Design, Synthesis, and Study of the Anxiolytic Activity of New Pyrrolo[1,2-a]pyrazine-Containing TSPO Ligands
- Authors: 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
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Affiliations:
- Research Zakusov Institute of Pharmacology
- Issue: Vol 49, No 2 (2023)
- Pages: 188-206
- Section: 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
Cite item
Abstract
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.
About the authors
G. V. Mokrov
Research Zakusov Institute of Pharmacology
Author for correspondence.
Email: g.mokrov@gmail.com
Russia, 125315, Moscow, ul. Baltiyskaya 8
А. S. Pantileev
Research Zakusov Institute of Pharmacology
Email: g.mokrov@gmail.com
Russia, 125315, Moscow, ul. Baltiyskaya 8
М. А. Yarkova
Research Zakusov Institute of Pharmacology
Email: g.mokrov@gmail.com
Russia, 125315, Moscow, ul. Baltiyskaya 8
I. V. Rybina
Research Zakusov Institute of Pharmacology
Email: g.mokrov@gmail.com
Russia, 125315, Moscow, ul. Baltiyskaya 8
Т. А. Gudasheva
Research Zakusov Institute of Pharmacology
Email: g.mokrov@gmail.com
Russia, 125315, Moscow, ul. Baltiyskaya 8
Yu. V. Vakhitova
Research Zakusov Institute of Pharmacology
Email: g.mokrov@gmail.com
Russia, 125315, Moscow, ul. Baltiyskaya 8
S. B. Seredenin
Research Zakusov Institute of Pharmacology
Email: g.mokrov@gmail.com
Russia, 125315, Moscow, ul. Baltiyskaya 8
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