A Practical Green Visit to the Functionalized [1,2,4]Triazolo [5,1-b]quinazolin-8(4H)one Scaffolds Using the Group-Assisted Purification (GAP) Chemistry and Their Pharmacological Testing

摘要

Herein, we established a straightforward synthetic route for biological relevant [1,2,4]triazolo[5,1-b]quinazolin-8(4H)one scaffolds using the group-assisted purification (GAP) chemistry via one-pot and three component reaction of 3-Amino-5- methylthio-1H-1,2,4-triazole (1), Aryl aldehyde(2a-g), and 1,3- cyclodione (3a-b) using L-proline and aqueous ethanol (1:1, v/ v) as green catalyst and reaction media respectively. This work shows some key features such as practical low Environment factor (E-factor) values, excellent atom economy, reaction mass efficiency, mild reaction condition, metal-free synthesis, and no use of column chromatography. In preliminary biological screening, the compounds, 2-(methylthio)-9-(4-nitrophenyl)- 5,6,7,9-tetrahydro-[1,2,4]triazolo[5,1-b]quinazolin-8(4H)-one (4i) and 6,6-dimethyl-2-(methylthio)-9-(pyridin-4-yl)-5,6,7,9-tetrahy- dro-[1,2,4]triazolo[5,1-b]quinazolin-8(4H)-one (4l) were found most potent against Gram-negative bacteria (E. coli) than the standard drugs ampicillin and chloramphenicol. Moreover, compounds 2-(methylthio)-9-phenyl-5,6,7,9-tetrahydro-[1,2,4]triazolo[5,1-b]quinazolin-8(4H)-one (4a) and 9-(4-methoxyphen- yl)-6,6-dimethyl-2-(methylthio)-5,6,7,9-tetrahydro-[1,2,4]triazolo [5,1-b]quinazolin-8(4H)-one (4f) exhibited excellent potency in comparison with the standard drugs ampicillin, chlorampheni- col, and ciprofloxacin against Gram-positive bacteria (S. aeruginosa and S. pneumoniae). In antifungal screening com- pounds, 9-(4-methoxyphenyl)-2-(methylthio)-5,6,7,9-tetrahydro- [1,2,4]triazolo[5,1-b]quinazolin-8(4H)-one (4e) and 2-(methyl- thio)-9-(4-nitrophenyl)-5,6,7,9-tetrahydro-[1,2,4]triazolo[5,1-b] quinazolin-8(4H)-one (4i) efficiently inhibited C. albicans fungi strain than that of standard drug griseofulvin. Noteworthy compounds 6,6-dimethyl-2-(methylthio)-9-phenyl-5,6,7,9-tetra- hydro-[1,2,4]triazolo[5,1-b]quinazolin-8(4H)-one (4b), 9-(4-chlor- ophenyl)-6,6-dimethyl-2-(methylthio)-5,6,7,9-tetrahydro-[1,2,4] triazolo[5,1-b]quinazolin-8(4H)-one (4d), and 2-(methylthio)-9- (pyridin-4-yl)-5,6,7,9-tetrahydro-[1,2,4]triazolo[5,1-b]quinazolin- 8(4H)-one (4k) were exhibited better potency against M. Tuberculosis.