Development of the optimal scheme for the synthesis of the dipeptide TSPO ligand, N-phenylpropionyl-L-tryptophanyl-L-leucine amide (GD-102), a potential anxiolytic drug

Previously at the Zakusov Research Institute of Pharmacology the first dipeptide ligand TSPO, the compound N-phenylpropionyl-L-tryptophanyl-L-leucine amide (laboratory code GD-102), was designed and synthesized. The anxiolytic activity was detected for this compound at the doses 0.01–1.0 mg/kg intra...

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Main Author: O. A. Deeva
Format: Article
Language:Russian
Published: LLC “Publisher OKI” 2024-01-01
Series:Фармакокинетика и Фармакодинамика
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Online Access:https://www.pharmacokinetica.ru/jour/article/view/396
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author O. A. Deeva
author_facet O. A. Deeva
author_sort O. A. Deeva
collection DOAJ
description Previously at the Zakusov Research Institute of Pharmacology the first dipeptide ligand TSPO, the compound N-phenylpropionyl-L-tryptophanyl-L-leucine amide (laboratory code GD-102), was designed and synthesized. The anxiolytic activity was detected for this compound at the doses 0.01–1.0 mg/kg intraperitoneally (ip) in mice. Dipeptide GD-102 also possessed antidepressant-like activity at the doses 0.01 and 0.05 mg/kg ip in BALB/c mice in the Porsolt forced swim test. The ligand properties of dipeptide GD-102 to TSPO were confirmed by pharmacological inhibitory analysis and molecular docking. This work is devoted to the development of the optimal scheme for the synthesis of the GD-102. 3 methods were tried — 1 activated succinimide esters method, 2 activated pentafluorophenyl ethers method and 3 imidazolide method. These three synthesis schemes have been compared in terms of yield and optical purity of the final product. It was shown that the optimal synthesis scheme is the first one, using succinimide esters.
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institution Kabale University
issn 2587-7836
2686-8830
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series Фармакокинетика и Фармакодинамика
spelling doaj-art-1ade5823bff54bbb94c5ec00bb590d1d2025-08-20T03:42:33ZrusLLC “Publisher OKI”Фармакокинетика и Фармакодинамика2587-78362686-88302024-01-0104839410.37489/2587-7836-2023-4-83-94359Development of the optimal scheme for the synthesis of the dipeptide TSPO ligand, N-phenylpropionyl-L-tryptophanyl-L-leucine amide (GD-102), a potential anxiolytic drugO. A. Deeva0Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical TechnologiesPreviously at the Zakusov Research Institute of Pharmacology the first dipeptide ligand TSPO, the compound N-phenylpropionyl-L-tryptophanyl-L-leucine amide (laboratory code GD-102), was designed and synthesized. The anxiolytic activity was detected for this compound at the doses 0.01–1.0 mg/kg intraperitoneally (ip) in mice. Dipeptide GD-102 also possessed antidepressant-like activity at the doses 0.01 and 0.05 mg/kg ip in BALB/c mice in the Porsolt forced swim test. The ligand properties of dipeptide GD-102 to TSPO were confirmed by pharmacological inhibitory analysis and molecular docking. This work is devoted to the development of the optimal scheme for the synthesis of the GD-102. 3 methods were tried — 1 activated succinimide esters method, 2 activated pentafluorophenyl ethers method and 3 imidazolide method. These three synthesis schemes have been compared in terms of yield and optical purity of the final product. It was shown that the optimal synthesis scheme is the first one, using succinimide esters.https://www.pharmacokinetica.ru/jour/article/view/396dipeptidegd-102tspo ligandpeptide synthesis
spellingShingle O. A. Deeva
Development of the optimal scheme for the synthesis of the dipeptide TSPO ligand, N-phenylpropionyl-L-tryptophanyl-L-leucine amide (GD-102), a potential anxiolytic drug
Фармакокинетика и Фармакодинамика
dipeptide
gd-102
tspo ligand
peptide synthesis
title Development of the optimal scheme for the synthesis of the dipeptide TSPO ligand, N-phenylpropionyl-L-tryptophanyl-L-leucine amide (GD-102), a potential anxiolytic drug
title_full Development of the optimal scheme for the synthesis of the dipeptide TSPO ligand, N-phenylpropionyl-L-tryptophanyl-L-leucine amide (GD-102), a potential anxiolytic drug
title_fullStr Development of the optimal scheme for the synthesis of the dipeptide TSPO ligand, N-phenylpropionyl-L-tryptophanyl-L-leucine amide (GD-102), a potential anxiolytic drug
title_full_unstemmed Development of the optimal scheme for the synthesis of the dipeptide TSPO ligand, N-phenylpropionyl-L-tryptophanyl-L-leucine amide (GD-102), a potential anxiolytic drug
title_short Development of the optimal scheme for the synthesis of the dipeptide TSPO ligand, N-phenylpropionyl-L-tryptophanyl-L-leucine amide (GD-102), a potential anxiolytic drug
title_sort development of the optimal scheme for the synthesis of the dipeptide tspo ligand n phenylpropionyl l tryptophanyl l leucine amide gd 102 a potential anxiolytic drug
topic dipeptide
gd-102
tspo ligand
peptide synthesis
url https://www.pharmacokinetica.ru/jour/article/view/396
work_keys_str_mv AT oadeeva developmentoftheoptimalschemeforthesynthesisofthedipeptidetspoligandnphenylpropionylltryptophanyllleucineamidegd102apotentialanxiolyticdrug