Design, synthesis and biological evaluation of novel 2-[(2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ylidene)hydrazono]-1,3-thiazolidin-4-ones as a new class of antimicrobial agents

Article abstract of DOI:10.1016/j.bmcl.2009.03.093

New series of 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one thiosemicarbazones (9-16) obtained from the corresponding 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones (1-8) upon cyclization with ethylbromoacetate in the presence of sodium acetate-acetic acid buffer afforded novel 2-[(2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ylidene)hydrazono]-1,3-thiazolidin-4-ones (17-24). The synthesized compounds have been characterized by their elemental, analytical and spectral studies. Besides, the reported compounds were screened for their antibacterial and antifungal activities against a spectrum of microbial organisms. These studies proved that compounds 11/18/20/23 against Staphylococcus aureus, 19/20/24 against Salmonella typhi show maximum inhibition potency at low concentration (6.25 μg/ml) whereas 18/19 against Candida albicans and 19/20/21 against Rhizopus sp. showed beneficial antifungal activity at minimum concentration.

Full text of DOI:10.1016/j.bmcl.2009.03.093

Bioorganic & Medicinal Chemistry Letters 19 (2009) 2819–2823
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Design, synthesis and biological evaluation of novel 2-[(2,4-diaryl-3-azabicy-
clo[3.3.1]nonan-9-ylidene)hydrazono]-1,3-thiazolidin-4-ones as a new class
of antimicrobial agents
*
R. Ramachandran, M. Rani, S. Kabilan
Department of Chemistry, Annamalai University, Annamalai Nagar 608 002, Tamil Nadu, India
a r t i c l e i n f o
a b s t r a c t
Article history:
New series of 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one thiosemicarbazones (9–16) obtained from the
corresponding 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones (1–8) upon cyclization with ethylbromoace-
tate in the presence of sodium acetate–acetic acid buffer afforded novel 2-[(2,4-diaryl-3-azabicy-
clo[3.3.1]nonan-9-ylidene)hydrazono]-1,3-thiazolidin-4-ones (17–24). The synthesized compounds
have been characterized by their elemental, analytical and spectral studies. Besides, the reported com-
pounds were screened for their antibacterial and antifungal activities against a spectrum of microbial
organisms. These studies proved that compounds 11/18/20/23 against Staphylococcus aureus, 19/20/24
against Salmonella typhi show maximum inhibition potency at low concentration (6.25 lg/ml) whereas
18/19 against Candida albicans and 19/20/21 against Rhizopus sp. showed beneficial antifungal activity
at minimum concentration.
Received 19 December 2008
Revised 28 February 2009
Accepted 23 March 2009
Available online 26 March 2009
Keywords:
Azabicyclo[3.3.1]nonan-9-ones
Thiazolidinones
Thiosemicarbazones
Cyclization
Ó 2009 Elsevier Ltd. All rights reserved.
Antibacterial activity
Antifungal activity
Thiazolidinones are an interesting backbone unit in medicinal
chemistry and responsible for numerous pharmacological proper-
ties and biological activity1 which gives the considerable research
interest in this area has been done towards the synthesis of thiazo-
lidinone unit. Jeyaraman and Avila2 have reviewed the importance
of bicyclic compounds as intermediates in the synthesis of a sev-
eral physiologically active compounds. Similarly, Lijinsky and Tay-
earlier work and as part of our ongoing research programme5 we
planned to design a system, which combines both bioactive piper-
idine and thiazolidinone components together to give a compact
structure like title compounds.
Many compounds with a thiosemicarbazone moiety exhibit sig-
nificant biological properties,6 because thiourea unit (NHCSNH)
can easily form chelation with metal ions like iron, zinc, magne-
sium etc. The parent bicyclic ketones (2,4-diaryl-3-azabicy-
clo[3.3.1]nonan-9-ones) were prepared according to the
literature precedent by Baliah et al.7 The ketones upon treatment
with thiosemicarbazide in the presence of few drops of mineral
acid afforded two different products, viz., 2,4-diaryl-3-azabicy-
clo[3.3.1]nonan-9-one thiosemicarbazones (9–16) and arylthiose-
micarbazones (9a–16a) (Scheme 1). The formation of by-product
(arylthiosemicarbazones) is due to poor mass balance while using
mineral acids (HCl or H2SO4) as catalyst in the condensation of high
molecular parent ketones with thiosemicarbazide. The cleavages of
the products were studied by retro mannich mechanism followed
by condensation reaction. Further, no more by-products were
found to be formed after workup.
lor3 have found that the presence of substituents at both the
a-
positions to that of ‘N’ in piperidin-4-one is important to exert
marked biological properties. In addition, several interesting inves-
tigations have been made through piperidine based heterocyclic
compounds and exhibited numerous biological properties such as
antibacterial, antifungal, antitumor, antiarrhythmic, antithrombic,
calcium antagonist, hypotensive and neuroleptic activities.4 An
essential component of the search for new leads in drug designing
program is the synthesis of molecules, which are novel still resem-
ble known biologically active molecule by virtue of the presence of
some pharmacophoric groups. Certain small heterocyclic mole-
cules act as highly functionalized scaffolds and are known pharma-
cophores of a number of biologically active and useful molecules.
Apart from the biological importance, these bridged bicyclic com-
pounds exhibit twin chair, chair-boat or twin boat conformations
possessing interesting stereochemistry. In connection with our
Thiazolidin-4-ones are well known for their pharmacological
activities. Literature survey reveals that several substituted
thiazolidinones have prepared from different synthetic routes.8 In
the present work, an attempt has been made to undertake the syn-
thesis of title compounds through the cyclization of key intermedi-
ate 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one thiosemicarbazones
* Corresponding author. Tel.: +91 9843444261.
E-mail address: chemkabilan@rediffmail.com (S. Kabilan).
0960-894X/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2009.03.093

2820
R. Ramachandran et al. / Bioorg. Med. Chem. Lett. 19 (2009) 2819–2823
O
R
R
CHO
O
CHO
1
2
1
2
R
R
R
R
a
R
R
R
N
H
+
1
1
R
1-8
2
NH OAc
2
4
R
R
b
O
S
NH
NH
NH
R
N
N
2
N
S
R
c
R
R
1
1
1
2
1
2
R
R
R
R
R
N
H
N
H
2
2
R
R
R
9-16
+
17-24
NH
NH
2
N
S
2
R
R
1
R
9a-16a
Scheme 1. Schematic diagram showing the synthesis of 1,3-thiazolidinones. Reagent and conditions: (a) EtOH/warm, rt?24 h; (b) MeOH–CHCl3, H2NNHCSNH2/H+, reflux,
80 °C?3 h; (c) EtOH, BrCH2COOC2H5, CH3COONa/CH3COOH, reflux, 80 °C?4 h.
with ethylbromoacetate under reflux condition (80 °C at 4 h) affor-
ded 2-[(2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ylidene)hydrazon-
o]-1,3-thiazolidin-4-ones (17–24). Moreover in order to study the
reactivity, varied conditions such as (i) sodium acetate or acetic
acid (ii) mixture of sodium acetate and acetic acid (iii) without so-
dium acetate or acetic acid were attempted for cyclization. Of the
three different reaction conditions, one with mixture of sodium
acetate and acetic acid condition afforded the target molecules
(17–24) with good yield, wherein the mixture of sodium acetate
and acetic acid act as buffer system to maintain the pH (4.5–5.0)
value of the reaction solution and avoid the C@N cleavage. During
the course of reaction, excess of sodium acetate was used to scav-
enge the hydrogen bromide whereas acetic acid act as the cyclizing
agent. However, reactions without acetic acid and sodium acetate
afforded (17–24) poor yield. Therefore, under optimal conditions,
compounds (17–24) were synthesized and characterized by spec-
tral and analytical methods. The analytical data of the compounds
9–24 are given in Table 1. To comprehend the structure–activity
relationship well, numberings of the target compound are done
(Fig. 1).
absorption bands appeared in the region 3152–3397 cmÀ1 which is
assigned to NH stretching frequency whereas C@N stretching fre-
quency appeared as strong and intense bands at 1648 and
1644 cmÀ1, respectively. Generally, the amide carbonyl stretching
frequency was noted in the region 1630–1690 cmÀ1. But in 17,
the amide carbonyl group shows a strong absorption band at
1713 cmÀ1. This is due to extended conjugation over the thiazolid-
inone unit.
All the synthesized compounds were characterized by 1H and
13C NMR spectral studies and the results were compared and as-
signed the signals with the help of earlier reports.9 In compounds
9 and 17, the benzylic protons appeared, two different signals
viz. 4.36, 4.26 ppm and 4.39, 4.26 ppm, respectively. Of the two
compound signals, deshielded signal is assigned to anti-H2a proton
while shielded one is attributed to syn-H4a proton. Similarly, the
bridgehead protons also resonated as two different signals at
2.97, 2.50 ppm and 3.56, 2.57 ppm for compounds 9 and 17,
respectively. Unlike, the syn
a-bridgehead proton (H5e) shows
highly deshielded region than anti
a
-bridgehead proton (H1e). This
is due to the non-bonded (spatial) interaction between H5e proton
In order to investigate the spectral assignments of reported
compounds (9–24), 9 and 17 are taken as the representative com-
pounds. The IR spectra of compounds 9 and 17 shows a collective
and ‘N’ in thiosemicarbazone or thiazolidinone unit (Fig. 2). Owing
to this interaction, syn
a-carbon get partially negative charge and
the attached proton acquires a slight positive charge (Fig. 2). Based

R. Ramachandran et al. / Bioorg. Med. Chem. Lett. 19 (2009) 2819–2823
2821
Table 1
Analytical data for compounds 9–24
Entry
R
R1
R2
Yield (%)
Mp (°C)
Elemental analysis
H (%)
C (%)
N (%)
Found
Calcd
Found
Calcd
Found
Calcd
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
H
H
H
H
Cl
H
H
H
H
H
H
H
Cl
H
H
H
H
H
F
H
H
H
H
OCH3
H
H
F
H
H
H
H
OCH3
H
F
H
Cl
65
60
65
67
69
71
85
75
72
75
72
77
79
74
78
76
160
196
172
202
210
150
133
141
220
212
164
153
150
143
202
90
—
62.95
—
58.21
—
70.37
—
—
68.25
—
62.71
—
58.34
69.43
64.64
—
69.20
62.98
62.98
58.20
58.20
70.38
65.07
65.07
68.29
62.71
62.71
58.35
58.35
69.41
64.63
64.63
—
5.55
—
5.12
—
7.19
—
—
5.99
—
5.00
—
4.71
6.52
6.07
—
6.64
5.48
5.48
5.12
5.12
7.18
6.65
6.65
5.98
5.03
5.03
4.68
4.68
6.52
6.07
6.07
—
13.98
—
12.95
—
14.27
—
—
13.88
—
12.72
—
11.81
12.93
12.05
—
15.37
13.99
13.99
12.93
12.93
14.25
13.20
13.20
13.85
12.70
12.70
11.83
11.83
12.95
12.06
12.06
H
CH3
OCH3
H
H
F
H
Cl
H
CH3
OCH3
H
integral value is unambiguously assigned to NH proton while the
same proton in 9 found to merge with H6e and H8e proton signals.
However, there are two broad singlets for 9 at 8.92 and 6.50 ppm
which corresponds to one and two protons integral values are as-
signed to NH and NH2 protons, respectively, in thiosemicarbazone
moiety. In 17, the exchangeable NH proton (thiazolidinone ring)
appeared as a singlet at 11.60 ppm and the methylene protons
(thiazolidinone unit) appeared as a sharp singlet at 3.74 ppm with
two proton integral value. In general, the aromatic proton signals
appeared at down field region due to their ring current or aniso-
tropic effect. Owing to this in compounds 9 and 17, the aromatic
proton signals resonated in the region 7.25–7.80 ppm as multiplet.
In 13C NMR spectrum of compound 17, a collection of signals
resonated in the aliphatic region at 32.92, 28.81, 27.65 and
21.23 ppm. Of the four signals in the aliphatic region, signals at
28.81, 27.65 and 21.23 ppm are assigned to C8, C6 and C7, respec-
tively. One more signal at 32.92 ppm is attributed to C5 methylene
carbon in the thiazolidinone ring. In addition to this, the benzylic
carbon signals C2 and C4 resonated at 64.94 and 63.57 ppm, respec-
tively, whereas the bridgehead carbons C1 and C5 appeared at
45.91 and 39.88 ppm, respectively. Moreover, a collection of sig-
nals appeared in the region 142.54–126.77 ppm which are unam-
biguously assigned to aryl carbons. Apart from the assigned
signals, two unassigned signals resonated in the most down field
region at 173.98 and 163.00 ppm and these signals belong to
C@O and C@N carbons respectively (refer Supplementary data).
In order to find the effect of potency of inhibitions in 9–24 by
in vitro method, we modified different substituentsat phenylgroups
in 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one thiosemicarbazones
and 2-[(2,4-diaryl-3-azabicyclo[3.3.1] nonan-9-ylidene)hydrazon-
o]-1,3-thiazolidin-4-ones. The reported compounds were tested
against bacterial strains viz., Staphylococcus aureus (ATCC-25825),
Bacillus subtilis (ATCC-451), Salmonella typhi (ATCC-24915), Esche-
richia coli (ATCC-25835) and Klebsiella pneumonia (ATCC-15490)
using the literature precedent by Dhar et al.,10 and their MIC values
aredepicted in Table 2. A glance at theMIC valuesin Table 2 indicates
thatcompound9 againstS. aureusexhibitminimuminhibitionactiv-
ity. However, para or meta fluorophenyl substituted compounds 10
against B. subtilis and S. typhi and 11 against S. aureus, B. subtilis and
K.pneumoniaexertedsignificantinhibition.Thecompound10,which
Figure 1. A well numbered target molecules (17–24).
Figure 2. Non-bonded interaction between C5(He) and NH group.
on this statement, shielded signal is attributed to H1e proton
whereas deshielded signal is assigned to H5e proton. However in
both 9 and 17, the signal to the methylene protons in cyclohexane
ring, a well resolved multiplet appeared at 2.83 and 2.82 ppm,
respectively, which corresponds to one proton integral. Hence,
these signals are attributed to H7a proton. In 9, the H6e and H8e pro-
tons appeared as double doublet at 1.84 ppm whereas H6a, H8a and
H7e protons resonated as multiplet in the region 1.40–1.58 ppm.
But in 17, all the methylene proton signals in the cyclohexane ring
(H6a, H6e, H7e, H8a and H8e) are merged together (except H7a) and
appeared as multiplet with five protons integral value. Moreover
in 17, a broad singlet resonated at 2.09 ppm with one proton
was inactive against E. coli even at maximum concentration (200 lg/
ml).
In thiazolidinone compounds with fluorine substituent, 18
against S. aureus and 19 against S. typhi shows good antibacterial

2822
R. Ramachandran et al. / Bioorg. Med. Chem. Lett. 19 (2009) 2819–2823
Table 2
Table 3
Antibacterial activity of compounds 9–24 against selected bacterial strains (MIC in
g/ml)
Antifungal activity of compounds 9–24 against selected fungal strains (MIC in lg/ml)
l
Compound
Minimum inhibitory concentration (MIC) in
lg/ml
Compound
Minimum inhibitory concentration (MIC) in lg/ml
C. neoformans C. albicans Rhizopus sp. A. niger A. flavus
S. aureus
B. Subtils
S. tyhpi
E. coli
K. pneumonia
9
100
25
25
200
50
25
—
200
100
25
100
100
200
200
50
200
6.25
50
6.25
100
—
100
—
200
100
50
100
50
25
—
200
50
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
50
50
100
25
25
100
100
100
50
50
25
25
50
25
100
25
50
100
12.5
200
12.5
50
100
50
100
—
100
6.25
100
50
200
100
25
200
50
100
100
100
50
100
—
50
—
25
25
50
25
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
100
100
50
6.25
25
200
12.5
25
25
25
100
200
50
100
50
200
200
—
50
50
6.25
6.25
25
25
100
200
100
200
100
6.25
6.25
6.25
50
—
200
200
100
12.5
6.25
6.25
50
100
100
6.25
50
50
25
50
50
—
12.5
50
100
100
25
50
100
50
25
200
100
25
25
—
100
50
50
6.25
100
6.25
100
25
6.25
100
50
12.5
12.5
100
100
50
50
100
100
50
200
100
25
100
Amphotericin B 25
25
Streptomycin
12.5
—, No inhibition even at maximum concentration.
—, No inhibition even at maximum concentration.
enhanced, respectively, by onefold rate. The compound 14, which
was inactive against A. flavus become potent by the cyclization of
thiosemicarbazone whereas 14 against C. neoformans, C. albicans
and Rhizopus sp. have registered minimum to moderate antifungal
activity. Due to modification of methyl analogue by methoxy group
in 14 and 22 (compounds 15, 16, 23 and 24) shows moderate activ-
ity against the entire tested fungal strains. Among the compounds
under the antifungal study, 9 against Rhizopus sp., 14, 16 and 23
against A. flavus, 15 against C. albicans and 17 and 22 against A. ni-
ger seldom show inhibition even at maximum concentration
activity at very low concentration (6.25 lg/ml). Besides, 18 against
S. typhi exhibit significant activity. Surprisingly replacement of
fluorine function by chlorine in 10, 11, 18 and 19 (compounds
12, 13, 20 and 21, respectively), compounds 12 against E. coli and
20 against S. typhi, were found to show superior activity than oth-
ers. However, 12 against B. subtilis and K. pneumonia shows a rever-
sal in activity, by two and three fold respectively, due to
replacement of fluorine by chlorine. Instead of halogens, methyl
or methoxy function substituted compounds 14 and 23 against S.
aureus and 24 against S. typhi markedly elevated the maximum
(200 lg/ml).
inhibition potency at minimum concentration (6.25 lg/ml).
In conclusion, we have synthesized a novel biologically impor-
tant thiosemicarbazones and their thiazolidinones. From the close
survey of the in vitro antibacterial and antifungal results against a
panel of microbial organisms revealed that the compound with
fluorine or chlorine substituents were found to be more active
against all the tested organisms.
The in vitro antifungal activity of the reported compounds 9-24
were examined with five fungal strains viz. Cryptococcus neofor-
mans (ATCC-3312), Candida albicans (ATCC-3122), Rhizopus sp.
(ATCC-2915), Aspergillus niger (ATCC-598) and Aspergillus flavus
(ATCC-485). Here, Amphotericin B was used as standard drug.
The obtained MIC values of the tested compounds and standard
are depicted in Table 3 that indicates all the tested compounds ex-
Acknowledgements
hibit a varied range 6.25–200
in compound 9 recorded minimum to moderate activity (100–
200 g/ml) against all the tested organisms except Rhizopus sp.
which did not show any inhibition potency even at maximum con-
centration at 200 g/ml whereas the same unsubstituted phenyl
lg/ml. Unsubstituted phenyl groups
We are thankful to Professor K. Pandiarajan, Head, Department
of Chemistry, Annamalai University for the facilities provided. We
also thank NMR Research Centre, IISc, Bangalore, for providing all
the NMR facilities to record NMR spectra. The authors place sincere
thanks to Mr. M. Karuppaiya, FEAT, Annamalai University for his
kind help in conducting screening studies.
l
l
group in thiazolidinone compound (17) shows one and twofold
enhancement in the antifungal activity against C. neoformans and
C. albicans, respectively. However, due to introduction of fluorine
functionality at the meta or para position of phenyl groups in 9
(compounds 10 and 11) noticed minimum to moderate inhibition
potency against all the tested fungal organisms with MIC ranging
Supplementary data
Complete experimental details and spectral data (IR, 1H NMR
and 13C NMR) for all the reported compounds data were given.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.bmcl.2009.03.093.
from 6.25 to 100
lg/ml. In which, 10 against A. flavus shows supe-
rior inhibition potency at minimum concentration (6.25
lg/ml)
whereas thiazolidinone compounds 18 against C. albicans and 19
against C. neoformans, C. albicans and Rhizopus sp. exhibited well
pronounced activity. Unlike, 18 and 19 against A. niger exhibit
one third decrease the inhibition potency upon cyclization. Modi-
fication of fluorine substituent by chlorine in 10, 11, 18 and 19
(compounds 12, 13, 20 and 21, respectively) registered minimum
antifungal activity against all the used strains, except 20 and 21
which shows superior activity against Rhizopus sp. In addition, 19
against C. neoformans, C. albicans and A. niger and 21 against A. niger
produced considerable impact on antifungal activity. Replacement
of one proton by methyl analogue in 9 (compound 14) against C.
neoformans and Rhizopus sp., the activity was decreased and
References and notes
1. (a) Vicini, P.; Geronikaki, A.; Incerti, M.; Zani, F.; Dearden, J.; Hewitt, M. Bioorg.
Med. Chem. 2008, 16, 3714; (b) Sonawane, N. D.; Verkman, A. S. Bioorg.
Med.Chem. 2008, 16, 8187; (c) Knutsen, L. J. S.; Hobbs, C. J.; Earnshaw, C. G.;
Fiumana, A.; Gilbert, J.; Mellor, S. L.; Radford, F.; Smith, N. J.; Birch, P. J.; Burley,
J. R.; Ward, S. D. C.; James, I. F. Bioorg. Med. Chem. Lett. 2007, 17, 662; (d)
Chaudhary, S. K.; Verma, M.; Chaturvedi, A. K.; Parmar, S. S. J. Pharm. Sci. 1974,
64, 614; (e) Dwivedi, C.; Gupta, T. K.; Parmar, S. S. J. Med. Chem. 1972, 15, 553;
(f) Nagar, S.; Singh, H. H.; Sinha, J. N.; Parmar, S. S. J .Med. Chem. 1973, 16, 178.
2. Jeyaraman, R.; Avila, S. Chem. Rev. 1981, 81, 149.
3. Lijinsky, W.; Taylor, H. W. Int. J. Cancer 1975, 16, 318.

R. Ramachandran et al. / Bioorg. Med. Chem. Lett. 19 (2009) 2819–2823
2823
4. (a) Rossi, C.; Figini, A.; Corpi, A. Ann. Ist. Supersanita 1968, 4, 333; . Chem. Abstr.
1969, 70, 85991s; (b) Chiavarelli, S.; Delcarmine, R.; Michalek, H. Ann. Ist.
6. (a) Ghosh, S.; Misra, A. K.; Bhatia, G.; Khan, M. M.; Khanna, A. K. Bioorg. Med.
Chem. Lett. 2009, 19, 386; (b) Krishnan, K.; Prathiba, K.; Jayaprakash, V.; Basu,
A.; Mishra, N.; Zhou, B.; Hu, S.; Yen, Y. Bioorg. Med. Chem. Lett. 2008, 18, 6248;
(c) Yang, Z. Y.; Wang, Y.; Wang, Y. Bioorg. Med. Chem. Lett. 2007, 17, 2096; (d)
Siles, R.; Chen, S. E.; Zhou, M.; Pinney, K. G.; Trawick, M. L. Bioorg. Med. Chem.
Lett. 2006, 16, 4405.
Supersanita 1972, 8, 156;
. Chem. Abstr. 1973, 78, 24098z; c Binning, F.;
Friedrich, L.; Hofmann, H. P.; Kreiskoh, H.; Raschack, M.; Muller, C. German
Patent, 2726571, 1978; Chem. Abstr. 1979, 90, 121568h.; . Chem. Abstr. 1979, 90,
121568h; (d) Ganellin, C. R.; Spickett, R. G. W. J. Med. Chem. 1965, 8, 619; El-
Subbagh, H. I.; Abu-Zaid, S. M.; Mahran, M. A.; Badria, F. A.; Al-obaid, A. M. J.
Med. Chem. 2000, 43, 2915.
7. Baliah, V.; Jeyaraman, R. Indian J. Chem. 1971, 9, 1020.
8. Dains, F. B.; Krober, O. A. J. Am. Chem. Soc. 1939, 61, 1830; Damico, J. J.;
Harman, M. H. J. Am. Chem. Soc. 1955, 77, 476; Bon, V.; Tisler, M. J. Org.
Chem. 1962, 27, 2878; Rao, R. P. J. Indian Chem. Soc. 1961, 38, 784; Bhargava,
P. N.; Chaurasia, M. R. J. Pharm. Sci. 1969, 58, 896; Chaubey, V. N.; Singh, H.
Bull. Chem. Soc. Jpn. 1970, 43, 2233; Wilson, F. J.; Burns, R. J. Chem. Soc. 1922,
121, 870; Bougault, J.; Cattelain, E.; Chabrier, P.; Quevauviller, A. Bull. Soc.
Chim. Fr. 1949, 16, 433; Surrey, R.; Cutler, R. A. J. Am. Chem. Soc. 1954, 76,
578.
5. (a) Aridoss, G.; Amirthaganesan, S.; Kumar, N. A.; Kim, J. T.; Lim, K. T.; Kabilan,
S.; Jeong, Y. T. Bioorg. Med. Chem. Lett. 2008, 18, 6542; (b) Karthikeyan, P.;
Meena Rani, A.; Saiganesh, R.; Balasubramanian, K. K.; Kabilan, S. Tetrahedron
2009, 65, 811; (c) Aridoss, G.; Parthiban, P.; Ramachandran, R.; Prakash, M.;
Kabilan, S.; Jeong, Y. T. Eur. J. Med. Chem. 2009, 44, 577; (d) Aridoss, G.;
Balasubramanian, S.; Parthiban, P.; Kabilan, S. Eur. J. Med. Chem. 2007, 42, 851;
(e) Aridoss, G.; Balasubramanian, S.; Parthiban, P.; Kabilan, S. Eur. J. Med. Chem.
2006, 41, 268; (f) Balasubramanian, S.; Ramalingan, C.; Aridoss, G.; Kabilan, S.
Eur. J. Med. Chem. 2005, 40, 694; (g) Aridoss, G.; Balasubramanian, S.; Parthiban,
P.; Kabilan, S. Spectrochim. Acta, Part A 2007, 68, 1153.
9. Parthiban, P. Ph.D Thesis, Annamalai University, India, 2007.
10. Dhar, M. H.; Dhar, M. M.; Dhawan, B. N.; Mehrotra, B. N.; Ray, C. Indian J. Exp.
Biol. 1968, 6, 232.