Design, Synthesis, Characterization, and Antimicrobial Screening of Novel Indazole Bearing Oxadiazole Derivatives

Article abstract of DOI:10.1002/jhet.2540

Ethyl 2-(2,6-dioxocyclohexyl)-2-oxoacetate was prepared by reacting cyclohexane-1,3-dione (1) and diethyl oxalate (2) with the help of sodium ethoxide in ethanol at 0–5°C. Subsequent treatment of ethyl 2-(2,6-dioxocyclohexyl)-2-oxoacetate with hydrazine h

Full text of DOI:10.1002/jhet.2540

Month 2016 Design, Synthesis, Characterization, and Antimicrobial Screening of Novel
Indazole Bearing Oxadiazole Derivatives
*
Satish M. Ghelani, Hasmukh R. Khunt, and Yogesh T. Naliapara
Department of Chemistry, Saurashtra University, Rajkot, Gujarat, India
*
E-mail: naliaparachem@yahoo.co.in
Received June 1, 2015
DOI 10.1002/jhet.2540
Published online in 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com).
Ethyl 2-(2,6-dioxocyclohexyl)-2-oxoacetate was prepared by reacting cyclohexane-1,3-dione (1) and
diethyl oxalate (2) with the help of sodium ethoxide in ethanol at 0–5°C. Subsequent treatment of ethyl
2-(2,6-dioxocyclohexyl)-2-oxoacetate with hydrazine hydrate in ethanol resulted into ethyl 4-oxo-
4,5,6,7-tetrahydro-2H-indazole-3-carboxylate while without solvent in excess hydrazine hydrate on
reflux resulted into 4-oxo-4,5,6,7-tetrahydro-2H-indazole-3-carbohydrazide (3). The synthesis of novel
indazole bearing oxadiazole derivatives (ODZ 01 to 16) has been achieved by the reaction of hydrazide of
2H-indazole (3) with acid (4a–p) in the presence of POCl3, and the antimicrobial activity of synthesized novel
compounds has been studied.
J. Heterocyclic Chem., 00, 00 (2016).
INTRODUCTION
as potent mimics of adenosine-3′,5′-cyclic monophosphates
[34]. Cortivazol [35] is an indazole-based drug possessing
glucocorticoid properties. Many indazoles act as enzyme
inhibitors [36–38], and some also show specific virucide
[39], bronchodilatory [40–42], vasodilatory [43], or
neuroprotectant [44] activities; others are used in the treat-
ment of diabetes [45]. 3-Trifluoromethyl-1H-indazoles pos-
sess trichomonacide properties [46], and fused indazoles
with an azasteroid ring system show antimicrobial activity
[47]. Some 1H-indazole-4,7-quinones possess anthelmintic
[48] and diuretic activity [49]. A series of indazole deriva-
tives exhibit herbicide activity, behave as growth inhibitors
[50–52], or are used as bactericides and fungicides in
polymer-based paints [53]. Guanidino-1H-indazoles are
used as sweeteners [54].
Although many derivatives of indazole show biological
activity, no special toxicity has been reported, and no spe-
cial handling precautions have been recommended. The
biodegradability of indazole is included in an ecological
survey of heterocyclic compounds [55].
1,3,4-Oxadiazole (1) is a thermally stable aromatic
heterocycle and exists in two partially reduced forms: 2,3-
dihydro-1,3,4-oxadiazole(1,3,4-oxadiazoline) (2) and 2,5-
dihydro-1,3,4-oxadiazole(1,3,4-oxadiazoline) (3), depending
on the position of the double bond. The completely reduced
form of the 1,3,4-oxadiazole is known as 2,3,4,5-tetrahydro-
1,3,4-oxadiazole (1,3,4-oxadiazolidine) (4) [56] (Fig. 2).
The systematic IUPAC name benzo[c]pyrazole is not
used in the ring index or in chemical abstract, and the
heterocycle is normally referred to its trivial name indazole
or more correctly 1H-indazole (CAS registry number 271-244-3).
Alternative names for indazole, such as 1,2-benzodiazole,
are not used. Benzo-fused derivatives are known as
benzopyrazoles (Fig. 1). The first indazoles were synthe-
sized in 1880 [1], and a systematic investigation of the
heterocycle was performed by V. Auwers in 1924 [2].
Indeed, general synthetic pathways to indazoles were
developed in the early years of the 20th century, and many
recent publications describe improvements of known
methods. Methods for the synthesis of indazoles are
described in Houben-Weyl [3], and well-tested procedures
for the synthesis of 1H-indazole [4–7], 2-phenyl-2H-
indazole [8], and 5-nitro-1H-indazole [9] can be found in
Organic Synthesis.
Natural products bearing an indazole structure are rare [10],
and at present only, two examples are known: nigellicine [11]
and nigellidine [12]. However, many synthetic indazoles are
known, and a number are important because of their pharma-
ceutical activity; some act as dopamine antagonists, anti-
inflammatory, and analgesic or antipyretic agents [13–20].
Others also exhibit CNS activity [21–23], and 6-
nitroindazoles and 7-nitroindazoles are used to study the
behavior of nitric oxide in vivo [24–26]. 1-Benzyl-1H-
indazole-3-carboxilic acids have antispermatogenetic and an-
ticancer activity [27–29], the latter effect being shared by other
indazole derivatives [30–32]. 1-Benzoyl-1H-indazoles behave
as anti-arthritic drugs [33], and 4-nitro- and 4-amino-2-
ribofuranosyl-2H-indazole 3′,5′-cyclic monophosphates act
RESULTS AND DISCUSSION
The following is the possible reaction mechanism for
compound (3) to (5a–p) (Table 1).
© 2016 HeteroCorporation

S. M. Ghelani, H. R. Khunt, and Y. T. Naliapara
Vol 000
and C. albicans MTCC-227. The result shows that the
compounds 02, 10, 12, 13, and 16 exhibited significant
(maximum) antibacterial activities, while other compounds
show moderate to low activity. All of the synthesized com-
pounds are given lower antifungal activity. On evaluation
of antibacterial screening data, it can be seen that the extent
of zone of inhibition is largely affected by the type of
substitutions at phenyl ring, irrespective of the positions
of substitution. Electron-withdrawing group at phenyl
ring considerably enhanced the antibacterial activity,
whereas electron-releasing groups on phenyl ring strongly
diminished the antibacterial activity, which can be evident
by antibacterial screening results. Further investigations in
the area of novel indazole bearing oxadiazole derivatives
incorporated with different substituent are in progress in
our laboratory.
Possible Reaction Mechanism for Compound (3) to (5a-p)
EXPERIMENTAL
Synthesis of 4-oxo-4,5,6,7-tetrahydro-2H-indazole-3-carbohydrazide
(3). To the stirred solution of sodium ethoxide (0.2 mol),
a mixture of cyclohexane-1,3-dione (1) (0.2 mol) and
diethyl oxalate (2) (0.2 mol) was added dropwise below
5–10°C. Vigorous stirring was required to prevent
complete solidification of the reaction mixture. After
completion of the reaction, the reaction mixture was
decomposed by the careful addition of cold dilute sulfuric
acid solution. The ethyl 2-(2,6-dioxocyclohexyl)-2-
oxoacetate separated as heavy oil. Ethyl 2-(2,6-
dioxocyclohexyl)-2-oxoacetate is added into access 80%
hydrazine hydrate and refluxed for 5 to 6h. The reaction
mixture was allowed to cool at room temperature, and the
precipitate obtained was filtered, dried and recrystallized
from ethanol to give analytical pure product in 85% yield.
Figure 1. Tautomeric forms of indazole.
Figure 2. Dihydro forms of 1,3,4-oxadiazolidine.
CONCLUSION
The results from in vitro antibacterial screening of all
synthesized compounds against S. aurues MTCC-96 and
B. subtillitis MTCC-441 were very much encouraging
than antifungal screening against A. niger MTCC-282
Table 1
Synthesis of substituted oxadiazole and triazole derivatives.
Entry
Code
R
Molecular formula
Molecular weight
Yield (%)
MP (°C)
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
ODZ 01
ODZ 02
ODZ 03
ODZ 04
ODZ 05
ODZ 06
ODZ 07
ODZ 08
ODZ 09
ODZ 10
ODZ 11
ODZ 12
ODZ 13
ODZ 14
ODZ 15
ODZ 16
4-CH3
4-OCH3
-H
2-CH3
4-Cl
4-Br
4-F
4-OH
3-Cl
3-Br
2-Cl
2-NO2
2,5-di-OMe
3,4-di-OMe
4-NO2
2-Br
C16H14N4O2
C16H14N4O3
C15H12N4O2
C16H14N4O2
C15H11ClN4O2
C15H11BrN4O2
C15H11FN4O2
C15H12N4O3
C15H11ClN4O2
C15H11BrN4O2
C15H11ClN4O2
C15H11N5O4
C17H16N4O4
C17H16N4O4
C15H11N5O4
C15H11BrN4O2
294
310
280
292
314
358
298
296
314
358
314
325
340
340
325
358
90
91
84
90
86
90
90
86
89
89
88
90
90
87
85
90
180–182
176–178
186–188
192–194
187–189
183–185
195–197
188–190
185–187
195–197
201–203
178–180
183–185
186–188
195–197
238–240
MP, melting point
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
Design, Synthesis, Characterization, and Antimicrobial Screening of Novel Indazole
Bearing Oxadiazole Derivatives
Yellowish white solid; Rf 0.37 (6:4 hexane-EtOAc); IR
(KBr) ν: 3280, 3140, 3078, 2941, 2862, 1680, 1668,
(m, 2H, Ar-H), 10.61 ppm (s, 1H, ÀNH-); 13C NMR
(400 MHz, DMSO): δ 20.22, 21.72, 23.36, 24.82, 118.21,
121.11, 128.14, 127.95, 131.65, 133.77, 135.15, 142.44,
146.46, 160.86, 165.95 ppm; MS: m/z 280 (M+). Anal.
Calcd. for C15H12N4O2: C, 63.82; H, 5.00; N, 19.85; O,
11.34. Found: C, 63.85; H, 5.03; N, 19.80; O, 11.41.
3-(5-(o-Tolyl)-1,3,4-oxadiazol-2-yl)-6,7-dihydro-2H-indazol-
4(5H)-one. Creamish solid; Rf 0.29 (6:4 hexane-EtOAc);
IR (KBr): 3207, 3123, 2959, 1658, 1546, 1472, 1265,
1
1579, 1467, 1259, 1024, 742cmÀ1; H NMR (400MHz,
DMSO): δ 2.15 (m, 2H, CH2), 2.68 (t, 2H, CH2), 2.82 (t,
2H, CH2), 4.58 (s, 2H, ÀNH2), 9.82 (s, 1H, ÀNH),
13.12 ppm (s, 1H, ÀNH); 13C NMR (400 MHz, DMSO):
δ 20.1, 24.2, 38.8, 121.5, 142.6, 153.8, 162.2, 197.2 ppm;
MS: m/z 194 (M+). Anal. Calcd. for C16H14N4O2: C,
49.48; H, 5.19; N, 28.85; O, 16.48. Found: C, 49.56; H,
5.21; N, 28.91; O, 16.42.
1
1041 cmÀ1; H NMR (400 MHz, DMSO): δ 1.80 (m, 2H,
CH2), 2.68 (t, 2H, CH2), 2.73 (s, 3H, ÀCH3), 2.88
(t, 2H, CH2), 7.24–7.34 (dd, 1H, Ar-H, 3J =8.8 Hz),
7.37–7.41 (m, 2H, Ar-H), 7.90–7.92 (dd, 1H, Ar-H,
3J=8.8Hz), 10.28ppm (s, 1H, ÀNH-); MS: m/z 294 (M+).
Anal. Calcd. for C16H14N4O2: C, 65.30; H, 4.79; N,
19.04; O, 10.87. Found: C, 65.42; H, 4.74; N, 19.09;
O, 10.85.
General procedure for the synthesis of 3-(5-aryl-1,3,4-
oxadiazol-2-yl)-6,7-dihydro-2H-indazol-4(5H)-one (5a–p) [ODZ
01 to 16]. Equimolar amount of 4-oxo-4,5,6,7-tetrahydro-
2H-indazole-3-carbohydrazide (3) and appropriate carboxylic
acid (4a–p) were taken in POCl3. The reaction mixture is
refluxed for 6 h, allowed to cool at room temperature,
poured into crushed ice, and stood by overnight. The solid
was filtered, dried, and recrystallized from ethanol to give
analytical pure product in 85–90% yield.
3-(5-(4-Chlorophenyl)-1,3,4-oxadiazol-2-yl)-6,7-dihydro-3aH-indazol-
4(5H)-one. White solid; Rf 0.34 (6:4 hexane-EtOAc); IR
(KBr): 3207, 3123, 2959, 1668, 1526, 1265, 1049cmÀ1
;
Spectral data of the synthesized compounds [ODZ 01 to 16].
3-(5-(p-tolyl)-1,3,4-oxadiazol-2-yl)-6,7-dihydro-3aH-indazol-4(5H)-
1H NMR (400MHz, DMSO): δ 1.79 (m, 2H, CH2), 2.67
(t, 2H, CH2), 2.84 (t, 2H, CH2), 7.21–7.23 (dd, 2H, Ar-
H, 3J = 8.4 Hz), 7.87–7.89 (dd, 2H, Ar-H, 3J =8.4Hz),
10.38 ppm (s, 1H, ÀNH-); 13C NMR (400MHz, DMSO):
δ 20.10, 20.83, 22.47, 72.15, 115.24, 122.00, 127.92,
128.77, 137.62, 140.66, 149.32, 161.72, 164.29; MS: m/z
314 (M+). Anal. Calcd. for C15H11ClN4O2: C, 56.88; H,
4.14; Cl, 11.19; N, 17.69; O, 10.10. Found: C, 56.93; H,
4.11; Cl, 11.21; N, 17.61; O, 10.13.
one.
Creamish solid; Rf 0.33 (6:4 hexane-EtOAc); IR
(KBr) ν: 3186, 3149, 3078, 3012, 2941, 2862, 1752,
1668, 1579,1467, 1249, 1014, 819, 777, 742 cmÀ1 1H
;
NMR (400 MHz, DMSO): δ 1.80 (m, 2H, CH2), 2.39
(s, 3H, ÀCH3), 2.69 (t, 2H, CH2), 2.88 (t, 2H, CH2),
7.25–7.27 (dd, 2H, Ar-H, 3J =8.4 Hz), 7.93–7.95 (dd,
2H, Ar-H, 3J = 8.4 Hz), 10.58ppm (s, 1H, ÀNH-); 13C
NMR (400 MHz, DMSO): δ 21.22, 21.44, 21.67, 22.36,
22.82, 117.22, 120.92, 126.84, 126.95, 129.71, 129.77,
133.15, 142.24, 142.46, 160.13, 163.93 ppm; MS: m/z
294 (M+). Anal. Calcd. for C16H14N4O2: C, 65.30; H,
4.79; N, 19.04; O, 10.87. Found: C, 65.41; H, 4.69; N,
19.08; O, 10.91.
3-(5-(4-Bromophenyl)-1,3,4-oxadiazol-2-yl)-6,7-dihydro-3aH-indazol-
4(5H)-one. Yellow solid; Rf 0.32 (6:4 hexane-EtOAc); IR
(KBr): 3207, 3123, 2990, 2862, 1653, 1509, 1461,
;
1061 cmÀ1 MS: m/z 358 (M+). Anal. Calcd. for
C15H11BrN4O2: C, 49.88; H, 3.63; Br, 22.12; N, 15.51;
O, 8.86. Found: C, 49.98; H, 3.59; Br, 22.14; N, 15.41;
O, 8.88.
3-(5-(4-Methoxyphenyl)-1,3,4-oxadiazol-2-yl)-6,7-dihydro-3aH-
indazol-4(5H)-one.
Creamish solid; Rf 0.35 (6:4 hexane-
EtOAc); IR (KBr) ν: 3394, 3115, 3068, 2939, 2850, 1763,
3-(5-(4-Fluorophenyl)-1,3,4-oxadiazol-2-yl)-6,7-dihydro-3aH-indazol-
4(5H)-one. Creamish solid; Rf 0.36 (6:4 hexane-EtOAc);
IR (KBr): 3223, 3149, 2990, 2862, 1653, 1509, 1437,
1597, 1566, 1458, 1253, 1168, 1126, 1024, 831, 723,
1
680 cmÀ1; H NMR (400MHz, DMSO): δ 1.82 (m, 2H,
1061 cmÀ1
;
MS: m/z 298 (M+). Anal. Calcd. for
CH2), 2.71 (t, 2H, CH2), 2.91 (t, 2H, CH2), 3.58 (s, 3H,
3
ÀCH3), 7.19–7.21 (dd, 2H, Ar-H, J= 8.4 Hz), 7.90–7.92
C15H11FN4O2: C, 60.00; H, 4.36; F, 6.33; N, 18.66; O,
10.66. Found: C, 60.18; H, 4.29; F, 6.31; N, 18.60; O,
10.61.
3-(5-(4-Hydroxyphenyl)-1,3,4-oxadiazol-2-yl)-6,7-dihydro-3aH-
indazol-4(5H)-one. Creamish solid; Rf 0.31 (6:4 hexane-
EtOAc); IR (KBr): 3227, 3193, 2966, 1628, 1522, 1456,
1217, 1041 cmÀ1; MS: m/z 296 (M+). Anal. Calcd. for
C15H12N4O3: C, 60.40; H, 4.73; N, 18.78; O, 16.09.
Found: C, 60.51; H, 4.75; N, 18.69; O, 16.04.
(dd, 2H, Ar-H, 3J= 8.4 Hz), 10.62 ppm (s, 1H, ÀNH-);
13C NMR (400MHz, DMSO): δ 21.22, 21.46, 21.75,
25.36, 27.82, 122.22, 129.92, 132.84, 136.95, 139.71,
139.77, 144.15, 151.24, 161.46, 169.13, 171.93 ppm; MS:
m/z 310 (M+). Anal. Calcd. for C16H14N4O3: C, 61.53;
H, 5.16; N, 17.94; O, 15.37. Found: C, 61.43; H, 5.19;
N, 17.84; O, 15.42.
3-(5-Phenyl-1,3,4-oxadiazol-2-yl)-6,7-dihydro-3aH-indazol-4(5H)-
one. White solid; Rf 0.30 (6:4 hexane-EtOAc); IR (KBr):
3186, 3149, 3078, 2950, 1668, 1579, 1467, 1161,
3-(5-(3-Chlorophenyl)-1,3,4-oxadiazol-2-yl)-6,7-dihydro-3aH-indazol-
4(5H)-one. Creamish solid; Rf 0.33 (6:4 hexane-EtOAc);
IR (KBr): 3227, 3173, 2989, 1648, 1586, 1468, 1251,
1
1030 cmÀ1; H NMR (400 MHz, DMSO): δ 1.84 (m, 2H,
;
1061 cmÀ1 MS: m/z 314 (M+). Anal. Calcd. for
CH2), 2.71 (t, 2H, CH2), 2.91 (t, 2H, CH2), 7.26–7.28
(m, 2H, Ar-H), 7.39–7.41 (t, 1H, Ar-H), 7.92–7.94
C15H11ClN4O2: C, 56.88; H, 4.14; Cl, 11.19; N, 17.69;
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

S. M. Ghelani, H. R. Khunt, and Y. T. Naliapara
Vol 000
O, 10.10. Found: C, 56.94; H, 4.10; Cl, 11.22; N, 17.58;
O, 10.05.
1539, 1431, 1061cmÀ1; MS: m/z 340 (M+). Anal. Calcd.
for C17H16N4O4: C, 59.64; H, 5.30; N, 16.37; O, 18.69.
Found: C, 59.69; H, 5.28; N, 16.32; O, 18.71.
3-(5-(3-Bromophenyl)-1,3,4-oxadiazol-2-yl)-6,7-dihydro-3aH-indazol-
4(5H)-one. Yellow solid; Rf 0.36 (6:4 hexane-EtOAc); IR
(KBr): 3442, 3226, 3143, 2986, 1642, 1566, 1447, 1241,
3-(5-(3,4-Dimethoxyphenyl)-1,3,4-oxadiazol-2-yl)-6,7-dihydro-
3aH-indazol-4(5H)-one.
Creamish solid; Rf 0.32 (6:4
1051 cmÀ1
;
MS: m/z 358 (M+). Anal. Calcd. for
hexane-EtOAc); IR (KBr): 3187, 3153, 2980, 1623,
1569, 1431, 1051cmÀ1; MS: m/z 340 (M+). Anal. Calcd.
for C17H16N4O4: C, 59.64; H, 5.30; N, 16.37; O, 18.69.
Found: C, 59.69; H, 5.26; N, 16.41; O, 18.72.
C15H11BrN4O2: C, 49.88; H, 3.63; Br, 22.12; N, 15.51;
O, 8.86. Found: C, 49.81; H, 3.54; Br, 22.08; N, 15.47;
O, 8.84.
3-(5-(2-Chlorophenyl)-1,3,4-oxadiazol-2-yl)-6,7-dihydro-3aH-indazol-
4(5H)-one. Creamish solid; Rf 0.29 (6:4 hexane-EtOAc);
IR (KBr) ν: 3314, 3171, 3042, 2937, 2856, 1758, 1589,
1527, 1492, 1433, 1049, 873, 756, 727 cmÀ1; MS: m/z
314 (M+). Anal. Calcd. for C15H11ClN4O2: C, 56.88; H,
4.14; Cl, 11.19; N, 17.69; O, 10.10. Found: C, 56.98; H,
4.11; Cl, 11.22; N, 17.58; O, 10.05.
3-(5-(2-Nitrophenyl)-1,3,4-oxadiazol-2-yl)-6,7-dihydro-3aH-
indazol-4(5H)-one. Yellow solid; Rf 0.28 (6:4 hexane-
EtOAc); IR (KBr): 3226, 3143, 2988, 1632, 1546, 1424,
1231, 1061 cmÀ1; MS: m/z 325 (M+). Anal. Calcd. for
C15H11N5O4: C, 55.05; H, 4.00; N, 21.40; O, 19.55.
Found: C, 55.19; H, 4.04; N, 21.37; O, 19.52.
3-(5-(4-Nitrophenyl)-1,3,4-oxadiazol-2-yl)-6,7-dihydro-3aH-
indazol-4(5H)-one. Yellow solid; Rf 0.34 (6:4 hexane-
EtOAc); IR (KBr): 3227, 3120, 2980, 1623, 1509, 1461,
1051 cmÀ1; MS: m/z 325 (M+). Anal. Calcd. for
C15H11N5O4: C, 55.05; H, 4.00; N, 21.40; O, 19.55.
Found: C, 55.19; H, 4.04; N, 21.42; O, 19.50.
3-(5-(2-Bromophenyl)-1,3,4-oxadiazol-2-yl)-6,7-dihydro-3aH-
indazol-4(5H)-one. Yellow solid; Rf 0.53 (6:4 hexane-
EtOAc); IR (KBr): 3414, 3171, 3143, 2937, 2856, 1589,
1492, 1276, 1049cmÀ1; MS: m/z 358 (M+). Anal. Calcd.
for C15H11BrN4O2: C, 49.88; H, 3.63; Br, 22.12; N,
15.51; O, 8.86. Found: C, 49.97; H, 3.57; Br, 22.17; N,
15.47; O, 8.87.
3-(5-(2,5-Dimethoxyphenyl)-1,3,4-oxadiazol-2-yl)-6,7-dihydro-
Antimicrobial screening.
The diverse biological
3aH-indazol-4(5H)-one.
hexane-EtOAc); IR (KBr): 3217, 3153, 2950, 1613,
Creamish solid; Rf 0.30 (6:4
screenings of indazole bearing oxadiazole derivatives
inspire us to screen the newly synthesized compounds.
Table 2
Antibiotic sensitivity assay (concentration 250/500/1000 μg/mL).
Sr. No. ODZ Pseudomonas aeruginosa
Proteus vulgaris
Escherichia coli
Staphylococcus aureus
Candida albicans
250
1.1
1.3
1.2
R
1.4
1
R
500
1.2
1.4
1.3
R
1.6
1.1
1
1000
1.3
1.9
1.5
R
250 500 1000 250 500 1000 250
500
1.2
1.5
1.6
R
1.2
1
1.2
1
1.2
1.4
1.3
1.2
1
1.2
1.8
1.5
1.9
2.2
2.0
—
1000
1.5
1.9
2
250 500 1000
1.
2.
3.
4.
5.
6.
7.
8.
01
02
03
04
05
06
07
08
09
10
11
12
13
14
15
16
A
R
1
1.2
2.1
1.6
1.7
1.4
1.3
1.8
1.5
1.7
1.3
1.2
1.8
2
1.1
1.2
1.3
1.1
R
1.2
1.5
1.4
1.3
R
1.4
2
1.9
1.6
R
1.1
1.1
1.2
R
1.1
R
1.1
R
1.1
1.2
1.1
R
1.1
1.1
1.2
1.1
1.2
R
1.1
1
1.1
1
1
1.1
R
1
1.5
1.3
1.5
1.4
1.5
1.4
1.5
1.1
1.3
1.2
1.2
1.3
1.2
1.5
1.1
1.2
2
1.9
1.6
2
1.8
2
1.5
1.7
1.8
1.7
1.8
1.5
2
1.4
1.7
1.1
R
1.3
1.1
1.1
1
1.7
1.4
1.3
1.2
1.1
1.6
1.3
1.4
1.1
1
1.4
1.7
1.3
R
1.3
1.8
2.1
1.9
—
R
2
1.5
1.4
1.3
1.3
1.5
1.7
1.5
1.7
1.2
1.4
1.4
1.2
1.3
1.1
R
1.5
1.8
1.7
1.6
2
R
R
R
R
1.1
1.1
1.2
R
1.4
1.2
1.3
R
1.1
1.2
1.1
1.4
1.2
1.4
1.5
1.3
1.5
1
2
1.7
2
R
R
9.
1.1
1.3
1.3
1.2
1.4
1.1
R
1.2
1.4
1.5
1.4
1.6
1.1
R
1.2
1.8
2.2
1.8
-
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
1
R
1.3
1.5
1.3
1.6
1.5
1.5
1.9
2.1
2.0
—
1.6
1.9
1.5
2
1.7
2
1.1
1.3
1.1
R
R
1.3
R
1.4
1.8
R
1.7
1.1
1.6
1.3
1.1
1
1.7
—
CPD
GF
GRF
FLC
—
—
2.6
2.8
-
—
—
—
ODZ, oxadiazole; R, resistant; A, ampicillin; CPD, cefpodoxime; GF, gatifloxacin, GRF, griseofulvin; FLC, fluconazole.
Note: Zone of inhibition interpretation is as follows.
1. Zone size <1.0 cm – R.
2. Zone size 1.0 to 1.5 cm – intermediate.
3. Zone size >1.5 cm – sensitive.
Standard antibiotic sensitivity assay concentration 40 μg/mL.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
Design, Synthesis, Characterization, and Antimicrobial Screening of Novel Indazole
Bearing Oxadiazole Derivatives
Many antimicrobial agents have been applied for treatment;
still, the medical field needs extensive efforts for the
development of new antimicrobial agents to overcome the
highly resistant species of microbes. The newly
synthesized compounds (01 to 20) were tested for
antibacterial screening using agar well diffusion method
against Staphylococcus aurues MTCC-96 and Bacillus
subtillitis MTCC-441 bacterial strain where antifungal
screening using agar well diffusion method against
Aspergillus niger MTCC-282 and Candida albicans
MTCC-227 at different concentrations (50, 100, and
250μg/mL), which were compared with ampicillin,
The one pot multi component synthetic strategies to
achieve indazole bearing oxadiazole derivatives are shown
in Figures 3 and 4. The structures of compounds were elu-
cidated by various analytical tools like mass, IR, 1H NMR,
13C NMR, and elemental analysis.
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