Synthesis, Structure, and Analgesic Activity of 4-(5-Cyano-{4-(fur-2-yl)-1,4-dihydropyridin-3-yl}carboxamido)benzoic Acids Ethyl Esters

Krivokolysko, D. S.; Dotsenko, V. V.; Bibik, E. Yu.; Myazina, A. V.; Кривоколыско, С. Г.; Vasilin, V. K.; Панков, А. А.; Аксенов, Н. А.; Аксенова, И. В.

doi:10.1134/s1070363221120306

Cited by 7 publications

(4 citation statements)

References 72 publications

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“…A similar reaction with 5-methylisatin led to the formation of a mixture of 1 H-thiolate 14a and 3 H-thiolate 14b in a molar ratio of 7:3 and yield of 83%. In the context of our interest in exploring the chemistry of biologically active nicotinonitriles [70][71][72][73][74][75][76][77][78][79] and indole-nicotinonitrile hybrids [80], it seemed reasonable to prepare new 6′-amino-5′-cyano-2-oxo-1,2-dihydro-1′H-spiro[indole-3,4′-pyridine]-3′-carboxamides and to study their reactions and properties.…”

Section: Synthesismentioning

confidence: 99%

“…In the context of our interest in exploring the chemistry of biologically active nicotinonitriles [ 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 ] and indole–nicotinonitrile hybrids [ 80 ], it seemed reasonable to prepare new 6′-amino-5′-cyano-2-oxo-1,2-dihydro-1′ H -spiro[indole-3,4′-pyridine]- 3′-carboxamides and to study their reactions and properties.…”

Section: Introductionmentioning

confidence: 99%

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New 6′-Amino-5′-cyano-2-oxo-1,2-dihydro-1′H-spiro[indole-3,4′-pyridine]-3′-carboxamides: Synthesis, Reactions, Molecular Docking Studies and Biological Activity

et al. 2023

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The purpose of this work was to prepare new isatin- and monothiomalondiamide-based indole derivatives, as well as to study the properties of the new compounds. The four-component reaction of 5-R-isatins (R = H, CH3), malononitrile, monothiomalonamide (3-amino-3-thioxo- propanamide) and triethylamine in hot EtOH yields a mixture of isomeric triethylammonium 6′-amino-3′-(aminocarbonyl)-5′-cyano-2-oxo-1,2-dihydro-1′H- and 6′-amino-3′-(aminocarbonyl)- 5′-cyano-2-oxo-1,2-dihydro-3′H-spiro[indole-3,4′-pyridine]-2′-thiolates. The reactivity and structure of the products was studied. We found that oxidation of spiro[indole-3,4′-pyridine]-2′-thiolates with DMSO-HCl system produced only acidification products, diastereomeric 6′-amino-5′-cyano-5-methyl-2-oxo-2′-thioxo-1,2,2′,3′-tetrahydro-1′H-spiro-[indole-3,4′-pyridine]- 3′-carboxamides, instead of the expected isothiazolopyridines. The alkylation of the prepared spiro[indole-3,4′-pyridine]-2′-thiolates upon treatment with N-aryl α-chloroacetamides and α-bromoacetophenones proceeds in a regioselective way at the sulfur atom. In the case of α-bromoacetophenones, ring-chain tautomerism was observed for the S-alkylation products. According to NMR data, the compounds consist of a mixture of stereoisomers of 2′-amino-6′-[(2-aryl- 2-oxoethyl)thio]-3′-cyano-2-oxo-1′H-spiro[indoline-3,4′-pyridine]-5′-carboxamides and 5′-amino- 3′-aryl-6′-cyano-3′-hydroxy-2-oxo-2′,3′-dihydrospiro[indoline-3,7′-thiazolo[3,2-a]pyridine]-8′-carboxamides in various ratios. The structure of the synthesized compounds was confirmed by IR spectroscopy, HRMS, 1H and 13C DEPTQ NMR studies and the results of 2D NMR experiments (1H-13C HSQC, 1H-13C HMBC). Molecular docking studies were performed to investigate suitable binding modes of some new compounds with respect to the transcriptional regulator protein PqsR of Pseudomonas aeruginosa. The docking studies revealed that the compounds have affinity for the bacterial regulator protein PqsR of Pseudomonas aeruginosa with a binding energy in the range of −5.8 to −8.2 kcal/mol. In addition, one of the new compounds, 2′-amino-3′-cyano-5-methyl- 2-oxo-6′-{[2-oxo-2-(p-tolylamino)ethyl]thio}-1′H-spiro-[indoline-3,4′-pyridine]-5′-carboxamide, showed in vitro moderate antibacterial effect against Pseudomonas aeruginosa and good antioxidant properties in a test with 1,1-diphenyl-2-picrylhydrazyl radical. Finally, three of the new compounds were recognized as moderately active herbicide safeners with respect to herbicide 2,4-D in the laboratory experiments on sunflower seedlings.

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Section: Synthesismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

New 6′-Amino-5′-cyano-2-oxo-1,2-dihydro-1′H-spiro[indole-3,4′-pyridine]-3′-carboxamides: Synthesis, Reactions, Molecular Docking Studies and Biological Activity

et al. 2023

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“…Webina thus simplifies the docking process, making it accessible even to novices. Though only recently published, several researchers have already used Webina to study compounds with analgesic [ 62 ], anti-cancer [ 63 , 64 ], anti-bacterial [ 65 ], anti-viral [ 66 , 67 , 68 ], and antioxidant [ 69 ] properties, among others [ 70 , 71 ]. The Webina app and source code are freely available online under the terms of the open-source Apache License, version 2.0 ( Table 1 ).…”

Section: Examples Of Cadd Browser Appsmentioning

confidence: 99%

Open-Source Browser-Based Tools for Structure-Based Computer-Aided Drug Discovery

Wang

Durrant

2022

Molecules

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We here outline the importance of open-source, accessible tools for computer-aided drug discovery (CADD). We begin with a discussion of drug discovery in general to provide context for a subsequent discussion of structure-based CADD applied to small-molecule ligand discovery. Next, we identify usability challenges common to many open-source CADD tools. To address these challenges, we propose a browser-based approach to CADD tool deployment in which CADD calculations run in modern web browsers on users’ local computers. The browser app approach eliminates the need for user-initiated download and installation, ensures broad operating system compatibility, enables easy updates, and provides a user-friendly graphical user interface. Unlike server apps—which run calculations “in the cloud” rather than on users’ local computers—browser apps do not require users to upload proprietary information to a third-party (remote) server. They also eliminate the need for the difficult-to-maintain computer infrastructure required to run user-initiated calculations remotely. We conclude by describing some CADD browser apps developed in our lab, which illustrate the utility of this approach. Aside from introducing readers to these specific tools, we are hopeful that this review highlights the need for additional browser-compatible, user-friendly CADD software.

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“…Continuing research in the field of functional cyanothioacetamide derivatives with potential biological activity [39][40][41][42][43], we focused our attention on the possibility of obtaining new heterocyclic products through the oxidation of 2-cyanothioacrylamides 2 with sodium nitrite in an acidic medium. NaNO 2 in the presence of acids can act as a nitrosating agent as well as mild oxidizing agent.…”

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Oxidation of 2-Cyanothioacrylamides with Sodium Nitrite in Acidic Medium

et al. 2022

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(E)-3-Aryl-2-cyanoprop-2-entioamides, prepared by Knoevenagel condensation between aromatic aldehydes and cyanothioacetamide, react with sodium nitrite in acetic acid to form (2E,2′E)-2,2′-(1,2,4-thiadiazole-3,5-diyl)bis[3-arylacrylonitriles]. A possible mechanism and limitations of the reaction are discussed. Molecular docking was carried out in order to search for possible protein targets for the obtained 1,2,4-thiadiazoles. One of the compounds showed a pronounced antidote effect against the herbicide 2,4-D in a laboratory experiment on sunflower seedlings and under field conditions.

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Synthesis, Structure, and Analgesic Activity of 4-(5-Cyano-{4-(fur-2-yl)-1,4-dihydropyridin-3-yl}carboxamido)benzoic Acids Ethyl Esters

Cited by 7 publications

References 72 publications

New 6′-Amino-5′-cyano-2-oxo-1,2-dihydro-1′H-spiro[indole-3,4′-pyridine]-3′-carboxamides: Synthesis, Reactions, Molecular Docking Studies and Biological Activity

New 6′-Amino-5′-cyano-2-oxo-1,2-dihydro-1′H-spiro[indole-3,4′-pyridine]-3′-carboxamides: Synthesis, Reactions, Molecular Docking Studies and Biological Activity

Open-Source Browser-Based Tools for Structure-Based Computer-Aided Drug Discovery

Oxidation of 2-Cyanothioacrylamides with Sodium Nitrite in Acidic Medium

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