Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Sujeet Kumar Gupta
1*
and Ashutosh Mishra
2
1
Department of Pharmaceutical Chemistry, Hygia Institute of Pharmaceutical Education and Re-
search, Lucknow-206020, India;
2
Department of Pharmaceutical Chemistry, Acharya Narendra
Deo College of Pharmacy, Babhnan, Gonda-271313, India
A R T I C L E H I S T O R Y
Received: December 14, 2015
Revised: February 09, 2016
Accepted: February 10, 2016
DOI:
10.2174/187152301566616021012
4545
Abstract: 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 signifi-
cant anti-inflammatory and less ulcerogenic activity. The present study deals with the synthe-
sis and pharmacological assessment of a series of novel quinoline derivatives bearing azetidi-
nones 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 + POCl
3
) 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 con-
firmed on the basis of elemental analysis, IR,
1
H NMR,
13
C 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,
1
H NMR,
13
C NMR and mass spectra were
found to be prominent. The anti-inflammatory activity test revealed that 3-chloro-1-(4-metho-
xyphenyl)-4-(tetrazolo[1,5-a] quinolin-4-yl)azetidin-2-one (6b), 3-chloro-1-(2-methoxyphe-
nyl)-4-(tetrazolo[1,5-a]quinolin-4-yl)azetidin-2-one (6a) exhibited significant anti-inflamma-
tory 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.
Keywords: Vilsmeier-Haack reaction, Quinoline, Azetidinones, Schiff base, Anti-inflammatory, Analge-
sic activity.
1. INTRODUCTION
Inflammation is a complex defensive mechanism.
During inflammation the body responds to different
*Address correspondence to this author at Department of
Pharmaceutical Chemistry, Hygia Institute of Pharmaceutical
Education and Research, Ghazipur Balram, Ghaila Road
Lucknow-206021 India; Tel: +919453409629;
Fax: +91-; 52226546437; E-mail: sujeet20gupta2@gmail.com
injuries where there is gathering of leukocytes and
local fluids which ultimately eliminate the noxious
stimulus. The development of persistent damaged
tissue is not properly repaired by inflammatory
cells in the pathological conditions [1, 2]. During
inflammation, some important mediators are re-
leased viz. histamine and serotonin. Edema and
inflammation have been produced by carrageenan
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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, 2016, 15, 31-43
31
RESEARCH ARTICLE
Synthesis, Characterization & Screening for Anti-Inflammatory &
Analgesic Activity of Quinoline Derivatives Bearing Azetidinones
Scaffolds