Synthesis and Bioactivity of Quinoline‐3‐carboxamide Derivatives

Abstract

Twelve novel substituted 2‐chloroquinoline‐3‐carboxamide derivatives were prepared from acetanilides using the Vilsmeier–Haack reaction, producing 2‐chloro‐3‐carbaldehyde quinolines, followed by oxidation of the 3‐carbaldehyde to the carboxylic acid and coupling this group with various anilines. The structures of the synthesized compounds were confirmed by NMR, mass spectrometry, and single crystal X‐ray diffraction. The chemical shifts of H‐5 and H‐8 were shown to be influenced by the substituent at C‐6. The substituent at C‐6 was also seen to affect the chemical shift of C‐5, C‐7, and C‐8, with C‐5 and C‐7 being more shielded in 5j (F substituted) in comparison with 5g (Cl substituted) and 5d (CH3 substituted). The compounds showed weak activity in the mM range against Gram‐positive and Gram‐negative bacteria of which 5b, 5d, and 5f showed the best activity with minimum bactericidal concentration values for 5b being 3.79 mM against methicillin‐resistant Staphylococcus aureus and 5d and 5f having minimum bactericidal concentration values of 3.77 and 1.79 mM against S. aureus ATCC 25923, respectively.

Quinoline‐derivatives as privileged scaffolds for medicinal and pharmaceutical chemists: A comprehensive review

“…Govender and coworkers introduced carboxamide functional group derivatives at third position of quinoline ring, and the best antimicrobial results was obtained with the compound 64a showing 3.79 mM against methicillin-resistant Staphylococcus aureus (MRSA) strains, and fluorine compound 64b as 1.79 mM against the S. aureus. Moreover, they found that F I G U R E 7 Quinoline derivatives with potential anti-tubercular activity the electron donating moieties at quinoline ring contributes to the antibacterial activity (Govender et al, 2018). Karad et al reported the synthesis of morpholinecontaining quinoline scaffolds with oxadiazole moiety at third position and performed an in-vitro antibacterial activity among which the compound 65 provides a good result against S. pneumonia with 0.146 mM MIC (Karad et al, 2017).…”

The synthesis, crystal structure and Hirshfeld analysis of 4-(3,4-dimethylanilino)-N-(3,4-dimethylphenyl)quinoline-3-carboxamide

“…There are two compounds in the database which have an amide group attached to C3, GICGIL [2-chloro-N-(4-fluorophenyl)-6-methylquinoline-3-carboxamide; Govender et al, 2018] and SUZHEB (N-isopropyl-6-methyl-2-phenylquinoline-3-carboxamide; Benzerka et al, 2010). In both these compounds, the amide group is inclined to the quinoline moiety, unlike in molecule 1.…”

Multi‐Component Approach for Synthesis of Quinolinyl‐1,4‐dihydropyridines, Evaluation of Cytotoxicity against MCF7 and Molecular Docking Studies

“…Initially, the reaction was attempted with quinoline-2-chloro-3-carbaldehyde (Scheme 1). Quinoline-2-chloro-3-carbaldehyde, 3-oxo-3-phenylpropanenitrile, and phenyl-β-enamine were refluxed in ethanol for 8 h (quinoline-2-chloro-3-carbaldehyde, [4,22] 3-oxo-3phenylpropanenitrile, [23] and β-enamines [24,25] were prepared following the literature reported procedure, refer ESI for detailed synthetic procedure). The reaction progress was monitored by TLC.…”