Synthesis of novel azabicyclo derivatives containing a thiazole moiety and their biological activity against pine-wood nematodes

Article abstract of DOI:10.1080/10426507.2019.1700260

To explore a new skeleton with nematicidal activity, a series of novel azabicyclo derivatives containing a thiazole moiety were designed, synthesized and evaluated for their nematicidal activities. The bioassay results against pine-wood nematodes (Bursaphelenchus xylophilus) showed that most of the title compounds displayed nematicidal activity at a concentration of 40 mg/L. Especially, the title compounds2-((8-methyl-8-azabicyclo[3.2.1]octan-3-yl)oxy)-4-(4-chlorophenyl)thiazole (7e), 2-((8-methyl-8-azabicyclo[3.2.1]octan-3-yl)thio)-4-phenylthiazole (10a) and 2-((8-methyl-8-azabicyclo [3.2.1]octan-3-yl)thio)-4-(4-chlorophenyl)thiazole (10e) exhibited more than 90% mortality against Bursaphelenchus xylophilus.

Full text of DOI:10.1080/10426507.2019.1700260

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: https://www.tandfonline.com/loi/gpss20
Synthesis of novel azabicyclo derivatives
containing a thiazole moiety and their biological
activity against pine-wood nematodes
Hui Li, Aoyun Lu, Yanqiu Zhang, Yanqing Peng & Gonghua Song
To cite this article: Hui Li, Aoyun Lu, Yanqiu Zhang, Yanqing Peng & Gonghua Song (2019):
Synthesis of novel azabicyclo derivatives containing a thiazole moiety and their biological activity
against pine-wood nematodes, Phosphorus, Sulfur, and Silicon and the Related Elements, DOI:
10.1080/10426507.2019.1700260
To link to this article: https://doi.org/10.1080/10426507.2019.1700260
View supplementary material
Published online: 23 Dec 2019.
Submit your article to this journal
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
https://www.tandfonline.com/action/journalInformation?journalCode=gpss20

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
https://doi.org/10.1080/10426507.2019.1700260
Synthesis of novel azabicyclo derivatives containing a thiazole moiety and their
biological activity against pine-wood nematodes
Hui Li , Aoyun Lu, Yanqiu Zhang, Yanqing Peng, and Gonghua Song
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, China
ABSTRACT
ARTICLE HISTORY
Received 20 September 2019
Accepted 29 November 2019
To explore a new skeleton with nematicidal activity, a series of novel azabicyclo derivatives con-
taining a thiazole moiety were designed, synthesized and evaluated for their nematicidal activities.
The bioassay results against pine-wood nematodes (Bursaphelenchus xylophilus) showed that most
of the title compounds displayed nematicidal activity at a concentration of 40 mg/L. Especially,
the title compounds2-((8-methyl-8-azabicyclo[3.2.1]octan-3-yl)oxy)-4-(4-chlorophenyl)thiazole (7e),
2-((8-methyl-8-azabicyclo[3.2.1]octan-3-yl)thio)-4-phenylthiazole (10a) and 2-((8-methyl-8-azabicyclo
[3.2.1]octan-3-yl)thio)-4-(4-chlorophenyl)thiazole (10e) exhibited more than 90% mortality against
Bursaphelenchus xylophilus.
KEYWORDS
Azabicyclo; PWNs;
nematicidal activity;
novel nematicide
GRAPHICAL ABSTRACT
Introduction
of nematicides, such as Abamectin or Emamectin benzoate,
is another control method to protect pine trees from the
nematode infection.[5,6] However, since those nematicides
have been widely used for many years, nematodes tend to
develop drug resistance due to recurrent exposure and
excessive usage. Therefore, the development of nematicides
with novel mechanism, high efficacy, low toxicity and envir-
onment-friendly is extremely urgent.
Phytonematodes are one of the most destructive crop pests
and can cause global annual agricultural losses of over 100
billion dollars.[1] Among them, pine-wood nematode (PWN)
has been ranked as the eighth most harmful genera of
parasitic
nematodes.[2]
The
pine-wood
nematode
(Bursaphelenchus xylophilus)is a notorious invasive species
that causes a fatal pine tree disease known as pine wilt dis-
ease (PWD).[3] Since the emergence of PWD in Nagasaki in
Azabicyclo compounds are a group of alkaloids that are
1905 which caused extensive damage of the pine forest, the ubiquitous in nature. Azabicyclo derivatives are emerging as
PWN has spread all over the world.[4] Today, PWD has potent pharmacophores showing distinctive biological activ-
been regarded worldwide as a severe threat to pine forests.
ities such as anti-microbial,[7,8] anti-depressant[9,10] and
Several strategies have been adopted to control the spread anti-inflammatory.[11] Some azabicyclo derivatives also dem-
of PWD. For example, Metham sodium was used to fumi- onstrated certain pesticidal activities.[12] In 1996, Zeneca
gate dead trees to kill the larvae of PWNs. A trunk injection reported a series of azabicyclo octane derivatives which had
CONTACT Gonghua Song
ghsong@ecust.edu.cn
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and
Technology, Shanghai 200237, China.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/gpss.
Supplemental data for this article can be accessed here.
ß 2019 Taylor & Francis Group, LLC

2
H. LI ET AL.
6a-w.[22] Then the 2-((8-methyl-8-azabicyclo[3.2.1]octan-3-
yl)thio)-thiazole derivatives (10a-w) were produced through sub-
stitution reaction by using intermediate 8 and 9a-w.
Two categories of azabicyclo[3.2.1]octane derivatives bear-
1
ing a thiazole moiety were identified by H NMR, 13C NMR
1
and HRMS. For example, in the H NMR spectrum of 7a
(Figure S1, Supplemental Materials), the absorption peaks at d:
7.77–7.29 ppm reveal the existence of phenyl protons. The
characteristic singlet at d: 6.89 ppm is attributed to the absorp-
tions of thiazole. The characteristic triplet at d: 5.43 ppm is due
to OCH of tropane. The characteristic singlets at d: 3.79 ppm
and d: 2.77 ppm are NH and NCH3 of tropane respectively.
The doublet at d: 3.04 ppm and multiplet at d: 2.46–2.23 ppm
are CH2 of tropane. Moreover, in the 13C NMR spectrum of
7a, the chemical shifts at d: 171.98–104.86 ppm are attributed
to the phenyl and thiazole. The chemical shifts at d:
72.34–24.55 ppm confirm the existences of tropane fragment
(Figure S2, Supplemental Materials). The structure assigned
for compound 7a was fully supported by its mass spectrum,
which showed a molecular formula C17H20N2OS (calcd for
C17H20N2OS (M)þ 300.1296; found, 300.1297) (Figure S3,
Supplemental Materials).
Figure 1. Azabicyclo derivatives with various pesticidal activities.
insecticidal activities against Myzus persicae (Figure 1A).[13]
Aventis Crop Science found that azabicyclo oxime ether
derivatives (Figure 1B) exhibited excellent mortality against
Heliothis virescens in 2001.[14] Moreover, Trowell and cow-
orkers proved that the human 5-HT3 receptor antagonist
MDL72222 (Figure 1C) had lethal effects on Caenorhabditis
elegans.[15] In our previous work, azabicyclo thiazole hydra-
zone derivatives have been found excellent bioactivity
against Bursaphelenchus xylophilus (Figure 1D).[16] As our
continuous efforts on the development of novel nematicides,
herein, two categories and 46 unreported compounds with
azabicyclo[3.2.1]octane scaffolds were synthesized by intro-
ducing an ether or thioether linkage between azabicyclo and
thiazole moieties (Figure 1E). The target compounds were
synthesized as described in Scheme 1 and the biological
activity against Bursaphelenchus xylophilus in vitro were
tested. The spectra data of synthesized compounds are pro-
vided in the supplemental materials.
Nematicidal activities
The nematicidal activity of title compounds (7a-w and 10a-w)
against Bursaphelenchus xylophilus at the concentration of
40 mg/L were listed in Table 1.
As shown in Table 1, the preliminary bioassays indicated
that some of the target compounds had good nematicidal
activity, for example, compound 7a, 7e, 10a, 10e, 10f and
10k exhibited more than 80% mortality. Especially, com-
pound 7e, 10a and 10e displayed nematicidal activities of
95%, 92% and 94% against Bursaphelenchus xylophilus at the
concentration of 40 mg/L respectively. In general, the thio-
ether compounds demonstrated higher nematicidal activity
than their counterparts with an ether linkage.
Results and discussion
Chemistry
The compounds with substitution at the para-position of the
benzene ring had higher nematicidal activity than those at the
meta- or ortho-positions, while there were no significant differ-
ences between the meta- and ortho-position. For example, para-
substituted compounds (7 b-e) showed higher activity than
their meta- (7i-l) or ortho- (7n-q) substituted counterparts .
When halogen groups were introduced into the phenyl ring, the
compounds (7d-f) exhibited relatively higher nematicidal activ-
ity than other electron-donating groups (7 b and 7c) or elec-
tron-withdrawing groups (7f and 7 g). Furthermore, by
changing the phenyl group into a furan group, pyridine group
or methyl, the nematicidal activity of the compounds decreased
quickly (7 u-w). When the linkage between azabicyclo and thia-
zole was changed from O to S, higher nematicidal activity was
achieved in most cases (7a-wvs10a-w).
The synthetic routes to target compounds 2-((8-methyl-8-
azabicyclo[3.2.1]octan-3-yl)oxy)-thiazole derivatives (7a–w)
and 2-((8-methyl-8-azabicyclo[3.2.1]octan-3-yl)thio)-thiazole
derivatives (10a-w) were described in Scheme 1. According
to the reported literatures,[17,18] the intermediate 4 (S-ethyl
O-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) carbonodithioate)
was synthesized by three steps without further purification.
The key intermediate 5 (O-(8-methyl-8-azabicyclo[3.2.1]oc-
tan-3-yl) carbamothioate) was prepared by a acylation reac-
tion of the intermediate 4 with ammonia in ethanol.[19]
Finally, the intermediate 5 was reacted with substituted ethyl
ketone 6a-w in ethanol under reflux temperature for 3 h to
obtain 2-((8-methyl-8-azabicyclo[3.2.1]octan-3-yl)oxy)-thia-
zole derivatives (7a–w) in moderate to good yields.[20]
According to the reported literatures,[21] the intermediate 8
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl ethanesulfonate) was
obtained via esterification reaction with 8-methyl-8-azabicy-
Due to the high activities of compound 7a, 7e, 10a and
10e, we further tested the nematicidal activity of these com-
pounds at 40, 20, 10 and 5 mg/L (Table 2) respectively. It
clo[3.2.1]octan-3-olate sodium 2 and ethane sulfonyl chloride. was found that even at 10 mg/L,7e, 10a and 10e still showed
The substituted thiazole-2-thiol 9a–w were synthesized by good nematicidal activity against Bursaphelenchus xylophilus
ammonium dithiocarbamate and substituted ethyl ketone of more than 60%.

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
3
Scheme 1. Synthetic routes of the target compounds.
Table 1. Nematicidal activities of title compounds against Bursaphelenchu sxylophilus.
Compd.
R
Mortality (%)a
Compd.
R
Mortality (%)a
7a
7b
7c
7d
7e
7f
7g
7h
7i
7j
7k
7l
7m
7n
7o
7p
C6H5
81
54
42
57
95
66
38
30
48
37
53
51
41
33
27
50
28
17
60
69
24
30
15
100
10a
10b
10c
10d
10e
10f
10g
10h
10i
10j
10k
10l
10m
10n
10o
10p
10q
10r
C6H5
92
72
72
77
94
82
63
59
63
63
82
76
60
64
61
79
73
56
73
76
39
45
36
100
4-CH3C6H5
4-OMeC6H5
4-FC6H5
4-CH3C6H5
4-OMeC6H5
4-FC6H5
4-ClC6H5
4-ClC6H5
4-BrC6H5
4-NO2C6H5
4-CF3C6H5
3-CH3C6H5
3-OMeC6H5
3-ClC6H5
3-BrC6H5
3-NO2C6H5
2-CH3C6H5
2-OMeC6H5
2-ClC6H5
2-BrC6H5
2-NO2C6H5
3,4-diClC6H5
3,5-diClC6H5
2-Furan
4-BrC6H5
4-NO2C6H5
4-CF3C6H5
3-CH3C6H5
3-OMeC6H5
3-ClC6H5
3-BrC6H5
3-NO2C6H5
2-CH3C6H5
2-OMeC6H5
2-ClC6H5
2-BrC6H5
2-NO2C6H5
3,4-diClC6H5
3,5-diClC6H5
2-Furan
7q
7r
7s
7t
7u
7v
10s
10t
10u
10v
10w
4-Pyridine
Methyl
4-Pyridine
Methyl
7w
Avermectinb
aMortality at 40 mg/L.
bAvermectin at the concentration of 5 mg/L.
through the reaction mixture continuously at reflux tempera-
ture for 2 h. After cooling to room temperature, the solvent was
evaporated under reduced pressure, aqueous sodium hydroxide
solution (10mL of a 1.0 M solution) was added and the mixture
was extracted with dichloromethane (3 ꢂ 10mL). The com-
bined organic layers were dried over anhydrous MgSO4, fil-
tered, and concentrated in vacuo. The residue was purified by
flash silica-gel column chromatography (DCM/MeOH ¼8:1,
v/v) to afford thiocarbamate 5 (35%) as a brown solid,
Experimental
Synthesis of O-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)
carbamothioate (5)
Tropine (1) (1 mmol) was dissolved in THF (2 mL) and added
dropwise to a suspension of sodium hydride (1.2 mmol) in THF
(2 mL) at 0 ꢀC. The mixture was stirred at 0 ꢀC for 1 h to give
ꢁ
the sodium salt 2. Then, carbon disulfide 1.5 mmol) in THF
(2 mL) was added and the mixture was stirred at room tempera-
ture for 1 h to give the xanthate 3. After that, iodoethane
(1.5 mmol) in THF (2mL) was added into and the mixture was
stirred at room temperature for 12 h. Methanol (2 mL) was used
to quench the reaction and the solvent was evaporated under
1
mp151.3–153.0 ꢀC. H NMR (400 MHz, CDCl3) d 6.91 (s, 2 H,
CONH2),5.31 (t, J ¼ 4.1 Hz, 1 H, OCH), 3.73 (s, 2 H, NCH),
3.11 (d, J ¼ 15.3 Hz, 2 H, tropaneCH2), 2.75 (s, 3 H, NCH3),
2.41 – 2.20 (m, 6 H, tropaneCH2). 13C NMR (101 MHz, CDCl3)
reduced pressure to give the xanthate 4. The residue was dis- d 191.98(C¼ O), 82.54(OCH), 60.95(2 NCH), 38.49 (NCH3),
solved in ethanol (10mL). Ammonia (600 mg) was bubbled 33.73(2 CH2), 24.50(2 CH2).

4
H. LI ET AL.
Table 2. Gradient filtration of target compounds.
Mortality (%)
pressure, aqueous sodium hydroxide solution (10 mL of a
1.0 M solution) was added and the mixture was extracted with
dichloromethane (3 ꢂ 10 mL). The combined organic layers
were dried over anhydrous MgSO4, filtered, and concentrated
in vacuo. The residue was purified by flash silica-gel column
chromatography (DCM/MeOH ¼10:1, v/v).
Compd.
40 mg/L
20 mg/L
10 mg/L
5 mg/L
7a
7e
10a
10e
82
95
92
95
67
74
81
79
57
66
67
64
33
36
40
43
100
Avermectin
The Supplemental Materials contains complete character-
ization data of the products 7a – 7w, 10a-w and sample
spectroscopic data of 7a and 10a (Figures S1–S6,
Supplemental Materials).
Synthesis of 2-((8-methyl-8-azabicyclo[3.2.1]octan-3-
yl)oxy)-thiazole 7a-w (general method)
Nematicidal bioassay
Thiocarbamate 5 (1 mmol) and 2-bromo-1-phenylethanone
6a-w (1.1 mmol) were dissolved in ethanol (10 mL) and
refluxed for 3–5 h (monitored by TLC). After cooling to room
temperature, the solvent was evaporated under reduced pres-
sure, aqueous sodium hydroxide solution (10 mL of a 1.0 M
solution) was added and the mixture was extracted with
dichloromethane (3 ꢂ 10 mL). The combined organic layers
were dried over anhydrous MgSO4, filtered, and concentrated
in vacuo. The residue was purified by flash silica-gel column
chromatography (DCM/MeOH ¼10:1, v/v).
Nematicidal activity of the title compounds against
Bursaphelenchus xylophilus were evaluated. Bursaphelenchus
xylophilus used in all tests were cultured by Huzhou
Modern Agricultural Biotechnology Innovation Center,
Chinese Academy of Sciences, China.
Pure compounds (7a-w and 10a-w) were dissolved in
DMSO and diluted with distilled water containing 0.15%
Triton X-100.Bursaphelenchus xylophilus were inoculated on
nematode agar plates at 25 ꢀC for 7 d. The test solution
(50 lL) was added to each well of a 96-well plate containing
50 nematodes in 50 lL of distilled water and performed in
quadruplicate. The concentration of tested compounds was
40 mg/L. Avermectin (5 mg/L) was used as the positive con-
trol and DMSO/H2O solution as the negative control. All
treatments were replicated twice. The plates were covered to
prevent the evaporation of solvent and maintained in dark-
ness at 25 ꢀC. After 72 h, the dead nematodes were counted.
The nematicidal activity is presented as the percent of
dead nematodes corrected according to Schneider-Orelli’s
formula.
Synthesis of 8-methyl-8-azabicyclo[3.2.1]octan-3-yl
ethanesulfonate (8)
Tropine (1) (1 mmol) was dissolved in THF (2 mL) and added
dropwise to a suspension of sodium hydride (1.2 mmol) in
THF (2 mL) at 0 ꢀC. The mixture was stirred at 0 ꢀC for 1vh to
give the sodium salt 2. Ethane sulfonyl chloride (1.2 mmol) in
THF (2 mL) was then added dropwise at 0 ꢀC and the mixture
was stirred at room temperature for 3 h. The solvent was
evaporated under reduced pressure, aqueous sodium hydrox-
ide solution (10 mL of a 1.0 M solution) was added and the
mixture was extracted with dichloromethane (3 ꢂ 10 mL). The
combined organic layers were dried over anhydrous MgSO4,
filtered, and concentrated in vacuo to give the ethyl sulfonate 8
(142 mg, 61%).
Corrected Mortality ð%Þ ¼ ðM in treat plot
– M in negative control plotÞ
=ð100 – M in negative control plotÞ ꢂ 100
Synthesis of thiazole-2-thiol 9a-w (general method)
Conclusions
Ammonium dithiocarbamate (2 mmol) was dissolved in a
mixture of ethanol (2 mL) and water (2 mL). 2-bromo-1-
phenylethanone 6a-w (1 mmol) in ethanol (2 mL) was added
dropwise at 0 ꢀC and the mixture was refluxed for 3–5 h.
The organic solvent was evaporated under reduced pressure
and extracted with ethyl acetate (3 ꢂ 10 mL). The combined
organic layers were dried over anhydrous MgSO4, filtered,
and concentrated in vacuo.
In conclusion, a series of novel azabicyclo[3.2.1]octan thiazole
derivatives with ether or thioether linkage were synthesized
and bio-assayed. Some target compounds exhibited good mor-
tality against pine-wood nematode Bursaphelenchus xylophilus
at 40 mg/L, which implied that it might be a potential nemati-
cidal active structure to be worth studying further.
Funding
Synthesis of 2-((8-methyl-8-azabicyclo[3.2.1]octan-3-
yl)thio)- thiazole 10a-w (general method)
Financial support for this study from the National Natural Science
Foundation of China (Grant No. 21572060) is gratefully acknowledged.
8-methyl-8-azabicyclo[3.2.1]octan-3-yl ethanesulfonate (8)
(1 mmol), thiazole-2-thiol 9a-w (1.1 mmol) and sodium car-
bonate (1.5 mmol) were dissolved in THF (10 mL) and
refluxed for 3–5 h (monitored by TLC). After cooling to room
ORCID
temperature, the solvent was evaporated under reduced Hui Li
http://orcid.org/0000-0003-1613-0320

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
5
[11] Hong, J.; Zhang, Z.; Lei, H.; Cheng, H.; Hu, Y.; Yang, W.;
Liang, Y.; Das, D.; Chen, S.-H.; Li, G. A Novel Approach to
Finafloxacin Hydrochloride (BAY35-3377). Tetrahedron Lett.
2009, 50, 2525–2528. DOI: 10.1016/j.tetlet.2009.03.051.
References
ꢀ
ꢀ
[1] Naves, P.; Inacio, M. L.; Nobrega, F.; Sousa, E.; Michielsen, M.
Pinewood Nematode Presence and survival in commercial
Pallets. Eur. J. Wood Prod. 2019, 77, 301–309. DOI: 10.1007/
s00107-019-01383-1.
[12] Cullen, T. G.; Silverman, I. R.; Yeager, W. H. Insecticidal N-
(arylalkyl)-4-[Bis(substituted
aryl)hydroxymethyl]azabicy-
[2] Mamiya, Y.; Kiyohara, T. Description of Bursaphelenchus ligni-
colus N. sp. (Nematoda: Aphelenchoididae) from Pine Wood
and Histopathology of Nematode–Infested Trees. Nematologica
1972, 18, 120–124. DOI: 10.1163/187529272X00296.
clo[3.3.1.]nonanes and [3.2.1.]octanes. USH1838 H, 2000.
[13] Clough, M. S.; Godfrey, C. R. A.; Lewis, T.; Salmon, R.; Urch,
C. J. Amines biclycliques utilises comme insecticide.
WO1996037494, 1996.
[3] Dropkin, V. H.; Foudin, A. S. Report of the Occurrence of
Bursaphelenchus lignicolus–Induced Pine Wilt Disease in
Missouri. Plant Dis. 1979, 63, 904–905.
[14] Lindell, S.; Sanft, U.; Thoenessen, M. T. Azabicyclo and azacy-
clo oxime and amine compounds as pesticides. WO2001015532,
2001.
[4] Mota, M. M.; Braasch, H.; Bravo, M. A. First Report of
Bursaphelenchus xylophilus in Portugal and in Europe.
Nematology 1999, 1, 727–734. DOI: 10.1163/156854199508757.
[5] Kwon, T. S. Change of Abundance of Arthropods in Pine
Forests Caused by Aerial Insecticide Spray. Arch. Environ.
Contam. Toxicol. 2008, 54, 92–106. DOI: 10.1007/s00244-007-
9013-5.
[6] Kwon, H. R.; Choi, G. J.; Choi, Y. H.; Jang, K. S.; Sung, N. D.;
Kang, M. S.; Moon, Y.; Lee, S. K.; Kim, J. C. Suppression of
Pine Wilt Disease by an Antibacterial Agent, Oxolinic Acid.
Pest. Manag. Sci. 2010, 66, 634–639. DOI: 10.1002/ps.1920.
[7] Chin, W.; Mons, M.; Dognon, J. P.; Piuzzi, F.; Tardivel, B.;
Dimicoli, I. Competition between Local Conformational
Preferences and Secondary Structures in Gas-Phase Model
Tripeptides as Revealed by Laser Spectroscopy and Theoretical
Chemistry. Phys. Chem. Chem. Phys. 2004, 6, 2700–2709. DOI:
10.1039/b315470j.
[15] Trowell, S.; Saubern, S.; Liao, C. Agonists and antagonists of
5H3-like receptors of invertebrates as pesticides. WO
2003015517, 2003.
[16] Song, G. H.; Xu, J.; Lu, Q.; Wang, J. Y. Azabicycle derivative,
preparation and application. CN105294674, 2016. DOI: 10.
1155/2016/4103847.
[17] Singh, S. K.; Singh, K. N. Superoxide Ion–Promoted Facile
One-Pot Synthesis of O-Alkyl-S-Methyl Dithiocarbonates from
Alcohol under Mild Reaction Conditions. Phosphorus, Sulfur
Silicon Relat. Elem. 2010, 186, 94–97. DOI: 10.1080/10426507.
2010.482545.
[18] Chaturvedi, D.; Ray, S. An Efficient, Basic Resin Mediated,
One-Pot Synthesis of O-alkyl-S-Methyl Dithiocarbonates from
the Corresponding Alcohols. J. Sulfur Chem. 2006, 27, 265–270.
DOI: 10.1080/17415990600701697.
[19] Humeres, E.; Sanchez, M. N. M.; Lobato, C. M. L.; Debacher,
N. A.; Souza, E. P. The Mechanisms of Hydrolysis of Alkyl
N-Alkylthioncarbamate Esters at 100 ꢀC. Can. J. Chem. 2005,
83, 1483–1491. DOI: 10.1139/v05-165.
[8] Raju, B.; Ramesh, M.; Borkar, R. M.; Raju, P.; Sanjay, K. B.
In Vivo Metabolic Investigation of Moxifloxacin Using Liquid
Chromatography/Electrospray
Ionization
Tandem
Mass
[20] Sudo, Y.; Yamaguchi, E.; Itoh, A. Photo-Oxidative Cross-
Dehydrogenative Coupling-Type Reaction of Thiophenes with
a-Position of Carbonyls Using a Catalytic Amount of Molecular
Iodine. Org. Lett. 2017, 19, 1610–1613. DOI: 10.1021/acs.orglett.
7b00428.
Spectrometry in Combination with Online Hydrogen/
Deuterium Exchange Experiments. Rapid Commun. Mass
Spectrom. 2012, 16, 1817–1831. DOI: 10.1002/rcm.6288.
[9] Carlisle, J. B.; Stevenson, C. A. Drugs for Preventing
Postoperative Nausea and Vomiting. Cochrane Db. Syst. Rev. [21] Lu, L.; He, C. H.; Yao, W. Q. Pyrazine derivatives as FGFR
2006, 3, 1–133. DOI: 10.1002/14651858.CD004125.pub3.
inhibitors. WO2014026125, 2014.
[10] Lee, S. S.; Peter, J.; Panagiota, M.; Wellington, A.; Antonio, A. [22] Monaem, B.; Aurelie, P.; Celine, M.; Marie, H.; Quentin, T.;
The Role of Second-Generation 5-HT3 Receptor Antagonists in
Managing Chemotherapy-Induced Nausea and Vomiting in
Hematological Malignancies. Crit. Rev. Oncol. Hematol. 2012, 1,
59–70. DOI: 10.1016/j.critrevonc.2011.09.005.
Mohamed, L. E.; Johan, W.; Steve, L. Synthesis of 4- and
5-Arylthiazolinethiones as Inhibitors of Indoleamine
2,3-Dioxygenase. Bioorg. Med. Chem. Lett. 2017, 15, 3607–3610.
DOI: 10.1016/j.bmcl.2016.06.052.