Syntheses and anti-allergic activity of 2-((bis(trimethylsilyl)methylthio/ methylsulfonyl)methyl)-5-aryl-1,3,4-oxadiazoles

Article abstract of DOI:10.1016/j.ejmech.2012.12.035

A new class of sila-substituted 1,3,4-oxadiazoles was synthesized by a convenient synthetic method. Both silathio/silasulfonyl acetic acids were efficiently condensed with benzohydrazides in the presence of phosphorus oxychloride to give sila-substituted 1,3,4-oxadiazoles in high yields. The compounds displayed variable extent of anti-allergic activity on IgE/Ag-stimulated RBL-2H3 cells at 50 and 100 μM concentrations. Compounds having sulfonyl moiety with bis(trimethylsilyl)-1,3,4-oxadiazoles (5a-c), exhibited better anti-allergic activities than those of compounds having sulphur moiety with bis(trimethylsilyl)-1,3,4-oxadiazoles (4a-c).

Full text of DOI:10.1016/j.ejmech.2012.12.035

European Journal of Medicinal Chemistry 62 (2013) 84e88
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European Journal of Medicinal Chemistry
journal homepage: http://www.elsevier.com/locate/ejmech
Original article
Syntheses and anti-allergic activity of 2-((bis(trimethylsilyl)
methylthio/methylsulfonyl)methyl)-5-aryl-1,3,4-oxadiazoles
Dinneswara Reddy Guda a, Sae-Jin Park b, Min-Woo Lee b, Tack-Joong Kim b,
,
Myong Euy Lee a
*
a Department of Chemistry & Medical Chemistry, College of Science and Technology, Research & Education Center for Advanced Silicon Materials,
Yonsei University, Wonju, Gangwon-Do 220-710, South Korea
b Division of Biological Science & Technology, College of Science and Technology, Yonsei University, Wonju, Gangwon-Do 220-710, South Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
A new class of sila-substituted 1,3,4-oxadiazoles was synthesized by a convenient synthetic method. Both
silathio/silasulfonyl acetic acids were efficiently condensed with benzohydrazides in the presence of
phosphorus oxychloride to give sila-substituted 1,3,4-oxadiazoles in high yields. The compounds dis-
Received 13 September 2012
Received in revised form
14 December 2012
Accepted 15 December 2012
Available online 23 December 2012
played variable extent of anti-allergic activity on IgE/Ag-stimulated RBL-2H3 cells at 50 and 100
mM
concentrations. Compounds having sulfonyl moiety with bis(trimethylsilyl)-1,3,4-oxadiazoles (5aec),
exhibited better anti-allergic activities than those of compounds having sulphur moiety with bis(-
trimethylsilyl)-1,3,4-oxadiazoles (4aec).
Keywords:
Sila-drug
Ó 2013 Elsevier Masson SAS. All rights reserved.
1,3,4-Oxadiazoles
RBL-2H3 cells
b-Hexosaminidase
Anti-allergy
1. Introduction
oxadiazoles (Iaec, IIaec) and their anti-allergic activities [22]. We
observed that IIc could be a suitable clinical candidate for treat-
Sila-substitution (C/Si exchange) into drug-like scaffolds has
attracted considerable attention as a consequence of unique biolog-
ical activities, chemical reactivities and physicochemical properties
of sila-drugs compared with their parent carbon compounds [1e5].
Tacke and Daiss synthesized various sila-substituted drugs such
as selective noradrenaline reuptake inhibitors [6,7], muscarinic
receptor antagonist [8e10], dopamine receptor antagonist [11e13],
retinoid agonist [14,15] etc., which were structurally characterized
and biologically evaluated.
In related to sila-substituted drugs, we have interested in sila-
substituted five-membered ring heterocycles such as 1,3,4-
oxadiazoles, 1,3,4-thiadiazoles, 1,2,4-triazoles, pyrazoles, iso-
xazoles, imidazoles as promising candidates for drug discovery.
Particularly various substituted 1,3,4-oxadiazoles displayed broad
spectra of biological activities [16e20].1,3,4-Oxadiazoles derivatives
have also been reported as promising anti-allergic agents [21,22].
We previously reported the synthesis of a series of 2-(((trime-
thylsilyl)methylthio/methylsulfonyl)methyl)-5-aryl-1,3,4-
ments of atopic disorders (Chart 1). Due to these attractive results,
we focused on bis(trimethylsilyl)-1,3,4-oxadiazoles. In this paper
we report the syntheses of 2-((bis(trimethylsilyl)methylthio/
methylsulfonyl)methyl)-5-aryl-1,3,4-oxadiazoles and their anti-
allergic activities.
2. Chemistry
2-(Bis(trimethylsilyl)methylthio)acetic acid (2) was synthesized
by the reaction of bis(trimethylsilyl)chloromethane (1) with mer-
captoacetic acid in the presence NaOH/MeOH, and then followed by
an oxidation of 2 in the presence of H2O2/CH3COOH to afford
compound 3. The 1H NMR spectra of both compounds 2 and 3
displayed three singlets at d 0.08, 1.01, 3.11 and 0.23, 2.21, 4.46 ppm
respectively, that are due to methyl, methine and methylene
protons. In addition to these chemical shifts 2 and 3 showed broad
singlets at
d 10.20 and 9.93 ppm, respectively due to OH, which
were disappeared on deuteration process. The desired heterocycles,
2-((bis(trimethylsilyl)methylthio)methyl)-5-aryl-1,3,4-oxadiazoles
(4) and 2-((bis(trimethylsilyl)-methylsulfonyl)methyl)-5-aryl-1,3,
4-oxadiazoles (5) were synthesized by the reactions of 2/3 with
benzohydrazides in the presence of phosphorus oxychloride [22]
* Corresponding author. Tel.: þ82 33 760 2237; fax: þ82 33 760 2182.
E-mail address: melgg@yonsei.ac.kr (M.E. Lee).
0223-5234/$ e see front matter Ó 2013 Elsevier Masson SAS. All rights reserved.
http://dx.doi.org/10.1016/j.ejmech.2012.12.035

D.R. Guda et al. / European Journal of Medicinal Chemistry 62 (2013) 84e88
85
Chart 1. Biologically active sila-substituted 1,3,4-oxadiazoles.
(Scheme 1). The 1H NMR spectra of 4a and 5a displayed three sharp
singlets for methyl, methine and methylene protons at 0.01, 0.88,
3.80 and at 0.26, 2.90, 4.56 ppm, respectively. Apart from these, 4a
and 5a displayed doublets and multiplet signals at 7.48, 8.02, and
7.50e7.62 ppm due to aromatic protons. The 29Si spectra of
compounds 4a and 5a appeared at 3.02, and 2.06 ppm, respec-
d
d
d
d
tively. The structures of the compounds 4 and 5 were further
confirmed by 13C NMR spectra.
3. Anti-allergic activity
Fig. 1. Effect of 4a, 4b, 4c, 5a, 5b and 5c compounds on
b
-hexosaminidase release of
Mast cells have a high affinity for immunoglobulin (Ig) E because
of having a specific IgE receptor, FcεR1, on their surface. As the IgE-
multivalent allergen complex binds to FcεR1, the mast cells become
activated and release a range of preformed species such as newly
synthesized mediators and cytokines that trigger potent allergic
reactions [23e27]. We evaluated the release of preformed allergic
IgE/Ag-stimulated RBL-2H3 cells. The cells were incubated overnight in 24-well plates
with 200 ng/mL of DNP-specific IgE. The medium was replaced with PIPES buffer
containing the indicated concentrations of 4a, 4b, 4c, 5a, 5b and 5c compounds, and
the cells were then challenged with 25 ng/mL DNP-HSA. After 15 min, b-hexosamin-
idase release was determined from the absorbance measured at 405 nm. The mean
values (ꢀS.D.) from three independent experiments are shown, where each was per-
formed in triplicate. *P < 0.05, **P < 0.01.
mediators using
b-hexosaminidase as a biomarker of degranulation
in the mast cells and then measured cytotoxicity. The release of
hexosaminidase was first measured following stimulation of the
IgE/Ag complex. Compounds 4a, 4b, 4c, 5a, 5b and 5c inhibited IgE/
b
-
bis(trimethylsilyl)-1,3,4-oxadiazoles (4aec). IC50 values of
compounds 5aec were 37.2 ꢀ 3.3, 62.3 ꢀ 2.3, and 75.5 ꢀ 4.1
mM,
respectively. In contrast, compound 4a weakly inhibited IgE/Ag-
Ag-induced b-hexosaminidase release in concentration-dependent
induced
b
m
-hexosaminidase release with an IC50 value of
M, whereas 4bec failed to inhibit half of IgE/Ag-induced
manner (Fig. 1). As shown in Fig. 1, compound 2-((bis(-
trimethylsilyl)-methylsulfonyl)methyl)-5-phenyl-1,3,4-oxadiazole
98.8 ꢀ 3.1
b-hexosaminidase release at a highest concentration of 100 mM.
(5a) showed much better inhibited IgE/Ag-induced
dase release at 50 M compared with the other compounds. But in
case of 100 M compounds 5aec showed much better inhibition
b-hexosamini-
Additionally, if the compounds have a toxic effect on cells, we
must distinguish such an effect from that of -hexosaminidase
m
b
m
release, which also reduces the viability of IgE/Ag-induced cells.
Therefore, we compared the cell cytotoxicity in RBL-2H3 cells
incubated with 4a, 4b, 4c, 5a, 5b and 5c compounds (0, 50 and
compared with the compounds 4aec. From these investigation,
compounds having sulfonyl moiety with bis(trimethylsilyl)-1,3,4-
oxadiazoles (5aec) unit exhibited good anti-allergic activity
compared with the compounds having sulphur moiety with
100 mM) for 24 h using the EZ-Cytox kit. As shown in Fig. 2, the RBL-
Scheme 1. Synthesis of 2-((bis(trimethylsilyl)methylthio/methylsulfonyl)methyl)-5-aryl-1,3,4-oxadiazoles.

86
D.R. Guda et al. / European Journal of Medicinal Chemistry 62 (2013) 84e88
analyzer. Mass spectra were recorded on a low-resolution (Agilent
Technologies GC/MS: 6890N, 5973N mass selective detector) EI
mass Spectrometer.
5.1.1. Synthesis of 2-(bis(trimethylsilyl)methylthio)acetic acid (2)
A solution of sodium hydroxide (30 mmol) in methanol (30 mL)
was taken in a 100 mL two-necked round-bottomed flask, fitted
with a reflux condenser, a dropping funnel and equipped over
a heating mantle. To this, mercaptoacetic acid (15 mmol) was added
slowly through the dropping funnel and followed bis(-
trimethylsilyl)chloromethane (15 mmol) was added portion-wise.
The contents of the flask were refluxed for 3e4 h, cooled and
poured into ice-cold water containing concentrated hydrochloric
acid. The resultant liquid was extracted with diethyl ether and
distilled to afford pure 2-(bis(trimethylsilyl)methylthio)acetic acid
(2.15 g, 86%); b.p. 143e145 ꢂC; IR (KBr): 3445 (OH), 1704 (C]O)
cmꢁ1; 1H NMR (CDCl3, 400 MHz):
SieCH), 3.11 (s, 2H, SeCH2), 10.20 (bs, 1H, OH) ppm; 13C NMR
(CDCl3, 100 MHz):
ꢁ1.01 (SieCH3), 16.04 (SieCH), 27.50 (SeCH2),
174.08 (C]O); 29Si NMR (CDCl3, 79 MHz):
2.96.
d 0.08 (s, 18H, SieCH3), 1.01 (s, 1H,
d
d
Fig. 2. Cytotoxicity of 4a, 4b, 4c, 5a, 5b and 5c compounds on RBL-2H3 cells. To assess
cytotoxicity, RBL-2H3 cells were incubated overnight in medium containing 200 ng/mL
of DNP-specific IgE, and then treated with 4a, 4b, 4c, 5a, 5b and 5c compounds at 0, 50
5.1.2. Synthesis of 2-(bis(trimethylsilyl)methylsulfonyl)acetic acid
(3)
To an ice-cold solution of 2-(bis(trimethylsilyl)methylthio)acetic
acid (2) (20 mmol) in 30 mL of glacial acetic acid in a 100 mL round-
bottomed flask, 30% hydrogen peroxide (12 mL) was added in
portions. The contents were allowed to attain laboratory temper-
ature and kept aside for 36 h. Then, acetic acid was removed under
reduced pressure. The residual portion was poured onto crushed
ice. The solid separated was filtered, dried and recrystallized from
water to get pure 2-(bis(trimethylsilyl)methylsulfonyl)acetic acid
(2.28 g, 81%); m.p. 71e73 ꢂC; IR (KBr): 3462 (OH), 1711 (C]O), 1308,
and 100 mM concentrations for 24 h. Cell viability was determined with the EZ-Cytox
kit from the absorbance at 450 nm. The results are expressed as the percentage of
surviving cells relative to compound-untreated control cells. The mean values (ꢀS.D.)
from three independent experiments are shown, where each was performed in trip-
licate. **P < 0.01.
2H3 cells were weakly affected following treatment with 5a, 5b and
5c at concentrations of 50 and 100
compound 5a does not cause cytotoxicity of cells only at 50
significantly inhibits -hexosaminidase release stimulated by IgE/
Ag at 50 M and 100 M. And also compounds 5b and 5c do not
cause cytotoxicity of cells at 50 M and 100 M, but significantly
inhibit -hexosaminidase release stimulated by IgE/Ag only at
100 M concentration.
mM. These results suggest that
mM, but
b
1133 (SO2) cmꢁ1; 1H NMR (CDCl3, 400 MHz):
2.21 (s, 1H, SieCH), 4.46 (s, 2H, SO2eCH2), 9.93 (bs, 1H, OH) ppm;
13C NMR (CDCl3, 100 MHz):
ꢁ0.61 (SieCH3), 40.02 (SieCH), 51.91
(SO2eCH2), 169.38 (C]O); 29Si NMR (CDCl3, 79 MHz):
2.04.
d 0.23 (s,18H, SieCH3),
m
m
m
m
d
b
d
m
5.1.3. General procedure for the synthesis of 2-((bis(trimethylsilyl)
methylthio)methyl)-5-aryl-1,3,4-oxadiazole (4aec)
4. Conclusion
A mixture of 2-(bis(trimethylsilyl)methylthio)acetic acid (2)
(10 mmol), benzohydrazides (10 mmol) and phosphorus oxy-
chloride (7 mL) was heated under reflux for 5e6 h. The excess POCl3
was removed under reduced pressure and the residue was poured
onto crushed ice. The resulting precipitate was filtered, washed
with saturated sodium bicarbonate solution and then with water,
dried and recrystallized from ethanol to obtain 4.
A
novel series of bis(trimethylsilyl)-1,3,4-oxadiazoles was
synthesized and investigated their anti-allergic activities in 50 and
100
sulfonyl moiety, bis(trimethylsilyl)-1,3,4-oxadiazoles (5aec)
showed much better inhibited IgE/Ag-induced -hexosaminidase
release at 50 and 100 M compared with the compounds having
sulphur moiety with bis(trimethylsilyl)-1,3,4-oxadiazoles (4aec).
Compound 5a showed the best anti-allergic activity at 100
concentration among 4aec and 5aec. However, in cytotoxicity
point of view, compound 5a could be the good candidate for anti-
allergy treatment at 50
mM concentrations. Among them the compounds having
b
m
mM
5.1.3.1. 2-((Bis(trimethylsilyl)methylthio)methyl)-5-phenyl-1,3,4-
oxadiazole (4a). Pale yellow solid (2.90 g, 83%); m.p. 81e83 ꢂC; IR
(KBr): 1608 (C]N) cmꢁ1; 1HNMR (CDCl3, 400 MHz):
d
0.01 (s,18H, Sie
CH3), 0.88 (s, 1H, SieCH), 3.80 (s, 2H, SeCH2) 7.48 (d, 3H, AreH), 8.02
(d, 2H, AreH) ppm; 13CNMR(CDCl3,100MHz):
mM, and 5b, 5c could also be the best
candidate for anti-allergy treatment at 100 mM concentration.
d
ꢁ0.64 (SieCH3),16.16
(SieCH), 28.83 (SeCH2), 163.69 (C-2), 165.48 (C-5), 123.72, 126.92,
5. Experimental section
129.05, 131.79 (aromatic carbons) ppm; 29Si NMR (CDCl3, 79 MHz):
d
3.02; MS m/z (relative intensity) 350 (Mþ ꢁ 15, 26.4), 231 (91.9), 163
5.1. Chemistry
(33.8),105 (32.3), 73 (100), 59 (14.7). Anal. Calcd for C16H26N2OSSi2: C,
54.81; H, 7.47; N, 7.99; Found: C, 54.74; H, 7.41; N, 8.03.
Melting points were determined in open capillaries on a Stuart
apparatus and were uncorrected. The purity of the compounds was
checked by TLC (silica gel H, BDH, ethyl acetate/hexane, 1:3). The IR
spectra were recorded on a Perkin Elmer Spectrum one FT-IR
Spectrometer as KBr pellets and the wave numbers were given in
cmꢁ1. The 1H NMR, 13C NMR and 29Si NMR spectra were recorded
on a Bruker AMX 400 NMR spectrometer in CDCl3. The micro-
analyses were performed using Perkin Elmer 240C elemental
5.1.3.2. 2-((Bis(trimethylsilyl)methylthio)methyl)-5-p-tolyl-1,3,4-
oxadiazole (4b). White solid (2.87 g, 79%); m.p. 89e91 ꢂC; IR (KBr):
1616 (C]N) cmꢁ1 1H NMR (CDCl3, 400 MHz):
; d 0.01 (s, 18H, Sie
CH3), 0.87 (s, 1H, SieCH), 2.40 (s, 3H, AreCH3), 3.79 (s, 2H, Se
CH2), 7.28 (d, J ¼ 8.0 Hz, 2H, AreH), 7.92 (d, 2H, J ¼ 8.0 Hz, AreH)
ppm; 13C NMR (CDCl3, 100 MHz):
CH), 21.64 (AreCH3), 28.84 (SeCH2), 163.39 (C-2), 165.64 (C-5),
d
ꢁ0.64 (SieCH3), 16.10 (Sie

D.R. Guda et al. / European Journal of Medicinal Chemistry 62 (2013) 84e88
87
120.96, 126.88, 129.76, 142.34 (aromatic carbons) ppm; 29Si NMR
5.2. Biological assays
5.2.1. Cell culture
Cells from the rat mast cell line RBL-2H3 were obtained from the
American Type Culture Collection (ATCC, Rockville, MD, USA) and
maintained in Eagle’s minimal essential medium (EMEM, Wel-
GENE, Inc., Daegu, Korea) supplemented with 10% heat-inactivated
(CDCl3, 79 MHz):
d
3.01; MS m/z (relative intensity) 364 (Mþ ꢁ 15,
17.6), 245 (48.5), 174 (17.6), 163 (16.9), 119 (30.1), 91 (26.4), 73 (100).
Anal. Calcd for C17H28N2OSSi2: C, 55.99; H, 7.74; N, 7.68; Found: C,
55.90; H, 7.81; N, 7.61.
5.1.3.3. 2-((Bis(trimethylsilyl)methylthio)methyl)-5-(4-chlorophenyl)-
1,3,4-oxadiazole (4c). White solid (3.22 g, 84%); m.p. 93e95 ꢂC; IR
foetal bovine serum and antibiotics (100 U/mL of penicillin, 100 mg/
(KBr): 1613 (C]N) cmꢁ1; 1H NMR (CDCl3, 400 MHz):
d
0.01 (s, 18H,
mL of streptomycin) in a humidified atmosphere of 5% CO2 and 95%
SieCH3), 0.85 (s, 1H, SieCH), 3.80 (s, 2H, SO2eCH2), 7.56 (d,
air at 37 ꢂC.
J ¼ 8.0 Hz, 2H, AreH), 7.96 (d, J ¼ 8.0 Hz, 2H, AreH) ppm; 13C NMR
(CDCl3, 100 MHz):
d
ꢁ0.66 (SieCH3), 16.21 (SieCH), 28.80 (SeCH2),
5.3.
b-Hexosaminidase release assay
163.88 (C-2), 164.69 (C-5), 122.15, 128.19, 129.48, 138.13 (aromatic
carbons) ppm; 29Si NMR (CDCl3, 79 MHz):
d 3.05. MS m/z (relative
As a marker of degranulation, we measured the release of
b
-
intensity) 384 (Mþ ꢁ 15, 4.4), 265 (15.4), 163 (11.7), 139 (27.2), 111
(13.2), 73 (100). Anal. Calcd for C16H25ClN2OSSi2: C, 49.91; H, 6.54; N,
7.27; Found: C, 49.82; H, 6.45; N, 7.31.
hexosaminidase [22]. Rat basophilic leukaemia (RBL)-2H3 cells
were distributed into 24-well plates (2 ꢃ 105 cells/well) and were
sensitized overnight with anti-dinitrophenylated (DNP)-specific
immunoglobulin (Ig) E at 200 ng/mL. The IgE-sensitized cells were
washed twice with piperazine-N,N0-bis[2-ethanesulfonic acid]
(PIPES) buffer (25 mM PIPES, pH 7.2, 110 mM NaCl, 4 mM KCl,
0.4 mM MgCl, 40 mM HCl, 5.6 mM glucose, a 1 mM CaCl2, and 0.1%
BSA), then treated for 30 min at 37 ꢂC with 4a, 4b, 4c, 5a, 5b and 5c
in PIPES buffer at the indicated concentrations. The cells were then
stimulated with dinitrophenylated human serum albumin (DNP-
HAS, 25 ng/mL) at 37 ꢂC for 15 min and chilled on ice to stop the
stimulation. To measure
from the IgE/Ag-stimulated cells in PIPES buffer and
minidase substrate (P-nitrophenyl-N-acetyl- -glucosaminide) in
0.1 M citrate buffer (pH 4.5) were mixed in 96-well plates and
incubated at 37 ꢂC for 1 h. This reaction was terminated by adding
0.1 M carbonate buffer (pH 10.5), and the absorbance at 405 nm was
measured using a microplate reader.
5.1.4. General procedure for the synthesis of 2-((bis(trimethylsilyl)
methylsulfonyl)methyl)-5-aryl-1,3,4-oxadiazole(5aec)
A
mixture of aryl acid hydrazide (10 mmol), 2-(bis(-
trimethylsilyl)methylsulfonyl)acetic acid (3) (10 mmol) and phos-
phorus oxychloride (7 mL) was heated under reflux for 5e6 h. The
excess POCl3 was removed under reduced pressure and the residue
was poured onto crushed ice. The resulting precipitate was filtered,
washed with saturated sodium bicarbonate solution and then with
water, dried and recrystallized from ethanol to obtain 5.
b
-hexosaminidase release, the supernatant
b
-hexosa-
b-D
5.1.4.1. 2-((Bis(trimethylsilyl)methylsulfonyl)methyl)-5-phenyl-1,3,4-
oxadiazole (5a). White solid (3.28 g, 86%); m.p. 97e99 ꢂC; IR (KBr):
1611 (C]N), 1328, 1161 (SO2) cmꢁ1 1H NMR (CDCl3, 400 MHz):
;
d
0.26 (s, 18H, SieCH3), 2.90 (s, 1H, SieCH), 4.56 (s, 2H, SO2eCH2)
7.50e7.62 (m, 5H, AreH) ppm; 13C NMR (CDCl3, 100 MHz):
ꢁ0.67 (SieCH3), 43.36 (SieCH), 53.44 (SO2eCH2), 157.96 (C-2),
166.45 (C-5), 123.14, 127.20, 129.18, 132.33 (aromatic carbons) ppm;
d
5.4. Cytotoxicity assay
29Si NMR (CDCl3, 79 MHz):
d 2.06; MS m/z (relative intensity) 382
RBL-2H3 cells were seeded at 2 ꢃ 104 cells per mL in 96-well
(Mþ, 13.3), 238 (9.6), 159 (62.2), 105 (100), 77 (53.3), 63 (9.6), 51
(9.6). Anal. Calcd for C16H26N2O3SSi2: C, 50.22; H, 6.85; N, 7.32;
Found: C, 50.21; H, 6.91; N, 7.24.
plates and incubated with 4a, 4b, 4c, 5a, 5b and 5c at 50 or 100 mM
concentrations for 23 h at 37 ꢂC. After incubation, cells were
exposed to 10% of the volume of an EZ-Cytox kit (Daeil Lab Service
Co., Ltd., Seoul, Korea) for 1 h at 37 ꢂC. Cytotoxicity was measured
using a microplate reader with absorbance at 450 nm. The results
are expressed as the percentage of surviving cells relative to
compound-untreated control cells.
5.1.4.2. 2-((Bis(trimethylsilyl)methylsulfonyl)methyl)-5-p-tolyl-1,3,4-
oxadiazole (5b). White solid (3.20 g, 81%); m.p. 103e105 ꢂC; IR
(KBr): 1617 (C]N), 1311, 1158 (SO2) cmꢁ1
;
1H NMR (CDCl3,
400 MHz):
d 0.25 (s, 18H, SieCH3), 2.41 (s, 3H, AreCH3), 2.90 (s, H,
SieCH), 4.55 (s, 2H, SO2eCH2), 7.30 (d, J ¼ 8.0 Hz, 2H, AreH), 7.94 (d,
J ¼ 8.0 Hz, 2H, AreH) ppm; 13C NMR (CDCl3, 100 MHz):
ꢁ0.61 (Sie
d
5.5. Statistical analysis
CH3), 21.31 (AreCH3), 41.83 (SieCH), 52.03 (SO2eCH2), 157.11 (C-2),
164.21 (C-5), 122.40, 125.01, 128.81, 131.40 (aromatic carbons) ppm;
Experimental results are expressed as means ꢀ standard devi-
ations. One-way analysis of variance (ANOVA) was followed by
Dunnett’s test for multiple comparisons. P-values less than 0.05 or
less than 0.01 were considered statistically significant, as indicated.
29Si NMR (CDCl3, 79 MHz):
d 2.03; MS m/z (relative intensity) 396
(Mþ, 29.6), 245 (14.0), 173 (50.7), 119 (100), 91 (15.6), 73 (37.5), 59
(14.0). Anal. Calcd for C17H28N2O3SSi2: C, 51.48; H, 7.12; N, 7.06;
Found: C, 51.41; H, 7.21; N, 7.01.
Acknowledgements
5.1.4.3. 2-((Bis(trimethylsilyl)methylsulfonyl)methyl)-5-(4-
chlorophenyl)-1,3,4-oxadiazole (5c). White solid (3.66 g, 88%); m.p.
111e113 ꢂC; IR (KBr): 1619 (C]N), 1324, 1143 (SO2) cmꢁ1; 1H NMR
This research was supported by Basic Science Research Program
through the National Research Foundation of Korea (NRF) funded
by the Ministry of Education, Science and Technology (2010-
0024877). G. D. Reddy also thanks BK-21 funds for the financial
support of his post-doc position.
(CDCl3, 400 MHz):
(s, 2H, SO2eCH2) 7.50 (d, J ¼ 8.0 Hz, 2H, AreH), 8.01 (d, J ¼ 8.0 Hz,
2H, AreH) ppm; 13C NMR (CDCl3, 100 MHz):
d 0.26 (s, 18H, SieCH3), 2.86 (s, 1H, SieCH), 4.58
d
ꢁ0.68 (SieCH3),
40.51 (SieCH), 51.17 (SO2eCH2), 157.32 (C-2), 165.81 (C-5), 121.44,
128.47, 129.66, 138.89 (aromatic carbons) ppm; 29Si NMR (CDCl3,
79 MHz):
d
2.09; MS m/z (relative intensity) 416 (Mþ, 25.0), 267
Appendix A. Supplementary data
(65.8), 163 (34.1), 105 (32.9), 91 (12.1), 73 (100). Anal. Calcd for
C16H25ClN2O3SSi2: C, 46.08; H, 6.04; N, 6.72; Found: C, 45.98; H,
6.12; N, 6.68.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.ejmech.2012.12.035.

88
D.R. Guda et al. / European Journal of Medicinal Chemistry 62 (2013) 84e88
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