A novel procedure to synthesize 3-chloro-1-(4a,10b-diazaphenanthrene-2-yl)- 4-phenyl azetidin-2-ones and exploration of their anti-inflammatory activity

Article abstract of DOI:10.1002/jhet.1086

Some new derivatives of 3-chloro-1-(4a,10b-diazaphenanthrene-2-yl)-4-phenyl azetidin-2-one were synthesized through the reaction of N-{4-[phenyldiazenyl] phenyl}-N-[phenyl methylene] amine with 4-[phenyldiazenyl] aniline. The resulting 3-chloro-4-phenyl-1-{4-[phenyldiazenyl] phenyl} azetidin-2-one intermediate in benzene was irradiated in a Pyrex vessel with 350 nm UV light in a photochemical reactor to give the desired derivatives (4a-j). Structures of the new compounds were verified on the basis of spectral and elemental methods of analyses. Nine of the prepared compounds were tested for their anti-inflammatory effects; most of these compounds showed potent and significant results compared with indomethacin.

Full text of DOI:10.1002/jhet.1086

E116
A Novel Procedure to Synthesize 3‐Chloro‐1‐(4a,10b‐
diazaphenanthrene‐2‐yl)‐4‐phenyl Azetidin‐2‐ones and
Exploration of Their Anti‐Inflammatory Activity
Vol 50
a
a
b
*
Manisha Sharma, Arti Maheshwari, and Nitin Bindal
aDepartment of Chemistry, Mangalayatan University, Aligarh, Uttar Pradesh, India
bDepartment of Physics, Mangalayatan University, Aligarh, Uttar Pradesh, India
*
E-mail: sharmamani21@gmail.com
Received May 20, 2011
DOI 10.1002/jhet.1086
Published online 14 February 2013 in Wiley Online Library (wileyonlinelibrary.com).
N
N
O
N
N
R
R
h / I
ν
2
Cl
N
Cl
N
stirring,8h
O
Some new derivatives of 3‐chloro‐1‐(4a,10b‐diazaphenanthrene‐2‐yl)‐4‐phenyl azetidin‐2‐one were syn-
thesized through the reaction of N‐{4‐[phenyldiazenyl] phenyl}‐N‐[phenyl methylene] amine with 4‐[phe-
nyldiazenyl] aniline. The resulting 3‐chloro‐4‐phenyl‐1‐{4‐[phenyldiazenyl] phenyl} azetidin‐2‐one
intermediate in benzene was irradiated in a Pyrex vessel with 350 nm UV light in a photochemical reactor
to give the desired derivatives (4a–j). Structures of the new compounds were verified on the basis of spectral
and elemental methods of analyses. Nine of the prepared compounds were tested for their anti‐inflammatory
effects; most of these compounds showed potent and significant results compared with indomethacin.
J. Heterocyclic Chem., 50, E116 (2013).
INTRODUCTION
herein report a short novel strategy to synthesize a number
of 3‐chloro‐1‐(4a,10b‐diazaphenanthrene‐2‐yl)‐4‐phenyl
azetidin‐2‐one derivatives to be followed by an exploration
of their anti‐inflammatory potential using rat carrageenan‐
induced paw edema tests.
Inflammation is considered as a primary physiologic
defense mechanism that helps body to protect itself against
infection, burn, toxic chemicals, allergens, or other noxious
stimuli. An uncontrolled and persistent inflammation may
act as an etiologic factor for many of these chronic illnesses
[22]. Although it is a defense mechanism, the complex events
and mediators involved the inflammatory reaction can induce,
maintain, or aggravate many diseases [23]. Currently used
anti‐inflammatory drugs are associated with some severe side
effects. Therefore, the development of potent anti‐inflammatory
drugs with fewer side effects is necessary.
A number of polycyclic aromatic hydrocarbons (PAHs),
including some nitrogen‐heterocyclic analogs and aza‐
derivatives, have been shown to be carcinogenic to some
extent in animals [1]. However, to greater extent PAHs
together with corresponding polycyclic aza‐aromatic
compounds are of immense importance in astrophysics
and life sciences [2–4]. Isolation of polycyclic aza‐aromatic
compounds from natural/environmental sources is very
difficult, and hence, under these conditions biochemical
studies has to rely on synthetic materials. A great deal of inter-
est in the chemistry of these substances and their interaction
with biomolecules is a subject of intense research now‐a‐days.
The development of efficient and mild methods of synthesis of
heterocyclic compounds represents a thrust area of intense
research and development of these compounds [5–10]. In this
context, nitrogen‐containing heterocycles are among the most
useful and widely demonstrated categories [11–16].
RESULTS AND DISCUSSION
Despite the great biological potential residing in these
compounds, little progress has been made in deducing
antimicrobial behavior of polyaromatic hydrocarbons,
which need to be investigated very thoroughly. Further, it
has been observed that potency of several bacteria against
commercially available drugs increases tremendously. As
a result, there is an urgent need for new antibiotic agents,
which can fight against bacterial infections. These threats
have rekindled our interest in search of new compounds
as potential antimicrobial agents. Thus in continuation of
our previous work on heterocyclic systems [17–21], we
Chemistry. The derivatives of 3‐chloro‐1‐(4a,10b‐
diazaphenanthrene‐2‐yl)‐4‐phenyl azetidin‐2‐one [stage D,
compound 4a–j] were synthesized through the reaction of
N‐{4‐[phenyldiazenyl]phenyl}‐N‐[phenyl methylene] amine
[stage B, compound 2] with 4‐[phenyldiazenyl] aniline
[stage A, compound 1]. The resulting 3‐chloro‐4‐phenyl‐
1‐{4‐[phenyldiazenyl] phenyl}azetidin‐2‐one [stage‐C,
compound 3] intermediate was irradiated in a Pyrex
vessel with 350 nm UV light in a photochemical reactor
in presence of benzene to give the desired derivatives
© 2013 HeteroCorporation

February 2013 A Novel Procedure to Synthesize 3‐Chloro‐1‐(4a,10b‐diazaphenanthrene‐2‐yl)‐4‐phenyl
Azetidin‐2‐ones and Exploration of Their Anti‐Inflammatory Activity
E117
Scheme 1. An overview of synthetic schemes for 3‐chloro‐1‐(4a,10b‐diazaphenanthrene‐2‐yl)‐4‐phenyl azetidin‐2‐one.
EXPERIMENTAL
[4a–j]. This method involves exposure of cis/trans 3‐chloro‐4‐
phenyl‐1‐{4‐[phenyldiazenyl] phenyl}azetidin‐2‐one [stage C,
compound 3] to UV light, which causes its isomerization to the
cis‐form. This form undergoes electrocyclic ring closure to
produce phenanthrenes, which on dehydrogenation generates
an azaphenanthrene derivatives [4a–j] (Scheme 1).
Material and methods. All the chemicals used were of
analytical grade purity. Melting points were taken in open
capillary tubes using an electric melting point apparatus. All the
1
melting points reported are uncorrected. H NMR spectra were
recorded at 300 MHz with a Bruker advance DRX 300
instrument using TMS as an internal stranded. IR spectra were
run on a Perkin‐Elmer model 377‐spectrophotometer using KBr
pellets. Analytical thin layer chromatography was performed
using E. Merck Silica gel‐G 0.50‐mm plates (Merck No. 5700).
Synthesis of 3‐chloro‐1‐(4a,10b‐diazaphenanthrene‐2‐yl)‐4‐
phenyl azetidin‐2‐one. Stage A: Synthesis of 4‐[phenyldiazenyl]
aniline {1}. An appropriate quantity of diazoaminobenzene (2.5 mL,
0.012M) and a pertinent aniline derivative (0.01M) was taken in a
100‐mL flask and 1.3‐g freshly prepared aniline hydrochloride was
added into it and allowed to undergo heating at 40–45°C for 1 h on
water bath with constant stirring. The reaction mixture was then
permitted to stand for 15 min at room temperature. Now, 15.0‐mL
glacial acetic acid (1:1 V/V) was added to the contents and shaken
thoroughly to remove excess aniline as aniline acetate. After
CONCLUSION
The results for compounds (4a–j) are presented in Table 2,
which revealed that within a 3‐h interval most of the test
compounds exhibited anti‐inflammatory activity comparable
with that of indomethacin. On the other hand, only
compounds 4e, 4f, and 4g exhibited almost comparable results
to those of indomethacin 5 h after injecting them, whereas
compounds 4i and 4j showed only 85 and 85.9% of the
activity of indomethacin.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

E118
M. Sharma, A. Maheshwari, and N. Bindal
Vol 50
Table 1
Characterization and spectral data of 3‐chloro‐4‐phenyl‐1‐{4‐[phenyldiazenyl]phenyl} azetidin‐2‐one {3}.
Elemental analysis found (calcd.)
(%)
Yield
(%)
S. No.
1
Ra
H
MP (°C)b
C
H
N
IR (υ, cm1)
1H NMR (δ, ppm)
138–39
82
69.55
(69.71)
4.22
(4.46)
11.44
(11.61)
3080 (C─H, sp2), 2010 (N═N),
1765 (C═O, four‐membered),
6.1 (s, CH, four‐membered ring),
7.1 (s, 10H, C6H5 × 2), 7.4–7.6
(d, 4H, Ar‐H)
1600, 1505, 1395 (
, ring
stretching), 810, 745 (subphenyl),
525 (C─Cl)
2
3‐Cl
4‐Cl
126–27
128–29
131–32
125–26
136–37
135–36
134–35
130–31
132–33
77
86
84
81
78
81
83
78
80
63.45
(63.65)
3.63
(3.82)
10.42
(10.60)
3072 (C─H, sp2), 2019 (N═N),
1760 (C═O, four‐membered),
5.16 (s, CH, four‐membered ring),
7.12–7.93 (s, 10H, C6H5 × 2),
7.4–7.6 (d, 4H, Ar‐H)
1600, 1515, 1390 (
, ring
stretching), 812, 740 (subphenyl),
528 (C─Cl)
3
63.41
(63.65)
3.61
(3.82)
10.41
(10.60)
3083 (C─H, sp2), 2012 (N═N),
1768 (C═O, four‐membered),
5.44 (s, CH, four‐membered ring),
7.08–7.94 (s, 10H, C6H5 × 2),
7.0–7.6 (d, 4H, Ar‐H)
1608, 1505, 1392 (
, ring
stretching), 819, 750 (subphenyl),
520 (C─Cl)
4
3‐OH
66.52
(66.76)
4.11
(4.27)
11.08
(11.12)
3075 (C─H, sp2), 2005 (N═N),
1770 (C═O, four‐membered),
5.16 (s, CH, four‐membered ring),
6.93–7.40 (s, 10H, C6H5 × 2),
7.30–7.96 (d, 4H, Ar‐H), 5.0
(bs, OH)
1610, 1500, 1402 (
, ring
stretching), 850, 765 (subphenyl),
580 (C─Cl)
5
3‐C2H5
4‐C2H5
4‐NO2
3‐CH3
4‐CH3
70.65
(70.85)
4.99
(5.17)
10.54
(10.78)
3070 (C─H, sp2), 2025 (N═N),
1760 (C═O, four‐membered),
5.18 (s, CH, four‐membered ring),
7.08–7.79 (s, 10H, C6H5 × 2),
7.2–7.8 (d, 4H, Ar‐H), 2.59
(t, 3H, CH3), 1.24 (q, 2H, CH2)
1602, 1500, 1390 (
, ring
stretching), 840, 775 (subphenyl),
598 (C─Cl)
6
70.64
(70.85)
5.01
(5.17)
10.52
(10.78)
3070 (C─H, sp2), 2025 (N═N),
1760 (C═O, four‐membered),
5.18 (s, CH, four‐membered ring),
7.08–7.79 (s, 10H, C6H5 × 2),
7.2–7.8 (d, 4H, Ar‐H),2.59
1602, 1500, 1390 (
, ring
stretching), 840, 775 (subphenyl),
598 (C─Cl)
(t, 3H, CH3), 1.24 (q, 2H, CH2)
7
(61.92)
(62.00)
3.56
(3.73)
13.58
(13.78)
3050 (C─H, sp2), 2015 (N═N),
1763 (C═O, four‐membered),
5.10 (s, CH, four‐membered ring),
7.12–8.86 (s, 10H, C6H5 × 2),
7.4–7.6 (d, 4H, Ar‐H)
1610, 1525, 1415 (
, ring
stretching), 1335 (NO2)820, 745
(subphenyl), 520 (C─Cl)
8
(70.15)
(70.30)
4.65
(4.83)
11.02
(11.18)
3050 (C─H, sp2), 2010 (N═N),
1765 (C═O, four‐membered),
6.1 (s, CH, four‐membered ring),
7.1 (s, 10H, C6H5 × 2), 7.4–7.6
(d, 4H, Ar‐H) 2.35 (t, 3H, CH3)
1600, 1505, 1395 (
, ring
stretching), 810, 745 (subphenyl),
575 (C─Cl)
9
70.12
(70.30)
4.60
(4.83)
11.01
(11.18)
3050 (C─H, sp2), 2010 (N═N),
1765 (C═O, four‐membered),
5.35 (s, CH, four‐membered ring),
7.1 (s, 10H, C6H5 × 2), 7.4–7.6
(d, 4H, Ar‐H), 2.35 (t, 3H, CH3)
1600, 1505, 1395 (
, ring
stretching), 810, 745 (subphenyl),
575 (C─Cl)
10
3‐
OCH3
67.22
(67.43)
4.45
(4.63)
10.56
(10.72)
3080 (C─H, sp2), 2010 (N═N),
1765 (C═O, four‐membered),
5.2 (s, CH, four‐membered ring),
7.1 (s, 10H, C6H5 × 2), 7.4–7.6
(d, 4H, Ar‐H), 3.73 (t,O‐CH3)
1600, 1505, 1395 (
, ring
stretching), 810, 745 (subphenyl),
525 (C─Cl)
aSubstituent numbering is given as per their corresponding position in pertinent aniline.
bAll the reported melting points are uncorrected.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

February 2013 A Novel Procedure to Synthesize 3‐Chloro‐1‐(4a,10b‐diazaphenanthrene‐2‐yl)‐4‐phenyl
Azetidin‐2‐ones and Exploration of Their Anti‐Inflammatory Activity
E119
Table 2
1505, 1395 (
, ring stretching), 810, 745 (subphenyl), 525
1
(C─Cl). H NMR (δ, ppm): 6.1 (s, CH, four‐membered ring),
7.1 (s, 10H, C6H5 × 2), 7.4–7.6 (d, 4H, Ar‐H). Yield 82%, m.
p. 126–27°C. Analytical data calculated for C21H16N3OCl: %
C: 69.99 (69.71), %H: 4.31 (4.46), %N: 11.55 (11.61).
Inhibitory effects of test compounds upon carrageenan induced paw
edema in rats.
Edema inhibition (%)
3‐Chloro‐1‐(4a,10b‐diazaphenanthren‐2‐yl)‐4‐(3′‐chloro)‐
phenylazetidin‐2‐ones{4b}. IR (υ, cm1); 3365 (NHasy), 3290 (NHsym),
3080 (C─H, sp2), 2010 (N═N), 1765 (C═O, four‐membered), 1600,
Time after compound injection (h)
Compound
0
1
2
3
5
1505, 1395 (
, ring stretching), 810, 745 (subphenyl), 525
(C─Cl). 1H NMR (δ, ppm): 6.1 (s, CH, four‐membered ring), 7.1 (s,
10H, C6H5 × 2), 7.4–7.6 (d, 4H, Ar‐H). Yield 82%, m.p. 126–27°C.
Analytical data calculated for C21H13N3OCl2: %C: 63.98 (64.01), %
H: 3.32 (3.46), %N: 10.66 (10.76).
5% gum acacia
–
–
–
–
–
Indomethacina
7.16
1.72
1.97
0.24
0.98
0.24
1.23
2.22
1.72
0.74
23.50
13.50
6.25
16.75
13.50
18.00
12.75
18.75
9.75
43.32
35.51
35.76
50.12
48.11
37.53
39.79
43.32
38.43
37.53
66.16
38.34
63.65
60.40
63.40
62.90
56.39
63.65
63.50
61.65
92.25
46.00
43.00
34.00
90.80
90.50
56.50
91.25
78.50
79.25
4ba
4ca
4da
4ea
4fa
3‐Chloro‐1‐(4a,10b‐diazaphenanthren‐2‐yl)‐4‐(4′‐chloro)‐
phenylazetidin‐2‐ones{4c}. IR (υ, cm1); 3371 (NHasy), 3292
(NHsym), 3080 (C─H, sp2), 2010 (N═N), 1765 (C═O, four‐
4ga
4ha
4ia
membered), 1600, 1505, 1395 (
, ring stretching), 810,
745 (subphenyl), 525 (C─Cl). 1H NMR (δ, ppm): 6.16 (s,
CH, four‐membered ring), 7.23 (s, 10H, C6H5 × 2), 7.1–7.9
(d, 4H, Ar‐H). Yield 78%, m.p. 129–130°C. Analytical data
calculated for C21H13N3OCl2: %C: 63.98 (64.01), %H: 3.32
(3.46), %N: 10.66 (10.76).
4ja
11.75
a10 mg kg−1 body mass.
3‐Chloro‐1‐(4a,10b‐diazaphenanthren‐2‐yl)‐4‐(3′‐hydroxy)‐
phenylazetidin‐2‐ones{4d}. IR (υ, cm1); 3365 (NHasy), 3290
(NHsym), 3396 (bs, O─H), 3088 (C─H, sp2), 2019 (N═N),
allowing the mixture to stand as such for 15‐min yellow crystals of 4‐
(diphenyldiazene)aniline were obtained.
Stage B: Synthesis of N‐{4‐[phenyldiazenyl] phenyl}‐N‐
[phenyl methylene] amine {2}. An appropriate quantity of 4‐
[phenyldiazenyl] aniline {1} (4.14 g, 0.02M) and benzaldehyde
(2.12 mL) was taken in a 100‐mL flask. To this, 3.0‐mL glacial
acidic acid in 25 mL of water was added and allowed to stand
for 30 min with occasional shaking. The reaction mixture was
then permitted to stand for 15 min at room temperature. Yellow
crystals of N‐{4‐[phenyldiazenyl]phenyl}‐N‐[phenylmethylene]
amine were obtained, filtered on Buchner funnel, and dried in
vacuum.
1761 (C═O, four‐membered), 1603, 1567, 1390 (
, ring
stretching), 821, 757 (subphenyl), 609 (C─Cl). 1H NMR (δ,
ppm): 5.42 (s, CH, four‐membered ring), 7.1 (s, 10H, C6H5 ×
2), 7.3–7.9 (d, 4H, Ar‐H). Yield 88%, m.p. 121–25°C.
Analytical data calculated for C21H14N3O2Cl: %C: 67.12
(67.27), %H: 3.75 (3.86), %N: 11.18 (11.26).
3‐Chloro‐1‐(4a,10b‐diazaphenanthren‐2‐yl)‐4‐(3′‐ethyl)‐
phenylazetidin‐2‐ones{4e}. IR (υ, cm1); 3364 (NHasy), 3298
(NHsym), 3083 (C─H, sp2), 2011 (N═N), 1763 (C═O, four‐
membered), 1598, 1509, 1385 (
, ring stretching), 818, 765
1
Stage C: Synthesis of 3‐chloro‐4‐phenyl‐1‐{4‐[phenyldiazenyl]
phenyl}azetidin‐2‐one{3}. To a constantly stirred solution of 1,4‐
dioxane (50 mL), chloroacetyl chloride (2.2 mL, 0.02M), and
triethylamine (2.3 mL, 0.02M), N‐{4‐[phenyldiazenyl]phenyl}‐N‐
[phenylmethylene] amine (5.7g, 0.02M) (compound 2, stage IVb)
was added. After the completion of reaction (6 h), the reaction
mixture was kept at room temperature for 30 min and then kept
overnight in freezer. The precipitates so obtained were filtered,
washed with water, and dried to obtain the crystals of 3‐chloro‐4‐
phenyl‐1‐{4‐[phenyl diazenyl]phenyl}azetidin‐2‐one. Physical
characteristics and structural assignments of all the synthesized
compounds are exhibited in Table 1.
Stage D: Synthesis of 3‐chloro‐1‐(4a,10b‐diazaphenanthrene‐2‐
yl)‐4‐phenyl azetidin‐2‐one {4a–j}. 3‐Chloro‐4‐phenyl‐1‐{4‐
[phenyldiazenyl]phenyl}azetidin‐2‐one {3} (1.97 g, 0.01M) in
benzene (1000 mL) was irradiated in a Pyrex vessel with 350‐nm
UV light in a photochemical reactor for 8 h with magnetic stirring.
Benzene was evaporated using a rotatory evaporator followed by
the addition of acetone (30 mL) to dissolve unreacted compound.
Yellow shiny crystals of 3‐chloro‐1‐(4a,10b‐diazaphenanthrene‐2‐
yl)‐4‐phenyl azetidin‐2‐one {4} were obtained upon vacuum
filtration. Overall illustration of procedure is depicted in Scheme 1.
Physical characteristics and structural assignments of all the
synthesized compounds are exhibited as follows:
(subphenyl), 545 (C─Cl). H NMR (δ, ppm): 5.2 (s, CH, four‐
membered ring), 7.23–8.12 (s, 10H, C6H5 × 2), 7.1–7.7 (d, 4H,
Ar‐H), 1.59 (q, 2H, CH2,), 1.26 (t, 3H, CH3). Yield 87%, m.p.
122–25°C. Analytical data calculated for C23H18N3OCl: %C:
71.22 (71.47), %H: 4.68 (4.76), %N: 10.83 (10.96).
3‐Chloro‐1‐(4a,10b‐diazaphenanthren‐2‐yl)‐4‐(4′‐ethyl)‐
phenylazetidin‐2‐ones{4f}. IR (υ, cm1); 3360 (NHasy), 3298
(NHsym), 3083 (C─H, sp2), 2011 (N═N), 1763 (C═O, four‐
membered), 1598, 1509, 1385 (
, ring stretching), 818,
1
765 (subphenyl), 545 (C─Cl). H NMR (δ, ppm): 5.2 (s, CH,
four‐membered ring), 7.21–8.12 (s, 10H, C6H5 × 2), 7.1–7.7
(d, 4H, Ar‐H), 1.62q, 2H, CH2,), 1.24 (t, 3H, CH3). Yield 81%,
m.p. 122–25°C. Analytical data calculated for C23H18N3OCl:
%C: 71.22 (71.47), %H: 4.68 (4.76), %N: 10.83 (10.96).
3‐Chloro‐1‐(4a,10b‐diazaphenanthren‐2‐yl)‐4‐(4′‐nitro)‐
phenylazetidin‐2‐ones{4g}. IR (υ, cm1); 3358 (NHasy), 3289
(NHsym), 3070 (C─H, sp2), 2016 (N═N), 1775 (C═O, four‐
membered), 1608, 1505, 1385 (
, ring stretching),
1336 (NO2), 817, 765 (subphenyl), 545 (C─Cl). 1H NMR (δ,
ppm): 5.24 (s, CH, four‐membered ring), 6.69–8.37 (s, 10H, C6H5
× 2), 7.08–7.21 (d, 4H, Ar‐H). Yield 88%, m.p. 127–29°C.
Analytical data calculated for C21H13N4O3Cl: %C: 62.31 (62.54), %
H: 3.24 (3.45), % N:13.86 (13.94).
3‐Chloro‐1‐(4a,10b‐diazaphenanthren‐2‐yl)‐4‐(3′‐methyl)‐
phenylazetidin‐2‐ones{4h}. IR (υ, cm1); 3369 (NHasy), 3295
(NHsym), 3084 (C─H, sp2), 2012 (N═N), 1780 (C═O, four‐
3‐Chloro‐1‐(4a,10b‐diazaphenanthrenes)‐4‐phenylazetidin‐2‐
ones{4a}. IR (υ, cm1); 3365 (NHasy), 3290 (NHsym), 3080
(C─H, sp2), 2010 (N═N), 1765 (C═O, four‐membered), 1600,
membered), 1600, 1500, 1392 (
, ring stretching), 811,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

E120
M. Sharma, A. Maheshwari, and N. Bindal
Vol 50
755 (subphenyl), 537 (C─Cl). 1H NMR (δ, ppm): 5.18 (s, CH,
four‐membered ring), 7.1–8.14 (s, 10H, C6H5 × 2), 7.0–7.21
(d, 4H, Ar‐H), 2.35 (s, 3H, CH3). Yield 89%, m.p. 126–27°
C. Analytical data calculated for C22H16N3OCl: %C: 70.68
(70.71), %H: 4.31 (4.40), %N:11.24 (11.32).
3‐Chloro‐1‐(4a,10b‐diazaphenanthren‐2‐yl)‐4‐(4′‐methyl)‐
phenylazetidin‐2‐ones{4i}. IR (υ, cm1); 3369 (NHasy), 3295
(NHsym), 3084 (C─H, sp2), 2012 (N═N), 1780 (C═O, four‐
The difference between the thicknesses of the two paws was
taken as a measure of edema. The measurement was carried out
at 0, 1, 2, 3, and 5 h after injection of the test compounds,
reference drug, and the vehicle. The results of anti‐inflammatory
activity of the test compounds and the reference drug are listed
in Table 2.
membered), 1600, 1500, 1392 (
, ring stretching), 811,
REFERENCES AND NOTES
755 (subphenyl), 537 (C─Cl). 1H NMR (δ, ppm): 5.18 (s,
CH, four‐membered ring), 6.91–8.17 (s, 10H, C6H5 × 2), 7.1–7.27
(d, 4H, Ar‐H), 2.31 (s, 3H, CH3). Yield: 91%, m.p. 27°C.
Analytical data calculated for C22 H16N3OCl: %C: 70.68 (70.71), %
H: 4.31 (4.40), %N: 11.24 (11.32).
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3‐Chloro‐1‐(4a,10b‐diazaphenanthren‐2‐yl)‐4‐(3′‐methoxy)‐
phenylazetidin‐2‐ones{4j}. IR (υ, cm1); 3358 (NHasy), 3294
(NHsym), 3089 (C─H, sp2), 2027 (N═N), 1760 (C═O, four‐
membered), 1600, 1500, 1391 (
, ring stretching), 1110
(C─O), 981, 785 (subphenyl), 615 (C─Cl). 1H NMR (δ,
ppm): 5.56 (s, CH, four‐membered ring), 6.91–8.17 (s, 10H,
C6H5 × 2), 7.4–7.8 (d, 4H, Ar‐H), 3.73 (s, 3H, CH3). Yield
88%, m.p. 132–35°C. Analytical data calculated for
C
22H16N3O2Cl: %C: 67.78 (67.86), %H: 4.14 (4.26), %
N:10.78 (10.86).
Anti‐inflammatory activity. Carrageenan‐induced paw
edema. Animals were housed in separate cages, six animals
each, in temperature‐controlled rooms at 25 °C. Animals were
allowed for free access to food and water and were maintained
at a 12‐h light/dark cycle. Work was conducted in accordance
with the internationally accepted principles for laboratory
animals use of anti‐inflammatory activities, all test compounds
and reference drugs were suspended in 5% solution of gum
acacia in normal saline. Suspensions of the test compounds,
reference drugs, and 5% gum acacia‐saline solution (negative
control) were injected 1 mL each i.p. The anti‐inflammatory
activity of nine representatives of the synthesized compounds
was evaluated according to the method described by Winter
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by subplantar injection of 0.2‐mL carrageenan (0.2%) suspension in
gum acacia into the right hind of the rats.
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2005, 61, 4273.
Male adult albino rats (100–120 g) were divided into groups, 11
groups altogether, of five animals each. The rat paw thickness was
measured with a vernier caliper (SMIEC, China) before and 1 h after
the carrageenan injection to detect the carrageenan‐induced
inflammation. Each test compound at a dose of 10 mg kg−1 was
injected i.p. to a separate group of rats 1 h after carrageenan
injection. Control group received the vehicle (5% gum acacia),
while the reference group received indomethacin, 10 mg kg−1.
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2004; pp 47–86.
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Altinier, G. A. J Ethanopharmacol 2004, 8, 211.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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