytic Activity of New Pyrrolo[1,2- a ]pyrazine-Containing TSPO Ligands

G. V. Mokrov; Мокров Г. В.; А. S. Pantileev; Пантилеев А. С.; М. А. Yarkova; Яркова М. А.; I. V. Rybina; Рыбина И. В.; Т. А. Gudasheva; Гудашева Т. А.; Yu. V. Vakhitova; Вахитова Ю. В.; S. B. Seredenin; Середенин С. Б.

doi:10.31857/S0132342323020173

Design, Synthesis, and Study of the Anxiolytic Activity of New Pyrrolo[1,2-a]pyrazine-Containing TSPO Ligands

Авторлар: Mokrov G.¹, Pantileev А.¹, Yarkova М.¹, Rybina I.¹, Gudasheva Т.¹, Vakhitova Y.¹, Seredenin S.¹
Мекемелер:
1. Research Zakusov Institute of Pharmacology
Шығарылым: Том 49, № 2 (2023)
Беттер: 188-206
Бөлім: Articles
URL: https://journals.rcsi.science/0132-3423/article/view/145878
DOI: https://doi.org/10.31857/S0132342323020173
EDN: https://elibrary.ru/PGKDNM
ID: 145878

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Аннотация
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Әдебиет тізімі
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Статистика

Аннотация

A new group of 1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamides, in which substituents at the amide nitrogen atom are alkyl, benzyl or alkoxyphenylalkyl groups, amino acid residues or their derivatives, has been obtained in this work. The synthesized compounds have high theoretical affinities for the 18 kDa translocator protein (TSPO) and a favorable profile of ADMET characteristics, which makes them promising for drug development. Anxiolytic activity was detected for eight compounds at doses of 0.1–5.0 mg/kg when administered intraperitoneally under conditions of emotional stress in the open field test in Balb/c mice and in the elevated plus maze test in ICR mice. N-Benzhydryl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide was selected as a lead compound for further development as a potential anxiolytic agent, which showed the presence of anti-anxiety activity in a wide range of doses in both tests used.

Негізгі сөздер

TSPO ligands, pyrrolo[1,2-a]pyrazines, molecular modeling, anxiolytic activity, animal models

Әдебиет тізімі

Mokrov G.V., Deeva O.A., Gudasheva T.A. // Curr. Pharm. Des. 2020. V. 27. P. 217–237. https://doi.org/10.2174/1381612826666200903122025
Sanabria E., Cuenca R.E., Esteso M.Á., Maldonado M. // Toxics. 2021. V. 9. P. 25. https://doi.org/10.3390/toxics9020025
Rupprecht R., Papadopoulos V., Rammes G., Baghai T.C., Fan J., Akula N., Groyer G., Adams D., Schumacher M. // Nat. Rev. Drug Discov. 2010. V. 9. P. 971–988. https://doi.org/10.1038/nrd3295
Sugasawa Y., Cheng W.W.L., Bracamontes J.R., Chen Z.W., Wang L., Germann A.L., Pierce S.R., Senneff T.C., Krishnan K., Reichert D.E., Covey D.F., Akk G., Evers A.S. // Elife. 2020. V. 9. P. 1–32. https://doi.org/10.7554/ELIFE.55331
Guennoun R., Labombarda F., Gonzalez Deniselle M.C., Liere P., De Nicola A.F., Schumacher M. // J. Steroid Biochem. Mol. Biol. 2015. V. 146. P. 48–61. https://doi.org/10.1016/j.jsbmb.2014.09.001
Rupprecht R., Ranimes G., Eser D., Baghai T.C., Schule C., Nothdurfter C., Troxler T., Gentsch C., Kalkman H.O., Chaperon F., Uzunov V., McAllister K.H., Bertaina-Anglade V., La Rochelle C.D., Tuerck D., Floesser A., Kiese B., Schumacher M., Landgraf R., Holsboer F., Kucher K. // Science. 2009. V. 325. P. 490–493. https://doi.org/10.1126/science.1175055
Da Pozzo E., Costa B., Martini C. // Curr. Mol. Med. 2012. V. 12. P. 426–442. https://doi.org/10.2174/156652412800163451
Barresi E., Robello M., Costa B., Da Pozzo E., Baglini E., Salerno S., Da Settimo F., Martini C., Taliani S. // Eur. J. Med. Chem. 2021. V. 209. P. 112924. https://doi.org/10.1016/j.ejmech.2020.112924
Mokrov G.V., Deeva O.A., Gudasheva T.A., Yarkov S.A., Yarkova M.A., Seredenin S.B. // Bioorg. Med. Chem. 2015. V. 23. P. 3368–3378. https://doi.org/10.1016/j.bmc.2015.04.049
Mokrov G.V., Pantileev A.S., Yarkova M.A., Gudasheva T.A., Seredenin S.B. // Med. Chem. 2022. V. 18. P. 497–508. https://doi.org/10.2174/1573406417666210806095051
Gudasheva T.A., Deeva O.A., Mokrov G.V., Dyabina A.S., Yarkova M.A., Seredenin S.B. // Med. Chem. 2018. V. 15. P. 383–399. https://doi.org/10.2174/1573406415666181119164846
Gudasheva T.A., Deeva O.A., Pantileev A.S., Mokrov G.V., Rybina I.V., Yarkova M.A., Seredenin S.B. // Molecules. 2020. V. 25. P. 5132. https://doi.org/10.3390/molecules25215132
Середенин С.Б., Мокров Г.В., Гудашева Т.А., Деева О.А., Ярков С.А., Яркова М.А., Жердев В.П., Алексеев К.В., Дурнев А.Д., Незнамов Г.Г. // Патент RU 2572076 C2, 2015.
Середенин С.Б., Яркова М.А., Поварнина П.Ю., Мокров Г.В., Гудашева Т.А. // Патент RU 2699568 C2, 2019.
Середенин С.Б., Мокров Г.В., Яркова М.А., Пантилеев А.С., Гудашева Т.А., Дурнев А.Д. // Патент RU 2734240 C2, 2020.
Schrödinger Release 2015-4: Maestro, Version 10.4, Schrödinger, LLC, New York, NY, 2015. https://www.schrodinger.com/products/maestro
Schrödinger Release 2015-2: LigPrep, Schrödinger, LLC, New York, NY, 2015. https://www.schrodinger.com/products/ligprep
ADMETlab 2.0: an Integrated Online Platform for Accurate and Comprehensive Predictions of ADMET Properties, 2021. https://admetmesh.scbdd.com/
Руководство по проведению доклинических исследований лекарственных средств. Часть первая / Под ред. Миронова А.Н. Москва: Гриф и К, 2012. 944 с.
Середенин С.Б., Ведерников А.А. // Бюлл. эксп. биол. и мед. 1979. Т. 88. № 7. С. 38–40.
Pellow S., Chopin P., File S.E., Briley M. // Neurosci. Meth. J. 1985. V. 14. P. 149–167.