Synthesis and Antiarrhythmic Activity of 2-Diethylamino-2′,6′-Dimethylphenylacetamide Derivatives

Сернов, Л. Н.; Skachilova, S. Ya.; Блинов, Д. С.; Druzhinina, V. V.; Kostin, Ya. V.; Shilova, E. V.

doi:10.1007/s11094-005-0152-6

Cited by 3 publications

(3 citation statements)

References 5 publications

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“…Two novel pharmacologic substances, developed at The All-Russian Research Centre for Safety of Biologically Active Compounds (Sernov et al 2005) and Ogarev Mordovia State University (Blinov et al 2014), were investigated ( Fig. 1 contains chemical structures of the substances) in the form of fine white water-soluble powder without or with insignificant odour.…”

Section: Substances and Drugsmentioning

confidence: 99%

“…In the early 2000s in Russia, a few novel molecules, DPA (Lidocaine) derivatives, were synthetised (Sernov et al 2005). The main reason for developing the substances was the short duration of Lidocaine therapeutic activity, which makes it impossible to administer the drug orally for prophylaxis (Collinsworth et al 1974).…”

Section: Introductionmentioning

confidence: 99%

“…The substances, representatives of both methods of chemical modification, have been experimentally studied for many years at The All-Russia Research Centre For Safety of Biologically Active Compounds (Sernov et al 2005), Ogarev Mordovia State University (Blinov et al 2004, Blinov et al 2014, Blinova et al 2015 and Tver State Medical University (Marasanov et al 2013A, Marasanov et al 2013b.…”

Section: Introductionmentioning

confidence: 99%

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On mechanism of antiarrhythmic action of some dimethylphenylacetamide derivatives

Yahya¹,

Kurganov²,

Blinova³

et al. 2018

RRP

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Abbreviations: AC – acetylcholyne; AF – atrial fibrillation; AP – action potential; BLM – bi-lipid membrane; DPA – Dimethylphenylacetamide; VA – ventricular arrhythmia Introduction: The study aim was to identify essential elements of the antiarrhythmic action mechanism of tertiary and quaternary derivatives of Dimethylphenylacetamide. Materials and Methods: The study was conducted in albino rats and mice of both sexes; isolated neurons of mollusc Limneastagnalis; and strips of rats’ right ventricle myocardium. Two compounds of Dimethylphenylacetamide LKhT-3-00 and LKhT-12-02 were studied. The cholynolytic property of the compounds was investigated by using a Schallek method in the authors’ modification. The adrenotropic activity of the derivatives was explored by Moore and Spear (1984), as well a by the method of catecholamine level detection in heart tissue. The permeability of derivatives through BLM was evaluated experimentally and theoretically. The derivatives’ influence on Na+-current was studied directly and indirectly. Results and Discussion: Neither tertiary nor quaternary derivatives possess the cholynolytic property. LKhT-3-00 prevented an increase in the adrenaline concentration in the left ventricle myocardium. The compounds prevent catecholamine arrhythmia and conductivity disorders. LKhT-3-00 like Lidocaine passes through the BLM of the cardiac cell in an ionised form, whereas the quaternary derivative permeates cardiac cell membrane in an electro-neutral form. Lidocaine derivatives restrain acute ischemia-induced oxidative process growth in the cardiac muscle. Simultaneously, the LKhT-3-00 compound can activate antioxidant mechanisms and prevent acidosis and optimise the balance between [O2] and [CO2] concentrations in coronary dark blood. At a concentration of 10 mg/ml, although the derivatives reduce the amplitude of the leading edge of AP and its rate of increase, they do not, however, affect the duration of AP. Conclusions: The compounds possess the Na+-blocking and cell-protecting properties. They do not affect K+-current through Kv4.3-channels.

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Section: Substances and Drugsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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On mechanism of antiarrhythmic action of some dimethylphenylacetamide derivatives

Yahya¹,

Kurganov²,

Blinova³

et al. 2018

RRP

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Computer-aided prediction for medicinal chemistry via the Internet

Geronikaki

Druzhilovsky

Zakharov

et al. 2008

SAR and QSAR in Environmental Research

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Some computational tools for medicinal chemistry freely available on the Internet were compared to examine whether the results of prediction obtained with different methods coincided or not. It was shown that the correlation coefficients varied from 0.65 to 0.90 for log P (seven methods), from 0.01 to 0.73 for aqueous solubility (four methods), and from 0.19 to 0.73 for drug-likeness (three methods). While for log P estimates, reasonable average pairwise correlation was found, for aqueous solubility and drug-likeness it was rather poor. Therefore, using computational tools freely available via the Internet, medicinal chemists should evaluate their accuracy versus experimental data for particular series of compounds. In contrast to prediction of above mentioned properties, which can be done with several Internet tools, wide profiling of biological activity can be obtained only with PASS Inet (http://www.ibmc.msk.ru/PASS). PASS Inet was tested by a dozen medicinal chemists for compounds from different chemical series with various kinds of biological activity, and in the majority of cases the results of prediction coincided with the experiments. New anxiolytics, antiarrhythmics, antileishmanials, and other biologically active agents have been identified on this basis. The advantages and limitations of computer-aided predictions for medicinal chemistry via the Internet are discussed.

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On local anesthetic action of some dimethylacetamide compounds

Новиков¹,

Blinova²,

Семелева³

et al. 2018

RRP

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The study aim was to explore local anesthetic properties of some tertiary and quaternary derivatives of dimethylacetamide. Materials and methods. The study was performed on white laboratory mice and rats of both sexes, male Agouti guinea pigs, and isolated sciatic nerves of lake frog. In the focus of the study there were two quaternary and eight tertiary compounds of dimethylacetamide with substituted anion with some amino and carbonic acids residue. A local anesthetic property was predicted by computational analysis. Acute toxicity of the most promising substances was studied in mice through subcutaneous route. Local anesthetic activity of tertiary compounds LKhT-3-00, LKhT-4-00 and quaternary LKhT-12-02 was studied on models of terminal, infiltration and conduction anesthesia. The influence of substances on mixed nerve conduction was investigated on lake frog’s isolated sciatic nerves. Results and discussion. The greatest probability of the local anesthetic activity during computational analysis was estimated for the tertiary derivatives of dimethylacetamide LKhT-3-00 and LKhT-4-00 and for the quaternary compound LKhT-12-02. According to their toxicological profile, the compounds belong to moderately toxic substances (class 3). On the model of terminal and infiltration anesthesia, substances LKhT-3-00 and LKhT-4-00 at concentrations of 0.5-1% rapidly cause deep and prolonged anesthesia. On the models of conduction anesthesia, the quaternary derivative of dimethylacetamide LKhT-12-02 has the greatest analgesic effect. The duration of the effect of the substance is over 3 hours. All the investigated compounds block sciatic nerve conduction. The longest effect is registered for LKhT-12-02. Conclusions. Dimethylacetamide derivatives at concentrations of 0.5-1.0% exhibit a local anesthetic activity, and are effective for terminal, conduction and infiltration anesthesia. Their effect is due to blockade of nerve conduction.

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Synthesis and Antiarrhythmic Activity of 2-Diethylamino-2′,6′-Dimethylphenylacetamide Derivatives

Cited by 3 publications

References 5 publications

On mechanism of antiarrhythmic action of some dimethylphenylacetamide derivatives

On mechanism of antiarrhythmic action of some dimethylphenylacetamide derivatives

Computer-aided prediction for medicinal chemistry via the Internet

On local anesthetic action of some dimethylacetamide compounds

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