Background: Non-steroidal anti-inflammatory drugs (NSAIDS) are clinically used
as anti-inflammatory, analgesic and antipyretic agents but they have the drawbacks such as
gastric irritation and gastric ulceration. Recently, quinoline derivatives have shown significant
anti-inflammatory and less ulcerogenic activity. The present study deals with the synthesis
and pharmacological assessment of a series of novel quinoline derivatives bearing azetidinones
scaffolds as anti-inflammatory and analgesic agents.
Methods: A series of newer 3-chloro-1-(substituted)-4-(tetrazolo [1,5-a]quinolin-4-
yl)azetidin-2-one derivatives (6a-l) was synthesized starting with acetanilide (1). Initially,
acetanilide (1) was allowed to react with Vilsmeier-Haack reagent (DMF + POCl3) to form 2-
chloro-3-formyl quinoline (2). The 2-chloro-3-formyl quinoline (2) was further treated with
p-toluenesulphonic acid and sodium azide which yielded Tetrazolo [1,5-1] quinoline-4-
carbaldehyde (3). The reaction of formyl group with various substituted amines (4a-l) formed
corresponding Schiff base intermediates (5a-l), which were further allowed to react with
chloroacetyl chloride to produce 3-chloro-1-(substituted)-4-(tetrazolo [1,5-a]quinolin-4-yl)
azetidin-2-one derivatives (6a-l). The structure of the final analogues (6a-l) has been confirmed
on the basis of elemental analysis, IR, 1H NMR, 13C NMR and mass spectra. All the
synthesized compounds were evaluated for their anti-inflammatory and analgesic activities by
using carrageenan induced rat paw model and Eddy’s hot plate method respectively.
Results: All the values of elemental analysis, IR, 1H NMR, 13C NMR and mass spectra were
found to be prominent. The anti-inflammatory activity test revealed that 3-chloro-1-(4-methoxyphenyl)-
4-(tetrazolo[1,5-a] quinolin-4-yl)azetidin-2-one (6b), 3-chloro-1-(2-methoxyphenyl)-
4-(tetrazolo[1,5-a]quinolin-4-yl)azetidin-2-one (6a) exhibited significant anti-inflammatory
and analgesic activity as compared to control group.
Conclusion: The results of the current study indicate that substitution at quinoline derivatives
bearing azetidinones scaffolds showed potent analgesic and anti-inflammatory activities.