Synthesis and Structure of 4-Aryl-3,6-dioxo-2,3,4,5,6,7-hexahydroisothiazolo[5,4-b]pyridine-5-carbonitriles

Dotsenko, V. V.; Jassim, N. T.; Темердашев, А. З.; Аксенов, Н. А.; Аксенова, И. В.

doi:10.1134/s1070363222120386

Cited by 2 publications

(3 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, isothiazolo[5,4-b]pyridines are much less studied, although some compounds showed anti-tuberculosis [ 85 ] effects, were reported as COX-1 cyclooxygenase inhibitors [ 86 ], analgesics [ 87 ] and strong inhibitors of histone acetyltransferases with potential anticancer effects [ 88 ]. Previously, we have reported that the DMSO–HCl system can be successfully used as a mild oxidizing agent to convert 2-mercaptopyridin-3-carboxamides into isothiazolo[5,4-b]pyridines [ 72 , 89 ]. Nevertheless, upon treatment of thiolates 14a + 14b with excess HCl in DMSO solution, only corresponding 2-thioxopyridine 16 was isolated in 88% yield instead of the expected products 15.…”

Section: Resultsmentioning

confidence: 99%

“…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%

“…tem can be successfully used as a mild oxidizing agent to convert 2-mercaptopyridin-3-carboxamides into isothiazolo [5,4-b]pyridines [72,89]. Nevertheless, upon treatment of thiolates 14a + 14b with excess HCl in DMSO solution, only corresponding 2-thioxopyridine 16 was isolated in 88% yield instead of the expected products 15.…”

Section: Scheme 5 the Local Shielding/deshielding Effects On The Conh...mentioning

confidence: 99%

See 2 more Smart Citations

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Synthesismentioning

confidence: 99%

Section: Scheme 5 the Local Shielding/deshielding Effects On The Conh...mentioning

confidence: 99%

See 1 more Smart Citation

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

Self Cite

View full text Add to dashboard Cite

show abstract

The chemistry of heterocycles in the 21st century

Charushin,

Verbitskiy,

Chupakhin

et al. 2024

RUSS CHEM REV

View full text Add to dashboard Cite

The chemistry of heterocyclic compounds has traditionally been and remains a bright area of chemical science in Russia. This is due to the fact that many heterocycles find the widest application. These compounds are the key structural fragments of most drugs, plant protection agents. Many natural compounds are also derivatives of heterocycles. At present, more than half of the hundreds of millions of known chemical compounds are heterocycles. This collective review is devoted to the achievements of Russian chemists in this field over the last 15–20 years. The review presents the achievements of leading heterocyclists representing both RAS institutes and university science. It is worth noting the wide scope of the review, both in terms of the geography of author teams, covering the whole of our large country, and in terms of the diversity of research areas. Practically all major types of heterocycles are represented in the review. The special attention is focused on the practical applications of heterocycles in the design of new drugs and biologically active compounds, high-energy molecules, materials for organic electronics and photovoltaics, new ligands for coordination chemistry, and many other rapidly developing areas. These practical advances would not be possible without the development of new fundamental transformations in heterocyclic chemistry.<br> Bibliography — 2237 references.

show abstract

Synthesis and Structure of 4-Aryl-3,6-dioxo-2,3,4,5,6,7-hexahydroisothiazolo[5,4-b]pyridine-5-carbonitriles

Cited by 2 publications

References 55 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

The chemistry of heterocycles in the 21st century

Contact Info

Product

Resources

About