Synthesis and anti-inflammatory activity of newer quinazolin-4-one derivatives

Article abstract of DOI:10.1016/j.ejmech.2008.03.018

2-Methyl-3-aminosubstituted-3H-quinazolin-4-ones (1-2), 2-methyl-3-(substituted-arylidene-amino)-substituted-3H-quinazolin-4-ones (3-10), 2-bromomethyl-3-(substituted-arylidene-amino)-substituted-3H-quinazolin-4-ones (11-18), 2-(5′-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-3-(substituted-arylidene-amino)-substituted-3H-quinazolin-4-ones (19-26), 3-(3-chloro-2-oxo-4-substituted-aryl-azetidin-1-yl)-2-(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-substituted-3H-quinazolin-4-ones (27-34) and 3-(4-oxo-2-substituted-aryl-thiazolidin-3-yl)-2-(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-substituted-3H-quinazolin-4-ones (35-42) were synthesized in present study. All the compounds exhibited anti-inflammatory activity at the dose 50 mg/kg p.o. varying degree from 16.3 to 36.3% inhibition of oedema. Compound 40 showed same activity at 25, 50 and 100 mg/kg p.o. like standard drugs. The structure of all these newly synthesized compounds was confirmed by their analytical (C, H, N) and spectral (IR and ¹H NMR) data.

Full text of DOI:10.1016/j.ejmech.2008.03.018

Available online at www.sciencedirect.com
European Journal of Medicinal Chemistry 44 (2009) 83e90
http://www.elsevier.com/locate/ejmech
Original article
Synthesis and anti-inflammatory activity of newer
quinazolin-4-one derivatives
1
*
Ashok Kumar , Chatrasal Singh Rajput
Medicinal Chemistry Division, Department of Pharmacology, L.L.R.M. Medical College, Gargh Road, Meerut, U.P. 250004, India
Received 17 September 2006; received in revised form 6 March 2008; accepted 13 March 2008
Available online 1 April 2008
Abstract
2-Methyl-3-aminosubstituted-3H-quinazolin-4-ones (1e2), 2-methyl-3-(substituted-arylidene-amino)-substituted-3H-quinazolin-4-ones
(3e10), 2-bromomethyl-3-(substituted-arylidene-amino)-substituted-3H-quinazolin-4-ones (11e18), 2-(50-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-
sulfanylmethyl)-3-(substituted-arylidene-amino)-substituted-3H-quinazolin-4-ones (19e26), 3-(3-chloro-2-oxo-4-substituted-aryl-azetidin-1-yl)-
2-(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-substituted-3H-quinazolin-4-ones (27e34) and 3-(4-oxo-2-substituted-aryl-thiazoli-
din-3-yl)-2-(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-substituted-3H-quinazolin-4-ones (35e42) were synthesized in present study.
All the compounds exhibited anti-inflammatory activity at the dose 50 mg/kg p.o. varying degree from 16.3 to 36.3% inhibition of oedema.
Compound 40 showed same activity at 25, 50 and 100 mg/kg p.o. like standard drugs. The structure of all these newly synthesized compounds
1
was confirmed by their analytical (C, H, N) and spectral (IR and H NMR) data.
Ó 2008 Elsevier Masson SAS. All rights reserved.
Keywords: Quinazolin-4-ones; Azetidinones; Thiazolidinones; Oxadiazoles; Anti-inflammatory activity
1. Introduction
2. Chemistry
Quinazolinone derivatives have been found to possess
potent wide spectrum of activities like antibacterial [1,2],
antifungal [3e5], anticonvulsant [6] and anti-inflammatory
[7e10]. It has been reported that substitution of different het-
erocyclic moieties at 2 or 3 position of quinazolinone nucleus
modulates the anti-inflammatory activity. A large numbers of
azetidinones [11,12], thiazolidinones [13,14] and oxadiazoles
[15e18] were reported to possess anti-inflammatory activity.
In the light of these observations this prompted us to synthe-
size a new series of quinazolinone derivatives by incorporation
the azetidinone and thiazolidinone moieties at 3rd position of
quinazolinone nucleus. The structures of all compounds have
been evaluated by elemental analysis and spectral analysis
Compound 2-methyl-3-aminosubstituted-3H-quinazolin-4-
ones (1e2) were prepared according to reported method by
Kumar et al. [19]. 2-Methyl-3-arylidene-amino-3H-quinazo-
lin-4-one (3), 2-methyl-3-( p-chloroarylidene)-amino-3H-qui-
nazolin-4-one (4), and 2-methyl-3-( p-methoxyarylidene)-
amino-3H-quinazolin-4-one (5) were prepared by known
method Arques et al. [20]. 2-Methyl-3-( p-hydroxyaryli-
dene)-amino-3H-quinazolin-4-one (6) and 2-methyl-3-(aryli-
dene)-amino-6-bromo-3H-quinazolin-4-one (7) were also
prepared according to reported method by Roshdy et al. [21]
and Sammour et. al. [22], respectively. Compounds 1e2 on re-
action with substituted-benzaldehyde converted in to
2-methyl-3-(substituted-arylidene)aminosubstituted-3H-quina-
zolin-4-ones (8e10). On bromination in glacial acetic acid
(3e10) yielded 2-bromomethyl-3-(substituted-arylidene)ami-
nosubstituted-3H-quinazalin-4-ones (11e18). Further, more
the reaction with 5-(4-pyridinyl)-1,3,4-oxadiazole-2-thiol in
pyridine gave 2-(50-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sul-
fanylmethyl)-3-(substituted-arylidene-amino)-substituted-3
1
(IR and H NMR). All the compounds have been screened
for their anti-inflammatory activity.
* Corresponding author. Tel.: þ91 1212764084.
E-mail address: rajputak@gmail.com (A. Kumar).
1
Part of Ph.D. thesis work.
0223-5234/$ - see front matter Ó 2008 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.ejmech.2008.03.018

84
A. Kumar, C.S. Rajput / European Journal of Medicinal Chemistry 44 (2009) 83e90
H-quinazolin-4-ones (19e26), 3-(3-chloro-2-oxo-4-substituted-
aryl-azetidin-1-yl)-2-(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-
sulfanylmethyl)-substituted-3H-quinazolin-4-ones (27e34) and
3-(4-oxo-2-substituted-aryl-thiazolidin-3-yl)-2-(5-pyridin-4-yl-
[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-substituted-3H-quina-
zolin-4-ones (35e42) were synthesized by the reaction of
compounds 19e26 with chloroacetyl chloride and thioglycolic
acid respectively.
compounds were screened for their anti-inflammatory profile
at the dose of 50 mg/kg p.o. exhibiting substantive anti-
inflammatory activity of varying degree from 16.3 to 36.3%
the biological results are given in Table 1. It was observed
that compound 40 showed maximum activity, which showed
36.3 inhibition of oedema. Interestedly this compound showed
equal anti-inflammatory activity like standard drug phenylbu-
tazone at the dose of 25, 50 and 100 mg/kg p.o.
Furthermore the substitution with phenyl group having
chloro group at p-position showed better anti-inflammatory
activity. Substitutions at 6 position of quinazolin-4-ones nu-
cleus with electronegative atom increase the anti-inflammatory
activity. Cyclisation of arylidene compounds into azetidinones
3. Pharmacological result and discussion
All these newly synthesis compounds 19e42 were tested in
vivo in order to evaluate their pharmacological activity. These
O
O
C
C
NH2
N
Absolute ethanol
CHO
N
CH
N
X
N
CH3
X
N
CH3
R
R
(1-2)
(3-10)
Br2/CH3COOH
O
C
CH
N
N
X
N
CH2Br
R
(11-18)
N
N
Pyridine
N
SH
R
O
O
C
N
N
CH
X
N
N
N
CH2S
N
O
(19-26)
SHCH2COOH
Anhy. ZnCl2
ClCH2COCl
Et3N:
O
Cl
O
C
CH
C
R
R
N
N
CH
N
O
O
S
X
N
C
N
N
CH
N
N
CH2S
N
O
X
N
(27-34)
N
CH2S
N
O
(35-42)

A. Kumar, C.S. Rajput / European Journal of Medicinal Chemistry 44 (2009) 83e90
85
the calculated. The IR spectra (cmꢁ1) were recorded in film
or in potassium bromide disks on a Beckman Acculab-10-
spectrophotometer (nmax in cmꢁ1). The 1H spectra were
recorded on a DPX-300 MHz Bruker FT-NMR spectrometer
in CDCl3/DMSO-d6 instrument.
Table 1
Characterizations and anti-inflammatory activity of compounds 19e42
Compound
no.
X
R
Dose
(mg/kg p.o.)
%
Anti-inflammatory
activity
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
H
H
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
25
50
100
50
50
25
50
100
16.3
23.7
20.0
18.2
19.4
26.4
24.4
22.3
25.1
27.9
26.1
25.7
26.3
29.9
28.6
27.4
30.1
34.1
33.8
31.7
31.3
25.2
36.3
66.9
35.3
32.7
25.4
36.8
66.4
H
p-Cl
p-OCH3
p-OH
H
H
5.1.1. 2-Methyl-3-[( p-chloroarylidene)
H
amino]-6-bromoquinazolin-4-one (8)
6 Br
6 Br
6 Br
6 Br
H
Yield 70% (benzene): mp 178 ꢂC; IR (KBr) nmax in cmꢁ1
2950 (CH3), 1690 (C]O), 1600 (C]N), 1542 (C]C aro-
:
p-Cl
p-OCH3
p-OH
H
1
matic), 795 (AreCl); H NMR (CDCl3) d in ppm: 8.52 (s,
1H, N]CHeAr), 7.24e8.01 (m, 7H, AreH), 2.40 (s, 3H,
CH3). Anal. Calcd for C16H11N3OBrCl: C, 50.99; H, 2.92;
N, 11.15. Found: C, 50.79; H, 2.94; N, 11.19. MS: [M]þ at
m/z 376.5.
H
p-Cl
p-OCH3
p-OH
H
H
H
6 Br
6 Br
6 Br
6 Br
H
p-Cl
p-OCH3
p-OH
H
5.1.2. 2-Methyl-3-[( p-methoxyarylidene)
amino]-quinazolin-4-one (9)
H
p-Cl
p-OCH3
p-OH
H
Yield 50% (ethanol): mp 155 ꢂC; IR (KBr) nmax in cmꢁ1
3025 (CH aromatic), 2950 (CH3), 1695 (C]O), 1602
:
H
H
6 Br
6 Br
1
(C]N), 1545 (C]C aromatic), 1175 (CeOeC); H NMR
p-Cl
(CDCl3) d in ppm: 8.50 (s, 1H, N]CHeAr), 7.28e8.04 (m,
7H, AreH), 3.31 (s, 3H, OCH3), 2.40 (s, 3H, CH3). Anal.
Calcd for C17H14N3O2Br: C, 54.84; H, 3.76; N, 11.29. Found:
C, 54.69; H, 3.78; N, 11.32. MS: [M]þ at m/z 372.
41
42
6 Br
6 Br
p-OCH3
p-OH
e
Phenylbutazone
5.1.3. 2-Methyl-3-[( p-hydroxyarylidene)
(27e34) enhanced the % anti-inflammatory activity of the
compounds (25.1e29.9%) and into thiazolidinones (35e42)
(30.1e36.3%), It is interesting to point out that thiazolidi-
nones derivative showed better anti-inflammatory activity
than that of azetidinones derivative.
amino]-quinazolin-4-one (10)
Yield 55% (ethanol): mp 135 ꢂC; IR (KBr) nmax in cmꢁ1
3425 (AreOH), 2950 (CH3), 1695 (C]O), 1600 (C]N),
:
1
1545 (C]C aromatic); H NMR (CDCl3) d in ppm: 11.30
(s, 1H, AreOH), 8.56 (s, 1H, N]CHeAr), 7.30e8.05 (m,
7H, AreH), 2.42 (s, 3H, CH3). Anal. Calcd for
C16H12N3O2Br: C, 53.63; H, 3.35; N, 11.73. Found: C,
53.81; H, 3.34; N, 11.77. MS: [M]þ at m/z 358.
4. Conclusion
It may be concluded that the compounds having 3-amino-2-
methyl-6-bromoquinazolin-4-onyl moiety showed more
protection than the compounds having 3-amino-2-methyl-qui-
nazolin-4-onyl moiety. Further, thiazolidinones showed more
potent anti-inflammatory activity in comparison to their corre-
sponding azetidinones.
Furthermore, we also conclude that substitution with p-
chloro phenyl group was found to increase the anti-inflammatory
activity.
5.1.4. 2-Bromomethyl-3-[(arylidene)
amino]-quinazolin-4-ones (11)
Compound 11 was synthesized by adding solution of bro-
mine (0.02 mol) in acetic acid drop wise with constant stirring
in the cold solution of compound 3 (0.01 mol). The reaction
mixture was further stirred for 4 h and left for over night.
The solvent was distilled off and the residue thus obtained
was washed with water, filtrated, dried and recrystallized
from ethanol to give compound 11. Yield 65%: mp 137 ꢂC;
IR (KBr) nmax in cmꢁ1: 2945 (CH2), 1690 (C]O), 1595
5. Experimental
1
5.1. Chemistry
(C]N), 1540 (C]C aromatic); H NMR (CDCl3) d in ppm:
8.53 (s, 1H, N]CHeAr), 7.35e8.00 (m, 9H, AreH), 3.69
(s, 2H, CH2eBr). Anal. Calcd for C16H12N3OBr: C, 56.14;
H, 3.51; N, 12.28. Found: C, 56.21; H, 3.53; N, 12.26. MS:
[M]þ at m/z 342.
The following compounds were prepared using a similar
procedure as described for compound 11.
Melting points were taken in open capillaries on Thomas
Hoover melting point apparatus and are uncorrected. The
purity of the compounds was checked on silica gel-G coated
plats. Elemental analysis (C, H, N) was performed on a Per-
kineElmer 2400 analyzer and values were with in ꢀ0.4% of

86
A. Kumar, C.S. Rajput / European Journal of Medicinal Chemistry 44 (2009) 83e90
5.1.5. 2-Bromomethyl-3-[( p-chloroarylidene)
amino]-quinazolin-4-ones (12)
C17H13N3O2Br2: C, 45.23; H, 2.88; N, 9.31. Found: C,
45.40; H, 2.86; N, 9.35. MS: [M]þ at m/z 451.
Yield 65% (ethanol): mp 182 ꢂC; IR (KBr) nmax in cmꢁ1
2940 (CH2), 1695 (C]O), 1590 (C]N), 1545 (C]C aro-
:
5.1.11. 2-Bromomethyl-3-[( p-hydroxyarylidene)
1
matic), 793 (AreCl); H NMR (CDCl3) d in ppm: 8.56 (s,
amino]-6-bromo-quinazolin-4-ones (18)
1H, N]CHeAr), 7.29e8.06 (m, 8H, AreH), 3.64 (s, 2H,
CH2eBr). Anal. Calcd for C16H11N3OBrCl: C, 50.99; H,
2.92; N, 11.15. Found: C, 51.11; H, 2.90; N, 11.17. MS:
[M]þ at m/z 376.5.
Yield 75% (ethanol): mp 144 ꢂC; IR (KBr) nmax in cmꢁ1
3420 (AreOH), 2940 (CH2), 1694 (C]O), 1598 (C]N),
:
1
1540 (C]C aromatic); H NMR (CDCl3) d in ppm: 11.38
(s, 1H, AreOH), 8.63 (s, 1H, N]CHeAr), 7.29e8.05 (m,
7H, AreH), 3.67 (s, 2H, CH2eBr). Anal. Calcd for
C16H11N3O2Br2: C, 43.94; H, 2.52; N, 9.61. Found: C,
43.83; H, 2.51; N, 9.62. MS: [M]þ at m/z 437.
5.1.6. 2-Bromomethyl-3-[( p-methoxyarylidene)
amino]-quinazolin-4-ones (13)
Yield 50% (benzene): mp 165 ꢂC; IR (KBr) nmax in cmꢁ1
2944 (CH2), 1698 (C]O), 1600 (C]N), 1540 (C]C aro-
:
1
matic), 1183 (CeOeC); H NMR (CDCl3) d in ppm: 8.56
5.1.12. 2-(5-Pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanyl
methyl)-3-(arylidene-amino)-quinazolin-4-one (19)
To a solution of compound 11 (0.01 mol) in pyridine
(s, 1H, N]CHeAr), 7.28e8.02 (m, 8H, AreH), 3.66 (s,
2H, CH2eBr), 3.36 (s, 3H, OCH3). Anal. Calcd for
C17H14N3OBr: C, 54.84; H, 3.76; N, 11.29. Found: C,
54.96; H, 3.78; N, 11.30. MS: [M]þ at m/z 372.
(80 ml)
and
5-(4-pyridinyl)
1,3,4-oxadiazole-2-thiol
(0.01 mol) were refluxed for 3 h. The contents were then
poured onto crushed ice bath and a solid mass, which sepa-
rated out, was filtered and recrystallized from ethanol to
give compound 19. Yield 55%: mp 125 ꢂC; IR (KBr) nmax in
cmꢁ1: 2935 (CH2), 1695 (C]O), 1598 (C]N), 1635, 1610,
1580, 1420, 1070 (st. of oxadiazole), 1540 (C]C aromatic);
1H NMR (CDCl3) d in ppm: 8.64 (s, 1H, N]CHeAr), 8.21
(dd, J ¼ 8 Hz, 2H, PyreH2), 7.30e8.02 (m, 11H, 9AreH,
2H, PyreH3), 3.10 (s, 2H, CH2eS). Anal. Calcd for
C23H16N6O2S: C, 62.73; H, 3.64; N, 19.09. Found: C, 62.89;
H, 3.63; N, 19.17. MS: [M]þ at m/z 440.
5.1.7. 2-Bromomethyl-3-[( p-hydroxyarylidene)
amino]-quinazolin-4-ones (14)
Yield 55% (acetone): mp 147 ꢂC; IR (KBr) nmax in cmꢁ1
3425 (AreOH), 2948 (CH2), 1694 (C]O), 1595 (C]N),
:
1
1543 (C]C aromatic); H NMR (CDCl3) d in ppm: 11.30
(s, 1H, AreOH), 8.54 (s, 1H, N]CHeAr), 7.28e7.99 (m,
8H, AreH), 3.66 (s, 2H, CH2eBr). Anal. Calcd for
C16H12N3O2Br: C, 53.63; H, 3.35; N, 11.73. Found: C,
51.51; H, 3.34; N, 11.75. MS: [M]þ at m/z 358.
The following compounds were prepared using a similar
procedure as described for compound 19.
5.1.8. 2-Bromomethyl-3-[(arylidene)
amino]-6-bromo-quinazolin-4-ones (15)
Yield 55% (methanol): mp 169 ꢂC; IR (KBr) nmax in cmꢁ1
2950 (CH2), 1700 (C]O), 1590 (C]N), 1540 (C]C aro-
:
5.1.13. 2-(5-Pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanyl
methyl)-3-( p-chloro arylidene-amino)-
quinazolin-4-one (20)
1
matic); H NMR (CDCl3) d in ppm: 8.59 (s, 1H, N]CHe
Yield 50% (ethanol): mp 178 ꢂC; IR (KBr) nmax in cmꢁ1
:
Ar), 7.20e8.08 (m, 8H, AreH), 3.70 (s, 2H, CH2eBr).
Anal. Calcd for C16H11N3OBr2: C, 45.61; H, 2.61; N, 9.98.
Found: C, 45.73; H, 2.60; N, 10.01. MS: [M]þ at m/z 421.
2938 (CH2), 1698 (C]O), 1590 (C]N), 1635, 1605, 1582,
1424, 1072 (st. of oxadiazole), 1544 (C]C aromatic), 785
1
(AreCl); H NMR (CDCl3) d in ppm: 8.60 (s, 1H, N]CHe
Ar), 8.23 (dd, J ¼ 8.2 Hz, 2H, PyreH2), 7.25e8.01 (m, 10H,
8AreH, 2PyreH3), 3.12 (s, 2H, CH2eS). Anal. Calcd for
C23H15N6O2SCl: C, 58.17; H, 3.16; N, 17.70. Found: C,
58.34; H, 3.18; N, 17.78. MS: [M]þ at m/z 474.5.
5.1.9. 2-Bromomethyl-3-[( p-chloroarylidene)
amino]-6-bromo-quinazolin-4-ones (16)
Yield 60% (methanol): mp 189 ꢂC; IR (KBr) nmax in cmꢁ1
2940 (CH2), 1694 (C]O), 1600 (C]N), 1546 (C]C aro-
:
1
matic) 785 (AreCl); H NMR (CDCl3) d in ppm: 8.62 (s,
1H, N]CHeAr), 7.15e7.98 (m, 7H, AreH), 3.65 (s, 2H,
CH2eBr). Anal. Calcd for C16H10N3OBr2Cl: C, 42.15; H,
2.19; N, 9.22. Found: C, 42.21; H, 2.17; N, 9.24. MS: [M]þ
at m/z 455.5.
5.1.14. 2-(5-Pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanyl
methyl)-3-( p-methoxyarylidene-
amino)-quinazolin-4-one (21)
Yield 52% (methanol): mp 214 ꢂC; IR (KBr) nmax in cmꢁ1
:
2940 (CH2), 1690 (C]O), 1595 (C]N), 1685, 1630, 1582,
1420, 1075 (st. of oxadiazole), 1542 (C]C aromatic), 1182
(CeOeC); 1H NMR (CDCl3) d in ppm: 8.56 (s, 1H,
N]CHeAr), 8.25 (dd, J ¼ 8.3 Hz, 2H, PyreH2), 7.26e8.05
(m, 10H, 8AreH, 2PyreH3), 3.18 (s, 2H, CH2eS), 3.39 (s,
3H, OCH3). Anal. Calcd for C24H18N6O3S: C, 61.28; H,
3.83; N, 17.87. Found: C, 61.12; H, 3.85; N, 17.94. MS:
[M]þ at m/z 470.
5.1.10. 2-Bromomethyl-3-[( p-methoxyarylidene)
amino]-6-bromo-quinazolin-4-ones (17)
Yield 60% (benzene): mp 172 ꢂC; IR (KBr) nmax in cmꢁ1
2948 (CH2), 1698 (C]O), 1600 (C]N), 1546 (C]C aro-
:
1
matic), 1180 (CeOeC); H NMR (CDCl3) d in ppm: 13 (s,
1H, N]CHeAr), 7.26e8.02 (m, 7H, AreH), 3.62 (s, 2H,
CH2eBr), 3.35 (s, 3H, OCH3). Anal. Calcd for

A. Kumar, C.S. Rajput / European Journal of Medicinal Chemistry 44 (2009) 83e90
87
5.1.15. 2-(5-Pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylme
thyl)-3-( p-hydroxy arylidene-amino)-quinazolin-4-one (22)
Yield 60% (benzene): mp 152 ꢂC; IR (KBr) nmax in cmꢁ1
2PyreH3), 3.14 (s, 2H, CH2eS). Anal. Calcd for
C23H15N6O3SBr: C, 51.59; H, 2.80; N, 15.70. Found: C,
51.75; H, 2.81; N, 15.76. MS: [M]þ at m/z 535.
:
3422 (AreOH), 2940 (CH2), 1690 (C]O), 1590 (C]N),
1630, 1608, 1580, 1422, 1072 (st. of oxadiazole), 1540
1
(C]C aromatic); H NMR (CDCl3) d in ppm: 11.33 (s, 1H,
5.1.20. 3-(3-Chloro-2-oxo-4-aryl-azetidin-1-yl)-2-
(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-
quinazolin-4-ones (27)
AreOH), 8.61 (s, 1H, N]CHeAr), 8.23 (dd, J ¼ 8.3 Hz,
2H, PyreH2), 7.21e8.04 (m, 10H, 8AreH, 2PyreH3), 3.13
(s, 2H, CH2eS). Anal. Calcd for C23H16N6O3S: C, 60.53; H,
3.51; N, 18.42. Found: C, 60.65; H, 3.52; N, 18.47. MS:
[M]þ at m/z 456.
To the stirred solution of compound 19 (0.01 mol) and trie-
thylamine (few drops) in ethanol (50 ml) was added mono-
chloroacetyl chloride (0.014 mol) at 50 ꢂC. The reaction
mixture was stirred for 30 min at room temperature on re-
fluxed for 6e8 h. The reaction mixture was filtered to remove
triethylamine hydrochloride and the resultant solution was
poured on to crushed ice with constant stirring. The solid
thus obtained was recrystallized from ethanol to give com-
5.1.16. 2-(5-Pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanyl
methyl)-3-(arylidene-amino)-6-bromoquinazolin-4-one (23)
Yield 65% (ethanol): mp 135 ꢂC; IR (KBr) nmax in cmꢁ1
:
2948 (CH2), 1700 (C]O), 1590 (C]N), 1635, 1615, 1575,
1420, 1071 (st. of oxadiazole), 1544 (C]C aromatic); 1H
NMR (CDCl3) d in ppm: 8.63 (s, 1H, N]CHeAr), 8.25
(dd, J ¼ 8.6 Hz, 2H, PyreH2), 7.20e8.01 (m, 10H, 8AreH,
2PyreH3), 3.15 (s, 2H, CH2eS). Anal. Calcd for
C23H15N6O2SBr: C, 53.18; H, 2.89; N, 16.18. Found: C,
53.37; H, 2.90; N, 16.10. MS: [M]þ at m/z 519.
pound 27. Yield 50%: mp 137 ꢂC; IR (KBr) nmax in cmꢁ1
:
2945 (CH2), 1730 (C]O, azetidine), 1690 (C]O), 1585
(C]N), 1635, 1610, 1570, 1420, 1070 (st. of oxadiazole),
1540 (C]C aromatic), 680 (CHeCl); 1H NMR (CDCl3)
d in ppm: 8.23 (dd, J ¼ 8.3 Hz, 2H, PyreH2), 7.14e8.05
(m, 11H, 9AreH, 2PyreH3), 6.20 (s, 1H, CHeAr), 4.54 (s,
1H, CHeCl), 3.10 (s, 2H, CH2eS). Anal. Calcd for
C25H17N6O3SCl: C, 58.08; H, 3.29; N, 16.26. Found: C,
58.27; H, 3.31; N, 16.31. MS: [M]þ at m/z 516.5.
5.1.17. 2-(5-Pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanyl
methyl)-3-( p-chloroarylidene-amino)-6-bromoquinazolin-
4-one (24)
Yield 62% (methanol): mp 197 ꢂC; IR (KBr) nmax in cmꢁ1
:
The following compounds were prepared using a similar
procedure as described for compound 27.
2940 (CH2), 1696 (C]O), 1599 (C]N), 1633, 1610, 1575,
1422, 1074 (st. of oxadiazole), 1540 (C]C aromatic), 790
1
(AreCl); H NMR (CDCl3) d in ppm: 8.61 (s, 1H, N]CHe
Ar), 8.23 (dd, J ¼ 8.3 Hz, 2H, PyreH2), 7.15e8.04 (m, 9H,
7AreH, 2PyreH3), 3.09 (s, 2H, CH2eS). Anal. Calcd for
C23H14N6O2SBrCl: C, 49.86; H, 2.53; N, 15.18. Found: C,
49.98; H, 2.50; N, 15.12. MS: [M]þ at m/z 553.5.
5.1.21. 3-(3-Chloro-2-oxo-4-{p-chloroaryl}-azetidin-1-yl)-
2-(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-
quinazolin-4-one (28)
Yield 55% (ethanol): mp 185 ꢂC; IR (KBr) nmax in cmꢁ1
:
2948 (CH2), 1735 (C]O azetidine), 1703 (C]O), 1595
(C]N), 1640, 1612, 1570, 1420, 1073 (st. of oxadiazole),
1544 (C]C aromatic), 686 (CHeCl); 1H NMR (CDCl3)
d in ppm: 8.26 (dd, J ¼ 8.6 Hz, 2H, PyreH2), 7.15e8.01
(m, 10H, 8AreH, 2PyreH3), 6.25 (s, 1H, CHeAr), 4.51 (s,
1H, CHeCl), 3.11 (s, 2H, CH2eS). Anal. Calcd for
C25H16N6O3SCl2: C, 54.45; H, 2.90; N, 15.24. Found: C,
54.61; H, 2.88; N, 15.19. MS: [M]þ at m/z 551.
5.1.18. 2-(5-Pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanyl
methyl)-3-( p-methoxyarylidene-amino)-6-bromoquinazolin-
4-one (25)
Yield 55% (methanol): mp 218 ꢂC; IR (KBr) nmax in cmꢁ1
:
2940 (CH2), 1690 (C]O), 1598 (C]N), 1635, 1610, 1580,
1420, 1072 (st. of oxadiazole), 1544 (C]C aromatic), 1175
(CeOeC); 1H NMR (CDCl3) d in ppm: 8.56 (s, 1H,
N]CHeAr), 8.22 (dd, J ¼ 8 Hz, 2H, PyreH2), 7.25e7.99
(m, 9H, 7AreH, 2PyreH3), 3.36 (s, 3H, OCH3), 3.12 (s,
2H, CH2eS). Anal. Calcd for C24H17N6O3SBr: C, 52.46; H,
3.10; N, 15.30. Found: C, 52.32; H, 3.11; N, 15.25. MS:
[M]þ at m/z 549.
5.1.22. 3-(3-Chloro-2-oxo-4-{p-methoxyaryl}-azetidin-1-
yl)-2-(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-
quinazolin-4-ones (29)
5.1.19. 2-(5-Pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanyl
methyl)-3-( p-hydroxyarylidene-amino)-6-bromoquinazolin-
4-one (26)
Yield 40% (methanol): mp 196 ꢂC; IR (KBr) nmax in cmꢁ1
:
2950 (CH2), 1732 (C]O azetidine), 1700 (C]O), 1600
(C]N), 1635, 1610, 1580, 1425, 1070 (st. of oxadiazole),
1540 (C]C aromatic), 683 (CHeCl); 1H NMR (CDCl3)
d in ppm: 8.25 (dd, J ¼ 8 Hz, 2H, PyreH2), 7.28e8.00 (m,
10H, 8AreH, 2PyreH3), 6.22 (s, 1H, CHeAr), 4.56 (s, 1H,
CHeCl), 3.36 (s, 3H, OCH3), 3.14 (s, 2H, CH2eS). Anal.
Calcd for C26H19N6O4SCl: C, 57.09; H, 3.48; N, 15.37.
Found: C, 57.21; H, 3.50; N, 15.43. MS: [M]þ at m/z 546.5.
Yield 65% (benzene): mp 218 ꢂC; IR (KBr) nmax in cmꢁ1
:
3428 (AreOH), 2945 (CH2), 1695 (C]O), 1590 (C]N),
1630, 1612, 1575, 1425, 1075 (st. of oxadiazole), 1540
1
(C]C aromatic), 1175 (CeOeC); H NMR (CDCl3) d in
ppm: 11.30 (s, 1H, AreOH), 8.55 (s, 1H, N]CHeAr), 8.24
(dd, J ¼ 8.3 Hz, 2H, PyreH2), 7.21e8.04 (m, 9H, 7AreH,

88
A. Kumar, C.S. Rajput / European Journal of Medicinal Chemistry 44 (2009) 83e90
5.1.23. 3-(3-Chloro-2-oxo-4-{p-hydroxyaryl}-azetidin-1-yl)-
2-(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-
quinazolin-4-ones (30)
5.1.27. 3-(3-Chloro-2-oxo-4-{p-hydroxyaryl}-azetidin-1-yl)-
2-(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-
6-bromoquinazolin-4-ones (34)
Yield 45% (methanol): mp 166 ꢂC; IR (KBr) nmax in cmꢁ1
:
Yield 55% (methanol): mp 153 ꢂC; IR (KBr) nmax in cmꢁ1
:
3425 (AreOH), 2940 (CH2), 1738 (C]O azetidine), 1700
(C]O), 1600 (C]N), 1635, 1615, 1580, 1420, 1075 (st. of
3420 (AreOH), 2945 (CH2), 1730 (C]O azetidine), 1705
(C]O), 1600 (C]N), 1642, 1615, 1560, 1420, 1073 (st. of
1
oxadiazole), 1540 (C]C aromatic), 689 (CHeCl); H NMR
1
oxadiazole), 1540 (C]C aromatic), 670 (CHeCl); H NMR
(CDCl3) d in ppm: 11.33 (s, 1H, AreOH), 8.26 (dd,
J ¼ 8.3 Hz, 2H, PyreH2), 7.17e8.02 (m, 10H, 8AreH,
2PyreH3), 6.24 (s, 1H, CHeAr), 4.54 (s, 1H, CHeCl), 3.16
(s, 2H, CH2eS). Anal. Calcd for C25H17N6O4SCl: C, 56.34;
H, 3.19; N, 15.77. Found: C, 56.52; H, 3.17; N, 15.72. MS:
[M]þ at m/z 532.5.
(CDCl3) d in ppm: 11.35 (s, 1H, AreOH), 8.28 (dd,
J ¼ 8.6 Hz, 2H, PyreH2), 7.20e8.05 (m, 9H, 7AreH,
2PyreH3), 6.28 (s, 1H, CHeAr), 4.56 (s, 1H, CHeCl), 3.11
(s, 2H, CH2eS). Anal. Calcd for C25H16N6O4SClBr: C,
49.06; H, 2.62; N, 13.74. Found: C, 49.21; H, 2.63; N,
13.79. MS: [M]þ at m/z 611.5.
5.1.28. 3-(4-Oxo-2-aryl-thiazolidin-3-yl)-2-(5-pyridin-4-yl-
[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-
quinazolin-4-one (35)
5.1.24. 3-(3-Chloro-2-oxo-4-aryl-azetidin-1-yl)-2-
(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-
6-bromoquinazolin-4-ones (31)
To a cool mixture of compound 19 (0.01 mol) and anhy-
drous ZnCl2 (1 pinch) in ethanol (50 ml), thioglycolic acid
(0.014 mol) was added drop wise with stirring at ambient tem-
perature and refluxed for 12 h. The reaction mixture was fil-
tered. The filtrate was concentrated, poured on crushed ice.
The resultant solid was recrystallized from methanol to give
compound 35. Yield 55%: mp 119 ꢂC; IR (KBr) nmax in
cmꢁ1: 1750 (C]O thiazolidin), 1690 (C]O), 1595 (C]N),
1635, 1620, 1565, 1422, 1075 (st. of oxadiazole), 1542
(C]C aromatic); 1H NMR (CDCl3) d in ppm: 8.25 (dd,
J ¼ 8.6 Hz, 2H, PyreH2), 7.20e8.01 (m, 11H, 9AreH,
2PyreH3), 6.24 (s, 1H, CHeAr), 3.60 (s, 2H, CH2 of thiazo-
lidin), 3.14 (s, 2H, CH2eS). Anal. Calcd for C25H18N6O3S2:
C, 58.37; H, 3.50; N, 16.34. Found: C, 58.55; H, 3.48; N,
16.41. MS: [M]þ at m/z 514.
Yield 52% (benzene): mp 147 ꢂC; IR (KBr) nmax in cmꢁ1
:
2947 (CH2), 1735 (C]O azetidine), 1690 (C]O), 1595
(C]N), 1640, 1615, 1570, 1420, 1070 (st. of oxadiazole),
1540 (C]C aromatic), 675 (CHeCl); 1H NMR (CDCl3)
d in ppm: 8.28 (dd, J ¼ 8.3 Hz, 2H, PyreH2), 7.20e8.05
(m, 10H, 8AreH, 2PyreH3), 6.23 (s, 1H, CHeAr), 4.51 (s,
1H, CHeCl), 3.08 (s, 2H, CH2eS). Anal. Calcd for
C25H16N6O3SClBr: C, 50.38; H, 2.69; N, 14.11. Found: C,
50.29; H, 2.68; N, 14.18. MS: [M]þ at m/z 595.5.
5.1.25. 3-(3-Chloro-2-oxo-4-{p-chloroaryl}-azetidin-1-yl)-
2-(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-
6-bromoquinazolin-4-ones (32)
The following compounds were prepared using a similar
procedure as described for compound 35.
Yield 55% (ethanol): mp 182 ꢂC; IR (KBr) nmax in cmꢁ1
:
2945 (CH2), 1735 (C]O azetidine), 1690 (C]O), 1590
(C]N), 1635, 1620, 1560, 1420, 1065 (st. of oxadiazole),
1545 (C]C aromatic), 673 (CHeCl); 1H NMR (CDCl3)
d in ppm: 8.29 (dd, J ¼ 8.6 Hz, 2H, PyreH2), 7.26e8.05
(m, 9H, 7AreH, 2PyreH3), 6.25 (s, 1H, CHeAr), 4.53 (s,
1H, CHeCl), 3.12 (s, 2H, CH2-S). Anal. Calcd for
C25H15N6O3SCl2Br: C, 47.62; H, 2.38; N, 13.33. Found: C,
47.73; H, 2.37; N, 13.25. MS: [M]þ at m/z 630.
5.1.29. 3-(4-Oxo-2-{p-chloroaryl}-thiazolidin-3-yl)-2-
(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-
quinazolin-4-one (36)
Yield 50% (methanol): mp 163 ꢂC; IR (KBr) nmax in cmꢁ1
:
1745 (C]O thiazolidin), 1700 (C]O), 1590 (C]N), 1640,
1615, 1570, 1420, 1078 (st. of oxadiazole), 1540 (C]C aro-
1
matic); H NMR (CDCl3) d in ppm: 8.25 (dd, J ¼ 8.6 Hz,
2H, PyreH2), 7.16e8.02 (m, 10H, 8AreH, 2 PyreH3), 6.26
(s, 1H, CHeAr), 3.65 (s, 2H, CH2 of thiazolidin), 3.10 (s,
2H, CH2eS). Anal. Calcd for C25H17N6O3S2Cl: C, 54.69; H,
3.10; N, 15.31. Found: C, 54.82; H, 3.12; N, 15.28. MS:
[M]þ at m/z 548.5.
5.1.26. 3-(3-Chloro-2-oxo-4-{p-methoxyaryl}-azetidin-1-
yl)-2-(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-
6-bromoquinazolin-4-ones (33)
Yield 40% (acetic acid): mp 191 ꢂC; IR (KBr) nmax in
cmꢁ1: 2953 (CH2), 1738 (C]O azetidine), 1695 (C]O),
1590 (C]N), 1640, 1615, 1560, 1425, 1068 (st. of oxadia-
zole), 1548 (C]C aromatic), 1180 (CeOeC), 675 (CHe
5.1.30. 3-(4-Oxo-2-{p-methoxyaryl}-thiazolidin-3-yl)-2-
(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-
quinazolin-4-one (37)
1
Cl); H NMR (CDCl3) d in ppm: 8.26 (dd, J ¼ 8.3 Hz, 2H,
Yield (40%) (ethanol): mp 155 ꢂC; IR (KBr) nmax in cmꢁ1
:
PyreH2), 7.22e8.00 (m, 9H, 7AreH, 2PyreH3), 6.21 (s,
1H, CHeAr), 4.54 (s, 1H, CHeCl), 3.39 (s, 3H, OCH3),
3.15 (s, 2H, CH2eS). Anal. Calcd for C26H18N6O4SClBr: C,
49.88; H, 2.88; N, 13.43. Found: C, 49.97; H, 2.91; N,
13.32. MS: [M]þ at m/z 625.5.
1755 (C]O thiazolidin), 1695 (C]O), 1590 (C]N), 1640,
1620, 1560, 1425, 1070 (st. of oxadiazole), 1544 (C]C aro-
1
matic); H NMR (CDCl3) d in ppm: 8.27 (dd, J ¼ 8.3 Hz,
2H, PyreH2), 7.26e8.02 (m, 10H, 8AreH, 2PyreH3), 6.20
(s, 1H, CHeAr), 3.64 (s, 2H, CH2 of thiazolidin), 3.39

A. Kumar, C.S. Rajput / European Journal of Medicinal Chemistry 44 (2009) 83e90
89
(s, 3H, OCH3), 3.16 (s, 2H, CH2eS). Anal. Calcd for
C26H20N6O4S2: C, 57.35; H, 3.68; N, 15.44. Found: C,
57.14; H, 3.71; N, 15.52. MS: [M]þ at m/z 544.
5.1.35. 3-(4-Oxo-2-{p-hydroxyaryl}-thiazolidin-3-yl)-2-
(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-
6-bromoquinazolin-4-one (42)
Yield 55% (ethanol): mp 169 ꢂC; IR (KBr) nmax in cmꢁ1
:
3425 (AreOH), 1755 (C]O thiazolidin), 1695 (C]O),
1592 (C]N), 1645, 1615, 1565, 1424, 1070 (st. of oxadia-
5.1.31. 3-(4-Oxo-2-{p-hydroxyaryl}-thiazolidin-3-yl)-2-
(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-
quinazolin-4-one (38)
1
zole), 1540 (C]C aromatic); H NMR (CDCl3) d in ppm:
11.35 (s, 1H, AreOH), 8.21 (dd, J ¼ 8.3 Hz, 2H, PyreH2),
7.16e8.00 (m, 9H, 7AreH, 2PyreH3), 6.26 (s, 1H, CHe
Ar), 3.60 (s, 2H, CH2 of thiazolidin), 3.11 (s, 2H, CH2eS).
Anal. Calcd for C25H17N6O4S2Br: C, 49.26; H, 2.79; N,
13.33. Found: C, 49.20; H, 2.80; N, 13.37. MS: [M]þ at m/z
609.
Yield 48% (ethanol): mp 178 ꢂC; IR (KBr) nmax in cmꢁ1
:
3330 (AreOH), 1751 (C]O thiazolidin), 1700 (C]O),
1600 (C]N), 1644, 1615, 1565, 1425, 1077 (st. of oxadia-
1
zole), 1540 (C]C aromatic); H NMR (CDCl3) d in ppm:
11.35 (s, 1H, AreOH), 8.22 (dd, J ¼ 8 Hz, 2H, PyreH2),
7.18e8.02 (m, 10H, 8AreH, 2PyreH3), 6.24 (s, 1H, CHe
Ar), 3.65 (s, 2H, CH2 of thiazolidin), 3.09 (s, 2H, CH2eS).
Anal. Calcd for C25H18N6O4S2: C, 56.60; H, 3.40; N, 15.85.
Found: C, 56.41; H, 3.43; N, 15.92. MS: [M]þ at m/z 530.
5.2. Biological activity
The experiments were performed with albino rats of the
CharleseFoster stain of either sex, excluding pregnant
females, of 70e95 days weighting 100e150 g. Acute toxicity
was tested in albino mice (15e25 g). Food (chaw pallet) and
water were given to the animals ad libitum. All the compounds
were dissolved in propylene glycol. Phenylbutazone drug was
used as reference drug.
5.1.32. 3-(4-Oxo-2-aryl-thiazolidin-3-yl)-2-(5-pyridin-4-yl-
[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-6-bromoquinazolin-
4-one (39)
Yield 52% (acetone): mp 162 ꢂC; IR (KBr) nmax in cmꢁ1
:
1753 (C]O thiazolidin), 1690 (C]O), 1595 (C]N), 1641,
1615, 1565, 1424, 1070 (st. of oxadiazole), 1540 (C]C aro-
1
matic); H NMR (CDCl3) d in ppm: 8.27 (dd, J ¼ 8 Hz, 2H,
5.2.1. Anti-inflammatory activity
PyreH2), 7.21e8.021 (m, 10H, 8AreH, 2PyreH3), 6.24 (s,
1H, CHeAr), 3.61 (s, 2H, CH2 of thiazolidin), 3.12 (s, 2H,
CH2eS). Anal. Calcd for C25H17N6O3S2Br: C, 50.59; H,
2.87; N, 14.16. Found: C, 50.77; H, 2.85; N, 14.14. MS:
[M]þ at m/z 593.
This study was done by following the procedure of Winter
et al. [23]. The rats were divided into 3 groups (control, drugs
treated and standard drugs) of 6 animals each. A freshly
prepared suspension of carrageenan (1% in 0.9% saline),
0.05 ml was injected under the planter aponeurosis of the right
hind paw of each rat. The percent anti-inflammatory activity
was calculated according to the formula as given below:
5.1.33. 3-(4-Oxo-2-{p-chloroaryl}-thiazolidin-3-yl)-2-
(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-6-
bromoquinazolin-4-one (40)
Percentage of inhibition of oedema ¼ ð1 ꢁ Vt=VcÞ100
Yield 56% (benzene): mp 202 ꢂC; IR (KBr) nmax in cmꢁ1
:
where Vt and Vc are the volume of oedema in right paw of rats
in the drug treated and control group, respectively.
1755 (C]O thiazolidin), 1705 (C]O), 1590 (C]N), 1635,
1617, 1565, 1423, 1075 (st. of oxadiazole), 1543 (C]C aro-
1
matic); H NMR (CDCl3) d in ppm: 8.29 (dd, J ¼ 8.3 Hz,
5.2.2. Acute toxicity
2H, PyreH2), 7.19e8.04 (m, 9H, 8AreH, 2PyreH3), 6.23
(s, 1H, CHeAr), 3.64 (s, 2H, CH2 of thiazolidin), 3.09 (s,
2H, CH2eS). Anal. Calcd for C25H16N6O3S2BrCl: C, 47.81;
H, 2.55; N, 13.39. Found: C, 47.72; H, 2.57; N, 13.32. MS:
[M]þ at m/z 627.5.
Approximate lethal doses (ALD50) of all the compounds
were investigated by the method of Smith [24]. All the com-
pounds were studied for acute toxicity ALD50 value were
found to be >1000 mg/kg p.o.
References
5.1.34. 3-(4-Oxo-2-{p-methoxyaryl}-thiazolidin-3-yl)-2-
(5-pyridin-4-yl-[1,3,4]-oxadiazol-2-yl-sulfanylmethyl)-
6bromoquinazolin-4-one (41)
[1] R.K. Saksena, P. Kant, Indian J. Chem Soc. 61 (8) (1984) 722e724.
[2] M.I. Husain, S. Shakla, Indian J. Chem. 25B (1986) 552e555.
[3] A.K.S. Gupta, H.K. Misra, Chem. Abstr. 94 (17) (1981) 759.
[4] A.D. Rao, C.R. Shankar, A.B. Rao, V.M. Reddy, Indian J. Chem. 25B
(1986) 665e667.
[5] A. Vyas, H.S. Joshi, H. Parkh, Chem. Abstr. 123 (1995) 913.
[6] Archana, V.K. Srivastava, Ramesh Chandra, Ashok Kumar, Eur. J. Med.
Chem. 37 (2002) 873e882.
Yield 40% (ethanol): mp 210 ꢂC; IR (KBr) nmax in cmꢁ1
:
1750 (C]O thiazolidin), 1690 (C]O), 1600 (C]N), 1640,
1615, 1560, 1420, 1073 (st. of oxadiazole), 1540 (C]C aro-
1
matic), 1175 (CeOeC); H NMR (CDCl3) d in ppm: 8.24
(dd, J ¼ 8.6 Hz, 2H, PyreH2), 7.20e8.01 (m, 9H, 7AreH,
2PyreH3), 6.21 (s, 1H, CHeAr), 3.66 (s, 2H, CH2 of thiazo-
lidin), 3.37 (s, 3H, OCH3), 3.15 (s, 2H, CH2eS). Anal. Calcd
for C26H19N6O4S2Br: C, 50.08; H, 3.05; N, 13.48. Found: C,
50.21; H, 3.03; N, 13.51. MS: [M]þ at m/z 622.
[7] N.A. Gangwal, B. Narasimhan, V.K. Mourya, A.S. Dhake, Indian J.
Heterocycl. Chem. 12 (2) (2002) 201e204.
[8] Ashok Kumar, Shalab Sharma, Archana, Kiran Bajaj, Shipra Sharma,
Hemant Panwar, Tripti Sigh, V.K. Srivastava, Bioorg. Med. Chem. 11
(2003) 5293e5299.

90
A. Kumar, C.S. Rajput / European Journal of Medicinal Chemistry 44 (2009) 83e90
[9] G. Daidone, B. Maggio, D. Raffa, S. Plescia, M.L. Bajardi, A. Caruso,
V.M.C.Cutuli, M. AmicoRoxas, Eur. J. Med. Chem. 29(9) (1994)707e711.
[17] L.V.G. Nargund, G.R.N. Reddy, V. Hariprasad, J. Pharm. Sci. 83 (2)
(1994) 246e248.
[10] A.A. Bekhit, N.S. Habib, J.Y. Park, Chem. Abstr. 142 (2005) 114000f.
[11] R. Agarwal, C. Agarwal, C. Singh, V.S. Mishra, Indian J. Chem. 28B
(1989) 893e896.
[18] B.R.Rani,U.T.Bhalerau,M.F.Rahman,IndianJ.Chem.29B(1990)995e998.
[19] A. Kumar, S. Singh, A.K. Saxena, K. Shanker, Indian J. Chem. 27B
(1988) 443e447.
[12] S.K. Srivastava, S.L. Srivastava, S.D. Srivastava, Indian J. Chem. 39B
(2000) 464e467.
[20] A. Arques, P. Molina, A. Soler, Synthesis 9 (1980) 702e704.
[21] S.M. Roshdy, K.M. Ghoneim, M. Khalifa, Pharmazie 30 (4) (1975)
210e213.
[22] A. Sammour, A. Rabie, M. Elhashash, M. Sayed, Egypt. J. Chem. 19 (4)
(1976) 571e588.
[13] S.K. Srivastava, R. Yadav, S.L. Srivastava, Indian J. Chem. 42B (2004)
399e405.
[14] Suma Mishra, S.K. Srivastava, S.D. Srivastava, Indian J. Chem. 36B
(1997) 826e830.
[23] C.A. Winter, E.A. Risley, G.M. Nuss, Proc. Soc. Exp. Biol. Med. 111
(1962) 544e550.
[24] Q.E. Smith, Pharmacological Screening Test Progress in Medicinal
Chemistry, vol. I, Butterworth, London, 1960.
[15] A. Mohmmad, A. Oberoi, A. Shah, Indian J. Chem. 38B (1999) 237e239.
[16] F.A. Omar, N.M. Mahfouz, M.A. Rahman, Eur. J. Med. Chem. 31 (10)
(1996) 819e825.