Targeted Synthesis and Analysis of Biologically Active Azomethine Derivatives of 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide

Introduction. Azomethine derivatives of 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide are acyclic precursors of biologically active compounds derived from 5,6,7,8-tetrahydro-3H-benzoteopheno[2,3-d]pyrimidine-4-one. Examples of these groups of compounds with different pharmacological properties are given in the literature, but their cytostatic effect is mainly described. These data and the preparative availability allow us to judge the prospects for further study and molecular design in a number of azomethine derivatives of 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide. Optimization of methods for the synthesis and analysis of substances of this series and the identification of structure-activity relationship are of considerable interest for medical chemistry and pharmaceutical science. The resulting leading compounds will allow us to further develop laboratory requirements for the synthesis of an active pharmaceutical substance.Aim. To make a predict, optimize the synthesis conditions and develop a method for high performance liquid chromatography (HPLC) analysis of pharmacologically active azomethine derivatives of 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide.Materials and methods. The prediction of biological activity was carried out through the web resource PASS Online. The synthesis of the target azomethines was carried out by the interaction of aromatic aldehydes with 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide in an ethanol. The reaction was monitored by thin-layer chromatography (TLC). The determination of related impurities was done by HPLC. The analysis was carried out under the conditions of isocratic elution with a mobile phase of acetonitrile – water (70:30).Results and discussion. The results of the prediction of the biological activity of the constructed structures suggest the manifestation of cytostatic, antitubercular and anti-inflammatory activity characteristic of all target azomethines. The analysis of the reactivity revealed the influence of substituents of aldehydes contained in the aromatic core on the completeness of the condensation reaction. The spectral characteristics clearly confirmed the structure of the products, and the HPLC results showed the purity of the obtained substances, which is more than 95 %.Conclusion. As a result of the conducted studies, the structure of promising azomethine derivatives of 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide was justified and the method of their synthesis and analysis by HPLC was optimized. In the future, the results of the research will allow us to identify the leading compounds with the specified pharmacological properties.

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SOME DIRECTIONS IN THE MODIFICATION OF AZOLES

SERIES CHEMISTRY AND TECHNOLOGY ◽

10.32014/2020.2518-1491.84 ◽

2020 ◽

Vol 5 (443) ◽

pp. 85-91

Author(s):

Ibrayev M.K., ◽

◽

Takibayeva A.T., ◽

Fazylov S.D., ◽

Rakhimberlinova Zh.B., ◽

...

Keyword(s):

13C Nmr Spectroscopy ◽

Biologically Active Compounds ◽

Biologically Active ◽

Active Compounds ◽

Synthesis Conditions ◽

Alkaloid Cytisine ◽

Azole Ring ◽

Cyclic Compounds ◽

New Compounds ◽

Derivatives Of

This article presents studies on the targeted search for new derivatives of azoles, such as benzthiazole, 3,5-dimethylpyrazole, 1,3,4-oxadiazole-2-thione, 1,3,4-thiadiazole. The possibility of combining in one molecule of the azole ring with other cyclic compounds: the alkaloid cytisine, morpholine, furan and some arenes has been studied. To obtain new compounds, the reactions of bromination, acylation, and interaction with isothiocyanates were studied. Optimal synthesis conditions were studied for all reactions. It was found that the reaction of 4-bromo-3,5-dimethylpyrazole with isothiocyanates, in contrast to the previously written derivatives of anilines, takes a longer time and requires heating the reaction mixture. The combination of a pirasol fragment with halide substituents often results in an enhanced therapeutic effect. The synthesized 2-bromine-N-(6-rodanbenzo[d]thiazole-2-yl)acetamide, due to the alkylbromide group, is an important synth in the synthesis of new benzthiazole derivatives. Its derivatives combine in one molecule the rest of rhodanbenzthiazole with alkaloid cytisine and biogenic amine morpholine and are potentially biologically active compounds, since the molecule structure contains several pharmacophoric fragments: benzthiazole and alkaloid (amine) heterocycles, rhodane and urea groups. The mechanism of formation of 1,3,4-oxadiazole-2-tyons from hydrazides under action on them by carbon disulfide was studied and assumed. It was shown that dithiocarbamates in acidic medium decompose with the release of hydrogen sulfide and the formation of highly reactive isothiocyanate group. Then, intra-molecular cyclization occurs, with the formation of end products - 1,3,4-oxadiazole-2-thions. The structures of the synthesized compounds were studied by 1H and 13C NMR spectroscopy. All synthesized substances are potentially biologically active compounds, since they contain several pharmacophore fragments in their structure.

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Biologically Active 2,5-Disubstituted-1,3,4-Oxadiazoles

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2009.2.1.2 ◽

2009 ◽

Vol 2 (1) ◽

pp. 390-406

Author(s):

Harish Rajak ◽

Murli Dhar Kharya ◽

Pradeep Mishra

Keyword(s):

Heterocyclic Compounds ◽

Medical Literature ◽

Biological Activities ◽

Biologically Active ◽

Pharmacological Properties ◽

Clinical Use ◽

Synthetic Drugs ◽

Physiologic Activity ◽

Pharmacologically Active

There are vast numbers of pharmacologically active heterocyclic compounds in regular clinical use. The presence of heterocyclic structures in diverse types of compounds is strongly indicative of the profound effects such structure exerts on physiologic activity, and recognition of this is abundantly reflected in efforts to find useful synthetic drugs. The 1,3,4-oxadiazole nucleus has emerged as one of the potential pharmacophore responsible for diverse pharmacological properties. Medical Literature is flooded with reports of a variety of biological activities of 2,5-Disubstituted-1,3,4-oxadiazoles. The present work is an attempt to summarize and enlist the various reports published on biologically active 2,5-disubstituted-1,3,4-oxadiazoles.

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Isolation, Structure Elucidation, and Biological Activity of a New Alkaloid from Zanthoxylum rhetsa

Natural Product Communications ◽

10.1177/1934578x1100601110 ◽

2011 ◽

Vol 6 (11) ◽

pp. 1934578X1100601

Author(s):

Karsten Krohn ◽

Stephan Cludius-Brandt ◽

Barbara Schulz ◽

Mambatta Sreelekha ◽

Pottachola Mohamed Shafi

Keyword(s):

Biological Activity ◽

Carboxylic Acid ◽

Medicinal Plant ◽

Plant Extract ◽

Structure Elucidation ◽

Biologically Active ◽

Reduction Product ◽

Pharmacological Properties ◽

Evergreen Tree

Several biologically active alkaloids (1-4, 6), including a new quinazoline-6-carboxylic acid (1), were isolated from the medicinal plant Zanthoxylum rhetsa, an evergreen tree, native to subtropical areas. Whereas the pharmacological properties of the plant extract and single constituents have been widely tested, we now show that all of the metabolites have antialgal activities, all but 6 are antibacterial, and 6 and the reduction product 5 (derived from 4) are also antifungal.

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FLAVONOID COMPOUNDS FROM ARTEMISIA GLABELLA KAR. ET. KIR., SYNTHESIS ON THEIR BASIS AND BIOLOGICAL ACTIVITY

chemistry of plant raw material ◽

10.14258/jcprm.2018033766 ◽

2018 ◽

pp. 215-222

Author(s):

Габиден (Gabiden) Маратович (Maratovich) Байсаров (Baysarov) ◽

Айдана (Аjdana) Рахманиякызы (Rakhmaniyakyzy) Жуматаева (Zhumatayeva) ◽

Гулим (Gulim) Кенесбековна (Kenesbekovna) Мукушева (Mukusheva) ◽

Эльвира (El'vira) Эдуардовна (Eduardovna) Шульц (Shul'ts) ◽

Роза (Roza) Батталовна (Battalovna) Сейдахметова (Seydakhmetova) ◽

...

Keyword(s):

Biological Activity ◽

Raw Materials ◽

Hepatoprotective Activity ◽

Biologically Active ◽

Secondary Amines ◽

Moderate Activity ◽

Amino Derivatives ◽

Anti Inflammatory ◽

Derivatives Of

As a result of complex chemical processing of medicinal raw materials of Artemisia glabella Kar. et Kir., including CO2 extraction and lactones isolation, we have investigated the chemical composition of flavonoids to select the biologically active ones and carry out modifications on their basis. Two flavonoids pectolinaringenin and cirsilineol have been isolated by partition chromatography from the secondary raw materials of Artemisia glabella Kar. et. Kir. and identified. To obtain new biologically active compounds, we have synthesized new amino derivatives of cirsilineol by the Mannich reaction with secondary amines (piperidine and N-methylpiperazine) in isopropanol with the presence of dimethylaminopyridine. In proton NMR spectrum of the synthesized compounds there are proton signals of the initial cirsilineol fragment; however, there is no N-8 proton signal, besides other signals typical for amines’ benzene ring have been observed at 1.53–3.90 ppm. It means that reaction occurred at the C-8 position of carbon in ring A. The synthesized compounds have been studied for various types of biological activity typical for this class, including hepatoprotective and anti-inflammatory activities. Amino derivatives of cirsilineol exhibit a moderate activity against HepG2 cell line, while cirsilineol at a dose of 5 mg/ml expresses a pronounced hepatoprotective activity. Moreover, all samples at a dose of 25 mg/kg show poor anti-inflammatory effects on the model of acute exudative reaction in vivo.

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Synthesis and Antimicrobial Activity of Some Derivatives of 5-Substituted Indole Dihydropyrimidines

E-Journal of Chemistry ◽

10.1155/2009/893812 ◽

2009 ◽

Vol 6 (3) ◽

pp. 770-774 ◽

Cited By ~ 6

Author(s):

L. C. C. Heda ◽

Rashmi Sharma ◽

C. Pareek ◽

P. B. Chaudhari

Keyword(s):

Antimicrobial Activity ◽

Minimum Inhibitory Concentration ◽

Multicomponent Reaction ◽

Inhibitory Concentration ◽

Biologically Active ◽

Pharmacological Properties ◽

Dilution Technique ◽

Mueller Hinton ◽

Derivatives Of ◽

Mueller Hinton Broth

P. Biginelli reported the synthesis of functionalized 3, 4 dihydropyrimidine-2 (1H)-ones via three component condensation of an aromatic aldehyde, urea and ethylacetoacetate. This multicomponent reaction is of much importance due to excellent pharmacological properties of dihydropyrimidines. In this account, we synthesized some halo substituted indole dihydropyrimidines and evaluated their antimicrobial activity. The minimum inhibitory concentration (MIC) was determined by micro dilution technique in Mueller-Hinton broth. The MICs were recorded after 24 hours of incubation at 37 °C. These results are promising, showing these compounds are biologically active.

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ChemInform Abstract: Studies on Biologically Active Heterocycles. Part 5. Synthesis and Biological Activity of Heterocyclic Azadienes and Phosphate/ Thiophosphate Derivatives of 1,3,4-Oxa- and Thiadiazoles (III), (V).

ChemInform ◽

10.1002/chin.199351170 ◽

2010 ◽

Vol 24 (51) ◽

pp. no-no

Author(s):

M. M. DUITA ◽

J. C. S. KATAKY

Keyword(s):

Biological Activity ◽

Biologically Active ◽

Derivatives Of

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PREDICTION OF BIOLOGICAL ACTIVITY AND SYNTHESIS OF AZOMETHINE DERIVATIVES OF 2-AMINO-4,5,6,7-TETRAHYDRO-1-BENZOTHIOPHENE-3-CARBOXAMIDE

Наука. Исследования. Практика: сборник избранных статей по материалам Международной научной конференции (Санкт-Петербург, Октябрь 2020) ◽

10.37539/srp293.2020.13.90.004 ◽

2020 ◽

Author(s):

Алексей Сергеевич Чиряпкин ◽

Иван Панайотович Кодониди ◽

Александр Владимирович Ивченко ◽

Лариса Ивановна Щербакова ◽

Александр Алексеевич Глушко

Keyword(s):

Biological Activity ◽

Computer Prediction ◽

Web Resource ◽

Pass Online ◽

Derivatives Of ◽

The Web

В статье представлены результаты компьютерного прогноза биологи-ческой активности азаметинов 2-амино-4,5,6,7-тетрагидро-1-бензотиофен-3-карбоксамида в веб-ресурсе PASS Online. Согласно им моделируемые соединения обладают выраженной противораковой и антимикобактериальной активностями. Затем был осуществлен синтез исследуемых соединений. The article presents the results of computer prediction of the biological activity of azomethines of 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide in the web resource PASS Online. According to them, the modeled compounds have pronounced anticancer and antimycobacterial activities. Then the synthesis of the studied compounds was carried out.

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ChemInform Abstract: BIOLOGICALLY ACTIVE DERIVATIVES OF THIOPHENE. II. SYNTHESIS AND BIOLOGICAL ACTIVITY OF SOME THIOPHENE UNSATURATED KETONES AND THEIR DERIVATIVES

Chemischer Informationsdienst ◽

10.1002/chin.198038204 ◽

1980 ◽

Vol 11 (38) ◽

Author(s):

D. A. KULIKOVA ◽

YU. D. CHURKIN ◽

L. V. PANFILOVA

Keyword(s):

Biological Activity ◽

Biologically Active ◽

Unsaturated Ketones ◽

Derivatives Of ◽

Biologically Active Derivatives

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Synthesis, Modification and Biological Activity of Diosgenyl β-d-Glycosaminosides: An Overview

Molecules ◽

10.3390/molecules25225433 ◽

2020 ◽

Vol 25 (22) ◽

pp. 5433

Author(s):

Daria Grzywacz ◽

Beata Liberek ◽

Henryk Myszka

Keyword(s):

Biological Activity ◽

Biological Activities ◽

Protecting Groups ◽

Pharmacological Properties ◽

Amino Group ◽

Reaction Conditions ◽

Naturally Occurring ◽

Anti Cancer ◽

Wide Group ◽

Derivatives Of

Saponins are a structurally diverse class of natural glycosides that possess a broad spectrum of biological activities. They are composed of hydrophilic carbohydrate moiety and hydrophobic triterpenoid or steroid aglycon. Naturally occurring diosgenyl glycosides are the most abundant steroid saponins, and many of them exhibit various pharmacological properties. Herein, we present an overview of semisynthetic saponins syntheses–diosgenyl β-d-glycosaminosides (d-gluco and d-galacto). These glycosides possess a 2-amino group, which creates great possibilities for further modifications. A wide group of glycosyl donors, different N-protecting groups and various reaction conditions used for their synthesis are presented. In addition, this paper demonstrates the possibilities of chemical modifications of diosgenyl β-d-glycosaminosides, associated with functionalisation of the amino group. These provide N-acyl, N-alkyl, N,N-dialkyl, N-cinnamoyl, 2-ureido and 2-thiosemicarbazonyl derivatives of diosgenyl β-d-glycosaminosides, for which the results of biological activity tests (antifungal, antibacterial, anti-cancer and hemolytic) are presented.

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