Anxiolytic Activity of 11H-2,3,4,5-Tetrahydro[1,3]Diazepino[1,2-a]Benzimidazole and 2-Mercaptobenzimizadole Derivatives

Spasov, A. A.; Zhukovskaya, O. N.; Maltsev, D. V.; Мирошников, М. В.; Skripka, Maria O.; Султанова, К. Т.; Морковник, А. С.

doi:10.1134/s1068162020010124

Cited by 6 publications

(3 citation statements)

References 4 publications

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“…In addition to the behavioral activity of the animals, the OF technique also made it possible to assess the nonspecific muscle relaxant capacity of new compounds (Maltsev et al 2020). A battery of muscle relaxation tests -Rotarod, Grid, and Wire -were described previously (Spasov et al 2020b).…”

Section: Open Field Test and Spontaneous Locomotor Activity Assessmentmentioning

confidence: 99%

Screening of anxiolytic properties and analysis of structure-activity relationship of new derivatives of 6-(4-methoxy)-7H-[1,2,4]triazolo[3,4-a][2,3]benzodiazepine under the code RD

Skripka¹,

Spasov²,

Maltsev³

et al. 2021

RRP

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Introduction: Searching for new compounds with anti-anxiety activity resulting from the combination of privileged scaffolds is a promising direction in medicinal chemistry and in the development of new drugs. Anxiolytic potential and cytotoxic properties of previously synthesized molecules, containing fragments of 2,3-benzodiazepine and 1,2,4-triazole – 6-(4-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-A][2,3]benzodiazepines under the generic code RD were studied. Materials and methods: Screening for anxiolytic activity was performed on elevated plus maze (EPM) and open field (OF) test models. Structural and functional analysis of the anti-anxiety activity of the studied substances was carried out. A degree of muscle relaxant effect of the substances was assessed in the tests Grid, Wire, and Rotarod. A cytotoxicity study of RD compounds was carried out using an MTT assay on human hepatocellular carcinoma cells HepG2. Results and discussion: For a number of novel triazolo[3,4-a][2,3]benzodiazepine derivatives, a prominent anxiolytic activity was manifested in terms of EPM test. The results of OF test were consistent with the obtained data and confirmed the presence of the sought activity in the leading compounds. There was no significant effect on muscle tone for the compounds under study. It was observed that RD compounds possessed no cytotoxic properties and were safe for further studies in vivo. Conclusion: Among the new derivatives of 6-(4-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-a][2,3]benzodiazepine under the code RD, substances (RD-4, 12, 13) with a high anxiolytic activity comparable to diazepam and tofisopam were found. The most promising compound is RD-4 due to its pronounced anxiolytic and low cytotoxic properties.

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Section: Open Field Test and Spontaneous Locomotor Activity Assessmentmentioning

confidence: 99%

Screening of anxiolytic properties and analysis of structure-activity relationship of new derivatives of 6-(4-methoxy)-7H-[1,2,4]triazolo[3,4-a][2,3]benzodiazepine under the code RD

Skripka¹,

Spasov²,

Maltsev³

et al. 2021

RRP

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“…Interaction with the serotonergic system was assessed by the severity of hyperkinesis (the number of nodding movements) within 60 min after administration of 5-hydroxytryptophan (300 mg/kg, i.p.) [22].…”

Section: -(5-oxotricyclomentioning

confidence: 99%

Synthesis and Evaluation of the Psychotropic Activity of Framework Derivatives of Alpha-Pyrrolidone

et al. 2021

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Derivatives of alpha-pyrrolidone and some derivatives of adamantane possess a wide spectrum of psychotropic activity. The synthesis of adamantane and homoadamantane derivatives of alpha-pyrrolidone and the assessment of their psychotropic activity were performed. A number of framework compounds containing a pyrrolidin-2-one fragment either in the side chain or as part of the framework system were synthesized. N-(Adamantan-1-yl)pyrrolidin-2-one (TIM-2) was obtained by the reaction of 1-bromadamantane with pyrrolidin-2-one. Homoadamantane-fused pyrrolidin-2-one (TIM-1) was obtained from β-dicarbonyl derivatives of homoadamantane. Synthesis of the starting 2-(5-oxohomoadamantyl)acetic acid was carried out by cleavage of the corresponding keto diester or cyanoketo ester of homoadamantane under the conditions of the Holler-Bauer reaction with sonication. Then, the resulting γ-keto acid was introduced into the Leuckart-Wallach reaction to obtain cis- decahydro-4,8:6,10-dimethanocyclononane[b]pyrrol-2(1H)-one (TIM-1). The psychotropic activity of the obtained compounds was evaluated in standard behavioral tests in experimental animals. Compound TIM-2 exhibited pronounced anxiolytic, antidepressant, and nootropic activity. Compound binding assays were performed by molecular docking of the synthesized compounds to the GABA-B receptor, which also showed high binding energies for TIM-2.

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“…In addition, compound RU-476, which has a 5-HT 2A antagonistic effect, reduced the severity of anxious behavior in animals both in conflict conditions (Vogel conflict test) and a non-conflict (Elevated Plus Maze) stressful situation, which is comparable to the effect of diazepam [ 15 ]. For 2-mercaptobenzimidazole derivatives under the code AZH-57-67, an anxiolytic action was shown in Elevated Plus Maze and Open Field tests [ 16 ]. Derivatives of 2-aminomethylbenzimidazole showed high analgesic and anti-inflammatory activity in the models “Acetic acid-induced writhing” and “Carrageenan-induced paw edema” in mice, comparable to nimesulide at a dose of 50 mg/kg [ 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Pharmacological Evaluation of Novel 2,3,4,5-tetrahydro[1,3]diazepino[1,2-a]benzimidazole Derivatives as Promising Anxiolytic and Analgesic Agents

et al. 2021

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A number of novel 2,3,4,5-tetrahydro[1,3]diazepino[1,2-a]benzimidazole derivatives 2 were obtained by alkylation mainly in the 1H-tautomeric form of 2,3,4,5-tetrahydro[1,3]diazepino[1,2-a]benzimidazole or its 8,9-dimethyl-substituted analog 4-chlorobenzyl bromide, 4-chloroacetic acid fluoroanilide, and 4-tert-butylphenacyl bromide in neutral medium. Compounds 3 were cyclized and synthesized earlier with 11-phenacyl-substituted diazepino[1,2-a]benzimidazoles upon heating in conc. HBr. The chemical structures of the compounds were clarified by using the 1H Nuclear Magnetic Resonance Spectroscopy (1H-NMR) technique. Anxiolytic properties were evaluated using the elevated plus maze (EPM) and open field (OF) tests. The analgesic effect of compounds was estimated with the tail flick (TF) and hot plate (HP) methods. Besides, possible the influence of the test compounds on motor activities of the animals was examined by the Grid, Wire, and Rotarod tests. Compounds 2d and 3b were the most active due to their prominent analgesic and anxiolytic potentials, respectively. The results of the performed in silico analysis showed that the high anxiolytic activity of compound 3b is explained by the combination of a pronounced interaction mainly with the benzodiazepine site of the GABAA receptor with a prominent interaction with both the specific and allosteric sites of the 5-HT2A receptor.

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Anxiolytic Activity of 11H-2,3,4,5-Tetrahydro[1,3]Diazepino[1,2-a]Benzimidazole and 2-Mercaptobenzimizadole Derivatives

Cited by 6 publications

References 4 publications

Screening of anxiolytic properties and analysis of structure-activity relationship of new derivatives of 6-(4-methoxy)-7H-[1,2,4]triazolo[3,4-a][2,3]benzodiazepine under the code RD

Screening of anxiolytic properties and analysis of structure-activity relationship of new derivatives of 6-(4-methoxy)-7H-[1,2,4]triazolo[3,4-a][2,3]benzodiazepine under the code RD

Synthesis and Evaluation of the Psychotropic Activity of Framework Derivatives of Alpha-Pyrrolidone

Synthesis and Pharmacological Evaluation of Novel 2,3,4,5-tetrahydro[1,3]diazepino[1,2-a]benzimidazole Derivatives as Promising Anxiolytic and Analgesic Agents

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