Psychotropic Effects of a New Pyrazolo[C]Pyridine Derivate GIZh-72 are Related to Functional Activity of Atp-Sensitive Potassium Channels

Касабов, Кирилл Алексеевич; Kudryashov, N. V.; Волкова, А. В.; Shimshirt, A A; Калинина, Татьяна Сергеевна; Zhmurenko, L. A.; Воронина, Т. А.

doi:10.1007/s10517-020-04729-5

Cited by 4 publications

(4 citation statements)

References 12 publications

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“…Thus, a large number of substituted pyrazolopyridine derivatives have been found to possess various biological properties including: A(1) adenosine receptor antagonists, 1 antimicrobial, 2 non-anionic antiplatelet agents 3 and compounds with psychotropic effects. 4 Some alkaloids of the pyrano [3,4-с]pyridine series possess universal effects, which include hypotensive, anticonvulsant, antipsychotic, anti-inflammatory and antitumor activities. [5][6][7] The current study is a continuation of our research on the synthesis and evaluation of neurotropic activity of fused tri-and tetracyclic systems containing pyridine ring.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, neurotropic activity and SAR of new S-alkyl derivatives of 8- pyrazol-1-yl pyrano[3,4-c]pyridines

Dashyan¹,

Paronikyan²,

Mamyan³

et al. 2022

Arkivoc

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8- 4,6,pyridine was synthesized by a newly developed method. Pyrazolo substituted 6-thioxo-and S-alkyl-derivatives of the pyrano [3,4-c]pyridines have also been synthesized. In this work, 8-(3,5-dimethyl-1H-pyrazol-1-yl)-3,3-dimethyl-6-oxo-3,4,6,7-tetrahydro-1Hpyrano[3,4-c]pyridine-5-carbonitrile was also synthesized via an intramolecular nucleophilic substitution (Smiles rearrangement). The study of the neurotropic activity of the synthesized compounds was carried out using convulsive models (pentylenetetrazole and maximal electroshock) and the rotating rod model was used to study central myorelaxation. Compounds were found to antagonize corazole, but did not exhibit muscle relaxation at the studied doses, while simultaneously, they showed anxiolytic and antidepressant psychotropic activity.

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Section: Introductionmentioning

confidence: 99%

“…

8- 4,6,pyridine was synthesized by a newly developed method. Pyrazolo substituted 6-thioxo-and S-alkyl-derivatives of the pyrano [3,4-c]pyridines have also been synthesized.

…”

mentioning

confidence: 99%

Synthesis, neurotropic activity and SAR of new S-alkyl derivatives of 8- pyrazol-1-yl pyrano[3,4-c]pyridines

Dashyan¹,

Paronikyan²,

Mamyan³

et al. 2022

Arkivoc

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“…The derivatives of condensed pyridines are of interest as biologically active substances [ 4 ]. Thus, a large number of substituted pyrazolopyridine derivatives have been found to possess various biological properties such as A(1) adenosine receptor antagonism [ 5 ], antimicrobial properties [ 6 ], nonanionic antiplatelet agents [ 7 ] and psychotropic effects [ 8 ]. Some alkaloids of the pyrano[3,4- c ]pyridine series exert universal effects: hypotensive, anticonvulsant, antipsychotic, anti-inflammatory and antitumor effects [ 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Neurotropic Activity and Molecular Docking Study of New Derivatives of pyrano[4″,3″:4′,5′]pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidines on the Basis of pyrano[3,4-c]pyridines

Dashyan¹,

Бабаев

Paronikyan³

et al. 2022

Molecules

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Background: Heterocyclic compounds and their fused analogs, which contain pharmacophore fragments such as pyridine, thiophene and pyrimidine rings, are of great interest due to their broad spectrum of biological activity. Chemical compounds containing two or more pharmacophore groups due to additional interactions with active receptor centers usually enhance biological activity and can even lead to a new type of activity. The search for new effective neurotropic drugs in the series of derivatives of heterocycles containing pharmacophore groups in organic, bioorganic and medical chemistry is a serious problem. Methods: Modern methodology of drugs involves synthesis, physicochemical study, molecular modeling and selection of active compounds through virtual screening and experimental evaluation of the biological activity of new chimeric compounds with pharmacophore fragments. For the synthesis of new compounds, classical organic methods were used and developed. For the evaluation of neurotropic activity of new synthesized compounds, some biological methods were used according to indicators characterizing anticonvulsant, sedative and antianxiety activity as well as side effects. For docking analysis,various soft ware packages and methods were used. Results: As a result of multistep reactions, 11 new, tri- and tetracyclic heterocyclic systems were obtained. The studied compounds exhibit protection against pentylenetetrazole (PTZ) seizures as well as some psychotropic effects. The biological assays evidenced that nine of the eleven studied compounds showed a high anticonvulsant activity by antagonism with pentylenetetrazole. The toxicity of the compounds is low, and they do not induce muscle relaxation in the studied doses. According to the study of psychotropic activity, it was found that the selected compounds have an activating behavior and anxiolytic effects on the “open field” and “elevated plus maze” (EPM) models. The data obtained indicate the anxiolytic (antianxiety) activity of the derivatives of tricyclic thieno[2,3-b]pyridines and tetracyclic pyridothieno[3,2-d]pyrimidin-8-ones, especially pronounced in compounds 3bf and 4e. The studied compounds increase the latent time of first immobilization on the “forced swimming” (FS) model and exhibit antidepressant effects; compounds 3e and 3f especially exhibit these effects, similarly to diazepam. Docking studies revealed that compounds 3c and 4b bound tightly in the active site of γ-aminobutyric acid type A (GABAA) receptors with a value of the scoring function that estimates free energy of binding (∆G) at −10.0 ± 5 kcal/mol. Compound 4e showed the best affinity ((∆G) at −11.0 ± 0.54 kcal/mol) and seems to be an inhibitor of serotonin(SERT) transporter. Compounds 3cf and 4e practically bound with the groove of T4L of 5HT_1A and blocked it completely, while the best affinity observed was in compound 3f ((∆G) at −9.3 ± 0.46 kcal/mol). Conclusions: Тhe selected compounds have an anticonvulsant, activating behavior and anxiolytic effects and at the same time exhibit antidepressant effects.

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“…В данной работе мы изучили нейропротекторную и противосудорожную активность нескольких новых производных трициклических пиразолилзамещенных тиено [2,3-c]изохинолинов (SHD-89 и SHD-91) и пирано [4,3-d]тиено [2,3-b] important core structure in many drug substances. A large number of substituted pyrazolopyridine derivatives were found to possess diverse biological properties, such as antimicrobial [12,13], antiviral [14], antileishmanial [15], and anti-inflammatory [16] non-anionic antiplatelet agents [17], as well as psychotropic effects [18].…”

Section: Introductionmentioning

confidence: 99%

Pathological investigation of neuroprotective activity of new derivatives of fused pyrazolyl-thienopyridines in Corazol-induced seizures

Gasparyan¹,

Buloyan²,

Pogosyan³

et al. 2021

Clin. Exp. Morphology

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Introduction. Seizures provoke several morphological alterations in the brain structures. These alterations are primarily located in the hippocampal CA1 region and the entorhinal cortex. Recurrent seizures are common in patients with epilepsy. Therapeutic options for this disease are very limited and most of them are aimed at relieving symptoms. In most cases, to treat epilepsy, anti-seizure drugs are used. Nevertheless, one-third of affected individuals have resistance to them. Thus, the study of new effective agents that can prevent epileptogenesis is still an ongoing challenge. In this work, we aimed to study the neuroprotective activity of several new derivatives of tricyclic pyrazolyl substituted thieno[2,3-c]isoquinolins (SHD-89 and SHD-91) and pyrano[4,3-d]thieno[2,3-b]pyridines (SHD-78 and SHD-85) as potential anti-seizure drugs. Materials and methods. The study was performed on mice (n=60). The action of compounds SHD-78, SHD-85, SHD-89, and SHD-91 was tested in seizures with and without Corazol administration. Histopathological examinations were performed in the hippocampus and the entorhinal cortex in different experimental groups. Results. The study showed that under the action of SHD-89 and SHD-78, there was a reduction in the number of neurons and activation of glial cells in examined regions of the brain. SHD-91 caused severe neurode-generative effects with changes in the brain structure. In contrast, under the action of SHD-85, the number of neurons was higher and with lower activation of glial cells. Conclusion. Studies showed that among the tested compounds SHD-85 possessed moderate neuroprotective activity and reduced gliosis and neuronal loss induced by Corazol. Keywords: anti-seizure drugs, pyrazolylthienopyridines, hippocampus, entorhinal cortex, histopathological examination

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Psychotropic Effects of a New Pyrazolo[C]Pyridine Derivate GIZh-72 are Related to Functional Activity of Atp-Sensitive Potassium Channels

Cited by 4 publications

References 12 publications

Synthesis, neurotropic activity and SAR of new S-alkyl derivatives of 8- pyrazol-1-yl pyrano[3,4-c]pyridines

Synthesis, neurotropic activity and SAR of new S-alkyl derivatives of 8- pyrazol-1-yl pyrano[3,4-c]pyridines

Evaluation of Neurotropic Activity and Molecular Docking Study of New Derivatives of pyrano[4″,3″:4′,5′]pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidines on the Basis of pyrano[3,4-c]pyridines

Pathological investigation of neuroprotective activity of new derivatives of fused pyrazolyl-thienopyridines in Corazol-induced seizures

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