Synthesis and antipsychotic and anticonvulsant activity of some new substituted oxa/thiadiazolylazetidinonyl/thiazolidinonylcarbazoles

Article abstract of DOI:10.1016/j.ejmech.2010.02.060

A novel substituted oxa/thiadiazolylazetidinonyl/thiazolidinonylcarbazoles (4a-j), (5a-j) and (6a-j) were synthesized and screened for their antipsychotic and anticonvulsant activities. It is concluded from the results compound 6j showed promising antipsy

Full text of DOI:10.1016/j.ejmech.2010.02.060

European Journal of Medicinal Chemistry 45 (2010) 2777e2783
Contents lists available at ScienceDirect
European Journal of Medicinal Chemistry
journal homepage: http://www.elsevier.com/locate/ejmech
Original article
Synthesis and antipsychotic and anticonvulsant activity of some new substituted
oxa/thiadiazolylazetidinonyl/thiazolidinonylcarbazoles
1
*
Hemlata Kaur , Sunil Kumar, Pinki Vishwakarma, Monica Sharma, K.K. Saxena, Ashok Kumar
Medicinal Chemistry Division, Department of Pharmacology, L.L.R.M. Medical College, Garh Road, Meerut 250004, Uttar Pradesh, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel substituted oxa/thiadiazolylazetidinonyl/thiazolidinonylcarbazoles (4a-j), (5a-j) and (6a-j) were
synthesized and screened for their antipsychotic and anticonvulsant activities. It is concluded from the
results compound 6j showed promising antipsychotic as well as anticonvulsant activity.
Ó 2010 Elsevier Masson SAS. All rights reserved.
Received 26 September 2009
Received in revised form
19 February 2010
Accepted 27 February 2010
Available online 7 March 2010
Keywords:
Oxa/thiadiazolyl-azetidinonyl carbazoles
Oxa/thiadiazolyl-thiazolidinonyl carbazoles
Antipsychotic activity
Anticonvulsant activity
Acute toxicity
1. Introduction
convulsions related to epilepsy. Carbazole contains almost similar
chemical structure as 5H-dibenzo [b,f] azepine exception that carba-
A psychosis is the major CNS disorder which causes the serious
distortion of capacityto recognize reality, affecting approximately10%
of world’s population. All clinically effective antipsychotics (except
clozapine like) have potent post synaptic dopaminergic D2 receptor
blocking action. Blockade of dopamine action in corpus striatum is
responsible for the extrapyramidal symptoms (EPS) so often associ-
ated with antipsychotic drugs. Some of the antipsychotic drugs such
as chlorpromazine have a number of adverse drug reactions such as
parkinsonism (tremor, muscular rigidity and akinesia) and many of
the endocrinal and metabolic disturbances such as gynaecomastia,
galactorrhea and aggravation of diabetes. Moreover, epilepsy is very
often associated with CNS psychiatric disorders, a drug with both
antipsychotic as well as antiepileptic activity will be more beneficial.
Therefore, the need for more effective and less toxic antipsychotic
drugs still exists. 5H-dibenzo [b,f] azepine heterocyclic nucleus is
present in carbamazepine. The discovery of carbamazepine leads to
the exploration of 5H-dibenzo [b,f] azepine nucleus [1]. Several
scientists further develops derivatives of 5H-dibenzo [b,f] azepine
such as prodrugs like oxacarbazepine [2e4] and Eslicarbazepine
(S-Licarbazepine) [4] which are used in further treatment of
zole contains two less carbon atoms in the middle ring. Carbazole
derivatives have documented consistent advances in the design of
novel antipsychotic [5], neuroleptic [6] and anticonvulsant [7] agents.
Furthermore, various congeners of oxadiazole, thiadiazole, azetidi-
none and thiazolidinone have also been reported to exhibit potential
antipsychotic [8e13], antidepressant [14e16] and anticonvulsant
[17e20] activity. In view of broad biological activity of carbazole
derivatives, we herein plan to synthesize a new carbazole derivatives
(4a-j),(5a-j)and(6a-j)byincorporatingnewpharmacophoressuchas
oxadiazole, thiadiazole, azetidinone and thiazolidinone at the 9th
positionofcarbazolenucleuswiththehopetogetbetterantipsychotic
as well as anticonvulsant drugs (Scheme 1, Table 1).
2. Chemistry
Carbazole react with ethyl chloro acetate to give Ethyl
N9-carbazolyl acetate
thiosemicarbazide
1
which on reaction with semi/
yielded
(N9-Carbazolylacetyl)-semi/thio-
semicarbazide i.e. compounds 2a/2b. Compounds 2a-b reacts with
conc. H2SO4 and ammonia to give 3a-b which on reaction with
various substituted aromatic aldehydes gave 4a-j. Compounds 4a-j
on reaction with chloro acetyl chloride furnished compounds 5a-j
Compounds 4a-j on further reaction with thioglycolic acid gave
compounds 6a-j.
* Corresponding author. Tel.: þ91 0121 2764084; þ919917053074 (mobile); fax:
þ91 121 2760888.
E-mail address: rajputak@gmail.com (A. Kumar).
Part of the Ph.D. thesis work.
1
0223-5234/$ e see front matter Ó 2010 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.ejmech.2010.02.060

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H. Kaur et al. / European Journal of Medicinal Chemistry 45 (2010) 2777e2783
Scheme 1. Synthetic route of oxa/thiadiazolylazetidinonyl/thiazolidinonylcarbazoles.
3. Results and discussion
4. Conclusions
All the compounds were evaluated for antipsychotic activity by
recording their responses towards amphetamine induced stereo-
typed behaviour, cataleptic behaviour and rotarod performance test
and for anticonvulsant activity by the MES test, at a dose of 40 mg/
kg each. Among the compounds 4a-j, compounds 4f-j (having
thiadiazole ring) showed good antipsychotic as well as anticon-
vulsant activity. The next step compounds (i.e. 5a-j) exhibited
better results towards amphetamine antagonism, cataleptic
behaviour and rotarod performance test than their parent
compounds (i.e. 4a-j). Compounds 5a-j showed varying degree of
(40e80%) of anticonvulsant activity. In these compounds, 5j
showed potent (80%) anticonvulsant activity. The compounds 6a-j
(having thiazolidinone ring) demonstrated more potent antipsy-
chotic as well as anticonvulsant activities as compared to their
corresponding azetidinone derivatives (i.e. 5a-j). Among the
compounds 6a-j, compounds 6j exhibited very good response
against stereotyped behaviour induced by amphetamine. Further-
more, compounds 6h and 6j (having 2-bromophenyl moiety) did
not exhibit any cataleptic behaviour. The latter compound showed
most promising results in rotarod performance test and MES test
(90% protection).
While considering all the newly synthesized compounds of this
series together, use may conclude that
eCompounds having thiadiazole ring showed better biological
activities than compounds having oxadiazole ring.
eCompounds having thiadiazolylthiazolidinonyl ring at 9th
position of carbazole nucleus) (i.e. compounds 6f-j) showed
good antipsychotic and anticonvulsant response when
compared to the other compounds and the reference drugs.
5. Experimental protocols
5.1. Chemistry
All reagents and solvents used in study are of analytical grade
and procured locally. The progress of the reaction is monitored by
TLC and product are purified through recrysttalization and purity of
the compounds was checked by thin layer chromatography (TLC)
performed on silica gel G coated plate of 0.5 mm thickness. The

H. Kaur et al. / European Journal of Medicinal Chemistry 45 (2010) 2777e2783
2779
Table 1
Antipsychotic and anticonvulsant activities of compounds synthesized 4a-j, 5a-j and 6a-j.
Com. no
R
X
Dose mg/kg i.p.
Catalepsy
scoredc
Amphetamine induced SB
(Mean score)d
MES % seizures
protection
Rotarod testf
Mean sec.
LD50g mg/kg
e
P.G.a
CPZa
HPLb
P.S.b
4a
4b
4c
4d
4e
4f
–
–
–
–
–
O
O
O
O
O
S
S
S
S
S
O
O
O
O
O
S
S
S
S
S
O
O
O
O
O
S
0.5 mL
4.0
0.5 mL
30
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
0.0
–
3.8
0.0
–
0
–
120.0
100.0
–
–
1.8
–
0
–
–
80***
20
30
30
20
4-OH
2.6
2.4
2.4
2.2
2.0
1.6
1.2
1.2
1.4
1.0
1.2
1.0
1.0
1.4
0.8
0.8
0.6
1.0
1.2
0.0
0.8
0.6
0.4
0.6
0.2
0.4
0.2
0.0
0.4
0.0
2.0
1.8
1.6
1.8
1.6
1.6
1.6
1.4
1.6
1.2
1.6
1.4
1.6
1.6
1.4
1.0
1.0
1.4
1.0
1.0
0.8
0.6
0.2
0.8
0.4
0.4
0.2
0.2
0.4
0.0
116.4
114.8
112.2
114.0
110.8
108.8
108.6
106.8
110.2
106.8
104.6
106.4
102.4
100.2
98.8
102.0
102.2
102.4
106.0
98.0
104.6
104.4
102.8
104.2
96.6
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1000
>1600
2,4-OH
4-OH, 3-OCH3
4-N(CH3)2
2-Br
30
40
4-OH
4g
4h
4i
2,4-OH
4-OH, 3-OCH3
4-N(CH3)2
2-Br
50*
50*
40
60**
40
50*
50*
40
60**
60**
50*
70***
50*
80***
60**
60**
70***
60**
70***
60**
70***
70***
60**
90**
4j
5a
5b
5c
5d
5e
5f
5g
5h
5i
4-OH
2,4-OH
4-OH, 3-OCH3
4-N(CH3)2
2-Br
4-OH
2,4-OH
4-OH, 3-OCH3
4-N(CH3)2
2-Br
5j
6a
6b
6c
6d
6e
6f
6g
6h
6i
4-OH
2,4-OH
4-OH. 3-OCH3
4-N(CH3)2
2-Br
4-OH
100.6
102.2
98.8
104.0
96.0
2,4-OH
4-OH, 3-OCH3
4-N(CH3)2
2-Br
S
S
S
S
6j
*P < .05, **P < .01, ***P < .001.
All the compounds were tested at the dose of 40 mg/kg i.p.
a
P.G. = Propylene glycol, CPZ = Chlorpromazine.
HPL = Haloperidol, P.S. = Phenytoin sodium.
b
c
Score of cataleptic behaviour with reference to propylene glycol treated group of rats; Haloperidol (0.5 mL i.p.) induced group 1.8 with reference to control group.
Protection against amphetamine (4 mg/kg) induced stereotyped bahaviour (SB).
Percentage protection against convulsions in Maximal Electroshock Seizure test.
Results reported in rotarod performance test.
d
e
f
g
LD50 of the compounds 4a-j, 5a-j and 6a-j.
elemental analysis, spectral studies, IR, NMR, Mass and 13C NMR
were determined by standard methods.
ring),1460 (NeCH2); 1H NMR (CDCl3þDMSOd6)
d in ppm: 1.24 (t, 3H,
-COOCH2CH3), 3.60 (s, 2H, eNCH2), 3.85 (q, 2H, eCOOCH2CH3),
7.10e7.90 (m, 8H, AreH). 13C NMR (CDCl3)
d ppm: 167.5, 130.8, 121.7,
121.4,119.8,112.3,109.6, 61.0, 56.5,14.1. Anal. Calcd. for C16H15NO2: C,
75.85; H, 5.97; N, 5.53; Found: C, 75.75; H, 5.87; N, 5.33%.
5.1.1. Preparation of ethyl N9-carbazolyl acetate 1
To a solution of carbazole (1.0 mol) in dry acetone (100 mL), ethyl
chloro acetate (1.0 mol) were added dropwise in the presence of
anhydrous K2CO3 (8 gm) and resulted mixture was refluxed on
a water-bath for about 13 h, cooled and the solid thus obtained was
filtered, dried and recrystallized from methanol to obtained
compound 1:
5.1.2. Preparation of (N9- carbazolyl acetyl)-semi/
thiosemicarbazide 2a-b
A mixture of Ethyl N9-Carbazolyl acetate (0.7 mol) and semi-
carbazide or thiosemicarbazide (0.7 mol) in 1, 4 dioxan (100 mL)
was refluxed on a water-bath for about 8 h. The excess solvent was
removed under reduced pressure and the product recrystallized
from appropriate solvents to give compounds 2a-b.
5.1.1.1. Ethyl N9-carbazolyl acetate (1). Yield 87% (methanol); m.p.
86 ꢀC. IR (KBr, nmax in cmꢁ1): 1725 (C¼O ester),1613 (C. C of aromatic

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H. Kaur et al. / European Journal of Medicinal Chemistry 45 (2010) 2777e2783
5.1.2.1. (N9-carbazolyl acetyl)-semicarbazide (2a). Yield 83%
(acetone); m.p. 92 ꢀC; IR (KBr, nmax in cmꢁ1): 3340 (NHNH2), 1672
(COeNH), 1669 (C¼O), 1615 (C.C of aromatic ring), 1H NMR
(eC¼N), 1585 (N¼CH), 1031 (CeOeC); 1H NMR (CDCl3þDMSOd6)
d
in ppm: 3.72 (s, 2H, NeCH2), 8.19e7.18 (m, 11H, AreH), 8.65 (s, 1H,
N¼CH), 11.12 (s, 2H, 2 ꢂ OH); 13C NMR (CDCl3)
d ppm: 162.5, 162.2,
(CDCl3 þ DMSOd6)
d
in ppm: 3.70 (s, 2H, eNCH2), 8.00e7.20 (m, 8H,
160.0, 135.5, 133.8, 122.9, 121.7, 121.4, 119.8, 113.1, 109.6, 103.7, 108.6,
58.1. Anal. Calcd. for C22H16N4O3: C, 68.74; H, 4.19; N, 4.21; Found: C,
78.69; H, 4.21; N, 15.56%.
AreH), 8.30 (m, 4H, eNHNHCONH2); 13C NMR (CDCl3)
d ppm:
164.4, 157.4, 130.8, 121.7, 121.4, 119.8, 112.3, 109.6, 45.0. Anal. Calcd.
for C15H14N4O2: C, 63.80; H, 5.00; N, 19.85; Found: C, 63.41; H, 4.89;
N, 19.59%.
5.1.4.3. 2-[40-(4-hydroxy, 3-methoxy benzylidenylamino-5-(N9-car-
bazolylmethylene)]-1,3,4-oxadiazole (4c). Yield 79% (acetone); m.p.
129 ꢀC. IR (KBr, nmax in cmꢁ1): 3438 (eOH), 1615 (C.C of aromatic
ring), 1591 (eC¼N), 1579 (N¼CH), 1224 (OCH3), 1029 (CeOeC); 1H
5.1.2.2. (N9-carbazolyl acetyl)-thiosemicarbazide (2b). Yield 83%
(ethanol); m.p. 93 ꢀC; IR (KBr, nmax in cmꢁ1): (eNHNH2) 3344,
1670 (COeNH), 1614 (C.C of aromatic ring), 1130 (C¼S); 1H NMR
NMR (CDCl3)
d in ppm: 3.39 (s, 3H, OCH3), 3.88 (s, 2H, NeCH2),
(CDCl3 þ DMSOd6)
d
in ppm: 3.80 (s, 2H, NeCH2), 7.99e7.02 (m,
8.21e7.20 (m, 11H, AreH), 8.66 (s, 1H, eN¼CH), 11.15 (s, 1H, OH), 13C
8H, AreH), 8.32 (m, 4H, -NHNHCSNH2); 13C NMR (CDCl3)
d
ppm:
NMR (CDCl3) d ppm: 160.0, 151.0, 149.3, 135.5, 130.9, 122.9, 121.7,
182.5, 164.4, 130.8, 121.7, 121.4, 119.8, 112.3, 109.6, 46.0. Anal. Calcd.
for C15H14N4OS: C, 60.36; H, 4.73; N, 18.78; Found: C, 60.55; H,
4.55; N, 18.56%.
121.4,119.8,117.0,109.6,112.1, 58.1, 56.0. Anal. Calcd. for C23H18N4O3:
C, 69.33; H, 4.55; N, 14.06; Found: C, 69.52; H, 4.57; N, 14.08%.
5.1.4.4. 2-[40-(4-NN0-dimethylaminobenzylidenylamino-5-(N9-carba-
zolylmethylene)]-1, 3, 4-oxadiazole (4d). Yield 80% (ethanol); m.
p. 123 ꢀC; IR (KBr, nmax in cmꢁ1): 1611 (C.C of aromatic ring), 1588
(eC¼N), 1578 (N¼CH), 1028 (CeOeC); 1H NMR (CDCl3 þ DMSOd6)
5.1.3. Preparation of 2-amino-5-(N9-Carbazolyl methylene)-
1, 3, 4-oxa/thiadiazole 3a-b
A solution of (N9-Carbazolyl acetyl)-semi/thiosemicarbazide
(2a-b, 0.3 mol) with conc. H2SO4 (25 mL) was kept overnight at
room temperature, then poured into ice-cold water, neutralized
with ammonia and extracted with ether. The ethereal solution was
distilled off and the product obtained was recrystallized from
suitable solvents to give compounds 3a-b.
d
in ppm: 1.81 (s, 6H, N(CH3)2), 3.90 (s, 2H, NeCH2), 8.22e7.19 (m,
12H, AreH), 8.89 (s, 1H, N¼CH); 13C NMR (CDCl3)
d ppm: 160.0,
153.4, 135.5, 128.3, 125.9, 122.9, 121.7, 121.4, 119.8, 111.9, 109.6, 58.1,
40.2. Anal. Calcd. for C24H21N5O: C, 72.89; H, 5.35; N, 17.70; Found:
C, 72.79; H, 5.25; N, 17.68%.
5.1.3.1. 2-Amino-5-S(N9-Carbazolyl methylene)-1, 3, 4-oxadiazole
(3a). Yield 82% (methanol); m.p. 111 ꢀC. IR (KBr, nmax in cmꢁ1):
3349 (NH2), 1615 (C.C of aromatic ring), 1600 (C¼N), 1294 (NeN),
5.1.4.5. 2-[40-(2-bromo benzylidenylamino-5-(N9-carbazolylmethylene)]-
1, 3, 4-oxadiazole (4e). Yield: 80% (petroleum ether); m.p. 132 ꢀC; IR (KBr,
nmax in cmꢁ1): 1619 (C.C of aromatic ring), 1587 (eC¼N), 1577 (N¼CH),
1025 (CeOeC); 1H NMR (CDCl3 þ DMSOd6)
d
in ppm: 3.80 (s, 2H,
1029 (CeOeC), 611 (CeBr); 1H NMR (CDCl3 þ DMSOd6)
d in ppm: 3.80
-NCH2), 4.20 (s, 2H, CeNH2) 7.89e7.09 (m, 8H, AreH); 13C NMR
(s, 2H, NeCH2), 8.19e7.18 (m, 12H, AreH) 8.79 (s, 1H, N¼CH); 13C NMR
(CDCl3)
d
ppm: 135.5, 122.9, 121.7, 121.4, 119.8, 109.6, 58.1. Anal.
(CDCl3) d ppm: 160.0, 135.5, 135.3, 132.3, 130.1, 127.8, 127.1, 122.9, 121.7,
Calcd. for C15H12N4O: C, 68.15; H, 4.57; N, 21.21; Found: C, 68.23; H,
4.32; N, 21.25%.
121.6, 121.4, 119.8, 109.6, 58.1. Anal. Calcd. for C22H15N4OBr: C, 61.28; H,
3.50; N, 12.99; Found: C, 61.28; H, 3.52; N, 12.77%.
5.1.3.2. 2-Amino-5-(N9-carbazolyl methylene)-1, 3, 4-thiadiazole
5.1.4.6. 2-[40-(4-hydroxy benzylidenylamino-5-(N9-carbazolylmethylene)]-
1, 3, 4-thiadiazole (4f). Yield: 77% (DMF); m.p.131 ꢀC; IR (KBr, nmax in
cmꢁ1): 3434 (eOH), 1617 (C.C of aromatic ring), 1590 (eC¼N), 1580
(3b). Yield 81% (acetone); m.p.119 ꢀC.1H NMR (CDCl3þDMSOd6)
d in
ppm: 3350 (NH2), 1618 (C.C of aromatic ring), 1606 (C¼N), 1293
(NeN) 712 (CeSeC); 1H NMR (
d
ppm): 3.83 (s, 2H, -NH2), 4.21 (s, 2H,
(N¼CH), 705 (CeSeC); 1H NMR (CDCl3 þ DMSOd6)
d in ppm: 3.89 (s, 2H,
CeNH2), 7.90e7.10 (m, 8H, AreH); 13C NMR (CDCl3)
d
ppm: 161.6,
NeCH2), 8.20e7.20 (m, 12H, AreH), 8.62 (s,1H, N¼CH), 11.07 (s, 1H, OH);
135.5,122.9,121.7,121.4,119.8,109.6, 58.1. Anal. Calcd. for C15H12N4S:
C, 64.25; H, 4.31; N, 19.98; Found: C, 64.25; H, 4.22; N, 19.88%.
13C NMR (CDCl3)
d ppm: 160.8, 160.0, 135.5, 130.6, 129.0, 122.9, 121.7,
121.4,119.8,116.0,109.6, 58.1. Anal. Calcd. for C22H16N4OS: C, 71.72, H, 4.19,
N, 14.57; Found: C, 71.75, H, 4.17; N, 14.52%.
5.1.4. Preparation of 2-[40-subsituted benzylidenylamino-5-
(N9-carbazolylmethylene)]-1, 3, 4-oxa/thiadiazoles 4a-j
5.1.4.7. 2-[40-(2, 4-dihydroxy benzylidenylamino-5-(N9-carbazolyl-
methylene)]-1, 3, 4-thiadiazole (4g). Yield 80% (methanol); m.p.
134 ꢀC; IR (KBr, nmax in cmꢁ1): 3432 (eOH), 1619 (C.C of aromatic
ring), 1591 (eCN), 1585 (N¼CH), 692 (CeOeC); 1H NMR
2-Amino-5-(N9-Carbazolyl methylene)-1, 3, 4-oxa/thiadiazole
(3a-b, 0.2 mol), various substituted aromatic aldehydes (0.2 mol)
and glacial acetic acid (5 mL) were refluxed in methanol (100 mL)
for about 6 h. The solid mass thus obtained was recrystallized from
suitable solvents to obtained compounds 4a-j.
(CDCl3 þ DMSOd6)
d in ppm: 3.85 (s, 2H, NeCH2), 8.20e7.19 (m,
11H, AreH), 8.64 (s, 1H, N¼CH), 11.10 (s, 2H, 2 ꢂ OH); 13C NMR
(CDCl3)
d ppm: 162.2, 162.5, 160.0, 135.5, 133.8, 122.9, 121.7, 121.4,
5.1.4.1. 2-[40-(4-hydroxybenzylidenylamino-5-(N9-carbazolyl-
methylene)]-1, 3, 4-oxadiazole (4a). Yield 80% (methanol); m.
p. 121 ꢀC. IR (KBr, nmax in cmꢁ1): 3440 (eOH), 1617 (C.C of aromatic
ring), 1592 (eC¼N), 1583 (N¼CH), 1031 (CeOeC); 1H NMR
119.8, 109.6, 108.6, 113.1, 103.7, 58.1. Anal. Calcd. for C22H16N4O2S: C,
65.98; H, 4.02; N, 13.99; Found: C: 65.82; H, 4.09; N, 13.89%.
5.1.4.8. 2-[40-(4-hydroxy, 3-methoxy benzylidenylamino-5-(N9-car-
bazolylmethylene)]-1, 3, 4-thiadiazole (4h). Yield 78% (ethanol); m.
p. 138 ꢀC; IR (KBr, nmax in cmꢁ1): 3432 (eOH), 1620 (C.C of
aromatic ring), 1594 (eC¼N), 1580 (N¼CH), 1223 (OCH3), 689
(CDCl3þDMSOd6)
d in ppm: 3.86 (s, 2H, NeCH2), 8.21e7.19 (m, 12H,
AreH), 8.60 (s, 1H, eN¼CH), 11.09 (s, 1H, OH); 13C NMR (CDCl3)
d
ppm: 160.8, 160.0, 135.5, 130.6, 129.0, 122.9, 121.7, 121.4, 119.8,
116.0, 109.6, 58.1. Anal. Calcd. for C22H16N4O2: C, 68.74; H, 4.33; N,
15.20; Found: C, 67.77; H, 4.35; N, 15.30%.
(CeSeC); 1H NMR (CDCl3þDMSOd6)
d in ppm: 3.40 (s, 3H, OCH3),
3.87 (s, 2H, eNeCH2), 8.16e7.19 (m, 11H, AreH), 8.61 (s, 1H,
eN¼CH), 11.13 (s, 1H, OH); 13C NMR (CDCl3)
d ppm: 160.0, 151.0,
5.1.4.2. 2-[40-(2, 4-dihydroxy benzylidenylamino-5-(N9-carbazolyl-
methylene)]-1, 3, 4-oxadiazole (4b). Yield 82% (DMF); m.p.126 ꢀC. IR
(KBr, nmax in cmꢁ1): 3435 (OH), 1617 (C.C of aromatic ring), 1592
149.3, 135.5, 130.9, 122.9, 121.7, 121.4, 119.8, 117.0, 112.1, 109.6, 58.1,
56.1. Anal. Calcd. for C23H18N4O2S: C, 66.65; H, 4.37; N, 13.51;
Found: C, 66.66; H, 4.29; N, 13.49%.

H. Kaur et al. / European Journal of Medicinal Chemistry 45 (2010) 2777e2783
2781
5.1.4.9. 2-[40-(4-NN0-dimethylaminobenzylidenylamino-5-(N9-car-
bazolylmethylene)]-1, 3, 4-thiadiazole (4i). Yield 81% (methanol); m.
p.134 ꢀC; IR (KBr, nmax in cmꢁ1): 3429 (eOH),1614 (C.C of aromatic
ring), 1588 (eC¼N), 1579 (N¼CH), 711 (CeSeC); 1H NMR
5.1.5.4. 9-[40-{4-NN0-Dimethylaminophenyl}-3-chloro-2-oxo-azeti-
din-100-yl-10, 30, 40-oxadiazol-50-yl] methylene carbazole (5d). Yield
85% (acetone); m.p. 126 ꢀC; IR (KBr, nmax in cmꢁ1): 1748 (C¼O), 1615
(C.C of aromatic ring), 1585 (eC¼N), 1022 (CeOeC), 1011 (CeCl);
(CDCl3þDMSOd6)
d
in ppm: 1.75 (s, 6H, N(CH3)2), 3.84 (s, 2H,
1H NMR (CDCl3 þ DMSOd6)
d in ppm: 1.82 (s, 6H, N(CH3)2), 3.77 (s,
2H, eNeCH2), 5.03 (d, 1H, J ¼ 5.10 Hz, CHCl), 5.54 (d, 1H, J ¼ 5.0 Hz,
eNeCH2), 8.17e7.18 (m, 12H, AreH), 8.67 (s, 1H, eN¼CH); 13C NMR
(CDCl3)
d
ppm: 160.0, 153.4, 135.5, 128.3, 125.9, 122.9, 121.7, 121.4,
eNeCHAr), 8.12e7.18 (m, 12H, AreH); 13C NMR (CDCl3)
d ppm:
119.8, 111.9, 109.6, 58.1, 40.2. Anal. Calcd. for C23H21N4S: C, 70.04; H,
5.14; N, 17.01; Found: C, 70.05; H, 5.18; N, 17.03%.
162.2, 149.1, 135.5, 133.0, 129.2, 122.9, 121.7, 121.4, 119.8, 112.7, 109.6,
62.8, 58.1, 40.2. Anal. Calcd. for C26H22N5O2Cl: C, 66.17; H, 4.69; N,
14.83; Found: C, 66.19, H, 4.66; N, 14.80%.
5.1.4.10. 2-[40-(2-bromobenzylidenylamino-5-(N9-carbazolylmethylene)]-
1, 3, 4-thiadiazole (4j). Yield 85% (acetone); m.p. 135 ꢀC; IR (KBr, nmax in
cmꢁ1): 1617 (C.C of aromatic ring), 1591 (eC¼N), 1576 (N¼CH), 710
5.1.5.5. 9-[40-{2-Bromophenyl}-3-chloro-2-oxo-azetidin-100-yl-10, 30,
40-oxadiazol-50-yl] methylene carbazole (5e). Yield 85% (petroleum
ether); m.p.132 ꢀC; IR (KBr, nmax in cmꢁ1): 1749 (C¼O),1612 (C.C of
aromatic ring), 1584 (eC¼N), 1020 (CeOeC), 1006 (CeCl), 609
(CeSeC), 612 (CeBr); 1H NMR (CDCl3þDMSOd6)
d in ppm: 3.91 (s, 2H,
eNeCH2), 8.16e7.17 (m, 12H, AreH), 8.63 (s, 1H, eN¼CH); 13C NMR
(CeBr); 1H NMR (CDCl3 þ DMSOd6)
d in ppm: 3.76 (s, 2H, eNeCH2),
(CDCl3) d ppm: 160.0, 135.5, 135.3, 132.8, 130.1, 127.8, 122.9, 121.7, 121.6,
5.04 (d, 1H, J ¼ 5.10 Hz, CHCl), 5.56 (d, 1H, J ¼ 5.10 Hz, eNeCHAr),
121.4, 119.8, 109.6, 127.1, 58.1. Anal. Calcd. for C22H15N4SBr: C: 59.06, H:
3.38, N: 12.52; Found: C, 59.16; H, 3.29; N, 12.45%.
8.09e7.17 (m, 12H, AreH); 13C NMR (CDCl3)
d ppm: 162.2, 145.7,
135.5, 132.5, 128.9, 127.5, 129.1, 122.9, 121.9, 121.7, 121.4, 119.8, 109.6,
61.3, 59.0, 58.1. Anal. Calcd. for C24H16N4O2ClBr: C, 58.77; H, 3.17; N,
11.03; Found: C, 58.70; H, 3.19; N, 11.24%.
5.1.5. Preparation of 9-[40-{Substitutedphenyl}-3-chloro-2-oxo-azetidin-
100-yl-10, 30, 40-oxa/thiadiazol-50-yl] methylene carbazoles 5a-j
To a stirred solution of 2-[40-(Substitutedbenzylidenylamino-5-
(N9-carbazolylmethylene)]-1, 3, 4-oxa/thiadiazoles (4a-j, 0.05 mol)
in dioxan (100 mL), chloro acetyl chloride (0.05 mol) was added
dropwise at 0e5 ꢀC temperature in presence of triethyl amine. The
reaction mixture was stirred for about 6 h and the precipitated
amine hydrochloride was filtered off. The filtrate was refluxed for
12 h and the separated solid was recrystallized from appropriate
solvents to furnish compounds 5a-j.
5.1.5.6. 9-[40-{4-Hydroxyphenyl}-3-chloro-2-oxo-azetidin-100-yl-10, 30,
40-thiadiazol-50-yl] methylene carbazole (5f). Yield 85% (acetone); m.
p.129 ꢀC. IR (KBr, nmax in cmꢁ1): 3439 (OH),1751 (C¼O),1618 (C.C of
aromatic ring), 1589 (eC¼N), 1008 (CeCl), 712 (CeSeC); 1H NMR
(CDCl3þDMSOd6)
d in ppm: 3.84 (s, 2H, eNeCH2), 5.02 (d, 1H,
J ¼ 5.12 Hz, CHCl), 5.55 (d, 1H, J ¼ 5.0 Hz, eNeCHAr), 8.03e7.19 (m,
12H, AreH), 11.17 (s, 1H, OH); 13C NMR (CDCl3)
d
ppm: 163.4, 162.2,
156.5, 136.1, 135.5, 127.0, 122.9, 121.7, 121.4, 119.8, 115.7, 109.6, 62.8,
62.0, 58.1. Anal. Calcd. for C24H17N4O2SCl: C, 62.53; H, 3.71; N, 12.15;
Found: C, 62.59; H, 3.79; N, 12.26%.
5.1.5.1. 9-[40-{4-Hydroxyphenyl}-3-chloro-2-oxo-azetidin-100-yl-10, 30,
40-oxadiazol-50-yl] methylene carbazole (5a). Yield 76% (ethanol); m.
p.124 ꢀC; IR (KBr, nmax in cmꢁ1): (eOH) 3429, 1752 (C¼O), 1619 (C.
C
5.1.5.7. 9-[40-{2,4-Dihydroxyphenyl}-3-chloro-2-oxo-azetidin-100-yl-10,
30, 40-thiadiazol-50-yl] methylene carbazole (5g). Yield 85% (meth-
anol); m.p. 128 ꢀC. IR (KBr, nmax in cmꢁ1): 3438 (OH), 1752 (C¼O),
1614 (C.C of aromatic ring),1583(eC¼N),1012 (CeCl), 711 (CeSeC);
of aromatic ring),1585 (eC¼N),1012 (CeOeC),1004 (CeCl); 1H NMR
(CDCl3þDMSOd6)
d in ppm: 3.92 (s, 2H, eNeCH2), 5.00 (d, 1H,
J ¼ 5.12 Hz, CHCl), 5.60 (d, 1H, J ¼ 5.0 Hz, eNeCHAr), 7.36e8.36 (m,
12H, AreH), 11.18 (s, 1H, OH). 13C NMR (CDCl3)
d
ppm: 162.2, 156.5,
1H NMR (CDCl3þDMSOd6)
d in ppm: 3.78 (s, 2H, eNeCH2), 5.05 (d,
136.1, 135.5, 127.0, 122.9, 121.7, 121.4, 119.8, 115.7, 109.6, 68.8, 68.0,
58.1. Anal. Calcd. for C24H17N4O3Cl: C, 64.79; H, 3.85; N,12.59; Found:
C, 64.99; H, 3.52; N, 12.49%.
1H, J ¼ 5.0 Hz, CHCl), 5.54 (d,1H, J ¼ 5.0 Hz, eNeCHAr), 8.04e7.16 (m,
11H, AreH), 11.21 (s, 2H, 2 ꢂ OH); 13C NMR (CDCl3)
d ppm: 163.4,
162.2, 157.9, 155.4, 135.5, 129.7, 123.5, 122.9, 121.7, 121.4, 119.8, 109.6,
108.3, 103.4, 62.3, 58.1, 56.6. Anal. Calcd. for C24H17N4O3SCl: C, 60.44;
H, 3.59; N, 17.74; Found: C, 60.38; H, 3.42; N, 11.61%.
5.1.5.2. 9-[40-{2,4-Dihydroxyphenyl}-3-chloro-2-oxo-azetidin-100-yl-10,
30, 40-oxadiazol-50-yl] methylene carbazole (5b). Yield 85% (ethanol);
m.p. 126 ꢀC. IR (KBr, nmax in cmꢁ1): 3429 (eOH), 1751 (C¼O), 1613
(C.C of aromatic ring), 1592 (eC¼N), (CeOeC) 1020, 1003 (CeCl);
5.1.5.8. 9-[40-{4-hydroxy-3-methoxyphenyl}-3-chloro-2-oxo-azeti-
din-100-yl-10, 30, 40-thiadiazol -50-yl] methylene carbazole (5h). Yield
85% (ethanol); m.p. 131 ꢀC. IR (KBr, nmax in cmꢁ1): 3543 (OH),: 1750
(C¼O),1619 (C.C of aromatic ring),1585 (eC¼N),1221 (OCH3),1014
1H NMR (CDCl3 þ DMSOd6)
d in ppm: 3.89 (s, 2H, eNeCH2), 5.05 (d,
1H, J ¼ 5.0 Hz, CHCl), 5.59 (d, 1H, J ¼ 5.0 Hz, eNeCHAr), 8.15e7.17 (m,
11H, AreH), 11.20 (s, 2H, 2 ꢂ OH). 13C NMR (CDCl3)
d ppm: 162.2,
(CeCl), 710 (CeSeC); 1H NMR (CDCl3 þ DMSOd6)
d in ppm: 3.39 (s,
3H, OCH3), 3.79 (s, 2H, eNeCH2), 5.04 (d, 1H, J ¼ 5.10 Hz, CHCl), 5.61
157.9, 155.4, 135.5, 129.7, 123.5, 122.9, 121.7, 121.4, 119.8, 109.6, 108.3,
62.3, 58.1,103.4, 56.6. Anal. Calcd. for C24H17N4O4Cl: C, 62.54; H, 3.71;
N, 12.15; Found: C, 62.51; H, 3.62; N, 12.18%.
(d, 1H, J ¼ 5.0 Hz, eNeCHAr), 8.07e7.18 (m, 11H, AreH), 11.23 (s, 1H,
OH); 13C NMR (CDCl3)
d ppm: 163.4, 162.2, 146.7, 147.3, 137.1, 135.5,
122.9, 121.7, 121.4, 119.8, 115.4, 110.2, 109.6, 62.0, 63.1, 58.1, 56.1.
Anal. Calcd. for C25H19N4O3SCl: C, 61.16; H, 3.90; N, 11.41; Found: C,
61.18; H, 3.85; N, 11.55%.
5.1.5.3. 9-[40-{4-hydroxy-3-methoxyphenyl}-3-chloro-2-oxo-azeti-
din-100-yl-10, 30, 40-oxadiazol-50-yl] methylene carbazole (5c). Yield
85% (DMF); m.p. 128 ꢀC; IR (KBr, nmax in cmꢁ1): 3429 (eOH), 1749
(C¼O), 1615 (C.C of aromatic ring), 1581 (eC¼N), 1220 (OCH3),
5.1.5.9. 9-[40-{4-NN0-Dimethylaminophenyl}-3-chloro-2-oxo-azeti-
din-100-yl-10, 30, 40-thiadiazol-50-yl] methylene carbazole (5i). Yield
85% (methanol); m.p. 130 ꢀC. IR (KBr, nmax in cmꢁ1): 1743C¼O),1614
(C.C of aromatic ring), 1588 (eC¼N), 1013 (CeCl), 709 (CeSeC); 1H
1025 (CeOeC), 1009 (CeCl); 1H NMR (CDCl3)
d in ppm: 3.37 (s, 3H,
OCH3), 3.81 (s, 2H, eNeCH2), 5.01 (d, 1H, J ¼ 5.12 Hz, CHCl), 5.62 (d,
1H, J ¼ 5.10 Hz, eNeCHAr), 8.02e7.18 (m, 11H, AreH), 11.19 (s, 1H,
OH); 13C NMR (CDCl3)
d
ppm: 162.2, 146.7, 147.3, 137.1, 135.5, 122.9,
NMR (CDCl3þDMSOd6)
d in ppm: 1.77 (s, 6H, N(CH3)2), 3.80 (s, 2H,
121.7, 121.4, 119.8, 119.3, 115.4, 110.2, 109.6, 62.0, 63.1, 58.1, 56.1.
Anal. Calcd. for C25H19N4O4Cl: C, 63.22; H, 4.03; N, 11.79; Found: C,
63.55; H, 3.68; N, 11.72%.
eNeCH2), 4.98 (d, 1H, J ¼ 5.0 Hz, CHCl), 5.66 (d, 1H, J ¼ 5.10 Hz,
eNeCHAr), 8.09e7.19 (m, 12H, AreH); 13C NMR (CDCl3)
ppm:
163.4, 162.2, 149.1, 135.5, 133.0, 129.2, 122.9, 121.7, 121.4, 119.8, 112.7,
d

2782
H. Kaur et al. / European Journal of Medicinal Chemistry 45 (2010) 2777e2783
109.6, 62.8, 58.1, 40.2. Anal. Calcd. for C26H22N5OSCl: C, 63.99; H,
4.54; N, 14.35; Found: C, 63.87; H, 4.55; N, 14.25%.
(s, 6H, N(CH3)2), 3.82 (s, 2H, eNeCH2), 3.97 (s, 2H, CH2 of thiazo-
lidinone ring), 5.60 (s,1H, eNeCHAr), 8.12e7.17 (m,12H, AreH); 13C
NMR (CDCl3)
d ppm: 171.2, 149.5, 135.5, 128.7, 127.4, 122.9, 121.7,
5.1.5.10. 9-[40-{2-Bromophenyl}-3-chloro-2-oxo-azetidin-100-yl-10, 30,
40- thiadiazol -50-yl] methylene carbazole (5j). Yield 85% (DMF); m.
p. 134 ꢀC. IR (KBr, nmax in cmꢁ1): 1750 (C¼O), 1611(C.C of aromatic
ring), 1579 (eC¼N), 1012 (CeCl), 711 (CeSeC), 615 (CeBr); 1H NMR
121.4, 119.8, 112.8, 109.6, 65.3, 58.1, 40.2, 33.2. Anal. Calcd. for
C26H23N5O2S: C, 66.50; H, 4.93; N, 14.91; Found: C, 66.80; H, 4.90;
N, 14.90%.
(CDCl3 þ DMSOd6)
d in ppm: 3.75 (s, 2H, eNeCH2), 4.96 (d, 1H,
5.1.6.5. 9-[40-{2-Bromophenyl}-2-oxo-thiazolidin-100-yl-10, 30, 40-oxa-
diazol-50-yl] methylene carbazole (6e). Yield 85% (acetone); m.p.
135 ꢀC. IR (KBr, nmax in cmꢁ1): 1762 (C¼O of thialactam ring), 1618
(C.C of aromatic ring), 1606 (C¼N), 1292 (NeN), 1022 (CeOeC),
J ¼ 5.10 Hz, CHCl), 5.62 (d, 1H, J ¼ 5.10 Hz, eNeCHAr), 8.10e7.18 (m,
12H, AreH); 13C NMR (CDCl3)
d
ppm: 163.4, 162.2, 145.7, 135.5,
132.5, 128.9, 127.5, 129.1, 122.9, 121.9, 121.7, 121.4, 119.8, 109.6, 61.3,
59.0, 58.1. Anal. Calcd. for C24H16N4OSClBr): C, 55.03; H, 3.07; N,
10.69; Found: C, 55.05; H, 3.27; N, 10.58%.
677 (CeSeC), 614 (CeBr); 1H NMR (CDCl3)
d in ppm: 3.74 (s, 1H,
eNeCHAr), 3.95 (s, 2H, CH2 of thiazolidinone ring), 5.58 (s, 1H,
eNeCH); 8.06e7.10 (m, 12H, AreH); 13C NMR (CDCl3)
d
ppm: 171.2,
5.1.6. Preparation of 9-[40-{Substituted phenyl}–2-oxo-thiazolidin-100-
yl-10, 30, 40-oxa/thiadiazol-50-yl] methylene carbazoles 6a-j
141.6, 135.5,132.6, 130.9, 129.6, 127.6, 123.7, 122.9, 121.7, 121.4, 119.8,
109.6, 61.5, 58.1, 33.5. Anal. Calcd. for C24H17N4O2SBr: C, 57.03; H,
3.39; N, 11.08; Found: C, 57.21; H, 3.35; N, 11.25%.
A solution of 9-[40-{Substitutedphenyl-1-yl}-3-chloro-2-oxo-
azetidin-100-yl-10, 30, 40-oxa/thiadiazol-50-yl] methylene carbazoles
(5a-j, 0.05 mol) and thioglycolic acid (0.05 mol) in methanol
(100 mL) in presence of anhydrous ZnCl2 (a pinch) was kept four
days at room temperature and the mixture was refluxed for 10 h
on water bath, distilled off, poured into ice-cold water, filtered
and finally recrystallized from appropriate solvents to give
compounds 6a-j.
5.1.6.6. 9-[40-{4-Hydroxyphenyl}-2-oxo-thiazolidin-100-yl-10, 30, 40-
thiadiazol-50-yl] methylene carbazole (6f). Yield 85% (ethanol); m.p.
130 ꢀC. IR (KBr, nmax in cmꢁ1): 3451 (OH), 1761 (C¼O of thialactam
ring), 1613 (C.C of aromatic ring), 1609 (C¼N), 1297 (NeN), 675
(CeSeC); 1H NMR (DMSOd6)
d in ppm: 3.73 (s, 2H, eNeCH2), 3.91
(s, 2H, CH2 of thiazolidinone ring), 5.66 (s, 1H, eNeCHAr), 8.15e7.16
(m, 12H, AreH), 11.22 (s, 1H, OH); 13C NMR (CDCl3)
d
ppm: 171.2,
5.1.6.1. 9-[40-{4-Hydroxyphenyl}-2-oxo-thiazolidin-100-yl-10, 30, 40-
oxadiazol -50-yl] methylene carbazole (6a). Yield 73% (acetone); m.
p. 128 ꢀC. IR (KBr, nmax in cmꢁ1): 3548 (OH), 1760 C¼O of thialactam
ring), 1613 (C.C of aromatic ring), 1602 (C¼N), 1295 (NeN), 1028
163.4, 156.9, 135.5, 131.8, 130.1, 122.9, 121.7, 121.4, 119.8, 115.8, 109.6,
65.3, 58.1, 33.5. Anal. Calcd. for C24H18N4O2S2: C, 62.86; H, 3.95; N,
12.21; Found: C, 62.92; H, 3.68; N, 12.20%.
(CeOeC), 673 (CeSeC); 1H NMR (CDCl3þDMSOd6)
d in ppm: 3.77
5.1.6.7. 9-[40-{2,4-Dihydroxyphenyl}-2-oxo-thiazolidin-100-yl-10, 30, 40-
thiadiazol-50-yl] methylene carbazole (6g). Yield 85% (acetone); m.p.
132 ꢀC. IR (KBr, nmax in cmꢁ1): 3452 (OH), 1762 C¼O of thialactam
ring), 1623 (C.C of aromatic ring), 1604 (C¼N) 1292, (NeN), 681
(s, 2H, eNeCH2), 3.90 (s, 2H, CH2 of thiazolidinone ring), 5.65 (s, 1H,
eNeCHAr), 7.17e8.10 (m, 12H, AreH), 11.20 (s, 1H, OH); 13C NMR
(CDCl3)
d ppm: 171.2, 156.9, 135.5, 131.8, 130.1, 122.9, 121.7, 121.4,
119.8, 115.8, 109.6, 65.3, 58.1, 33.5. Anal. Calcd. for C24H18N4O3S: C,
65.14; H, 4.10; N, 12.66; Found: C, 65.22; H, 4.12; N, 12.59%.
(CeSeC); 1H NMR (CDCl3 þ DMSOd6)
d in ppm: 3.76 (s, 2H,
eNeCH2), 3.96 (s, 2H, CH2 of thiazolidinone ring), 5.63 (s, 1H,
5.1.6.2. 9-[40-{2,4-Dihydroxyphenyl}-2-oxo-thiazolidin-100-yl-10, 30, 40-
oxadiazol-50-yl] methylene carbazole (6b). Yield 85% (DMF); m.p.
129 ꢀC; IR (KBr, nmax in cmꢁ1): 3449 (OH), 1762 (C¼O of thialactam
ring), 1615 (C.C of aromatic ring), 1607 (C¼N), 1296 (NeN), 1025
eNeCHAr), 8.13e7.16 (m, 11H, AreH), 11.22 (s, 2H, 2 ꢂ OH); 13C NMR
(CDCl3)
d ppm: 171.2, 163.4, 158.3, 157.2, 135.5, 131.5, 122.9, 121.7,
121.4, 119.8, 110.7, 109.6, 108.4, 103.5, 59.1, 58.1, 33.5. Anal. Calcd. for
C24H18N4O3S2: C, 60.74; H, 3.82; N, 11.80; Found: C, 60.64; H, 3.72;
3.68; N, 11.70%.
(CeOeC), 676 (CeSeC); 1H NMR (CDCl3)
d in ppm: 3.75 (s, 2H,
eNeCH2), 3.92 (s, 2H, CH2 of thiazolidinone ring), 5.64 (s, 1H,
eNeCHAr), 8.10e7.16 (m, 12H, AreH), 11.19 (s, 1H, OH); 13C NMR
5.1.6.8. 9-[40-{4-hydroxy-3-methoxyphenyl}-2-oxo-thiazolidin-100-yl-10,
30, 40-thiadiazol-50-yl] methylene carbazole (6h). Yield 85% (methanol);
m.p.134 ꢀC. IR (KBr, nmax in cmꢁ1):3445 (OH),1760 (C¼O of thialactam
ring), 1617 (C.C of aromatic ring), 1605 (C¼N), 1297 (NeN), 1228
(CDCl3)
d ppm: 171.2, 158.3, 157.2, 135.5, 131.5, 122.9, 121.7, 121.4,
119.8, 110.7, 109.6, 108.4, 103.5, 59.1, 58.1, 33.5. Anal. Calcd. for
C24H18N4O4S: C, 62.87; H, 3.95; N, 12.22; Found: C, 62.53; H, 3.88;
N, 12.55%.
(OCH3), 673 (CeSeSeC); 1H NMR (CDCl3)
d in ppm: 3.35 (s, 3H, OCH3),
3.83 (s, 2H, eNeCH2), 3.91 (s, 2H, CH2 of thiazolidinone ring), 5.61 (s,
5.1.6.3. 9-[40-{4-hydroxy-3-methoxyphenyl}-2-oxo-thiazolidin-100-yl-10,
30, 40-oxadiazol-50-yl] methylene carbazole (6c). Yield 85% (ethanol); m.
p. 132 ꢀC; IR (KBr, nmax in cmꢁ1): 3448 (OH), 1761 (C¼O of thialactam
ring), 1623 (C.C of aromatic ring), 1609 C¼N), 1295 (NeN), 1228
1H, eNeCHAr), 8.15e7.17 (m, 11H, AreH), 11.22 (s, 1H, OH); 13C NMR
(CDCl3) d ppm: 171.2, 163.4, 147.4, 147.1, 135.5, 132.8, 122.9, 122.4, 121.7,
121.4, 119.8, 115.5, 114.2, 109.6, 65.6, 58.1, 33.5. Anal. Calcd. for
C25H20N4O3S2: C, 61.45; H, 4.12; N, 11.46; Found: C, 61.59; H, 4.26;
3.68; N, 11.32%.
(OCH3), 1020 (CeOeC), 678 (CeSeC); 1H NMR (CDCl3 þ DMSOd6)
d in
ppm: 3.33 (s, 3H, OCH3), 3.76 (s, 2H, eNeCH2), 3.94 (s, 2H, CH2 of
thiazolidinone ring), 5.42 (s, 1H, eNeCHAr), 8.11e7.15 (m, 11H, AreH),
11.18 (s, 1H, OH), 13C NMR (CDCl3)
d
ppm: 171.2,147.4,147.1, 135.5,132.8,
5.1.6.9. 9-[40-{4-NN0-diphenylphenyl}-2-oxo-thiazolidin-100-yl-10, 30,
40-thiadiazol-50-yl] methylene carbazole (6i). Yield 85% (methanol);
m.p. 138 ꢀC. IR (KBr, nmax in cmꢁ1): 1764 (C¼O of thialactam ring),
1621 (C.C of aromatic ring),1611 (C¼N),1293 (NeN), 676 (CeSeC);
122.9, 122.4, 121.7, 121.4, 119.8, 115.5, 114.2, 109.6, 65.6, 58.1, 33.5. Anal.
Calcd. for C25H20N4O4S: C, 63.54; H, 4.26; N, 11.85; Found: C, 63.75; H,
4.44; N, 11.82%.
1H NMR (CDCl3þDMSOd6)
d in ppm: 1.80 (s, 6H, N(CH3)2), 3.89 (s,
2H, CH2 of thiazolidinone ring), 3.98 (s, 2H, eNeCH2), 5.59 (s, 1H,
5.1.6.4. 9-[40-{4-NN0-diphenylphenyl}-2-oxo-thiazolidin-100-yl-10, 30,
40-oxadiazol-50-yl] methylene carbazole (6d). Yield 85% (methanol);
m.p. 131 ꢀC; IR (KBr, nmax in cmꢁ1): 1766 (C¼O of thialactam ring),
1617 (C.C of aromatic ring), 1605 (C¼N), 1294 (NeN), 1024
eNeCHAr), 8.19e7.16 (m, 12H, AreH); 13C NMR (CDCl3)
d ppm:
171.2, 163.4, 149.5, 135.5, 128.7, 127.4, 122.9, 121.7, 121.4, 119.8, 112.8,
109.6, 65.3, 58.1, 40.2, 33.2. Anal. Calcd. for C26H23N5OS2: C, 64.30;
H, 4.77; N, 14.83; Found: C, 64.29; H, 4.75; N, 14.77%.
(CeOeC), 679 (CeSeC); 1H NMR (CDCl3 þ DMSOd6)
d in ppm: 1.89

H. Kaur et al. / European Journal of Medicinal Chemistry 45 (2010) 2777e2783
2783
5.1.6.10. 9-[40-{2-Bromophenyl}-2-oxo-thiazolidin-100-yl-10, 30, 40-
Acknowledgement
thiadiazol-50-yl] methylene carbazole (6j). Yield 85% (methanol); m.
p. 136 ꢀC. IR (KBr, nmax in cmꢁ1):1763 (C¼O of thialactam ring), 1616
(C.C of aromatic ring), 1610 (C¼N), 1296 (NeN), 677 (CeSeC), 611
We are thankful to SAIF Punjab University, Chandigarh India for
spectral and analytical analysis of newly synthesized compounds.
One of the author, Hemlata Kaur is also thankful to UGC New Delhi,
India for the award of J.RF e Rajiv Gandhi National Junior Research
Fellowship and financial support for this work.
(CeBr); 1H NMR (CDCl3)
d in ppm: 3.77 (s, 2H, eNeCH2), 3.92 (s, 2H,
CH2 of CH2 of thiazolidinone ring), 5.58 (s, 1H, eNeCHAr) 8.19e7.14
(m, 12H, AreH); 13C NMR (CDCl3)
d
ppm: 171.2, 163.4, 141.6, 135.5,
132.6, 130.9, 129.6, 127.6, 123.7, 122.9, 121.7, 121.4, 119.8, 109.6, 61.5,
58.1, 33.5. Anal. Calcd. for C24H17N4OS2Br: C, 55.28; H, 3.28; N,
10.74; Found: C, 55.33; H, 3.29; N, 10.57%.
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)