4-alkyl-6-amino-4-N 3,N 5-diaryl-2-thioxo-1,2,3,4-tetrahydropyridine-3,5-dicarboxamides: I. Tandem synthesis and alkylation. Molecular and crystal structure of 6-allylsulfanyl-2-amino-4-isobutyl-N 3,N 5-di-m-tolyl-3,4-dihydropyridine-3,5-dicarboxamide

Dyachenko, V. D.; Karpov, E. N.

doi:10.1134/s1070363213070153

Cited by 5 publications

(1 citation statement)

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“…However, while nicotinonitriles have been fairly well studied, the related synthetic nicotinamides and 1,4-dihydronicotinamides have been less studied and require further investigation. One of the most accessible and efficient approaches to the synthesis of functionalized nicotinamides is based on the reaction of active methylene malonamides and malonthioamides with 1,3-C 3 dielectrophiles [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. Monothiomalonamide 1 (3-amino-3-thioxopropanamide) is known as a very convenient reagent for the preparation of substituted nicotinamides.…”

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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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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