Synthesis and pharmacological activity of 10-alkylaminoethyl-2,3,4,10-tetrahydropyrimido[1,2-a]benzimidazoles

Anisimova, V. A.; Толпыгин, И. Е.; Spasov, A. A.; Yakovlev, D. S.; Kolobrodova, N. A.; Гурова, Н. А.; Salaznikova, O. A.; Науменко, Л. В.; Косолапов, В. А.; Mitina, T. M.; Воронкова, М П; Lenskaya, K. V.

doi:10.1007/s11094-012-0791-3

Cited by 8 publications

(4 citation statements)

References 4 publications

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“…In some cases, their analgesic and anti-inflammatory effects are described [26]. There are works describing their antiarrhythmic properties [3,4,33,51,52].…”

Section: Results Of a Study Of The Local Anaesthetic Activity Of Pipe...mentioning

confidence: 99%

Synthesis and Experimental Study of the Local Anesthetic Activity of New Modified Piperazine Derivatives

KHAIITOVA¹

2023

FARMACIA

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N-substituted piperazines, an important class of compounds with different pharmacological activities were taken as the basic starting object for the synthesis and study of α-aminophosphonates. The objective of the study was the synthesis, analysis of biological effects (toxicity and local anaesthetic activity) of some new piperazine derivatives, and the evaluation of their potential pharmacological effects. The new piperazine derivatives were coded as LAS-276, LAS-277, LAS-278, where LAS is a local anaesthetic substance. The compounds were synthesized under the conditions of the Kabachnik-Fields reaction. Their acute toxicity in mice, the local anaesthetic activity in a regional and infiltration anaesthesia models were studied, and their estimated pharmacological activity was analysed using the online PASS (Prediction of Activity Spectra for Substances) program. In a series of experiments the administration of high doses of the studied compounds has not caused death of laboratory animals. The study of local anaesthetic activity in the infiltration anaesthesia model showed varying degrees of activity. The compounds showed moderate activity on the regional anaesthesia model. The PASS analysis revealed a very high probability of thrombolytic, anticoagulant, antisclerotic effects and stimulation of endothelin receptors. The implemented studies revealed the low toxicity, moderate local anaesthetic activity of the studied piperazine compounds. There is also a high probability of their thrombolytic activity, which requires further research. RezumatPiperazinele N-substituite sunt o clasă importantă de compuși cu activitate farmacologică ce stau la baza sintezei și studiul αaminofosfonaților. Obiectivele studiului au fost sinteza, analiza efectelor biologice (toxicitate și activitate anestezică locală) și evaluarea efectelor farmacologice ale noilor derivați de piperazină. Compușii au fost sintetizați în condițiile reacției Kabachnik-Fields. Apoi s-a studiat toxicitatea lor după administrarea în doză unică la șoareci, activitatea anestezică locală într-o anestezie regională și modele de infiltrație. Activitatea lor farmacologică a fost evaluată folosind programul online PASS (Predicția Spectrelor de Activitate pentru Substanțe). Într-o serie de experimente, administrarea de doze mari din compușii studiați nu a provocat moartea animalelor de laborator. Studiul activității anestezice locale în modelul de anestezie prin infiltrare a arătat grade variate de activitate. Compușii au prezentat activitate moderată în modelul de anestezie regională. Analiza PASS a relevat o probabilitate foarte mare de efecte trombolitice, anticoagulante, antisclerotice și de stimulare a receptorilor de endotelină. Studiile implementate au evidențiat toxicitatea scăzută, precum și activitatea anestezică locală moderată a compușilor piperazinici studiați. Există, de asemenea, o probabilitate mare a activității lor trombolitice, ceea ce necesită cercetări suplimentare.

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“…In some cases, their analgesic and anti-inflammatory effects are described [26]. There are works describing their antiarrhythmic properties [3,4,33,51,52].…”

Section: Results Of a Study Of The Local Anaesthetic Activity Of Pipe...mentioning

confidence: 99%

Synthesis and Experimental Study of the Local Anesthetic Activity of New Modified Piperazine Derivatives

KHAIITOVA¹

2023

FARMACIA

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“…It was revealed that 2-methoxy-phenyl-and 2-oxyphenyl-substituted 1-dialkylaminoalkyl-IMBI [8], N-acylmethyl derivatives of 9H-2,3-dihydro-IMBI and 10H-2,3,4,10-tetrahydropyrimido[1,2-a]benzimidazoles [9], most of 3-(2,2,2-trichloro-1-hydroxyethyl)-IMBI [12] и 3-acetyl-2-R-9-dialkylaminoethyl-IMBI [13], 1-dialkyl(alkyl)aminoethyl-2,3-dihydro-IMBI [14], and 3-(n,n-disubstituted)acetamide-1-r-2-aminobenzimidazolium [17] showed the weak antioxidant activity compared to the reference drug. Among 10-alkylaminoethyl-2,3,4,10-tetrahydropyrimido[1,2-a]benzimidazoles [16] and phenyl-and alkylthiocarbamides of 2,9-disubstituted IMBI [19], antioxidant action has not been found.…”

Section: The Resultsmentioning

confidence: 99%

Condensed Benzimidazoles Are a Novel Scaffold for Antioxidant Agents’ Search and Development

Косолапов¹,

Спасов²,

Анисимова³

et al. 2019

Antioxidants

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Taking into account that the imidazole ring has π-electron redundancy, condensed benzimidazole derivatives have attracted our attention as a promising class for the search for antioxidant substances. Synthesis was carried out, and information on the antioxidant activity of imidazo-and tetrahydropyrimido benzimidazoles was provided. Highly active antioxidant substance enoxifol has been revealed. The data on the synthesis and study of the pharmacodynamic, pharmacokinetic, and toxicological properties of the new antioxidant compound enoxifol are presented. The antioxidant activity of the compound is due to its ability to inactivate superoxide, hydroxyl, and peroxyl radicals, thereby reducing the overall oxidation rate due to a decrease in the total initiation rate. It has been shown that enoxifol has hepatoprotector, antihypoxic, cerebroprotective, nootropic, stressprotective, neuropsychotropic, actoprotective, cardioprotective, antiaggregant, and antithrombogenic properties and is able to prevent rheological disorders in diabetes mellitus.

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“…The synthesis of novel 2-aminobenzimidazole (AmBI) [13,14] derivatives and fused benzimidazole derivatives was carried out, including N 9 -imidazo [1,2-a] benzimidazoles (N 9 -ImBI) [15][16][17], N 1 -imidazo[1,2-a]benzimidazoles (N 1 -ImBI) [18,19], N 9 -2,3-dihydroimidazo[1,2-a]benzimidazoles (N 9 -DhImBI) [20,21], N 1 -2,3-dihydroimidazo[1,2-a]benzimidazoles (N 1 -DhImBI) [18,19], and 2,3,4,10-tetrahydropyrimido[1,2-a]benzimidazoles (PrmBI) [22][23][24].…”

Section: Resultsmentioning

confidence: 99%

Antidiabetogenic Features of Benzimidazoles

Спасов¹,

Vassiliev²,

Анисимова³

et al. 2019

Chemistry and Applications of Benzimidazole and Its Derivatives

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Literature data on the insulinogenic effect of 2-aminobenzimidazole prompted us to investigate its novel derivatives, particularly those containing an additional fused cycle in C1,2-α position, including imidazole, dihydroimidazole, or tetrahydropyrimidine ring. Consensus analysis of the hypoglycemic effect of these compounds performed with IT Microcosm and PASS system revealed that activity is mostly characteristic for N 9 -2,3-dihydroimidazo[1,2-a]benzimidazole derivatives. Substructural analysis of hypoglycemic activity identified substituents that determine the greatest pharmacological effect. According to the in silico assessment of the ADME properties, RU-254 was nominated as a lead compound due to the most optimal calculated and experimental activity and pharmacokinetic parameters. Preclinical studies have shown that identified compound has a pronounced insulinogenic effect and hypoglycemic effect, both in intact animals and in animals with experimental diabetes mellitus. RU-254 also reduces the level of glycated hemoglobin upon chronic administration, slightly decreases the activity of DPP-4, and increases the average number of Langerhans islets in the pancreas. Pharmaceutical drug formulation of RU-254 was developed and investigated for pharmacokinetic, pharmacodynamic, and toxicological properties. The dosage form of the drug under the name limiglidol (compound RU-254, diabenol) was evaluated in the full cycle of clinical studies that confirmed the safety, tolerability, and prominent antidiabetic properties of the drug.

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Synthesis and pharmacological activity of 10-alkylaminoethyl-2,3,4,10-tetrahydropyrimido[1,2-a]benzimidazoles

Cited by 8 publications

References 4 publications

Synthesis and Experimental Study of the Local Anesthetic Activity of New Modified Piperazine Derivatives

Synthesis and Experimental Study of the Local Anesthetic Activity of New Modified Piperazine Derivatives

Condensed Benzimidazoles Are a Novel Scaffold for Antioxidant Agents’ Search and Development

Antidiabetogenic Features of Benzimidazoles

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