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

作者: Mokrov G.V.¹, Pantileev А.S.¹, Yarkova М.А.¹, Rybina I.V.¹, Gudasheva Т.А.¹, Vakhitova Y.V.¹, Seredenin S.B.¹
隶属关系:
1. Research Zakusov Institute of Pharmacology
期: 卷 49, 编号 2 (2023)
页面: 188-206
栏目: Articles
URL: https://ogarev-online.ru/0132-3423/article/view/145878
DOI: https://doi.org/10.31857/S0132342323020173
EDN: https://elibrary.ru/PGKDNM
ID: 145878

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详细

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.

关键词

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

参考

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