Design and synthesis of 2-chloroquinoline derivatives as non-azoles antimycotic agents

A series of secondary amines ( 4 – 19 ) containing 2-chloroquinoline as lipophilic domain have been synthesized based on the structural requirements essential for allylamine/benzylamine antimycotics by nucleophilic substitution reaction of 3-chloromethyl-2-chloroquinoline 3 with various aliphatic and aromatic amines in absolute ethanol in the presence of triethylamine. Some N -methyl derivatives ( 20 – 25 ) were also synthesized by N -methylation using (CH 3 ) 2 SO 4 /NaH. The structures of newly synthesized compounds were established by the combined use of IR, 1 H-NMR, 13 C-NMR, and Mass spectra. Compounds 4 – 25 were screened in vitro at conc. of 200 g/ml for their antifungal activity against Aspergillus niger MTCC 281, Aspergillus flavus MTCC 277, Monascus purpureus MTCC 369, and Penicillium citrinum NCIM 768 by cup-plate method using Terbinafine as a references drug. Among the secondary amines, compounds 4 , 5 , 8 , 10 , 14 , and 16 exhibited potential antifungal activity and their corresponding N -methyl ( 20 – 25 ) derivatives also showed further increase in antifungal activity against fungal strain Aspergillus niger MTCC 281, Aspergillus flavus MTCC 277. Compounds 3-chloro- N -[(2-chloroquinolin-3-yl)methyl]-4-fluoro- N -methylaniline ( 24 ) and 3,4-dichloro- N -[(2-chloroquinolin-3-yl)methyl]- N -methylaniline ( 25 ) were the most potent derivatives of the series.