Facile Synthesis of Aryl-Pyridyl, Pyridazinyl, Pyrazinyl, and Triazinyl Acetonitriles

Farahat, Abdelbasset A.; Boykin, David W.

doi:10.1002/jhet.1535

Cited by 5 publications

(3 citation statements)

References 17 publications

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“…The syntheses of the key N ‐methylbenzimidazole heterocycles are outlined in Scheme . Reaction of the readily available bromoheteroaryl aldehydes 1 with 4‐cyanophenylboronic acid under standard Suzuki coupling conditions conveniently provided the 5‐(4‐cyanophenyl)‐2‐formyl 5‐ring heterocycles 2 , which could be used to prepare both the tri ‐ and tetra ‐heteroaryl target molecules 4 and 6 . Oxidative condensation and cyclization, mediated by sodium metabisulfite, of the aldehydes 2 with 3‐amino‐4‐(methylamino) benzonitrile gave the bis ‐nitriles 3 in acceptable yields .…”

Section: Resultsmentioning

confidence: 99%

The Thiophene “Sigma‐Hole” as a Concept for Preorganized, Specific Recognition of G⋅C Base Pairs in the DNA Minor Groove

Guo

Kumar

Farahat

et al. 2016

Chemistry A European J

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In spite of its importance in cell function, targeting DNA is under-represented in the design of small molecules. A barrier to progress in this area is the lack of a variety of modules that recognize G•C base pairs (bp) in DNA sequences. To overcome this barrier an entirely new design concept for modules that can bind to mixed GC and AT sequences of DNA is reported. Because of their successes in biological applications, minor-groove-binding heterocyclic cations were selected as the platform for design. Binding to AT sequences requires H-bond donors while recognition of the G-NH2 requires an acceptor. The concept that we report here uses preorganized N-methylbenzimidazole (N-MeBI) thiophene modules for selective binding with mixed bp DNA sequences. The interaction between the thiophene sigma-hole (positive electrostatic potential) and electron donor nitrogen of N-MeBI preorganizes the conformation for accepting an H-bond from G-NH2. The compound-DNA interactions were evaluated with a powerful array of biophysical methods and the results show that N-MeBI-thiophene monomer compounds can strongly and selectively recognize single G•C bp sequences. Replacing the thiophene with other moieties significantly reduces binding affinity and specificity, as predicted by the design concept. These results show that the use of molecular features, such as sigma-hole, can lead to new approaches for small molecules in biomolecular interactions.

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Section: Resultsmentioning

confidence: 99%

The Thiophene “Sigma‐Hole” as a Concept for Preorganized, Specific Recognition of G⋅C Base Pairs in the DNA Minor Groove

Guo

Kumar

Farahat

et al. 2016

Chemistry A European J

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“…Finally, we used sodium borohydride and Pd(C) in methanol/dichloromethane as a solvent to get the intermediate tetraamine 3a–c in good yield. This amine was subjected to an oxidative cyclization reaction using different aldehydes 9 and sodium metabisulfite in DMSO to furnish the intermediate imidazobenzimidazole 4a–f. 10 The bis-nitriles 4a–f were allowed to react with lithium bis(trimethylsilyl)amide in THF, followed by subsequent deprotection of the silylated amidines with ethanolic HCl (gas) to furnish the hydrochloride salts of the diamidines 5a–f.…”

Section: Resultsmentioning

confidence: 99%

Engineered modular heterocyclic-diamidines for sequence-specific recognition of mixed AT/GC base pairs at the DNA minor groove

2021

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“…For the preparation of compound 7, we started by making the boronic ester 6 via reaction of bis(pinacolato)diboron 4 with the bromo derivative 5. Suzuki coupling using palladium (0) [21,22] was applied between the bromo compound 1 and the boronic ester 6 to produce the formyl intermediate 7 in good yield.…”

Section: Resultsmentioning

confidence: 99%

Facile synthesis of benzobisimidazole and bibenzimidazole‐based bisnitriles as potential precursors for DNA minor groove binders

Farahat

Iwamoto

Roche

et al. 2021

Journal of Heterocyclic Chem

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The synthesis of bisnitrile derivatives of benzobisimidazole and bibenzimidazole in a good yield is described in detail for the first time. Nucleophilic substitution of 1,5-difluoro-2,4-dinitrobenzene using different amines produced the intermediate diamines that were reduced using sodium borohydride/Pd(C) to produce the tetramines. These tetramines were allowed to couple with different aldehydes to produce the final benzimidazoles. In a different investigation, these bisnitrile derivatives will be used to make benzimidazole diamidines that could be used as potential mixed sequence minor groove binders.

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Facile Synthesis of Aryl-Pyridyl, Pyridazinyl, Pyrazinyl, and Triazinyl Acetonitriles

Cited by 5 publications

References 17 publications

The Thiophene “Sigma‐Hole” as a Concept for Preorganized, Specific Recognition of G⋅C Base Pairs in the DNA Minor Groove

The Thiophene “Sigma‐Hole” as a Concept for Preorganized, Specific Recognition of G⋅C Base Pairs in the DNA Minor Groove

Engineered modular heterocyclic-diamidines for sequence-specific recognition of mixed AT/GC base pairs at the DNA minor groove

Facile synthesis of benzobisimidazole and bibenzimidazole‐based bisnitriles as potential precursors for DNA minor groove binders

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