Synthesis characterization and biological evaluation of some alkoxyphthalimide derivatives of 3-(4-substituted phenyl)-6, 6-diphenyl-3,3a-dihydro-2H-imidazo[2,1-b]pyrazolo[3,4-d] [1,3]thiazol-7(6H)-one

Article abstract of DOI:10.1007/s00044-010-9392-4

A series of 2-N-ethoxyphthalimido 3-(4-substitutedphenyl)- 6,6-diphenyl-3,3a-dihydro-2H-imidazo[2,1-b] pyrazolo[3,4-d][1,3]thiazol-7(6H)- one(7a-e) and 4-(4-substituted phenyl)-2-(N-ethoxyphthalimido amino)-7,7-diphenylimidazo[ 2',1':2,3][1,3]thiazolo[4,5-d] pyrimidin-8(7H)-one (9a-e) have been designed and synthesized starting from thiohydentoin (1). The structure of all synthesized compounds has been established by IR, ¹H NMR, ¹³C NMR and mass studies. These compounds have been screened for antimicrobial activities in order to evaluate the possibility of the derivatives to be used as potential chemotherapeutic agents. Springer Science+Business Media, LLC 2010.

Full text of DOI:10.1007/s00044-010-9392-4

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2011) 20:1490–1498
DOI 10.1007/s00044-010-9392-4
ORIGINAL RESEARCH
Synthesis characterization and biological evaluation of some
alkoxyphthalimide derivatives of 3-(4-substituted phenyl)-6,
6-diphenyl-3,3a-dihydro-2H-imidazo[2,1-b]pyrazolo[3,4-d]
[1,3]thiazol-7(6H)-one
•
Raja Ram Dangi Nasir Hussain Ganpat Lal Talesara
•
Received: 27 February 2010 / Accepted: 12 July 2010 / Published online: 31 July 2010
Ó Springer Science+Business Media, LLC 2010
Abstract A series of 2-N-ethoxyphthalimido 3-(4-substi-
tutedphenyl)-6,6-diphenyl-3,3a-dihydro-2H-imidazo[2,1-b]
pyrazolo[3,4-d][1,3]thiazol-7(6H)-one(7a–e) and 4-(4-substi-
tuted phenyl)-2-(N-ethoxyphthalimido amino)-7,7-dipheny-
limidazo[20,10:2,3][1,3]thiazolo[4,5-d] pyrimidin-8(7H)-one
(9a–e) have been designed and synthesized starting from
thiohydentoin (1). The structure of all synthesized com-
biological activities such as antibacterial (Hans, 1978),
antifungal (Wilson et al., 2001), anti-inflammatory (Berlin
and Herd, 1991), antitumor activity (Kumar et al., 1993)
and cytotoxic activities (Plouvier et al., 1995). The pyr-
azoline nucleus is a ubiquitous feature of pharmacological
interest and has been proven to be a fertile source of
medicinal agents such as cytotoxic (Bhat et al., 2005),
antiamoebic (Abid and Azam, 2005), antibacterial (Azari-
far and Maseud 2002), cyclo-oxygenase-II (COX-IISS)
(Kumar et al., 2004), antiproliferative (Chimichi et al.,
2006) and anticancer (Tandon et al., 2005). Pyrimidine
derivatives serve both as biomimetic and reactive phar-
macophores due to their diverse medicinal properties such
as antitumor (Sasaki et al., 2003), anticancer (lungs, breast
and CNS cancer) (Sondhi et al., 2001), immunodilator
(Heiba et al., 1998), antiviral (Nasr and Gineinah, 2002),
etc. Pyrimidine derivatives have activities like tyrosine
kinase inhibitors (Frey and Wishart, 2005), COX-2 inhib-
itor (Reddy et al., 2005), calcium channel blockers plus
antihypertensive (Kappe, 2004) and also activity against
Y181C HIV-1 mutant strain (Gupta et al., 2005), etc.
Diverse biological activities like anticonvulsant (Loscher,
1946), diuretic (Cornish et al., 1966), fungicidal (Kau-
nowasky et al., 1966) and trypanocidal (Hayashi, 1956)
have been observed for alkoxyphthalimide and related
functionalities. The ability to inhibit growth of malarial
parasite Plasmodium falsiparum (Mamalis, 1971) have also
been observed for several aminoxy derivatives. Heterocy-
clic rings attached to alkoxyphthalimide group have been
synthesized (Banu et al., 2000) and tested for antimicrobial
and antimalarial (Singh et al., 2004) activity. We planned
to undertake the synthesis and characterization of some
imidazole derivatives carrying the above biodynamic het-
erocyclic systems with the hope to achieve enhanced bio-
logical activity.
1
pounds has been established by IR, H NMR, 13C NMR
and mass studies. These compounds have been screened for
antimicrobial activities in order to evaluate the possibility
of the derivatives to be used as potential chemotherapeutic
agents.
Keywords Imidazole ꢀ Thiazole ꢀ Pyrazole ꢀ Pyrimidine ꢀ
Antimicrobial activity
Introduction
Imidazole derivatives have evoked considerable attention
in recent years as these are endowed with a wide range of
pharmaceutical activities like antifungal (Enguehard et al.,
2000), antihypertensive (Hadizadeh et al., 2005), IL-1
inhibitor (Chang et al., 2001), antioxidant (Goker et al.,
2002), cardiotonic (Insuasty et al., 2002), antithrombotic
(Zhou et al., 2005) anticonvulsant (Shafiee et al., 2004),
antihepatitis B and C virus activity (Zhang et al., 2005),
etc. Thiazoles and their derivatives are found in many
natural and synthetic products with a wide spectrum of
R. R. Dangi ꢀ N. Hussain ꢀ G. L. Talesara (&)
Synthetic Organic Chemistry Laboratory,
Department of Chemistry, M. L. Sukhadia University,
Udaipur 313 001, Rajasthan, India
e-mail: glntalesara@yahoo.com
123

Med Chem Res (2011) 20:1490–1498
1491
Results and discussion
bromoalkoxyphthalimide (6) to yield the final compounds
4-(4-substituted phenyl)-2-(N-ethoxyphthalimidoamino)-
7,7-diphenylimidazo[20,10:2,3][1,3]thiazolo[4,5-d]pyrimi-
din-8(7H)-one (9a–e). Schematic presentation of reaction
sequence is given in Scheme 1. Positive fluorescence test of
7a–e and 9a–e also confirmed the inclusion of alkoxyph-
thalimide chromophore in these molecules.
Simple base catalyzed condensation of a-diketone (benzil),
with thiourea in absolute ethanol followed by pinacol-pina-
colone type rearrangement furnished to 5,5-diphenyl-2-
thioxoimidazolidin-4-one (1) Formation of this product was
confirmed appearance stretching bands in IR spectrum at
1705, 3294 cm-1 which indicates the presence of CONH
group and 1215, 3236 cm-1 is for the presence of CSNH
moiety and disappearance of NH2 peak at 3367,3267. In
1H-NMR spectrum shows two singlets at d 9.90 and d 9.10,
which would be assigned for NH proton of amide. It was
condensed with chloroacetic acid in glacial acetic acid
presence of anhydrous sodium acetate to yielded the
6,6-diphenylimidazo[2,1-b][1,3]thiazole-3,5(2H,6H)-dione
(2). Its structure was confirmed by appearance of singlet at d
3.65 for CH2 of thizole ring and disappearance of both NH
signals in 1H NMR spectra. This was condensed with various
4-substituted araldehydes in the presence of anhydrous
sodium acetate in glacial acetic acid to give corresponding 2-
(4-subsituted phenyle)-6,6-diphenylimidazo[2,1-b][1,3]thi-
azole-3,5(2H,6H)-dione derivatives (4a–e). Reaction of
hydrazine hydrate on these compounds (4a–e) underwent
cyclocondensation reaction afforded 3-(4-substituted phe-
nyl)-6,6-diphenyl-3,3a-dihydro-2H-imidazo[2,1-b]pyrazol-
o[3,4-d][1,3]thiazol-7(6H)-one (5a–e). The structures of
these compounds were inferred by IR absorption band at
3270 cm-1 and 1H NMR spectra at d 6.83 corresponding to
the NH proton of the pyrazole ring. The N–H proton of
(5a–e) was replaced by reaction with bromoalkoxyphthali-
mide (6) in ethanolic media using pyridine as base. The
resulting product was identified as 2-N-ethoxyphthalimido
3-(4-substituted phenyl)-6,6-diphenyl-3,3a-dihydro-2H-im-
idazo[2,1-b]pyrazolo[3,4-d][1,3]thiazol-7(6H)-one (7a–e).
The IR spectra of (7a–e) displayed strong absorption band
for CO–N–CO group at around 1726–1705 cm-1, while
N–O and C–O bond give relatively weak absorption bands at
1492 and 1013 cm-1, respectively. Disappearance of NH
stretching band around 3270 cm-1 also confirmed the
replacement of hydrogen of pyrazole by ethoxyphthalimide
moiety, which was present in its precursor. Additional proof
for the proposed structure of (7a–e) was provided by close
Antimicrobial activity
Ten synthesized compounds 7a–e and 9a–e were in vitro
screened for their antibacterial and antifungal activity
using cup or well method (Simmons, 1996). Antibacterial
activity of the compounds (500 ppm im DMF media)
have been evaluated against four bacterial strains viz.,
Escherichia coli, Bacillus subtilis, Proteus mirabilis and
Pseudomonas aeruginosa. The activity was measured as a
function of zone of inhibition in mm. Results were
compared with the reference drug ciprofloxacin by mea-
suring their zone of inhibition and activity index (Table 1;
Scheme 1).
All the compounds show poor activity against B. subtilis
and P. mirabilis where as these show moderate to strong
activity against E. coli and P. aeruginosa. Compound 9b
displayed activity index more then one against E. coli and
9c against P. aeruginosa. Activity index of 9e is compa-
rable to the standard used against E. coli and P. aerugin-
osa. The same is also true for 7d against P. aeruginosa.
Moderate activity of compounds 7a, 7b, 7c, 7e, 9a, 9c, 9d
against E. coli, 7d, 9c, 9d against B. subtilis, 9b against P.
mirabilis, 7b, 7c, 9a, 9b and 9d against P. aeruginosa was
observed. Overall antibacterial activity of synthesized
compounds is moderate as compared to ciprofloxacin but
when cefuroxime was used as a reference drug, the activity
looks to be strong.
Screening of above compounds in a concentration of
500 ppm for antifungal activity by the same technology
was carried out against two fungal strains viz., Can-
dida albicans and Aspergillus fumigates using Amphoter-
icin B as a control. It was pleasure to note that maximum
number of compounds shows stronger activity then the
standard used against C. albicans. Activity index for 7a,
7b, 7c, 7d, 7e, 9b, 9c, 9d and 9e is more then one. Activity
against A. fumigates using same control is insignificant
(Table 1).
1
observation of H NMR spectra, which showed disappear-
ance of NH signal at d 6.2 and presence of new signals for
NCH2 and OCH2 protons resonating at d 3.75 and 4.44,
respectively. In an another route (4a–e) when treated
with guanidine nitrate in presence of concentrated ethanolic
alkali gave 2-amino-4-(4-substitutedphenyl)-7,7-diphenyl-
[4,5-d]pyrimidin-8(7H)-one (8a–e). Formation of Pyrimi-
dine ring in 8a–e was confirmed by IR spectra at
3212–3357 cm-1 and 1H NMR spectra exhibited a singlet at
d 6.74 for NH2 proton. These were further condensed with
It may be concluded from the activity study that the
synthesized compounds have high versatility in activity
against various microbes viz., stronger against C. albicans,
moderate against E. coli and P. eruginosa, weaker against
B. subtilis, P. mirabilis and A. fumigates.
123

1492
Med Chem Res (2011) 20:1490–1498
Antifungal activity
Table 1 Antimicrobial activity
of the synthesized compounds
7a–e and 9a–e
Compd.
no.
Antibacterial activity
Escherichia
coli
Bacillus
subtilis
Proteus
mirabilis
Pseudomonas
aeruginosa
Candida
albicans
Aspergillus
fumigatus
7a
7b
7c
7d
7e
9a
9b
9c
9d
9e
C1
11
4
5
9
20
6
(0.68)
12
(0.25)
9
(0.31)
3
(0.50)
14
(1.17)
19
(0.60)
4
(0.75)
12
(0.52)
6
(0.18)
8
(0.77)
11
(1.11)
20
0.40)
5
(0.75)
9
(0.35)
11
(0.50)
6
(0.61)
17
(1.17)
18
(0.50)
3
(0.56)
10
(0.68)
7
(0.37)
5
(0.94)
10
(1.05)
17
(0.30)
2
(0.65)
13
(0.41)
5
(0.31)
4
(0.55)
13
(1.00)
11
(0.20)
6
(0.81)
18
(0.29)
7
(0.25)
10
(0.72)
14
(0.64)
26
(0.60)
2
(1.12)
13
(0.41)
13
(0.62)
8
(0.77)
21
(1.52)
23
(0.20)
4
Zone of growth inhbition (mm)
(activity index)
(0.81)
11
(0.76)
12
(0.50)
6
(1.16)
12
(1.35)
21
(0.40)
5
(Activity index) = Inhibition
zone of compound/Inhibition
zone of the standard drug
(0.68)
15
(0.70)
10
(0.37)
7
(0.66)
11
(1.23)
19
(0.50)
8
For antibacterial activity:
C1 = ciprofloxacin
(0.93)
16
(0.58)
17
(0.43)
16
(0.61)
18
(1.11)
17
(0.80)
10
For antifungal activity:
C1 = amphotericin B
Experimental section
Yield 94%, m.p. 136°C; IR (KBr) cm-1: 3255 (N–H
amide, CO–NH–CS); 3135 (N–H, CPh2–NH–CS); 3010
1
(C–H Ar–H); 1705 (C=O); 1215 (C=S); H NMR (DMSO
General procedures
d6) d: 6.97–7.69 (m, 3H, Ar–H), d 9.90 (s, 1H, NH, CO–
NH–CO); d 9.10 (s, 1H, NH, CO–NH–CPh2);13C-NMR
(DMSO) d: 180.65, 174.54, 139.70, 129.10, 128.78,
126.76, 73.87. Anal. calcd. for C15H12N2OS: C, 67.16; N,
10.44; S, 11.94%. Found C, 67.08; N, 10.10; S, 11.75%;
MS: m/z 268 [M]?.
All the melting points were determined in open capillary
tube and are uncorrected. The IR spectra were recorded on
Perkin–Elmer spectrometer. The 1H NMR spectra were
scanned on a DRX-300 MHz spectrometer (300 MHz) in
CDCl3/DMSO-d6 using TMS as internal standard and
chemical shifts are expressed in d ppm. The mass spectra
were recorded on jeol SX-102 (FAB). m-Nitrobenzyl
alcohol (NBA) was used as a matrix. Purity of synthesized
compounds was checked by TLC using silica gel-G. Spots
were exposed in an iodine chamber. Compound 6 was
synthesized by literature method (Bauer and Suresh, 1963).
Synthesis of 6,6-diphenylimidazo[2,1-b][1,3]thiazole-3,
5(2H,6H)-dione (2)
A mixture of 1 (0.01 mol) and chloroacetic acid (0.01 mol)
was dissolved in gl.acetic acid in presence (0.02 mol)
anhydrous sodium acetate and was refluxed for 8 h. The
reaction mixture was cooled and poured into cold ice water
with stirring. The solid formed was filtered and crystallized
from ethanol. Yield 89%, m.p. 162°C; IR (KBr) cm1: 3045
(C–H Ar–H); 2952 (C–H, CH2), 1695 (C=O), 1594 (C=N);
1H NMR (DMSO d6) d: 7.85–7.67 (m, 10H, Ar–H),3.65
(s,CH2, thizole); 13C-NMR (DMSO d6) d: 167.21, 170.03,
162.56, 143.14, 129.23, 128.11, 126.10, 73.05, 32.70. Anal.
calcd. for C17H12N2O2S: C, 66.32; N, 9.09; S, 10.38%.
Found C, 66.02; N, 10.08; S, 10.05%; MS: m/z 308 [M]?.
Synthesis of 5,5-diphenyl-2-thioxoimidazolidin-4-one (1)
Benzil (0.05 mol), thiourea (0.05 mol) and 15 ml of 30%
aq. NaOH was refluxed in 75 ml of ethanol for 2 h; it was
allowed to cool and poured into crushed ice with constant
stirring. The solid separated was filtered and the insoluble
by product was removed. The filtrate was acidified with
conc. HCl and the obtained precipitated solid was filtered,
dried and recrystallized from ethanol.
123

Med Chem Res (2011) 20:1490–1498
1493
Scheme 1
H
S
Ph
Ph
O
O
H2N
H2N
N
HO
Ph
1) NaOH / EtOH
2) H3O+
S
+
NH
Ph
OH
O
O
O
H
N
Ph
Ph
OH
Cl
CH3COONa/ CH3COOH
S
Ph
Ph
N
NH
N
S
CH3COONa/ CH3COOH
O
X
CHO
(2)
(1)
(3a-e)
O
NH2
O
O
N
Ph
Guanidine nitrate
40%NaOH
Ph
Ph
N
N
N
Ph
N
N
S
S
(4a-e)
(8a-e)
NH2NH2.H2O
X
X
EtOH
Acetone/ K2CO3
6
N
NH
O
H
O
N
N
R
Ph
Ph
Ph
N
S
N
N
X
Ph
N
N
(5a-e)
S
Pyridine
EtOH
6
(9a-e)
R
N
N
O
X
N
Ph
Ph
S
N
X
O
(7a-e)
N
O
R-Br =
a
b
c
d
e
X=Cl
H
F
OCH3 N(CH3)2
6
O
Br
Synthesis of 2-(4-chlorobenzylidene)-6,
6-diphenylimidazo[2,1-b][1,3]thiazole-3,
5(2H,6H)-dione (4a)
N, 6.51, S, 7.44%. Found C, 66.54; N, 6.45; S, 7.24%; MS:
m/z 430 [M]?, 432 [M ? 2]?.
Compounds (2b–e) were also prepared by similar
method with some change in reflux time and reaction work
up. Their characteristic spectral and analytical data are
given below:
An equimolar mixture of 2 (0.01mol) and 4-chlorobenz-
alde-hyde 3a (0.01mol) in glacial acetic acid was taken in a
round bottom flask and anhydrous sodium acetate (0.02
mol) was added and refluxed for 8 h. Reaction mixture was
allowed to cool and solid separated was recrystallized from
ethanol. Yield 84%, m.p. 189°C; IR (KBr) cm-1: 3025 (C–
H, Ar–H), 1691 (C=O), 1590 (C=N), 758 (C–Cl); 1H NMR
(DMSO d6) d: 7.62–7.76 (m, 14H, Ar–H), 6.12 (s, 1H,
=CH–Ar); 13C-NMR (DMSO d6) d: 171.05, 166.30,163.0,
142.05, 140.15, 132.23, 129.24, 128.80, 127.12, 126.35,
120.67, 80.05. Anal. calcd. for C24H15ClN2O2S; C, 66.97;
2-Benzylidene-6,6-diphenylimidazo[2,1-b][1,3]thiazole-3,
5(2H,6H)-dione (4b)
Yield 81%, m.p. 180°C; IR (KBr) cm-1: 3027 (C–H, Ar–H),
1693 (C=O), 1594 (C=N); 1H NMR (DMSO d6) d: 7.56–7.64
(m, 14H, Ar–H), 6.09 (s, 1H, =CH–Ar); 13C-NMR (DMSO
d6) d: 170.60, 165.90, 162.85, 142.15, 139.63, 132.12,
129.04, 128.65, 127.10, 126.17, 120.20, 78.34. Anal. calcd.
123

1494
Med Chem Res (2011) 20:1490–1498
for C24H15N2O2S; C, 72.72; N, 7.07; S, 8.08%. Found C,
72.54; N, 6.90; S, 7.89%; MS: m/z 396 [M]?.
(DMSO d6) d: 174.12, 154.16, 164.03, 144.02, 140.56,
139.23, 132.80, 129.20, 128.58, 128.89, 128.01, 12.27,
80.17, 48.10, 50.18. Anal. calcd. for C24H17ClN4OS; C,
64.86; N, 12.61; S, 7.17%. Found C, 64.53; N, 12.20; S,
7.01%; MS: m/z 444[M]?, 446 [M ? 2]?.
2-(4-Flurobenzylidene)-6,6-diphenylimidazo[2,1-b]
[1,3]thiazole-3,5-(2H,6H)-dione (4c)
Same procedure was adopted for the synthesis of com-
pound (5b-e). Spectral data of these are mentioned below:
Yield 86%, m.p. 192°C; IR (KBr) cm-1: 3037 (C–H, Ar–H),
1697 (C=O), 1597 (C=N), 1158 (C–F); 1H NMR (DMSO d6)
d: 7.65–7.84 (m, 14H, Ar–H), 6.16 (s, 1H, =CH–Ar); 13C-
NMR (DMSOd6) d:171.68, 166.10, 163.58, 142.85, 139.90,
132.65, 129.86, 128.96, 127.18, 126.67, 120.45, 78.94. Anal.
calcd. for C24H15FN2O2S; C, 69.56; N, 6.76; S, 7.29%.
Found C, 69.14; N, 6.35; S, 7.10%; MS: m/z 414[M]?.
3,6,6-Triphenyl-3,3a-dihydro-2H-imidazo
[2,1-b]pyrazolo[3,4-d][1,3]thiazol-7(6H)-one (5b)
Yield 79%, m.p. 216°C; IR (KBr) cm-1 3265 (N–H str.)
3042 (C–H, Ar–H), 1724 (C=O), 1528 (C=N); H NMR
1
(DMSO d6) d: 6.9–7.6 (m, 14H, Ar–H), 6.78 (s, 1H, NH),
4.58 (d, 1H, –CH–Ar), 3.41 (d, 1H, –CH–S); 13C-NMR
(DMSO d6) d: 174.08, 154.10, 163.93, 143.82, 140.26,
139.12, 132.43, 129.03, 128.16, 128.29, 127.87, 126.02,
79.97, 47.10, 49.18. Anal. calcd. for C24H18N4OS; C,
70.24; N, 13.65; S, 7.80%. Found C, 70.73; N, 13.40; S,
7.57%; MS: m/z 410[M]?.
2-(4-Methoxybenzylidene)-6,6-diphenylimidazo[2,1-b]
[1,3]thiazole-3,5(2H,6H)-dione (4d)
Yield 83%, m.p. 184°C; IR (KBr) cm-1: 3028 (C–H, Ar–
H), 1687 (C=O), 1589 (C=N), 1098 (C–O); 1H NMR
(DMSO d6) d:7.60–7.74 (m, 14H, Ar–H), 6.02 (s, 1H,
=CH–Ar) 3.64 (3H, s, OCH3); 13C-NMR (DMSO d6) d:
170.46, 166.18, 163.18,141.35, 139.10, 132.25, 128.16,
127.93, 127.34, 125.97, 120.23, 56.78, 78.14. Anal. calcd.
for C25H18N2O3S; C, 70.40; N, 6.27; S, 7.05%. Found C,
70.12; N, 6.05; S, 7.16%; MS: m/z 446 [M]?.
3-(4-Fluorophenyl)-6,6-diphenyl-3,3a-dihydro-2H-
imidazo[2,1-b]pyrazolo[3,4-d][1,3]thiazol-7(6H)-one (5c)
Yield 82%, m.p. 231°C; IR (KBr) cm-1. 3274 (N–H str.)
3049 (C–H, Ar–H), 1729 (C=O), 1537 (C=N), 1178 (C–F);
1H NMR (DMSO d6) d: 7.2–7.8 (m, 14H, Ar–H), 6.82 (s,
1H, NH), 4.64 (d, 1H, –CH–Ar), 3.48 (d, 1H, –CH–S); 13C-
NMR (DMSO d6) d: 174.78, 154.56, 164.19, 144.18,
140.76, 139.67, 132.84, 130.13, 128.87, 128.89, 127.77,
126.78, 80.27, 47.45, 49.98. Anal. calcd. for C24H17
FN4OS; C, 67.28; N, 13.08; S, 7.47%. Found C, 67.08; N,
12.94; S, 7.08%; MS: m/z 428 [M]?.
2-[4-(N,N-dimethylamino)benzylidene]-6,
6-diphenylimidazo[2,1-b][1,3]thiazole-3,
5(2H,6H)-dione (4e)
Yield 87%, m.p. 182°C; IR (KBr) cm-1: 13043 (C–H, Ar–
1
H), 1681 (C=O), 1584 (C=N); H NMR (DMSO d6) d:
7.57–7.34 (m, 14H, Ar–H), 6.14 (s, 1H, =CH–Ar), 3.15
(6H,s,N(CH3)2; 13C-NMR (DMSO d6) d: 171.16, 166.10,
162.98, 141.45, 139.20, 132.53, 128.34, 127.83, 127.14,
125.65, 119.93, 56.43, 78.35, 43.78. Anal. calcd. for
C26H21N3O2S; C, 71.07; N, 9.56; S, 7.28%. Found C,
69.98; N, 9.35; S, 7.02%; MS: m/z 439 [M]?.
3-(4-Methoxybenzylidene)-6,6-diphenyl-3,3a-dihydro-2H-
imidazo[2,1-b]pyrazol[3,4-d][1,3] thiazol-7(6H)-one (5d)
Yield 80%, m.p. 228°C; IR (KBr) cm-1. 3271 (N–H str.)
3047 (C–H Ar–H), 1731 (C=O), 1532 (C=N), 1103 (C–O);
1H NMR (DMSO d6) d: 6.7–7.1 (m, 14H, Ar–H), 6.62 (s,
1H, NH), 4.54 (d, 1H, –CH–Ar), 3.38 (d, 1H, –CH–S), 3.60
(3H, s, OCH3); 13C-NMR (DMSO d6) d: 173.34, 154.23,
164.02, 143.88, 140.46,139.27, 132.17, 130.37, 128.67,
129.18, 127.78, 126.78, 79.12, 55.95, 47.65, 49.37. Anal.
calcd. for C25H20N4O2S; C, 68.18; N, 12.72; S, 7.27%.
Found C, 67.80; N, 12.34; S, 6.87%; MS: m/z 440 [M]?.
Synthesis of 3-(4-chlorophenyl)-6,6-diphenyl-3,3a-dihydro-
2H-imidazo[2,1-b]pyrazolo[3,4-d] [1,3]thiazol-7(6H)-one
(5a)
Compound 4a (0.01 mol) and hydrazine hydrate (0.02 mol)
were taken in absolute alcohol (20 ml) and a catalytic
amount of acetic acid were added to it. It was refluxed for
8 h, cooled and poured into crushed ice. The product
obtained was washed several times with water and then
dried. It was recrystallized from alcohol. Yield 83%, m.p.
223°C; IR (KBr) cm-1: 3270 (N–H str.) 3048 (C–H, Ar–
H), 1726 (C=O), 1524 (C=N), 747 (C–Cl); 1H NMR
(DMSO d6) d: 7.1–7.8 (m, 14H, Ar–H), 6.83 (s, 1H, NH),
4.62 (d, 1H, –CH–Ar), 3.43 (d, 1H,–CH-S); 13C-NMR
3-(4-N,N-Dimethylbenzylidene)-6,6-diphenyl-3,
3a-dihydro-2H-imidazo[2,1-b]pyrazolo[3,4-d]
[1,3]thiazol-7(6H)-one (5e)
Yield 79%, m.p. 219°C; IR (KBr) cm-1 3268 (N–H str.)
3039 (C–H, Ar–H), 1724 (C=O), 1562 (C=N); H NMR
1
123

Med Chem Res (2011) 20:1490–1498
1495
1
(DMSO d6) d: 6.9–7.4 (m, 14H, Ar–H), 6.52 (s, 1H, NH),
4.32 (d, 1H, –CH–Ar), 3.45 (d, 1H, –CH–S), 3.12 (6H, s,
N(CH3)2; 13C-NMR (DMSO d6) d:173.23, 154.56, 164.72,
143.64, 140.26,139.12, 132.11, 130.43, 128.54, 129.58,
127.78, 126.17, 79.34, 55.65, 47.87, 49.37, 42.76. Anal.
calcd. for C26H23N5OS; C, 68.87; N, 15.45; S, 7.06%.
Found C, 68.56; N, 15.23; S, 6.78%; MS: m/z 453 [M]?.
1498 (N–O), 1018 (C–O),1185 (C–Cl); H NMR (DMSO
d6) d: 7.2–7.8 (m, 18H, Ar–H), 4.47 (t, 2H, OCH2,
J = 6.1), 3.77 (t, 2H, NCH2, J = 5.8), 4.28 (d, 1H, –CH–
Ar), 3.36 (d, 1H, –CH–S); 13C-NMR (DMSO d6) d:172.86,
163.16, 161.50, 155.90, 141.96, 136.16, 131.95, 129.96,
129.42, 129.68, 128.75, 128.43, 125.87, 79.45, 65.46,
51.87, 49.19, 45.15, Anal. calcd. for C34H24FN5O4S; C,
66.12; N, 11.34; S, 5.18%. Found C, 65. 70; N, 11.21; S,
4.96%; MS: m/z 617 [M]?.
Synthesis of 2-N-ethoxyphthalimido 3-(4-chlorophenyl)-6,
6-diphenyl-3,3a-dihydro-2H-imidazo
[2,1-b]pyrazolo[3,4-d][1,3]thiazol-7(6H)-one (7a)
2-N-ethoxyphthalimido-3-(4-methoxybenzylidene)-6,
6-diphenyl-3,3a-dihydro-2H-imidazo[2,1-b]pyrazolo
[3,4-d][1,3]thiazol-7(6H)-one (7d)
A mixture of 5a (0.01 mol) and bromoalkoxyphthalimide
(0.01 mol) in absolute ethanol (15 ml) was refluxed for 16 h.
using pyridine (0.02 mol) as a base. It was concentrate by
removing the solvent under reduced pressure and the resultant
filtrate was poured into crushed ice to obtain solid product,
which was filtered, dried and recrystallized from alcohol.
Yield 77%, m.p. 194°C; IR (KBr) cm-1: 3032 (C–H,
Ar–H), 2963 (C–H, CH2 str.), 1726, 1705 (C=O), 1527
Yield 75%, m.p. 184°C; IR (KBr) cm-1: 3042 (C–H, Ar–
H), 2964 (C–H, CH2), 1727,1711 (C=O), 1544 (C=N),
1
1487 (N–O), 1016 (C–O); H NMR (DMSO d6) d: 6.8–7.3
(m, 18H, Ar–H), 4.38 (t, 2H, OCH2, J = 5.9), 3.72 (t, 2H,
NCH2, J = 5.7), 4.21 (d, 1H, –CH–Ar), 3.29 (d, 1H, –CH–
S), 3.34 (3H, s, OCH3); 13C-NMR (DMSO d6) d:172.45,
163.29, 161.48, 155.50, 141.76, 137.06, 132.15, 129.86,
129.65, 129.52, 128.23, 128.65, 125.67, 79.21, 65.53,
51.62. 49.34, 46.25. Anal. calcd. for C35H27N5O5S; C,
66.77; N, 11.12; S, 5.08%. Found C, 66. 25; N, 11.05; S,
4.76%; MS: m/z 629 [M]?.
1
(C=N), 1492 (N–O), 1013 (C–O), 747 (C–Cl); H NMR
(DMSO d6) d: 7.3–7.9 (m, 18H, Ar–H), 4.44 (t, 2H, OCH2,
J = 6.0), 3.75 (t, 2H, NCH2, J = 5.7), 4.29 (d, 1H, –CH–
Ar), 3.34 (d, 1H, –CH–S); 13C-NMR (DMSO d6) d: 172.84,
162.45, 161.60, 155.36, 142.80, 135.10, 132.15, 130.0,
129.70, 129.10, 128.90, 128.20, 126.03, 79.80, 65.80,
52.40, 49.12, 45.30. Anal. calcd. for C34H24ClN5O4S; C,
64.45; N, 11.04; S, 5.03%. Found C, 64.16; N, 10.50; S,
4.85%; MS: m/z 633 [M]?, 635 [M ? 2]?.
2-N-ethoxyphthalimido-3-(4-N,N-dimethylbenzylidene)-6,
6-diphenyl-3,3a-dihydro-2H-imidazo [2,1-b]
pyrazolo[3,4-d][1,3]thiazol-7(6H)-one (7e)
Compounds (7b–e) were prepared in similar way with
minor changes in reflux time. Their spectral data are given
below:
Yield 76%, m.p. 191°C; IR (KBr) cm-1: 3040 (C–H, Ar–
H), 2958 (C–H,CH2), 1724, 1698 (C=O), 1547 (C=N),
1
1482 (N–O), 1021 (C–O); H NMR (DMSO d6) d: 6.7–7.2
2-N-ethoxyphthalimido-3,6,6-triphenyl-3,3a-dihydro-2H-
imidazo[2,1-b]pyrazolo[3,4-d][1,3] thiazol-7(6H)-one (7b)
(m, 18H, Ar–H), 4.34 (t, 2H, OCH2, J = 5.8), 3.67 (t, 2H,
NCH2, J = 5.5), 4.18 (d, 1H, –CH–Ar), 3.23 (d, 1H,
-CH-S), 3.25 (6H, s, N(CH3)2; 13C-NMR (DMSO d6)
d:172.76, 163.23, 161.94, 155.80, 141.12, 137.34, 132.46,
129.26, 129.75, 129.78, 128.45, 128.25, 125.10, 78.89,
65.43, 51.41. 49.20, 46.55. Anal. calcd. for C36H30N6O4S;
C, 67.28; N, 13.08; S, 4.98%. Found C, 67. 15; N, 12.90; S,
4.50%; MS: m/z 642 [M]?.
Yield 74%, m.p. 187°C; IR (KBr) cm-1: 3028 (C–H, Ar–H),
2953 (C–H, CH2), 1720,1702 (C=O), 1523 (C=N), 1490 (N–
O), 1019 (C–O); 1H NMR (DMSO d6) d: 7.0–7.7 (m, 18H,
Ar–H), 4.34 (t, 2H, OCH2, J = 5.9), 3.72 (t, 2H, NCH2,
J = 5.6), 4.23 (d, 1H, –CH–Ar), 3.30 (d, 1H, –CH–S); 13C-
NMR (DMSO d6) d:171.34, 162.56, 161.20, 155.65, 141.98,
135.36, 131.45, 129.90, 129.20, 129.08, 128.25, 128.12,
125.80, 78.85, 64.72, 51.20. 48.92, 44.94. Anal. calcd. for
C34H25N5O4S; C, 68.11; N, 11.68; S, 5.34%. Found C, 67.60;
N, 11.30; S, 5.05%; MS: m/z 599 [M]?.
Synthesis of 2-amino-4-(4-chlorophenyl)-7,
7diphenylimidazo[20,10:2,3][1,3]thiazolo[4,5-d]
pyrimidin-8(7H)-one (8a)
A mixture of compound 4a (0.01 mol) and guanidine
nitrate (0.01 mol) in absolute alcohol was refluxed. An
aqueous solution of NaOH (40%, 5 ml) was added to it
portion-wise during 3 h. The heating was continued for the
next 8 h. The reaction mixture was cooled and poured into
crushed ice. The yellow-coloured solid separate was fil-
tered, dried and recrystallized from absolute alcohol. Yield
2-N-ethoxyphthalimido-3-(4-fluorophenyl)-6,6-diphenyl-3,
3a-dihydro-2H-imidazo[2,1-b]pyrazolo[3,4-d]
[1,3]thiazol-7(6H)-one (7c)
Yield 78%, m.p. 198°C; IR (KBr) cm-1: 3048 (C–H, Ar–
H), 2967 (C–H, CH2), 1732,1710 (C=O), 1554 (C=N),
123

1496
Med Chem Res (2011) 20:1490–1498
72%, m.p.[300°C; IR (KBr) cm-1: 3212, 3357 (N–H, 2H,
NH2), 3032 (C–H, Ar–H), 1657 (C=O), 1489 (C=N), 1384
2-Amino-4-(4-N,N-dimethylbenzylidene)-7,
7diphenylimidazo[20,10:2,3][1,3]thiazolo[4,5-d]
pyrimidin-8(7H)-one (8e)
1
(C–N), 748 (C–Cl); H NMR (DMSO d6) d: 6.8–7.4 (m,
18H, Ar–H), 6.74 (s, 2H, NH2); 13C-NMR (DMSO d6) d:
167.34, 164.78, 163.05, 152.80, 151.22, 142.85, 134.10,
133.32, 129.46, 129.04, 128.86, 128.10, 127.15, 125.50,
78.60. Anal. calcd. for C25H16ClN5OS; C, 63.96; N, 14.92;
S, 6.79%. Found C, 63.40; N, 14.58; S, 6.45%; MS: m/z
469 [M]?, 471 [M ? 2]?.
Yield 70%, m.p. 286°C; IR (KBr) cm-1: 3213–3332 (N–H,
2H, NH2), 3031 (C–H, Ar–H), 1670 (C=O), 1482 (C=N),
1380 (C–N), 1016 (C–O); 1H NMR (DMSO d6) d: 6.7–7.1
(m, 18H, Ar–H), 6.72 (s, 2H, NH2), 3.12 (6H, s, N(CH3)2;
13C-NMR (DMSO d6) d: 166.37, 164.75, 163.13, 152.87,
151.45, 142.56, 134.23, 133.76, 130.34, 129.54, 128.34,
128.67, 127.16, 125.28, 78.37. Anal. calcd. for
C27H22N6OS; C, 67.78; N, 17.57; S, 6.69%. Found C,
66.41; N, 17.20; S, 6.42%; MS: m/z 478 [M]?.
Similarly, other compound (8b–e) was also synthesized
and its characteristic data are given below:
2-Amino-4,7,7-triphenylimidazo[20,10:2,3][1,3]thiazolo
[4,5-d]pyrimidin-8(7H)-one (8b)
Synthesis of 4-(4-chlorophenyl)-2-(N-ethoxyphthalimido
amino)-7,7-diphenylimidazo[20,10:2,3] [1,3]thiazolo
[4,5-d]pyrimidin-8(7H)-one (9a)
Yield 71%, m.p. 289°C; IR (KBr) cm-1: 3208, 3345 (N–
H, 2H, NH2), 3028 (C–H, Ar–H), 1653 (C=O), 1485
1
(C=N), 1382 (C–N); H NMR (DMSO d6) d: 6.4–7.1 (m,
Compound 8a (0.01 mol) was refluxed in dry acetone
(20 ml) containing K2CO3 (0.01 mol) as base and bro-
moalkoxyphthalimide 6 (0.01 mol) for 16–20 h. Excess of
solvent was removed under reduced pressure. The sepa-
rated solid was filtered, washed and recrystallized from
ethanol. Yield 70%, m.p. 124°C; IR (KBr) cm-1: 3360 (N–
H, str), 3042 (C–H, Ar–H), 2947 (C–H, CH2), 1722, 1708
18H, Ar–H), 6.72 (s, 2H, NH2); 13C-NMR (DMSO d6) d:
167.17, 164.34, 163.25, 152.56, 151.31, 142.75, 134.34,
133.12, 129.43, 129.54, 128.76, 128.24, 127.46, 125.67,
78.32 Anal. calcd. for C25H17N5OS; C, 68.96; N, 16.09;
S, 7.35% Found C, 68.76; N, 15.98; S, 7.02%; MS: m/z
435 [M]?.
1
(C=O), 1565 (C=N), 1490 (N–O), 762 (C–Cl); H NMR
2-Amino-4-(4-fluorophenyl)-7,7diphenylimidazo[20,10:2,3]
[1,3]thiazolo[4,5-d]pyrimidin-8(7H)-one (8c)
(DMSO d6) d: 6.6–7.8 (m, 18H, Ar–H), 7.07 (s, 1H, N–H),
4.44 (t, 2H, OCH2, J = 6.0), 3.75 (t, 2H, NCH2, J = 5.7);
13C-NMR (DMSO d6) d: 175.17, 175.79, 155.96, 139.90,
138.34, 128.75, 128.49, 128.42, 128.01, 126.56, 72.94,
70.19, 40.35, 40.07, 39.79, 39.51, 39.24, 38.96, 38.68.
Anal. calcd. for C35H23ClN6O4S; C, 63.63; N, 12.72; S,
4.86%. Found C, 63.16; N, 12.45; S, 4.35%; MS: m/z 660
[M]?, 662 [M ? 2]?.
Yield 76%, m.p. [300°C; IR (KBr) cm-1: 3226,3364 (N–
H, 2H, NH2), 3047 (C–H, Ar–H), 1664 (C=O), 1496
1
(C=N), 1389 (C–N), 1178 (C–F); H NMR (DMSO d6)
7.2–7.8 (m, 18H, Ar–H), 6.83 (s, 2H, NH2); 13C-NMR
(DMSO d6) d: 166.87, 164.56, 163.78, 152.77, 151.68,
142.87, 134.74, 133.54, 130.12, 129.68, 128.77, 128.64,
127.87, 125.98, 78.56. Anal. calcd. for C25H16FN5OS; C,
66.22; N, 15.45; S, 7.06%. Found C, 66.00; N, 15.08; S,
6.68%; MS: m/z 453 [M]?.
Compounds (9b–e) were synthesized in similar way
with alteration in reflux time. Their spectral data are given
below:
2-(N-ethoxyphthalimidoamino)-4,7,7-triphenylimidazo
[20,10:2,3][1,3]thiazolo[4,5-d]pyrimidin-8(7H)-one (9b)
2-Amino-4-(4-methoxybenzylidene)-7,7diphenylimidazo
[20,10:2,3][1,3]thiazolo[4,5-d]pyrimidin-8(7H)-one (8d)
Yield 69%, m.p. 119°C; IR (KBr) cm-1: 3358 (N–H, str),
3040 (C–H, Ar–H), 2937 (C–H, CH2), 1719, 1703 (C=O),
1559 (C=N), 1487 (N–O); 1H NMR (DMSO d6) d: 6.2–6.8
(m, 18H, Ar–H), 7.02 (s, 1H, N–H), 4.40 (t, 2H, OCH2,
J = 5.9), 3.73 (t, 2H, NCH2, J = 5.7); 13C-NMR (DMSO
d6) d: 168.10, 165.67, 163.45, 161.78, 153.23, 142.45,
134.67, 133.13, 132.45, 131.89, 129.56, 128.45, 128.67,
128.23, 128.19, 127.35, 125.34, 79.67, 70.90, 49.96.
Anal. calcd. for C35H24N6O4S; C, 67.30; N, 13.46; S,
5.12%. Found C, 67.19; N, 13.21; S, 4.87%; MS: m/z 624
[M]?.
Yield 73%, m.p. 292°C; IR (KBr) cm-1: 3207,3342 (NH,
2H, NH2), 3034 (C–H, Ar–H), 1674 (C=O), 1488 (C=N),
1
1384 (C–N), 1012 (C–O); H NMR (DMSO d6) 6.5–6.9
(m, 18H, Ar–H), 6.78 (s, 2H, NH2), 3.12 (3H, s, OCH3);
13C-NMR (DMSO d6) d: 166.74, 164.46, 163.83, 152.63,
151.45, 142.67, 134.13, 133.17, 130.46, 129.79, 128.84,
128.94, 127.56, 125.18, 78.34. Anal. calcd. for
C26H19N5O2S; C, 67.09; N, 15.05; S, 6.88%. Found C,
66.96; N, 14.80; S, 6.54%; MS: m/z 465 [M]?.
123

Med Chem Res (2011) 20:1490–1498
1497
Sharma, Department of Botany, M. L. Sukhadia University for
evaluating the antimicrobial activity.
4-(4-Fluorophenyl)-2-(N-ethoxyphthalimido amino)-7,
7-diphenylimidazo[20,10:2,3][1,3]thiazolo
[4,5-d]pyrimidin-8(7H)-one (9c)
Yield 74%, m.p. 136°C; IR (KBr) cm-1: 3367 (N–H, str),
3047 (C–H, Ar–H), 2956 (C–H, CH2), 1727,1714 (C=O),
References
Abid M, Azam A (2005) 1-N-substituted thiocarbamoyl-3-phenyl-2-
pyrazolines: synthesis and in vitro antiamoebic activities. Eur J
Med Chem 40:935–942
Azarifar D, Maseud S (2002) Synthesis and characterization of new
3,5-dinaphthyl substituted 2-pyrazolines and study of their
antimicrobial activity. Molecules 7:885–895
1
1568 (C=N), 1496 (N–O),1176 (C–F); H NMR (DMSO
d6) d: 6.7–7.4 (m, 18H, Ar–H), 7.13 (s, 1H, N–H), 4.48 (t,
2H, OCH2, J = 6.0), 3.78 (t, 2H, NCH2, J = 5.9);
13C-NMR (DMSO d6) d: 168.46, 165.54, 163.32, 161.45,
153.23, 142.34, 134.12, 133.26, 132.34, 131.67, 129.36,
128.25, 128.33, 128.87, 128.99, 127.12, 125.45, 79.34,
70.98, 50.23. Anal. calcd. for C35H23FN6O4S; C, 65.42; N,
13.08; S, 4.98%. Found C, 65.06; N, 12.60; S, 4.36%. MS:
m/z 642 [M]?.
Banu T, Rajora, Talesara GL (2000) J Indian Chem Soc 77:300
¨
Bauer L, Suresh KS (1963) S-[i-(aminooxy)alkyl]isothiuronium salts,
0
¨
i,i -bis (aminooxy) alkanes and related compounds. J Org Chem
28:1604
Berlin KD, Herd MD (1991) Novel 2-amino-4-aryl-substituted-and 2-
amino-4, disubstituted-thiazoles. Proc Okala Acad Sci 71:29–33
Bhat BA, Dhar KL, Puri SC, Saxena AK, Shanmugave M, Qazi GN
(2005) Synthesis and biological evaluation of chalcones and
their derived pyrazoles as potential cytotoxic agents. Bioorg Med
Chem Lett 15:3177
Chang LL, Sidler KL, Cascieri MA (2001) Substituted imidazoles as
glucagon receptor antagonists. Bioorg Med Chem Lett 11:2549
Chimichi S, Boccalini M, Hassan M M M, Viola G, Dall Acqua F,
Curini M (2006) Synthesis, structural determination and photo-
antiproliferative activity of new 3-pyrazolyl or -isoxazolyl
substituted 4-hydroxy-2(1h)-quinolinones. Tetrahedron 62:90
Cornish EJ, Lee GE, Wargg WR (1966) The diuretic activity of
clorexolone and some related phthalimides and 1-oxoisoindo-
lines. J Pharma Pharmacol 18:65
Enguehard C, Renou JL, Allouchi H, Leger JM, Guiffier A (2000)
Synthesis of diaryl-substituted imidazo[1,2-a]pyridines designed
as potential aromatase inhibitors. Chem Pharm Bull 48:935
Frey R, Wishart N (2005) Thienopyrimidine ureas as novel and potent
multitargeted receptor tyrosine kinase inhibitors. J Med Chem
48:6066
Goker H, Kus C, Botkin D, Altanlar N (2002) Synthesis of some new
2-substituted-phenyl-1H-benzimidazole-5-carbonitriles and their
potent activity against Candida species. Bioorg Med Chem
10:2589
4-(4-Methoxybenzylidene)-2-(N-ethoxyphthalimido
amino)7,7-diphenylimidazo[20,10:2,3][1,3]
thiazolo[4,5-d]pyrimidin-8(7H)-one (9d)
Yield 71%, m.p. 121°C; IR (KBr) cm-1: 3362 (N–H, str),
3043 (C–H, Ar–H), 2942 (C–H, CH2), 1722, 1711 (C=O),
1
1548 (C=N), 1487 (N–O), 1018 (C–O); H NMR (DMSO
d6) d: 6.4–6.8 (m, 18H, Ar–H), 7.07 (s, 1H, N–H), 4.34 (t,
2H, OCH2, J = 5.7), 3.68 (t, 2H, NCH2, J = 5.6), 3.24 (s,
3H, OCH3); 13C-NMR (DMSO d6) d: 168.34, 164.23,
163.65, 161.63, 153.87, 142.35, 134.10, 133.32, 132.65,
131.42, 129.76, 129.41, 128.93, 128.43, 127.99, 127.36,
125.23, 79.45, 70.56, 50.12. Anal. calcd. for C36H26N6O5S;
C, 66.05; N, 12.84; S, 4.89%. Found C, 65.96; N, 12.60; S,
4.46%; MS: m/z 654 [M]?.
4-(4-N,N-dimethylbenzylidene)-2-(N-ethoxyphthalimi-
doamino)-7,7-diphenylimidazo[20,10:2,3]
[1,3]thiazolo[4,5-d]pyrimidin-8(7H)-one (9e)
Gupta G, Jain RK, Maikhuri JP, Shukla PK, Kumar M, Roy AK
(2005) Discovery of substituted isoxazolecarbaldehydes as
potent spermicides, acrosin inhibitors and mild anti-fungal
agents. Hum Reproduction 20:2301
Yield 69%, m.p. 137°C; IR (KBr) cm-1: 3356 (N–H, str),
3034 (C–H, Ar–H), 2940 (C–H, CH2), 1719, 1710 (C=O),
1543 (C=N), 1489 (N–O); 1H NMR (DMSO d6) d: 6.3–6.7
(m, 8H, Ar–H), 7.10 (s, 1H, N–H), 4.30 (t, 2H, OCH2,
J = 5.9), 3.64 (t, 2H, NCH2, J = 5.8), 3.26 (s, 6H,
N(CH3)2; 13C-NMR (DMSO d6) d: 167.23, 164.45, 162.95,
161.33, 152.54, 143.45, 134.67, 133.12, 132.32, 131.67,
130.16, 129.14, 128.45, 128.78, 128.19, 127.76, 124.33,
80.41, 70.34, 50.56. Anal. calcd. for C37H29N7O4S; C,
66.56; N, 14.69; S, 4.79%. Found C, 66.10; N, 14.31; S,
4.16%; MS: m/z 667 [M]?.
Hadizadeh F, Bamashad M, Poorsoghat H, Fatehi-Hassanabad M
(2005) Synthesis and antihypertensive activity of new 1,4-
dihydropyridines Indian J Chem 44B: 2343
Hans N (1978) Chem Abstr 22:886
Hayashi (1956) Japan Patent 1898
Heiba JI, Ghorab MM, Amin NE, Ramadan L, Egypt J (1998)
Biotechnol 4:16
Insuasty B, Fernandez F, Qulroga J, Martinez R, Gavino R, Angeles E
(2002) Heterocycle Commun 8:151
Kappe CO (2004) Stadle Organic Reaction 63:1
Kaunowasky H, Cherwat R, Delage B, Jondet A (1966) Chim Thera
209
Kumar Y, Green R, Wise DS, Wotring LL, Townsend LB (1993)
Synthesis of 2,4 disubstituted thiazoles and selenazoles as
potential antifilarial and antitumor agents.
36:3849–3852
Kumar A, Archana Sharma S, Malik N, Sharma P, Kaushik K, Saxena
K, Srivastava K (2004) Synthesis of anti-inflammatory, analgesic
and COX-II inhibitory activities of indolylpyrazolines. Indian J
Chem 43B:1532
J Med Chem
Acknowledgments The authors are thankful to the Head, Depart-
ment of Chemistry, M. L. Sukhadia University, Udaipur for providing
laboratory facilities and to the director, RSIC, CDRI, Lucknow, India
for providing spectral and analytical data. The authors are also
grateful to antimicrobial research laboratory, particularly Dr. Kanika
123

1498
Med Chem Res (2011) 20:1490–1498
Loscher WG (1946) Eur J Pharmacol 51:342
Mamalis P (1971) Some biological properties associated with amino-
oxy containing compounds xenobiotica 1:569–571
Nasr MN, Gineinah MM (2002) Pyrido[2,3-d]pyrimidines and
pyrimido[50,40:5, 6]pyrido[2,3-d]pyrimidines as new antiviral
agents: synthesis and biological activity. Arch Pharm 335:289
Plouvier B, Houssin R, Helbecque N, Colson P, Houssier CJ, Bailly C
(1995) Anticancer Drugs 10:155
4-aryl-6-aryliminothiazolidino[2,3-b] pyrimidines and related
compounds. Indian J Chem 43B:1306
Sondhi SM, Johar M, Rajvanshi S, Dastidor SG, Shukla R, Raghubir R,
Lown JW (2001) Anticancer, antiinflammatory and analgesic
activity evaluation of heterocyclic compounds synthesized by the
reaction of 4-isothiocyanato-4-methylpentan-2-one with substi-
tuted o-phenylenediamines, o-diaminopyridine and (un)substi-
tuted diaminopyrimidine. Aust J Chem 54:69
Reddy GJ, Sailaja S, Srinivasa Rao K (2005) Synthesis of 2-aryl-7-(3-
as
Tandon VK, Yadav DB, Charurvedi AK, Shukla PK (2005) Synthesis
of (1,4)-naphthoquinono-[3,2-c]-1H-pyrazoles and their (1,4)-
naphthohydroquinone derivatives as antifungal, antibacterial,
and anticancer agents. Bioorg Med Chem Lett 15:3288
oxo-2H-[1,4]-benzoxazin-6-yl)pyrazolo[1,5-a]pyrimidines
potential COX-2 inhibitors. Indian J Chem 44B:204
Sasaki S, Cho N, Nara Y, Harada M, Endo S, Suzuki N, Furuya S,
Fujino M (2003) Discovery of a thieno[2,3-d]pyrimidine-2,4-
dione bearing a p-methoxyureidophenyl moiety at the 6-position:
a highly potent and orally bioavailable non-peptide antagonis for
the human luteinizing hormone-releasing hormone receptor.
J Med Chem 46:113
Shafiee A, Rastkari N, Sharifzadeh (2004) Anticonvulsant activities
of new1,4-dihydropyridine derivatives containing 4-nitroimidaz-
olyl substituents. DARU 12:81
Simmons A (1996) Practical medical microbiology, 14th edn, vol 11.
Churchill Livingstone, Edinberg, p 163
Singh B, Mehta D, Baregama LK, Talesara GL (2004) Synthesis and
biological evaluation of 7-N-(n-alkoxyphthalimido)-2-hydroxy-
Wilson KJ, Utig CR, Subhasinghe NJ, Molloy C, Bone R, Green D,
Randall
J (2001) Synthesis of thiophene-2-carboxamidines
containing 2-aminothiazoles and their biological evaluation as
urokinase inhibitors. Bioorg Med Chem Lett 11:915–918
Zhang P, Zhang N, Korba B, Hasmane SR (2005) Synthesis and in
vitro anti-hepatitis B and C virus activities of ring-expanded
(‘fat’) nucleobase analogues containing the imidazo[4,5-
e][1,3]diazepine-4,8-dione ring system. Bioorg Med Chem Lett
15:5377
Zhou JF, Song YZ, Yang YL, Zhu YL, Tu SJ (2005) One-step
synthesis of 2-Aryl-4,5-diphenylimidazoles under microwave
irradiation. Synthetic Commun 35:1369–1373
123