Synthesis of some novel 3-(1-(1-substitutedpiperidin-4-yl)-1H-1,2,3- triazol-4-yl)-5-substituted phenyl-1,2,4-oxadiazoles as antifungal agents

Article abstract of DOI:10.1016/j.ejmech.2011.01.015

A novel series of 3-(1-(1-substituted piperidin-4-yl)-1H-1,2,3-triazol-4- yl)-5-substituted phenyl-1,2,4-oxadiazoles bearing 1,2,3-triazole and piperidine ring has been synthesized in one step from amidoxime using Carbonyl diimidazole (CDI) and K₂CO₃. All the synthesized compounds (4a-4r) are novel and evaluated for their in vitro antifungal activities. SAR for the series has been developed by comparing their MIC values with miconazole and fluconazole. Some of the compounds from the series like 4j was equipotent with miconazole against Cryptococcus neoformans whereas activities of compound 4m against Aspergillus niger and Aspergillus flavus were comparable to miconazole. Also compound 4r shows activity comparable to miconazole against Candida albicans, A. niger and A. flavus.

Full text of DOI:10.1016/j.ejmech.2011.01.015

European Journal of Medicinal Chemistry 46 (2011) 1040e1044
Contents lists available at ScienceDirect
European Journal of Medicinal Chemistry
journal homepage: http://www.elsevier.com/locate/ejmech
Original article
Synthesis of some novel 3-(1-(1-substitutedpiperidin-4-yl)-1H-1,2,3-triazol-4-yl)-
5-substituted phenyl-1,2,4-oxadiazoles as antifungal agents
*
Jaiprakash N. Sangshetti, Devanand B. Shinde
Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431004 (MS), India
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel series of 3-(1-(1-substituted piperidin-4-yl)-1H-1,2,3-triazol-4-yl)-5-substituted phenyl-1,2,
4-oxadiazoles bearing 1,2,3-triazole and piperidine ring has been synthesized in one step from ami-
doxime using Carbonyl diimidazole (CDI) and K2CO3. All the synthesized compounds (4ae4r) are novel
and evaluated for their in vitro antifungal activities. SAR for the series has been developed by comparing
their MIC values with miconazole and fluconazole. Some of the compounds from the series like 4j was
equipotent with miconazole against Cryptococcus neoformans whereas activities of compound 4m against
Aspergillus niger and Aspergillus flavus were comparable to miconazole. Also compound 4r shows activity
comparable to miconazole against Candida albicans, A. niger and A. flavus.
Received 20 April 2010
Received in revised form
5 January 2011
Accepted 12 January 2011
Available online 20 January 2011
Keywords:
Amidoxime
1,2,4-Oxadiazole
1,2,3-Triazole
Piperidine
Ó 2011 Elsevier Masson SAS. All rights reserved.
Antifungal activity
MIC values
SAR
1. Introduction
heterocycles [17], here we wish to report synthesis and anti-
fungal activity of novel series of 3-(1-(1-substituted piperidin-4-
1,2,3-Triazole and its derivatives are important heterocycles
with different activities like potent antineoplastic [1], antimicrobial
[2e4], analgesic [5], anti-inflammatory, local anesthetic [6], anti-
convulsant [7], antimalarial [8] and anti HIV agents [9]. Some 1,2,
3-triazole derivatives were used as DNA cleaving agents [10],
potassium channel activators [11], cannabinoid CB1 receptor
antagonists [12] and antitubercular agents [13].
yl)-1H-1,2,3-triazol-4-yl)-5-substituted phenyl-1,2,4-oxadiazoles
from amidoxime and substituted benzoic acid using CDI, K2CO3/
DMF. From the data of activity, SAR for the series has been
developed.
2. Chemistry
1,2,4-Oxadiazole and its derivatives are important pharma-
cophore with diversified pharmacological activities like anti-
bacterial, analgesic and anti-inflammatory [14]. Especially 3, 5
disubstituted oxadiazole have gained much attention due to its
biological potential. Recently 3,5 disubstituted oxadiazole has
The starting substituted amidoxime compounds 2ae2r were
synthesized from the commercially available starting material
N-Boc piperidone as described in our previous report [17d]. The
amidoxime compound thus prepared on reaction with substituted
benzoic acid and CDI (2 equivalents) using 2 equivalents K2CO3 in
DMF at 110 ꢀC gave the target compounds Scheme 1 and 2.
Optimization of the reaction was carried out considering
synthesis of 4a.
From the study it is observed that use of 2 equivalent K2CO3 is
more advantageous giving 93% yield in 4 h. The synthetic procedure
was extended for synthesis of all the compounds 4ae4r using
different substituted benzoic acid. Results are summarized in
Table 1. The yields were obtained in the range of 89e93%. All
synthesized derivatives were characterized using mass and 1H
NMR. 1H NMR spectra were recorded on a 400 MHz Varian-Gemini
spectrometer and are reported as parts per million (ppm)
been reported as a
b amyloid-imaging probe, which plays an
important role in Alzheimer’s drug discovery [15]. 3,5 disubsti-
tuted oxadiazole are generally prepared from amidoximes and
acid compound using base [16]. However, some of these
methods suffer from one or more drawbacks like harsh reaction
conditions, and low yields. Considering biological significance of
1,2,3-triazole and 1,2,4-oxadiazole and in continuation of our
work on synthesis of some pharmacologically important
* Corresponding author. Tel.: þ91 240 2403307; fax: þ91 240 2400413.
E-mail address: dbshinde.2007@rediffmail.com (D.B. Shinde).
0223-5234/$ e see front matter Ó 2011 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.ejmech.2011.01.015

J.N. Sangshetti, D.B. Shinde / European Journal of Medicinal Chemistry 46 (2011) 1040e1044
1041
OSO2CH3
OH
N3
O
N
c
a
b
N
N
N
Boc
Boc
Boc
Boc
1
d
OH
OH
O
N
N
O
CN
NH2
NH2
N
N
N
N
N
N
N
N
N
N
N
N
N
N
e
f
g
h
N
N
R
Boc
Boc
Boc
2a-2r
Scheme 1. Synthesis of amidoxime compounds (2ae2r) from N-Boc piperidone. (a) NaBH4, ethanol, rt, 2 h; (b) Methanesulfonyl chloride, triethylamine, dichloromethane; (c) NaN3,
DMF, 80 ꢀC, 8 h; (d) Ethyl Propiolate, CuI, acetonitrile, rt, 12 h; (e) ammonia, ethanol, rt, 12 h; (f) TFAA, dichloromethane, rt, 2 h; (g) Hydroxylamine hydrochloride, sodium
bicarbonate, methanol, reflux, 14 h (h) TFA, dichloromethane, rt, 14 h; triethylamine, R-X or RCOX, tetrahydrofuran, 0e5 ꢀC to rt, 2 h.
downfield from
spectra were taken with Micromass - QUATTRO-II of WATER mass
spectrometer.
a
tetramethylsilane internal standard. Mass
using standard agar method [18]. Miconazole and fluconazole were
used as a standard for the comparison of antifungal activity. MIC
values of the tested compounds are presented in Table 2.
3. Antifungal activity
4. Results and discussion
All the synthesized novel compounds were screened for in vitro
antifungal activity. The antifungal activity was evaluated against
different fungal strains such as Candida albicans, Fusarium oxy-
sporum, Aspergillus flavus, Aspergillus niger, Cryptococcus neoformans.
Minimum inhibitory concentration (MIC) values were determined
Many of the newly synthesized compounds were found to show
good antifungal activity. From the antifungal activity data (Table 2),
it was observed that compound 4j, 4m and 4r are the most active
compounds. N-protected compound 4a shows very less antifungal
activity comparable to miconazole and fluconazole. Deprotected
OH
N
O
R1
N
N
NH2
N
N
N
N
N
N
N
COOH
CDI
+
DMF/K2CO3
N
R1
R
R
3
2a-2r
4a- 4r
Scheme 2. Synthesis of 3-(1-(1-substituted piperidin-4-yl)-1H-1,2,3-triazol-4-yl)-5-substituted phenyl-1,2,4-oxadiazoles (4a-4r) from amidoximes (2ae2r).

1042
J.N. Sangshetti, D.B. Shinde / European Journal of Medicinal Chemistry 46 (2011) 1040e1044
Table 1
C. neoformans where as it is reduced against C. albicans, F. oxy-
sporum and A. flavus. Introduction of acetyl group on nitrogen 4e
enhances the antifungal against C. albicans, F. oxysporum compared
to 4d. There was further decrease in antifungal activity if acetyl
group was replaced by propionyl 4f and butyryl 4g against C.
albicans, F. oxysporum and A. flavus. Introduction of benzoyl group
on nitrogen 4h doesn’t affect the activity compared with butyryl
substituents against C. albicans whereas there is net reduction in
activity against F. oxysporum, A. flavus and A. niger. Introduction of
Cl group on 4 position of benzoyl 4i increases the antifungal activity
compared with unsubstituted analog against all tested organisms.
Introduction of mesyl group on piperidine nitrogen 4j shows
increase in activity against all tested organisms compared with
unsubstituted nitrogen. Compound 4j was equipotent with mico-
nazole against C. neoformans. Replacement of mesyl group by tosyl
group 4k reduces the antifungal activity against all tested organ-
isms except A. Niger. Introduction of Cl on 5-phenyl of 1,2,4-oxa-
diazole ring shows enhancement of antifungal activity compared
with unsubstituted phenyl (4me4r). Among the Cl substituted
derivatives compound 4m with methyl group on piperidine
nitrogen and 4r with methylsulfonyl group on piperidine nitrogen
shows significant rise in activity compared with its unsubstituted
analogs.
Experimental data of the synthesized compounds 4ae4r.
Entry
R
R1
Time Yield % Molecular formula/Molecular
in hrs
Weight
4a
4b
4c
4d
4e
4f
eBoc
eH
eH
eH
-H
4
93
90
92
90
93
89
89
90
92
93
90
89
92
92
93
90
90
92
C20H24N6O3
396
C15H16N6O
296
C16H18N6O
310
C17H20N6O
324
C17H18N6O2
338
C18H20N6O2
352
C19H22N6O2
366
C22H20N6O2
400
C22H29 Cl N6O2
434
C16H18N6O3S
374
C22H22N6O3S
450
C22H22N6O
386
C16H17 Cl N6O
344
C17H19 Cl N6O
358
C17H17 Cl N6O2
372
C18H19 Cl N6O2
386
eH
4
eCH3
4
-CH2CH3
eCOCH3
eCOCH2CH3
eCOC3H7
eCOC6H5
4.5
4
eH
eH
eH
eH
4
4g
4h
4i
4.5
4.5
4.5
4
eCOC6H4, 4 Cl eH
eSO2CH3 eH
eSO2C6H4CH3 eH
4j
4k
4l
4.5
4.5
4
eCH2C6H5
eCH3
eH
4m
4n
4o
4p
4q
4r
e4Cl
5. Conclusion
eCH2CH3
eCOCH3
eCOCH2CH3
eCOC6H5
eSO2CH3
e4Cl 4.5
e4Cl
In conclusion, synthesis and antifungal activity of a novel series
of 3-(1-(1-substituted piperidin-4-yl)-1H-1,2,3-triazol-4-yl)-5-
substituted phenyl-1,2,4-oxadiazoles has been presented. Use of
K2CO3 with DMF helps in fast conversion of amidoxime to
5-phenyl-1,2,4-oxadiazoles proving its advantage. Newly synthe-
sized compounds were evaluated for antifungal activity. Based on
the activity data, SAR for the series has been developed. From
activity it is observed that compound 4j was equipotent with
miconazole against C. Neoformans whereas compound 4m and 4r
shows antifungal activity comparable to miconazole against C.
albicans, A. flavus and A. niger. Thus suggesting that the compound
from the present series with methyl or methylsulfonyl group on
piperidine nitrogen and 4 Cl substitution on phenyl at 5 position of
1,2,4-oxadiazole can serve as important gateway for the design and
4
e4Cl 4.5
e4Cl 4.5
C22H19 Cl N6O2
434
C16H19 Cl N6O3S
409
e4Cl
4
compound 4b shows considerable rise in activity compared to 4a.
Substitution of methyl group 4c on piperidine nitrogen increases
the antifungal activity compared with unsubstituted nitrogen 4b
against C. albicans, F. oxysporum and A. flavus. Substitution of ethyl
group 4d on nitrogen enhances activity against A. niger and
Table 2
Antifungal activity of the synthesized compounds.
Entry
R
R1
MIC Values in m
g/mLa
C. Albicans
F. Oxysporum
A. Flavus
A. Niger
C. Neoformans
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
eBoc
eH
eCH3
eH
eH
eH
eH
eH
eH
eH
eH
eH
eH
eH
eH
e4Cl
e4Cl
e4Cl
e4Cl
e4Cl
e4Cl
80
60
50
90
35
50
90
90
45
50
60
50
35
70
40
35
75
30
25
5
*
85
50
30
35
*
100
100
*
120
90
*
100
60
100
35
60
100
*
eCH2CH3
eCOCH3
eCOCH2CH3
eCOC3H7
eCOC6H5
eCOC6H4, 4 Cl
eSO2CH3
eSO2C6H4CH3
eCH2C6H5
eCH3
eCH2CH3
eCOCH3
eCOCH2CH3
eCOC6H5
eSO2CH3
47.5
95
150
*
30
35
65
40
40
45
50
15
35
150
30
65
15
12.5
5
*
*
47.5
*
150
100
45
25
40
70
*
40
30
70
65
50
80
30
40
85
35
25
5
42.5
40
37.5
150
15
40
70
100
*
100
*
*
4q
4r
100
40
25
5
15
12.5
10
Miconazole
Fluconazole
* - No activity was observed up to 200
Values are the average of three readings.
m
g/mL.
a

J.N. Sangshetti, D.B. Shinde / European Journal of Medicinal Chemistry 46 (2011) 1040e1044
1043
development of new antifungal agent with potent activity and
minimal toxicity.
13C NMR (CDCl3)
d
¼ 20.4, 27.7, 44.2, 60.8, 124.9, 127.5, 128.6,
129.6, 130.6, 131.1, 164.1, 173.2, 176.0
MS: m/z ¼ 339 [M þ H]þ.
6. Experimental
6.1.6. 1-(4-(4-(5-Phenyl-1,2,4-oxadiazol-3-yl)-1H-1,2,3-triazol-1-
yl)piperidin-1-yl)propan-1-one (4f)
6.1. Typical experimental procedure
Yellowish solid. Melting Point-145e146 ꢀC.
1H NMR (400 MHz, CDCl3):
d
¼ 7.42e7.74 (m, 5H), 7.30 (s,
To a stirred solution of amidoxime 2ae2r (10 mmol) in 15 mL
dimethyl formamide (1:2) were added substituted benzoic acid 3
(10 mmol), CDI (20 mmol) and K2CO3 (20 mmol). The reaction
mixture was heated at 110 ꢀC for 4e4.5 h. After completion
(Monitored by TLC), distilled water was added to the mixture and
then extracted with 3 portions of dichloromethane. The combined
organic layers were washed with 1 N HCl and sat. NaHCO3. The
DCM layer on drying (Na2SO4) and concentrating in vacuo gave the
desired compounds 4ae4r.
1H), 4.90e4.81 (m, 1H), 4.40e4.44 (q, 2H), 4.24e4.29 (m, 2H),
2.98e2.84 (m, 2H), 2.23e2.18 (m, 2H), 1.88e2.12 (m, 2H),
1.48e1.44(t, 3H).
13C NMR (CDCl3)
d
¼ 11.4, 25.8, 27.6, 44.0, 60.8, 124.5, 128.6,
129.2, 130.2, 130.9, 131.7, 164.8, 173.0, 176.0
MS: m/z ¼ 353 [M þ H]þ.
6.1.7. 1-(4-(4-(5-Phenyl-1,2,4-oxadiazol-3-yl)-1H-1,2,3-triazol-1-
yl)piperidin-1-yl)butan-1-one (4g)
Brown solid. Melting Point-178e179 ꢀC.
6.1.1. Tert-butyl 4-(4-(5-phenyl-1,2,4-oxadiazol-3-yl)-1H-1,2,3-
triazol-1-yl)piperidine-1-carboxylate (4a)
1H NMR (400 MHz, CDCl3): 7. 75e7.40 (m, 5H), 7.31 (s, 1H),
4.81e4.76 (m, 1H), 4.11e3.92 (m, 2H), 2.91e2.83 (t, 2H), 2.41e2.35
(m, 2H), 2.11e2.05 (m, 2H), 1.86e1.80 (m, 2H), 1.45e1. 40 (m, 2H), 1.
20e1. 00 (t, 3H)
Off white solid. Melting Point-201e202 ꢀC.
1H NMR (400 MHz, CDCl3):
d
¼ 7.65e7.45 (m, 5H), 7.35 (s, 1H),
4.90e4.81 (m, 1H), 4.28e4.24 (m, 2H), 2.96e2.85 (m, 2H),
2.24e2.17 (m, 2H), 2.12e1.89 (m, 2H), 1.44 (s, 9H)
13C NMR (CDCl3)
d
¼ 12.6, 22.2, 27.0, 36.5, 44.2, 62.1, 124.2, 128.2,
129.0, 130.1, 130.9, 131.9, 164.6, 173.2, 176.1
13C NMR (CDCl3)
d
¼ 26.9, 28.6, 45.2, 60.5, 80.2, 125.3, 128.0,
MS: m/z ¼ 367 [M þ H]þ.
130.4, 131.2, 158.3, 165.5, 176.0
MS: m/z ¼ 397 [M þ H]þ.
6.1.8. Phenyl(4-(4-(5-phenyl-1,2,4-oxadiazol-3-yl)-1H-1,2,3-
triazol-1-yl)piperidin-1-yl)methanone (4h)
6.1.2. 5-Phenyl-3-(1-(piperidin-4-yl)-1H-1,2,3-triazol-4-yl)-1,2,4-
oxadiazole (4b)
Off white solid. Melting Point-209e211 ꢀC.
1H NMR (400 MHz, CDCl3):
d
¼ 7.88e7.38 (m, 10H), 7.30 (s, 1H),
Dark brown colored semisolid.
4.82e4.70(m, 1H), 4.10e4.02 (m, 2H), 2.95e2.85 (m, 2H), 2.17e2.10
(m, 2H), 1.85e1.81 (m, 2H)
1H NMR (400 MHz, CDCl3):
d
¼ 7. 76e7. 40 (m, 5H), 7.35 (s, 1H),
4.87e4.81 (m, 1H), 4. 32e4. 27 (m, 2H), 2.98e2.86 (m, 2H), 2. 66e2.
31 (m, 2H), 2.10e2.02 (m, 1H), 1.97e1.78 (m, 2H)
13C NMR (CDCl3)
d
¼ 27.0, 44.0, 61.6, 125.0, 128.0, 129.3, 130.4,
130.9, 132.0, 135.0, 164.6, 172.4, 175.3
13C NMR (CDCl3)
d
¼ 29.2, 44.8, 60.4, 125.3, 128.5, 129.1, 130.7,
MS: m/z ¼ 401 [M þ H]þ.
131.4, 158.3, 164.9, 175.2
MS: m/z ¼ 297[M þ H]þ.
6.1.9. (4-Chlorophenyl)(4-(4-(5-phenyl-1,2,4-oxadiazol-3-yl)-1H-
1,2,3-triazol-1-yl)piperidin-1-yl)methanone (4i)
Yellowish solid. Melting Point-174e175 ꢀC.
6.1.3. 3-(1-(1-Methylpiperidin-4-yl)-1H-1,2,3-triazol-4-yl)-5-
phenyl-1,2,4-oxadiazole (4c)
1H NMR (400 MHz, CDCl3):
d
¼ 7.8e7.3 (m, 9H), 7.27 (s, 1H),
Yellow solid. Melting Point-211e212 ꢀC.
4.80e4.70(m, 1H), 4.10e4.00 (m, 2H), 2.90e2.85 (m, 2H), 2.10e2.05
(m, 2H), 1.84e1.80 (m, 2H)
1H NMR (400 MHz, CDCl3):
d
¼ 7. 72e7. 40 (m, 5H), 7.32 (s, 1H),
4.88e4.81 (m, 1H), 4.32e4.28 (m, 2H), 3.24 (s, 3H), 2.92e2.86 (m,
2H), 2. 65e2.30 (m, 2H), 2.10e1.88 (m, 2H)
13C NMR (CDCl3)
d
¼ 27.1, 44.1, 61.6, 125.0, 128.2, 129.5, 130.4,
130.9, 132.1, 135.0, 164.5, 172.5, 175.4
13C NMR (CDCl3)
d
¼ 28.0, 45.2, 55.05, 59.9, 125.0, 128.2, 129.3,
MS: m/z ¼ 435 [M þ H]þ.
130.7, 131.2, 158.3, 164.5, 175.0
MS: m/z ¼ 311 [M þ H]þ.
6.1.10. 3-(1-(1-(Methylsulfonyl)piperidin-4-yl)-1H-1,2,3-triazol-4-
yl)-5-phenyl-1,2,4-oxadiazole (4j)
6.1.4. 3-(1-(1-Ethylpiperidin-4-yl)-1H-1,2,3-triazol-4-yl)-5-phenyl-
1,2,4-oxadiazole (4d)
Off white solid. Melting Point-201e202 ꢀC.
1H NMR (400 MHz, CDCl3):
d
¼ 7 70e7. 40 (m, 5H), 7.30 (s, 1H),
Yellow solid. Melting Point-189e190 ꢀC
4.87e4.80 (m, 1H), 4.32e4.28 (m, 2H), 3.24 (s, 3H), 2.90e2.86 (m,
2H), 2.67e2. 30 (m, 2H), 2.09e1.85 (m, 2H)
13C NMR (CDCl3) 28.0, 43.2, 51.0, 60.0, 125.5, 128.1, 129.3, 130.5,
131.0, 160.0, 164.5, 175.0.
1H NMR (400 MHz, CDCl3):
d
¼ 7.72e7.40 (m, 5H), 7.35 (s, 1H),
4.90e4.81 (m, 1H), 4.455e4. 38 (q, 2H), 4.30e4.24 (m, 2H),
2.98e2.84 (m, 2H), 2.22e2.18 (m, 2H), 2.12e1.90 (m, 2H), 1.44e1.40
(t, 3H)
MS: m/z ¼ 375 [M þ H]þ.
13C NMR (CDCl3)
d
¼ 14.3, 28.2, 51.2, 53.6, 61.1,124.8,127.8,128.9,
130.2, 131.0, 163.6, 174.6
6.1.11. 5-Phenyl-3-(1-(1-tosylpiperidin-4-yl)-1H-1,2,3-triazol-4-
yl)-1,2,4-oxadiazole (4k)
MS: m/z ¼ 325 [M þ H]þ.
White solid. Melting Point-218e219 ꢀC.
6.1.5. 1-(4-(4-(5-Phenyl-1,2,4-oxadiazol-3-yl)-1H-1,2,3-triazol-1-
yl)piperidin-1-yl)ethanone (4e)
1H NMR (400 MHz, CDCl3):
d
¼ 7.72e7.30(m, 9H), 7.20 (s, 1H),
4.80e4.70 (m,1H), 4.09e4.02 (m, 2H), 3.20 (s, 3H), 2.90e2.85 (m,
2H), 2.07e2.04 (m, 2H), 1.85e1.82 (m, 2H)
Brown solid. Melting Point-198e200 ꢀC.
1H NMR (400 MHz, CDCl3):
d
¼ 7. 80e7. 30 (m, 5H), 7.28 (s, 1H),
13C NMR (CDCl3)
d
¼ 22.0, 27.2, 45.0, 61.5, 125.0, 128.1, 129.3,
4.92e4.80 (m, 1H), 4.32e4.29 (m, 2H), 3.32 (s, 3H), 2.90e2.88 (m,
2H), 2. 64e2. 30 (m, 2H), 2.10e1.86 (m, 2H)
130.5, 131.0, 131.9, 138.3, 147.7, 165.0, 173.2.
MS: m/z ¼ 451[M þ H]þ

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J.N. Sangshetti, D.B. Shinde / European Journal of Medicinal Chemistry 46 (2011) 1040e1044
6.1.12. 3-(1-(1-Benzylpiperidin-4-yl)-1H-1,2,3-triazol-4-yl)-5-
phenyl-1,2,4-oxadiazole (4l)
13C NMR (CDCl3)
d
¼ 27.2, 44.2, 61.4, 124.8, 128.1, 129.3, 130.2,
131.0, 132.1, 134.1,135.0, 164.4, 172.4, 175.2
Yellowish white solid. Melting Point-221e222 ꢀC.
MS: m/z ¼ 435 [M þ H]þ.
1H NMR (400 MHz, CDCl3):
d
¼ 7.9e7.4 (m, 10H), 7.32 (s, 1H),
4.80e4.70(m, 1H), 4.09e4.02 (m, 2H), 3.22 (s, 2H), 2.90e2.85 (m,
2H), 2.07e2.04 (m, 2H), 1.85e1.82 (m, 2H)
6.1.18. 5-(4-Chlorophenyl)-3-(1-(1-(methylsulfonyl)piperidin-4-yl)-
1H-1,2,3-triazol-4-yl)-1,2,4-oxadiazole (4r)
13C NMR (CDCl3)
d
¼ 27.2, 50.1, 61.6, 66.2, 124.5, 127.6, 128.1,
Off white solid. Melting Point-201e203 ꢀC
128.9, 129.6, 130.5, 131.0, 138.3, 147.0, 164.5, 174.7.
1H NMR (400 MHz, CDCl3):
d
¼ 7. 77e7. 45 (m, 4H), 7.32 (s, 1H),
MS: 387 [M þ H]þ.
4.79e4.68 (m, 1H), 4.34e4.29(m, 2H), 3.24 (s, 3H), 2.90e2.86 (m,
2H), 2.64e2.32 (m, 2H), 2.09e1.84 (m, 2H)
13C NMR (CDCl3) 27.0, 41.5, 49.0, 61.0, 125.5, 128.2, 129.1, 130.0,
130.8, 135.1, 164.1, 176.0.
6.1.13. 5-(4-Chlorophenyl)-3-(1-(1-methylpiperidin-4-yl)-1H-1,2,3-
triazol-4-yl)-1,2,4-oxadiazole (4m)
MS: m/z ¼ 410 [M þ H]þ.
Yellowish solid. Melting Point-224e226 ꢀC.
1H NMR (400 MHz, CDCl3):
d
¼ 7.86e7.44 (m, 4H), 7.21 (s, 1H),
Acknowledgment
4.86e4.80 (m, 1H), 3.84e3.63 (m, 2H), 3.37e3.22 (m, 2H), 3.02 (s,
3H), 2.00e1.89 (m, 2H) 1.84e1.78 (m, 2H).
13C NMR (CDCl3)
d
¼ 27.0, 47.4, 56.2, 61.5, 124.1, 128.1, 129.0,
The authors are thankful to Council for Scientific and Industrial
Research (CSIR), New Delhi for financial assistance. The authors are
thankful to Principal, Maharashtra Institute of Pharmacy Pune for
providing the facility for in vitro antifungal activity. The authors are
also thankful to the Head, Department of Chemical Technology,
Dr. Babasaheb Ambedkar Marathwada University, Aurangabad-
431004 (MS), India for providing the laboratory facility.
130.4, 131.2, 135.0, 164.1, 175.3
MS: m/z ¼ 345 [M þ H]þ.
6.1.14. 5-(4-Chlorophenyl)-3-(1-(1-ethylpiperidin-4-yl)-1H-1,2,3-
triazol-4-yl)-1,2,4-oxadiazole(4n)
White solid. Melting Point-267e269 ꢀC.
1H NMR (400 MHz, CDCl3):
d
¼ 7.75e7.42 (m, 4H), 7.35 (s, 1H),
References
4.89e4.80 (m, 1H), 4.45e4. 38 (q, 2H), 4.28e4.24 (m, 2H),
3.00e2.92 (m, 2H), 2.22e2.18 (m, 2H), 2.12e1.90 (m, 2H), 1.43e1.40
(t, 3H).
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Farmaco 5 (2004) 397e404.
13C NMR (CDCl3)
d
¼ 14.0, 28.0, 50.2, 53.5, 61.0, 124.8, 127.7,
128.9, 130.0, 131.1,134.5, 163.0, 174.5
MS : m/z ¼ 359 [M þ H]þ.
6.1.15. 1-(4-(4-(5-(4-Chlorophenyl)-1,2,4-oxadiazol-3-yl)-1H-1,2,3-
triazol-1-yl)piperidin-1-yl)ethanone (4o)
Yellow solid. Melting Point-233e234 ꢀC.
1H NMR (400 MHz, CDCl3):
d
¼ 7.79e7.30 (m, 4H), 7.28 (s, 1H),
4.90e4.81 (m, 1H), 4.30e4.26 (m, 2H), 3.30(s, 3H), 2.90e2.87 (m,
2H), 2.65e2.35 (m, 2H), 2.10e1.86 (m, 2H)
13C NMR (CDCl3)
d
¼ 20.8, 27.5, 43.0, 60.8, 123.5, 127.5, 128.4,
129.5, 130.6, 133.2, 165.1, 174.3, 177.0
MS: m/z ¼ 373 [M þ H]þ.
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6.1.16. 1-(4-(4-(5-(4-Chlorophenyl)-1,2,4-oxadiazol-3-yl)-1H-1,2,3-
triazol-1-yl)piperidin-1-yl)propan-1-one (4p)
Yellowish solid. Melting Point-198e200 ꢀC.
1H NMR (400 MHz, CDCl3):
d
¼ 7.74e7.42 (m, 5H), 7.30 (s, 1H),
b) L.B. Clapp, in: A.R. Katritzky, C.W. Rees (Eds.), Comprehensive Heterocyclic
Chemistry, vol. 6, Pergamon, Oxford, 1984, pp. 365e391;
c) S.J. De Melo, A.D. Sobral, H.L. Lopes, R.M. Srivastava, J. Braz. Chem. Soc.
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4.90e4.81 (m,1H), 4.40e4.44 (q, 2H), 4.24e4.29 (m, 2H), 2.98e2.84
(m, 2H), 2.23e2.18 (m, 2H), 1.88e2.12 (m, 2H), 1.48e1.44(t, 3H).
13C NMR (CDCl3)
d
¼ 11.2, 26.0, 27.2, 44.3, 60.6, 123.7, 128.6,
[15] M. Ono, M. Haratake, H. Saji, M. Nakayama, Bioorg. Med. Chem. 16 (2008)
6867e6872.
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D.C. Pevear, F.J. Dutko, J. Med. Chem. 37 (1994) 2421e2436.
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40 (2005) 1325e1330;
129.2, 130.2, 130.9,134.1, 164.0, 173.9, 176.1
MS: m/z 387 [M þ H]þ.
6.1.17. (4-(4-(5-(4-Chlorophenyl)-1,2,4-oxadiazol-3-yl)-1H-1,2,3-
triazol-1-yl)piperidin-1-yl)(phenyl)methanone (4q)
Yellow solid. Melting Point-223e224 ꢀC.
b) N.D. Kokare, J.N. Sangshetti, D.B. Shinde, Synthesis 18 (2007) 2829e2834;
c) J.N. Sangshetti, N.D. Kokare, D.B. Shinde, J. Heterocycl. Chem. 45 (2008)
1191e1194;
d) J.N. Sangshetti, R.R. Nagawade, D.B. Shinde, Bioorg. & Med. Chem. Lett. 19
(2009) 3564e3567.
1H NMR (400 MHz, CDCl3):
4.82e4.70(m, 1H), 4.10e4.02 (m, 2H), 2.93e2.85 (m, 2H), 2.15e2.10
(m, 2H), 1.84e1.81 (m, 2H)
d
¼ 7.90e7.38 (m, 9H), 7.35 (s, 1H),
[18] a) D. Greenwood, R.C.B. Slack, J.F. Peutherer, Medical Microbiology, fourteenth
ed. ELBS, London, 1992, 1.