Novel pyrethrin derivatives containing hydrazone and 1,3,4-oxadiazole thioether moieties: Design, synthesis, and insecticidal activity

Article abstract of DOI:10.1080/10426507.2019.1700416

A series of novel pyrethrin derivatives containing hydrazone and 1,3,4-oxadiazole thioether moieties were designed, synthesized, and evaluated for their insecticidal activity. Bioassays indicated that some of the target compounds exhibited good insecticid

Full text of DOI:10.1080/10426507.2019.1700416

Phosphorus, Sulfur, and Silicon and the Related Elements
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Novel pyrethrin derivatives containing hydrazone
and 1,3,4-oxadiazole thioether moieties: Design,
synthesis, and insecticidal activity
Zai-Bo Yang, Pei Li & Yin-Ju He
To cite this article: Zai-Bo Yang, Pei Li & Yin-Ju He (2019): Novel pyrethrin derivatives containing
hydrazone and 1,3,4-oxadiazole thioether moieties: Design, synthesis, and insecticidal activity,
Phosphorus, Sulfur, and Silicon and the Related Elements, DOI: 10.1080/10426507.2019.1700416
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PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
https://doi.org/10.1080/10426507.2019.1700416
Novel pyrethrin derivatives containing hydrazone and 1,3,4-oxadiazole thioether
moieties: Design, synthesis, and insecticidal activity
a#
a,b#
a
Zai-Bo Yang , Pei Li , and Yin-Ju He
a
b
School of Chemistry and Chemical Engineering, Qiannan Normal University for Nationalities, Duyun, P.R. China; Qiandongnan Engineering
and Technology Research Center for Comprehensive Utilization of National Medicine/Key Laboratory for Modernization of Qiandongnan
Miao & Dong Medicine, Qiandongnan Traditional Medicine Research & Development Center, Kaili University, Kaili, P.R. China
ABSTRACT
ARTICLE HISTORY
A series of novel pyrethrin derivatives containing hydrazone and 1,3,4-oxadiazole thioether moieties
were designed, synthesized, and evaluated for their insecticidal activity. Bioassays indicated that
some of the target compounds exhibited good insecticidal activities against Plutella xylostella
Received 2 September 2019
Accepted 29 November 2019
KEYWORDS
Pyrethrin; trans-ethyl
chrysanthemate; hydrazone;
(
(
P. xylostella), Vegetable aphids (V. aphids), and Empoasca vitis (E. vitis). In particular, compound (E)-2-
(5-(2,2-dimethyl-3-(2-methylprop-1-en-1-yl)cyclopropyl)-1,3,4-oxadiazol-2-yl)thio)-N’-(4-(trifluoromethyl)-
benzylidene)acetohydrazide (6s) revealed excellent insecticidal activities against P. xylostella, V. aphids,
and E. vitis with the 50% lethal concentration (LC ) values of 5.23, 7.07, and 1.61 mg/L, respectively,
1
,3,4-oxadiazole thioether;
50
synthesis; insecti-
cidal activity
which were similar to or even better than those of chlorpyrifos, beta cypermethrin, spinosad, and
azadirachtin. These results indicated that novel pyrethrin derivatives containing hydrazone and 1,3,4-
oxadiazole thioether moieties could be developed as novel and promising insecticides.
GRAPHICAL ABSTRACT
Introduction
important class of heterocyclic derivatives, represented a key
structure in pharmaceutical and pesticide chemistry due to
In recent years, crop damage from harmful pests has become
more and more common and traditional pesticides application
can often lead to the development of resistance pests, thus
[19,20]
their wide range of bioactivities including antifungal,
[21–24]
[25]
[26]
antibacterial,
cancer,
insecticidal,
herbicidal,
[30]anti-
[27]
[28]
[29]
anti-HIV-1,
anti-inflammatory
antihepatitis,
activities. In addition, recent works
antitumor,
and
[
1,2]
bringing about enormous losses in crop production.
[31]
Nowadays, some insecticides, such as fluobendiamide, chlor-
pyrifos, tebufenozide, RH-5849, chlorantraniliprole, have been
used to control plant harmful pests in agricultural produc-
have highlighted that the thioether group is a highly efficient
pharmacophore that is widely concerned in the research of
new pesticide creation due to their wide range of biological
[
3,4]
tion.
However, the long-term use of available traditional
[32]
[24]
[33]
activities, such as antifungal,
nematicidal,
antibacterial,
antiviral,
[
24,34]
[35]
insecticides not only leads to the drug resistance but also
results in a harmful influence on the safety of environment
and plants. Therefore, the development of novel and promis-
ing insecticides with a new mode of action is an urgent task.
Hydrazone, a highly efficient pharmacophore and widely
and insecticidal
activities.
Esbiothrin is one of the most important insecticides
derived from natural sources. Its molecular framework is
ethyl chrysanthemate which is the main component isolated
[
36]
from the natural plant pyrethrum.
Literature reports that
used in drug design, has demonstrated significant insecti- ethyl chrysanthemate is a natural insecticide with good
[
5,6]
[7,8]
[9,10]
[9]
cidal,
fungicidal,
antibacterial,
antioxidant,
insecticidal activity, high efficiency, low toxicity, broad spec-
[
10]
[11,12]
[13,14]
anti-tumor,
antimalarial,
anticonvulsant,
and anti-tuberculosis
anti-inflammatory,
trum, good biodegradability, environmentally friendly, and
[
15]
[16–18]
[36]
activities. harmless to humans and animals.
However, due to the
Meanwhile, 1,3,4-oxadiazole and their derivatives, an instability of ultraviolet light in natural light, it is greatly
CONTACT Pei Li
pl19890627@126.com
School of Chemistry and Chemical Engineering, Qiannan Normal University for Nationalities, Duyun 558000,
P.R. China.
#
These authors contributed equally to this work.
Supplemental data for this article is available online at https://doi.org/10.1080/10426507.2019.1700416.
ß 2019 Taylor & Francis Group, LLC

2
Z.-B. YANG ET AL.
Scheme 1. Synthetic route of the target compounds 6a26u.
1
limited in the wide application, limited to the use of indoor yields of 81.3–87.3%, and confirmed their structures by IR, H
13
health pest control. Since the successful development of the NMR, C NMR, ESI-MS, and elemental analysis.
1
first light-stable pyrethroid insecticide Phenothrin in the
The H NMR spectra of the title compounds 6a–6u
1
970s, which has been widely used in agricultural pest con- exhibited a singlet at 11.77–12.12 and 8.00–8.43 ppm, which
trol. However, due to their repellent effect on bees, high indicated the presence of ꢁNHꢁ and ꢁN¼CHꢁ, respect-
toxic to silkworms and natural enemies, pyrethroid insecti- ively. A doublet at 5.00–5.01 ppm indicated the presence
cides cannot be used in orchards, silkworm breeding and of ꢁC¼CHꢁ. Meanwhile, typical chemical shifts at
13
surrounding areas, rice fields, rivers, ponds and surrounding 173.74–159.25 ppm in the C NMR spectra confirmed the
[
37]
areas.
In order to solve the light stability and reduce the
presence of oxadiazole ring and C ¼ O. In addition, the IR
harm to aquatic organisms of pyrethroid insecticides,
many chemists optimized the molecular structure of ethyl
chrysanthemate by introducing new active groups into the
molecular structure to build a novel family of pyrethroid
insecticides, such as cypermethrin, fenpropathrin, cis-
cypermethrin, deltamethrin, fenvalerate.
spectra exhibited characteristic absorption near 2970ꢁ2950,
ꢁ
1
2
920, 1680, and 1570 cm , which indicated the presence of
–
CH , –CH –, C ¼ C, and C ¼ N, respectively.
3
2
Biological evaluations
To develop highly active and readily available insecticidal
inhibitors, in this study, we aim to introduce the hydrazone
and 1,3,4-oxadiazole thioether moieties to the trans-ethyl
chrysanthemate skeleton to build a novel family of bioactive
molecules against Plutella xylostella (P. xylostella), Vegetable
aphids (V. aphids), and Empoasca vitis (E. vitis). To the best
of our knowledge, it is the first report on the insecticidal
activity of pyrethrin derivatives containing hydrazone and
In this study, the insecticidal activities of the target com-
pounds 6a–6u against P. xylostella, V. aphids, and E. vitis
[38–41]
were evaluated using the previously reported methods.
The commercial insecticides of chlorpyrifos, beta cypermeth-
rin, spinosad, and azadirachtin, which were commonly used
in China, were used as the positive controls and evaluated at
the same conditions. The results of the preliminary bioas-
says, as listed in Table S 1 (Supplemental Materials), indi-
cated that the target compounds 6a–6u showed good
insecticidal activities against P. xylostella, V. aphids, and
E. vitis at the concentration of 500 mg/L, with the inhibitory
effect values of 53.33–100.00%, 53.33–100.00%, and
1
,3,4-oxadiazole thioether moieties.
Results and discussion
Chemistry
5
6.67–100.00%, respectively. Meanwhile, Table S 1 also
The synthetic route of the target compounds 6a–6u was showed that compounds 6c, 6d, 6j, 6k, 6l, 6m, 6p, 6q, 6r,
depicted in Scheme 1. As shown in Scheme 1, using trans-ethyl 6s, 6t, and 6u exhibited significant insecticidal activities
chrysanthemate as the starting material, the intermediates 2–5 against P. xylostella and E. vitis, with a value of 100.00% at
[
19–24]
was prepared according to the reported methods.
The the concentrations of 500 mg/L. Similar, compounds 6j, 6m,
target compounds 6a–6u were obtained under microwave 6r, 6s, 6t, and 6u exhibited significant insecticidal
ꢀ
irradiation reaction at 90 C and 150 W for 30 min with the activity against V. aphids, with a value of 100.00% at the

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
3
concentrations of 500 mg/L, which were equally to those of Technologies, Palo Alto, Canada). Microwave experiments
chlorpyrifos (100.00%), beta cypermethrin (100.00%), were carried out using a CEM Discover Labmate microwave
spinosad (100.00%), and azadirachtin (100.00%).
apparatus (300 W with ChemDriver Software). Analytical
The 50% lethal concentration (LC ) values of the target TLC was performed on silica gel GF254 (200–300 mesh). All
50
compounds as well as the commercial pesticides chlorpyrifos, solvents were dried by standard methods in advance and
beta cypermethrin, spinosad, and azadirachtin against P. xylos- distilled before use. The Supplemental Materials contains
1
13
tella, V. aphids, and E. vitis were also determined and pre- sample H, C NMR and IR spectra for products 6a–6u
sented in Table S 2 (Supplemental Materials). Tables S2 (Figures S 1–S 84).
showed that the target compounds 6a–6u exhibited insecti-
cidal activities against P. xylostella, V. aphids, and E. vitis
with the LC50 values of 2.23–312.42, 7.07–334.77, and
Preparation of the key intermediate 5
1
.61–266.58 mg/L, respectively. Especially, compound 6s As shown in Scheme 1, a mixture of trans-ethyl chrysanthe-
revealed the best insecticidal activities against P. xylostella, V. mate (19.6 g, 100 mmol) and 80% hydrazine hydrate (18.8 g,
aphids, and E. vitis with the LC50 values of 5.23, 7.07, and 300 mmol) was dissolved in anhydrous ethanol (50 mL) in a
1
.61 mg/L, respectively, which were similar to or even better 250 mL of reaction flask. Then, the mixture was further
ꢀ
than those of chlorpyrifos (7.71, 11.37, and 6.25 mg/L, respect- reacted at 100 C for 18 h. Upon completion of the reaction
ively), beta cypermethrin (12.77, 8.41, and 4.67 mg/L, respect- (monitored by TLC), the mixture was concentrated and
ively), spinosad (4.88, 13.55, and 7.93 mg/L, respectively), and dried under vacuum, the intermediate 2 was obtained after
azadirachtin (10.22, 18.28, and 14.34 mg/L, respectively). recrystallization from ethanol.
These results indicated that novel pyrethrin derivatives con-
A mixture of intermediate 2 (18.2 g, 100 mmol) and KOH
taining hydrazone and 1,3,4-oxadiazole thioether moieties (8.4 g, 150 mmol) were dissolved in anhydrous ethanol
could be developed as novel and promising insecticides.
(150 mL) in a 500 mL of reaction flask. Then, CS
(22.8 g,
2
3
00 mmol) was added dropwise to completely dissolve the
reaction mixture under stirring at room temperature. Upon
completion of addition, the reaction solution was continu-
ously stirred for 18 h at 72 C. The solvent was removed
under reduced pressure, and the obtained mixture was
adjusted to pH ¼ 4ꢁ5 with diluted HCl. The residue was
dried and the intermediate 3 was attained after recrystalliza-
tion from ethanol.
Structure-activity relationship analysis
ꢀ
Based on the insecticidal activities of the target compounds
against P. xylostella, V. aphids, and E. vitis, shown in
Table S 2, the preliminary structure-activity relationship
(SAR) showed that the type and position of the substituent
group R at the phenyl ring had an important effect on the
insecticidal activities of the target compounds. First, with the
presence of electron-drawing groups (–CF , –OCF , and –F) at
A mixture of intermediate 3 (22.4 g, 100 mmol), anhyd-
rous K CO (13.8 g, 100 mmol), and KI (1.7 g, 10 mmol) was
2
3
3
3
dissolved in anhydrous ethanol (150 mL) in a 500 mL of
reaction flask. Then, ethyl bromoacetate (25.1 g, 150 mmol)
was added dropwise to completely dissolve the reaction mix-
ture under stirring at room temperature. Upon completion
2
and/or 4-position of phenyl, the corresponding com-
pounds presented better bioactivities against P. xylostella,
V. aphids, and E. vitis in the order of 6s > 6e, 6r > 6f, and
6
drawing group on phenyl, the insecticidal activities against
P. xylostella, V. aphids, and E. vitis of the corresponding
compounds with the R substituent group at 4-position is
higher than those of at 2-position in the order of 6a > 6b,
j > 6i. Second, compared with the same electron with-
of addition, the reaction solution was continuously stirred at
ꢀ
7
2 C. Upon completion of the reaction (monitored by
TLC), the mixture was concentrated under vacuum, followed
by filtration. The residue was dried and the intermediate 4
was obtained after recrystallization from ethanol.
6
c > 6d, and 6s > 6r.
To a solution of intermediate 4 (31.0 g, 100 mmol) in
anhydrous ethanol (50 mL), 80% hydrazine hydrate (18.8 g,
300 mmol) was slowly added at room temperature. Then,
Experimental
ꢀ
the mixture was further reacted at 100 C for 10 h. The solv-
General methods
ent was removed under reduced pressure, and the crude
The melting points of the products were determined on a product was further recrystallized from ethanol to obtain the
XT-4 binocular microscope (Beijing Tech Instrument Co., key intermediate 5.
China) and were not corrected. The IR spectra were
recorded on a Bruker VECTOR 22 spectrometer (Bruker,
1
13
Preparation of the target compounds 6a26u
Rheinstetten, Germany) in KBr disk. H NMR and
C
NMR (solvent DMSO-d ) spectral analyses were performed To a 50 mL round-bottom flask fitted with a magnetic stir-
6
on
a
Bruker DRX-400 NMR spectrometer (Bruker, ring bar, intermediate 5 (3.0 g, 1 mmol) and the solution of
Rheinstetten, Germany) at room temperature using TMS as substituted benzaldehyde (1.2 mmol) in anhydrous ethanol
an internal standard. Elemental analysis was carried out (10 mL) were added in order, then the round-bottom flask
using an Elemental Vario-III CHN analyzer (Elementar, was sealed and placed in the synthetic reactor and reacted
ꢀ
Hanau, German). Mass spectral studies were conducted on under microwave irradiation at 90 C with 150 W for
an Agilent 5973 organic mass spectrometer (Agilent 20 min. Upon completion of the reaction (monitored by

4
Z.-B. YANG ET AL.
TLC), the mixture was concentrated under vacuum and the agar-coated petri dish above. Thirty larvae of third-instar
purified after recrystallization from ethanol to obtain the V. aphids were carefully transferred to the petri dish, sealed
target compounds 6aꢁ6u. The physical characteristics, IR, with a perforated fresh-keeping film, and placed in the arti-
1
13
H NMR, C NMR, ESI-MS, and elemental analysis data ficial climate chamber with a light-dark period of 14:10 h at
ꢀ
for all the target compounds 6a–6u are shown in 25 ± 1 C and 75% relative humidity.
Supplementary Materials, and the data for the representative
compound 6s are shown below.
Insecticidal activity against E. vitis
(E)-2-((5-(2,2-dimethyl-3-(2-methylprop-1-en-1-yl)cyclopropyl)-
1
,3,4-oxadiazol-2-yl)thio)-N’-(4-(trifluoromethyl)benzylidene)ace-
Fresh the tender tea shoots (length 13 cm) were dipped into
the prepared solutions containing compounds 6aꢁ6u for
10 s, dried in air and wrapped with wet cotton and parafilm
film, then packed in test tube (3 ꢂ 20 cm). Ten tender tea
stems were placed in each test tube. Thirty larvae of second-
third-instar E. vitis were carefully transferred to the tube.
Finally, the opening of the tube was wrapped with gauze
ꢀ
1
tohydrazide (6s). White solid; mp 156ꢁ157 C; yield 84.1%; H
NMR (400 MHz, DMSO-d , ppm) d: 12.06 (s, 1H,
6
ꢁ
ꢁ
N¼ CHꢁ), 8.27 ꢁ 8.31 (q, 2 H, ArꢁH), 8.13 (s, 1 H,
NHꢁ), 7.97 (d, 2 H, J¼ 11.60 Hz, ArꢁH), 5.01 (d, 1 H,
J¼ 10.40 Hz, ꢁC¼ CHꢁ), 4.60 (s, 1 H, ꢁCH ꢁ), 4.17 (s, 1 H,
2
ꢁ
CH ꢁ), 1.97ꢁ2.06 (m, 2 H, 2 ꢂ ꢁCHꢁ), 1.67 (d, 6 H,
2
J¼ 13.20 Hz, 2 ꢂ ꢁCH ), 1.15 (s, 3 H, ꢁCH ), 1.08 (s, 3 H, and placed in the artificial climate chamber with a light-
3
3
13
ꢀ
ꢁ
CH ); C NMR (100MHz, DMSO-d , ppm) d: 168.98, dark period of 14:10 h at 25 ± 1 C and 75% rela-
3
6
1
1
2
2
1
8
67.82, 163.80, 162.64, 148.33, 145.38, 142.23, 140.65, 135.36, tive humidity.
28.61, 128.39, 124.52, 121.40, 39.40, 35.23, 31.54, 27.71, 26.50,
ꢁ
1
5.79, 21.64, 18.73; IR (KBr, cm ) ꢀ: 3419, 3214, 3075, 2923,
875, 1705, 1687, 1616, 1563, 1524, 1488, 1457, 1410, 1362,
343, 1326, 1236, 1186, 1108, 1081, 1009, 992, 973, 956, 882,
55, 836, 750, 726; Anal. Calcd for C H F N O S: C 55.74%,
Conclusions
In conclusion, a series of novel pyrethrin derivatives con-
taining hydrazone and 1,3,4-oxadiazole thioether moieties
were designed and synthesized. Bioassays indicated that
some of the target compounds exhibited better insecticidal
activities against P. xylostella, V. aphids, and E. vitis.
Especially, compound 6s revealed the best insecticidal activ-
ities against P. xylostella, V. aphids, and E. vitis which were
21 23 3 4 2
H 5.12%, F 12.60%, N 12.38%; found: C 55.96%, H 5.33%, F
þ
12.73%, N 12.48%; ESI-MS: 452.0 [M þ H] .
Insecticidal biological assay
All bioassays were performed on test organisms reared in similar to or even better to those of chlorpyrifos, beta cyper-
ꢀ
the lab and repeated at 25 ± 1 C according to statistical methrin, spinosad, and azadirachtin. Our research demon-
requirements. Mortalities were corrected using Abbott’s for- strated that novel pyrethrin derivatives containing
[
21,22]
mula.
(
Evaluations were based on a percentage scale hydrazone and 1,3,4-oxadiazole thioether moieties could
complete eradication). effectively control P. xylostella, V. aphids, and E. vitis.
0 ¼ no activity and 100%
¼
Chlorpyrifos, beta cypermethrin, spinosad, and azadirachtin Furthermore, according to the requirements of pesticide
were used as controls, and the solvent water was used as registration in China, further field studies on the photo-
blank control. Three replicates and at least five concentra- stability, biological efficacies, crop safety, and toxicities of
tions were performed for each experiment and mortalities compound 6s as insecticidal candidates will be performed in
were determined after 72 h.
our next work.
Insecticidal activity against P. xylostella
Acknowledgement
Fresh cabbage discs (diameter 2 cm) were dipped into the This research was funded by the National Natural Science Foundation
of China, grant number 21466031, Youth Science and Technology
Talent Growth Program of Guizhou Province’s Department of
Education, grant number Qian Jiaohe KY [2018] 350.
prepared solutions containing compounds 6aꢁ6u for 10 s,
dried in air and placed in a petri dish (diameter 9 cm) lined
with filter paper. Thirty larvae of second-instar P. xylostella
were carefully transferred to the petri dish, and placed in
the artificial climate chamber with a light-dark period of Conflicts of interest
ꢀ
1
4:10 h at 25 ± 1 C and 75% relative humidity.
The authors declare no conflict of interest.
Insecticidal activity against V. aphids
References
The agar was mixed with distilled water to form agar solu-
tion with 1.3% mass fraction. 5 ml liquid agar was absorbed
by a micropipette and added into a culture dish 5 cm in
diameter and 2 cm in height. The liquid agar was cooled
and solidified. Fresh cabbage discs (diameter 4 cm) were
dipped into the prepared solutions containing compounds
[
1] Thomas, A. B.; Nanda, R. K.; Kothapalli, L. P.; Deshpande, A. D.
Synthesis and Antimicrobial Activity of N-[2-(Aryl/Substituted
Aryl)-4-Oxo-1,3-Thiazolidin-3-yl]Pyridine-4-Carboxamide. J. Kor.
Chem. Soc. 2011, 55, 960–968. DOI: 10.5012/jkcs.2011.55.6.960.
2] Oerke, E. C. Crop Losses to Pests. J. Agric. Sci. 2006, 144,
[
[
31–43. DOI: 10.1017/S0021859605005708.
3] Lahm, G. P.; Stevenson, T. M.; Selby, T. P.; Freudenberger,
J. H.; Cordova, D.; Flexner, L.; Bellin, C. A.; Dubas, C. M.;
6a ꢁ 6u for 10 s, dried in air and placed the back face up in

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
5
TM
Smith, B. K.; Hughes, K. A.; et al. Rynaxypyr : A New [18] Xia, Y.; Fan, C. D.; Zhao, B. X.; Zhao, J.; Shin, D. S.; Miao,
Insecticidal Anthranilic Diamide That Acts as a Potent and
Selective Ryanodine Receptor Activator. Bioorg Med. Chem.
Lett. 2007, 17, 6274–6279. DOI: 10.1016/j.bmcl.2007.09.012.
4] Lahm, G. P.; Selby, T. P.; Freudenberger, J. H.; Stevenson,
T. M.; Myers, B. J.; Seburyamo, G.; Smith, B. K.; Flexner, L.;
J. Y. Synthesis and Structure–Activity Relationships of Novel
1-Arylmethyl-3-Aryl-1H-Pyrazole-5-Carbohydrazide Hydrazone
Derivatives as Potential Agents against A549 Lung Cancer
Cells. Eur. J. Med. Chem. 2008, 43, 2347–2353. DOI: 10.1016/j.
ejmech.2008.01.021.
[
Clark, C. E.; Cordova, D. Insecticidal Anthranilic Diamides: A [19] Liu, F.; Luo, X. Q.; Song, B. A.; Bhadury, P.; Yang, S.; Jin,
New Class of Potent Ryanodine Receptor Activators. Bioorg.
Med. Chem. Lett. 2005, 15, 4898–4906. DOI: 10.1016/j.bmcl.
L. H.; Xue, W.; Hu, D. Y. Synthesis and Antifungal Activity of
Novel Sulfoxide Derivatives Containing Trimethoxyphenyl
Substituted 1,3,4-Thiadiazole and 1,3,4-Oxadiazole Moiety.
Bioorg. Med. Chem. 2008, 16, 3632–3640. DOI: 10.1016/j.bmc.
2008.02.006.
2
005.08.034.
[
5] Wu, J.; Song, B. A.; Hu, D. Y.; Yue, M.; Yang, S. Design,
Synthesis and Insecticidal Activities of Novel Pyrazole Amides
Containing Hydrazone Substructures. Pest Manag. Sci. 2012, 68, [20] Chen, C. J.; Song, B. A.; Yang, S.; Xu, G. F.; Bhadury, P.; Jin,
8
01–810. DOI: 10.1002/ps.2329.
L. H.; Hu, D. Y.; Li, Q. Z.; Liu, F.; Xue, W.; et al. Synthesis and
Antifungal Activities of 5-(3,4,5-Trimethoxyphenyl)-2-Sulfonyl-
1,3,4-Thiadiazole and 5-(3,4,5-Trimethoxyphenyl)-2-Sulfonyl-
1,3,4-Oxadiazole Derivatives. Bioorg. Med. Chem. 2007, 15,
3981–3989. DOI: 10.1016/j.bmc.2007.04.014.
[
6] Tian, P. Y.; Liu, D. Y.; Liu, Z. J.; Shi, J.; He, W. J.; Qi, P. Y.; Chen,
J. X.; Song, B. A. Design, Synthesis, and Insecticidal Activity
Evaluation of Novel 4-(N, N-Diarylmethylamines)Furan-2(5H)-
One Derivatives as Potential Acetylcholine Receptor Insecticides.
Pest Manag. Sci. 2019, 75, 427–437. DOI: 10.1002/ps.5132.
[21] Li, P.; Yin, J.; Xu, W. M.; Wu, J.; He, M.; Hu, D. Y.; Yang, S.;
Song, B. A. Synthesis, Antibacterial Activities, and 3D-QSAR of
Sulfone Derivatives Containing 1,3,4-Oxadiazole Moiety. Chem.
Biol. Drug Des. 2013, 82, 546–556. DOI: 10.1111/cbdd.12181.
[
[
[
7] Wang, X. B.; Ren, Z. J.; Wang, M. Q.; Chen, M.; Lu, A. M.; Si,
W. J.; Yang, C. L. Design and Synthesis of Novel 3-(Thiophen-
2
-yl)-1,5-Dihydro-2H-Pyrrol-2-One Derivatives Bearing
a
Hydrazone Moiety as Potential Fungicides. Chem. Chem Cent J. [22] Li, P.; Shi, L.; Yang, X.; Yang, L.; Chen, X. W.; Wu, F.; Shi,
2
018, 12, 83. DOI: 10.1186/s13065-018-0452-z
Q. C.; Xu, W. M.; He, M.; Hu, D. Y.; Song, B. A. Design,
Synthesis, and Antibacterial Activity against Rice Bacterial Leaf
Blight and Leaf Streak of 2,5-Substituted-1,3,4-Oxadiazole/
Thiadiazole Sulfone Derivative. Bioorg. Med. Chem. Lett. 2014,
24, 1677–1680. DOI: 10.1016/j.bmcl.2014.02.060.
8] Li, L.; Li, Z.; Wang, K. L.; Liu, Y. X.; Li, Y. Q.; Wang, Q. M.
Synthesis and Antiviral, Insecticidal, and Fungicidal Activities
of Gossypol Derivatives Containing Alkylimine, Oxime or
Hydrazine Moiety. Bioorg Med. Chem. 2016, 24, 474–483. DOI:
1
0.1016/j.bmc.2015.08.015.
[23] Li, P.; Hu, D. Y.; Xie, D. D.; Chen, J. X.; Jin, L. H.; Song, B. A.
Design, Synthesis, and Evaluation of New Sulfone Derivatives
Containing a 1, 3, 4-Oxadiazole Moiety as Active Antibacterial
Agents. J. Agric. Food Chem. 2018, 66, 3093–3100. DOI: 10.
1021/acs.jafc.7b06061.
9] Gurkok, G.; Altanlar, N.; Suzen, S. Investigation of
Antimicrobial Activities of Indole-3-Aldehyde Hydrazide/
Hydrazone Derivatives. Chemotherapy 2009, 55, 15–19. DOI:
1
0.1159/000166999.
€
[
10] K u€ c¸ u€ kg u€ zel, S. G.; Mazi, A.; Sahin, F.; Ozt u€ rk, S.; Stables, J. [24] Li, P.; Tian, P. Y.; Chen, Y. Z.; Song, X. P.; Xue, W.; Jin, L. H.;
Synthesis and Biological Activities of Diflunisal
Hu, D. Y.; Yang, S.; Song, B. A. Novel Bisthioether Derivatives
Containing 1,3,4-Oxadiazole Moiety: Design, Synthesis,
Hydrazide–Hydrazones. Eur. J. Med. Chem. 2003, 38, 1005–1013.
DOI: 10.1016/j.ejmech.2003.08.004.
a
Antibacterial and Nematocidal Activities. Pest Manage. Sci.
2018, 74, 844–852. DOI: 10.1002/ps.4762.
[
11] Wu, J.; Kang, S. H.; Song, B. A.; Hu, D. Y.; He, M.; Jin, L. H.;
Yang, S. Synthesis and Antibacterial Activity against Ralstonia [25] Fitzjohn, S.; Robinson, M. P. Benzoxazole and Benzothiazole
solanacearum for Novel Hydrazone Derivatives Containing a
Derivatives. WO Patent 1 994 067 83, 1994.
Pyridine Moiety. Chem. Cent. J. 2012, 6, 28. DOI: 10.1186/ [26] Andrew, P.; Jutta, E. B.; Janice, B.; Timothy, D. S. Isoxazoline
1
752-153X-6-28
Derivatives and Their Preparation, Herbicidal Composition,
and Use As Herbicides to Control Weeds or Plant Growth
Inhibition. WO Patent 2 006 024 820, 2006.
[
[
[
[
12] G u€ rk o€ k, G.; Coban, T.; Suzen, S. J. Melatonin Analogue New
Indole Hydrazide/Hydrazone Derivatives with Antioxidant
Behavior: Synthesis and Structure–Activity Relationships. [27] Vedula, M. S.; Pulipaka, A. B.; Venna, C.; Chintakunta, V. K.;
Enzym. Inhib. Med. Chem. 2009, 24, 506–515. DOI: 10.1080/
4756360802218516.
13] Mohareb, R. M.; Ibrahim, R. A.; Moustafa, H. E. Hydrazide-
Hydrazones in the Synthesis of 1, 3, 4-Oxadiazine, 1, 2, 4-
Jinnapally, S.; Kattuboina, V. A.; Vallakati, R. K.; Basetti, V.;
Akella, V.; Rajgopal, S.; et al. New Styryl Sulfones as Anticancer
Agents. Eur. J. Med. Chem. 2003, 38, 811–824. DOI: 10.1016/
S0223-5234(03)00144-2.
1
Triazine and Pyrazole Derivatives with anti-Tumor Activities. [28] Silvestri, R.; Artico, M.; La Regina, G.; De Martino, G.; La
Open Org. Chem. J. 2010, 4, 8–14. DOI: 10.2174/
874095201004010008.
14] Rahman, V. M.; Mukhtar, S.; Ansari, W. H.; Lemiere, G. Synthesis,
Stereochemistry and Biological Activity of Some Novel Long Alkyl
Chain Substituted Thiazolidin-4-Ones and Thiazan-4-One from
Colla, M.; Loddo, R.; La Colla, P. Anti-HIV-1 Activity of Pyrryl
Aryl Sulfone (PAS) Derivatives: Synthesis and SAR Studies of
Novel Esters and Amides at the Position 2 of the Pyrrole
Nucleus. Farmaco 2004, 59, 201–210. DOI: 10.1016/j.farmac.
2003.11.004.
1
1
0-Undecenoic Acid Hydrazide. Eur. J. Med. Chem. 2005, 40, [29] Gong, P.; Chai, H. F.; Zhao, Y. F.; Zhao, C. S. Synthesis and
1
73–184. DOI: 10.1016/j.ejmech.2004.10.003.
in Vitro anti-Hepatitis B Virus Activities of Some Ethyl
5-Hydroxy-1H-Indole-3-Carboxylates. Bioorg. Med. Chem.
2006, 14, 2552–2558. DOI: 10.1016/j.bmc.2005.11.033.
15] Dimmock, J. R.; Vashishtha, S. C.; Stables, J. P. Anticonvulsant
Properties of Various Acetylhydrazones, Oxamoylhydrazones
and Semicarbazones Derived from Aromatic and Unsaturated [30] Tai, X. S.; Yin, X. H.; Tan, M. Y. Crystal Structure and Antitumor
0
Carbonyl Compounds. Eur. J. Med. Chem. 2000, 35, 241–248.
DOI: 10.1016/S0223-5234(00)00123-9.
Activity of Tri[2-[N-(4 -Methyl-Benzylsulfonyl)Amino]Ethyl]-
Amine. Chin. J. Struc. Chem. 2003, 22, 411–414.
[
[
16] Yapia, R.; La Mara, M. P.; Massieu, G. H. Modifications of [31] Fang, S. H.; Padmavathi, V.; Rao, Y. K.; Venkata Subbaiah,
Brain Glutamate Decarboxylase Activity by Pyridoxal
D. R. C.; Thriveni, P.; Geethangili, M.; Padmaja, A.; Tzeng, Y.
M. Biological Evaluation of Sulfone Derivatives as anti-
Inflammatory and Tumor Cells Growth Inhibitory Agents. Int.
Immunopharmacol. 2006, 6, 1699–1705. DOI: 10.1016/j.intimp.
2006.07.004
Phosphate-c-Glutamyl Hydrazine. Biochem. Pharmacol. 1967,
16, 1211–1218. DOI: 10.1016/0006-2952(67)90152-9.
17] Sava, G.; Perissin, L.; Lassiani, L.; Zabucchi, G. Antiinflammatory
Action of Hydrosoluble Dimethyl-Triazenes on the Carrageenin-
Induced Edema in guinea Pigs. Chem. Biol. Interact. 1985, 53, [32] Shi, J.; Luo, N.; Ding, M. H.; Bao, X. P.
7–43. DOI: 10.1016/S0009-2797(85)80082-X. Synthesis, in Vitro Antibacterial and Antifungal Evaluation of
3

6
Z.-B. YANG ET AL.
Novel 1,3,4-Oxadiazole Thioether Derivatives Bearing the 6- [37] Selvi, M.; C¸ ava ¸s , T.; C¸ a ꢀg lan Karasu Benli, A.; Ko c¸ ak Memmi,
Fluoroquinazolinylpiperidinyl Moiety. Chin. Chem. Lett. 2019.
DOI: 10.1016/j.cclet.2019.06.037.
B.; C¸ inkılı c¸ , N.; Din c¸ el, A. S.; Vatan, O€ .; Yılmaz, D.; Sarıkaya,
R.; Zorlu, T.; Erko c¸ , F. Sublethal Toxicity of Esbiothrin
Relationship with Total Antioxidant Status and in Vivo
Genotoxicity Assessment in Fish (Cyprinus Carpio L., 1758)
Using the Micronucleus Test and Comet Assay. Environ.
Toxicol. 2013, 28, 644–651. DOI: 10.1002/tox.20760.
[
33] Gan, X. H.; Hu, D. Y.; Li, P.; Wu, J.; Chen, X. W.; Xue, W.;
Song, B. A. Design, Synthesis, Antiviral Activity and Three-
Dimensional Quantitative Structure–Activity Relationship Study
of Novel 1,4-Pentadien-3-One Derivatives Containing the 1,3,4-
Oxadiazole Moiety. Pest Manage. Sci. 2016, 72, 534–543. DOI
DOI: 10.1002/ps.4018.
34] Chen, J. X.; Chen, Y. Z.; Gan, X. H.; Song, B. J.; Hu, D. Y.;
Song, B. A. Synthesis, Nematicidal Evaluation, and 3D-QSAR
Analysis of Novel 1,3,4-Oxadiazole–Cinnamic Acid Hybrids.
J. Agric. Food Chem. 2018, 66, 9616–9623. DOI: 10.1021/acs.
jafc.8b03020.
35] Guo, Y.; Wang, X. G.; Fan, J. P.; Zhang, Q.; Wang, Y.; Zhao,
Y.; Huang, M. X.; Ding, M.; Zhang, Y. B. Semisynthesis and
Insecticidal Activity of Some Novel Fraxinellone-Based
Thioethers Containing 1,3,4-Oxadiazole Moiety. R Soc. Open
Sci. 2017, 4, 171053. DOI: 10.1098/rsos.171053.
[
38] Feng, Q.; Liu, Z. L.; Xiong, L. X.; Wang, M. Z.; Li, Y. Q.; Li,
Z. M. Synthesis and Insecticidal Activities of Novel
[
[
[
Anthranilic
Diamides
Containing
Modified
N-
Pyridylpyrazoles. J. Agric. Food Chem. 2010, 58, 12327–12336.
DOI: 10.1021/jf102842r.
[
39] Zhao, Q. Q.; Li, Y. Q.; Xiong, L. X.; Wang, Q. M. Design,
Synthesis and Insecticidal Activity of Novel Phenylpyrazoles
Containing a 2,2,2-Trichloro-1-Alkoxyethyl Moiety. J. Agric.
Food Chem. 2010, 58, 4992–4998. DOI: 10.1021/jf1001793.
40] Cahill, M.; Byrne, F. J.; Gorman, K.; Denholm, I.; Devonshire, A. L.
Pyrethroid and Organophosphate Resistance in the Tobacco
Whitefly Bemisia tabaci (Homoptera: Aleyrodidae). Bull. Entomol.
Res. 1995, 85, 181–187. DOI: 10.1017/S0007485300034258.
[
36] Gordin, P. J.; Sleeman, R. J.; Snarey, M.; Thain, E. M. The
Jasmolins, New Insecticidally Active Constituents of
Chrysanthemum Cinerariaefolium Vis. J. Chem. Soc. C 1966, [41] Sudoi, V. Evaluation of Neem Seed Oil Product for Control of
32–334. DOI: 10.1039/j39660000332. Tea Pests in Kenya. Tea 1998, 19, 62–65.
3