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A Practical Green Visit to the Functionalized [1,2,4]Triazolo[5,1‐ b ]quinazolin‐8(4 H )one Scaffolds Using the Group‐Assisted Purification (GAP) Chemistry and Their Pharmacological Testing
Author(s) -
Patel Divyang M.,
Vala Ruturajsinh M.,
Sharma Mayank G.,
Rajani Dhanji P.,
Patel Hitendra M.
Publication year - 2019
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201803605
Subject(s) - chemistry , aryl , aldehyde , ciprofloxacin , chloramphenicol , stereochemistry , combinatorial chemistry , ethanol , medicinal chemistry , catalysis , organic chemistry , antibiotics , biochemistry , alkyl
Herein, we established a straightforward synthetic route for biological relevant [1,2,4]triazolo[5,1‐ b ]quinazolin‐8(4 H )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 (2 a–g) , and 1,3‐cyclodione (3 a–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(4 H )‐one ( 4 i) and 6,6‐dimethyl‐2‐(methylthio)‐9‐(pyridin‐4‐yl)‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐ b ]quinazolin‐8(4 H )‐one ( 4 l) 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(4 H )‐one (4 a) and 9‐(4‐methoxyphenyl)‐6,6‐dimethyl‐2‐(methylthio)‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐ b ]quinazolin‐8(4 H )‐one (4 f) exhibited excellent potency in comparison with the standard drugs ampicillin, chloramphenicol, and ciprofloxacin against Gram‐positive bacteria ( S. aeruginosa and S. pneumoniae ). In antifungal screening compounds, 9‐(4‐methoxyphenyl)‐2‐(methylthio)‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐ b ]quinazolin‐8(4 H )‐one (4 e) and 2‐(methylthio)‐9‐(4‐nitrophenyl)‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐ b ]quinazolin‐8(4 H )‐one (4 i) 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‐tetrahydro‐[1,2,4]triazolo[5,1‐ b ]quinazolin‐8(4 H )‐one (4 b) , 9‐(4‐chlorophenyl)‐6,6‐dimethyl‐2‐(methylthio)‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐ b ]quinazolin‐8(4 H )‐one (4 d) , and 2‐(methylthio)‐9‐(pyridin‐4‐yl)‐5,6,7,9‐tetrahydro‐[1,2,4]triazolo[5,1‐ b ]quinazolin‐8(4 H )‐one (4 k) were exhibited better potency against M. Tuberculosis .