Synthesis and pharmacological activity of amides of 2,3-dihydroimidazo- and 2,3,4,10-tetrahydropyrimido[1,2-a]benzimidazolyln-acetic acids

Anisimova, V. A.; Spasov, A. A.; Косолапов, В. А.; Толпыгин, И. Е.; Тибирькова, Е. В.; Salaznikova, O. A.; Кузнецова, В. А.; Гурова, Н. А.; Lenskaya, K. V.; Yakovlev, D. S.; Maltsev, D. V.; Kolobrodova, N. A.; Mitina, T. M.; Grechko, O. Yu.

doi:10.1007/s11094-013-0862-0

Cited by 8 publications

(5 citation statements)

References 7 publications

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“…The compounds from the series of 1-substituted 2-benzylaminobenzimidazoles with phenyl methoxyls acted similarly [20]. Amides of 2,3-dihydroimidazo-and 2,3,4,10-tetrahydropyrimido[1,2-a]benzimidazolyl-acetic acids showed moderate AO activity compared to dibunol [18]. 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.…”

Section: The Resultsmentioning

confidence: 99%

“…Condensed benzimidazole derivatives were synthesized, and experimental screening of the antioxidant activity of new chemical compounds was carried out among the derivatives of 2-(hetaryl) imidazo[1,2-a]benzimidazoles (IMBI) [5], 3-aroyl-and 3-hetaroyl-IMBI [6], 2-methoxyphenyl-substituted 9-dialkylaminoethyl-IMBI [7], 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], 9-dialkylaminoethyl-2-oxy(dioxy)phenyl-IMBI [10], aroylmethyl derivatives of tricyclic benzimidazole systems containing hydroxy groups in aroyl radicals [11] [17], amides of 2,3-dihydroimidazo-and 2,3,4,10-tetrahydropyrimido[1,2-a]benzimidazolyl-acetic acids [18], phenyl-and alkylthiocarbamides of 2,9-disubstituted IMBI [19], and 1-substituted 2-benzylaminobenzimidazoles with phenyl methoxyls [20]. Butylated hydroxytoluene (BHT, CAS Number 128-37-0), also known as dibunol, was chosen as a comparative drug.…”

Section: The Resultsmentioning

confidence: 99%

“…The study of the enoxifol action on hemorheology was carried out in the model of "increased viscosity syndrome" according to the method [57]. An improvement in blood flow, membrane plasticity, and inhibition of erythrocyte aggregation under the influence of enoxifol administration in dose 5 mg/kg was found [18]. An increase in the rate of local cerebral blood flow and a direct effect on the tone of cerebral vessels in a similar dose were determined in the method of tissue microcirculation [58].…”

Section: Action On Hemorheologymentioning

confidence: 99%

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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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Section: The Resultsmentioning

confidence: 99%

Section: The Resultsmentioning

confidence: 99%

Section: Action On Hemorheologymentioning

confidence: 99%

See 1 more Smart Citation

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

Косолапов¹,

Спасов²,

Анисимова³

et al. 2019

Antioxidants

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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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“…Ðàíåå íàìè áûëî âûÿâëåíî íîâîå ñîåäèíåíèå -ýìåòàçîë (ïðîèçâîäíîå èìèäàçî[1,2-a]áåíçèìèäàçîëà), äëÿ êîòîðîãî ïîêàçàíà 5-ÍÒ 3 -áëîêèðóþùàÿ è àíòèýìåòè÷åñêàÿ àêòèâíîñòü [14,8]. Ïðèíèìàÿ âî âíèìàíèå ó÷àñòèå 1…”

Section: ââåäåíèåunclassified

Спазмолитический и висцеральный анальгетический эффекты нового 5-HT<sub>3</sub>-антагониста эметазола в эксперименте

Яковлев¹,

Любашина²,

Бусыгина³

et al. 2018

Эксп. и клин. фармакол.

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Эметазол (дигидрохлорид 1-пиперидинопропил-2-(4-фторфенил)имидазо[1,2-α]бенз- имидазола, соединение РУ-1276) был изучен на способность снижать серотонинзависимый спазм тонкого кишечника морских свинок in vitro и уменьшать болевую чувствительность в условиях моделирования абдоминальной боли у бодрствующих собак. Показано, что для изучаемого соединения характерен высокий уровень антиспастического действия, не уступающий таковому для ондансетрона и превосходящий соответствующую активность метоклопрамида в 2,5 раза (p < 0,05), а также характерен выраженный висцеральный анальгетический эффект, проявлявшийся в подавлении висцеромоторной и сердечно-сосудистой реакций бодрствующего животного на болевое ректальное растяжение на (46,7 ± 6,8) % и (29,4 ± 7,9) %, соответственно, (p < 0,0001). Полученные результаты позволяют позиционировать эметазол как биологически активное вещество для лечения кишечных гипермоторики и гиперчувствительности при синдроме раздраженной кишки и указывают на целесообразность проведения соответствующих доклинических исследований.

show abstract

Synthesis and pharmacological activity of amides of 2,3-dihydroimidazo- and 2,3,4,10-tetrahydropyrimido[1,2-a]benzimidazolyln-acetic acids

Cited by 8 publications

References 7 publications

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

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

Antidiabetogenic Features of Benzimidazoles

Спазмолитический и висцеральный анальгетический эффекты нового 5-HT<sub>3</sub>-антагониста эметазола в эксперименте

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