Synthesis, crystal structure and biological activity of two 1,2,3-thiadiazole derivatives

Article abstract of DOI:10.1007/s10870-011-0101-z

The title compounds, quinolin-8-yl 4-methyl- 1,2,3-thiadiazole-5- carboxylate 2a and 2-nitrophenyl 4-methyl-1,2,3-thiadiazole-5-carboxylate 2b, synthesized by the reaction of 4-methyl-1,2,3-thiadiazole-5-carbonyl chloride with 8-hydroxyquinoline and 2-nit

Full text of DOI:10.1007/s10870-011-0101-z

J Chem Crystallogr (2011) 41:1348–1354
DOI 10.1007/s10870-011-0101-z
ORIGINAL PAPER
Synthesis, Crystal Structure and Biological Activity of Two
1,2,3-Thiadiazole Derivatives
•
Shou-Xin Wang Jie Huang Zhi-Jin Fan Huan Wang
•
•
•
•
•
•
Yi-Feng Fu Na Mi Zheng-Cai Zhang Hai-Bin Song
•
•
Nataliya P. Belskaya Vasiliy A. Bakulev
Received: 13 January 2011 / Accepted: 15 April 2011 / Published online: 30 April 2011
Ó Springer Science+Business Media, LLC 2011
Abstract The title compounds, quinolin-8-yl 4-methyl-
1,2,3-thiadiazole-5-carboxylate 2a and 2-nitrophenyl
4-methyl-1,2,3-thiadiazole-5-carboxylate 2b, synthesized
by the reaction of 4-methyl-1,2,3-thiadiazole-5-carbonyl
chloride with 8-hydroxyquinoline and 2-nitrophenol, were
confirmed by single-crystal X-ray diffraction [CCDC
783328 and 784970]. The 2a crystallizes in triclinic
Keywords X-ray diffraction ꢀ Single crystal structure ꢀ
Synthesis ꢀ 1,2,3-Thiadiazole ꢀ Biological activity
Introduction
˚
space group P-1 with cell parameters a = 7.957(7) A,
1,2,3-Thiadiazoles are a versatile class of compounds which
present a wide range of biological activities such as anti-
virus activity [1, 2], systemic acquired resistance [3], anti
HIV [4], fungicide activity [3, 5–8], insecticide activity [9],
antitumor activity [10], and herbicide activity [11, 12].
Moreover, the properties of easy breakdown of the 1,2,3-
thiadiazole ring into low molecular weight compounds
through release of N2 favor the use of its derivatives as
environmentally friendly pesticide candidates with low
toxicity [13]. Some 1,2,3-thiadiazoles including acibenzo-
lar-S-methyl (BTH) [14] and tiadinil (TDL) [15] are com-
mercialized as plant activators [4, 16]. The plant activator is
any compound with low or no direct activity against a
pathogen, but acts by stimulating the immunosystem of the
host plants to produce systemic acquired resistance against
the succeeding pathogen attacking [16, 17].
˚
˚
b = 8.378(7) A, c = 10.097(10) A, a = 100.63(2)°, b =
112.742(17)°, c = 93.287(4)° and Z = 2. The 2b crystal-
lizes in triclinic space group P-1 with cell parameters
˚
˚
˚
a = 7.134(4) A, b = 8.154(4) A, c = 10.254(5) A, a =
99.501(9)°, b = 91.311(7)°, c = 109.518(8)° and Z = 2.
Packing in the compound 2a is dominated by weak
C–HꢀꢀꢀN and C–HꢀꢀꢀO hydrogen bonds. In the compound
2b, molecules are linked through intermolecular C–HꢀꢀꢀO
hydrogen bonds interactions. The preliminary bioassay
showed that the title compound 2a had excellent antifungal
activity with the EC50 detected as from 2.99 to 28.35 lg/mL
and the EC90 detected as from 21.041 to 175.17 lg/mL.
Both of the title compounds 2a and 2b had good inhibition
activity of tobacco mosaic virus (TMV) and good induction
activity of tobacco against TMV with potential systemic
acquired resistance.
Our group has focused attention on the synthesis and
characterization of various 1,2,3-thiadiazole derivatives and
their biological activities. The previous studies explored
series of thiazole-, oxadiazole- and active substructure of
3-chloro-4-methylphenyl containing 1,2,3-thiadiazole
derivatives and discovered their good systemic acquired
resistance to tobacco against TMV and certain degree of
fungi growth inhibition in vitro or in vivo [3, 7, 18]. By
introducing 2-naphthyl into 1,2,3-thiadiazole carboxylic
acid ester, a compound was found to be active against fungi
and tobacco mosaic virus (TMV) [19], prompted by these
observations, more new 1,2,3-thiadiazole carboxylic acid
S.-X. Wang ꢀ J. Huang ꢀ Z.-J. Fan (&) ꢀ H. Wang ꢀ Y.-F. Fu ꢀ
N. Mi ꢀ Z.-C. Zhang ꢀ H.-B. Song
State Key Laboratory of Elemento Organic Chemistry, Nankai
University, 94 Weijin Road, Nankai District, Tianjin 300071,
China
e-mail: fanzj@nankai.edu.cn
N. P. Belskaya ꢀ V. A. Bakulev
The Ural Federal University Named after the First President
of Russia B. N. Yeltsin, Yeltsin UrFU, 620002 Ekaterinburg,
Russia
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J Chem Crystallogr (2011) 41:1348–1354
1349
Quinolin-8-yl 4-methyl-1,2,3-thiadiazole-5-carboxylate
(2a). (0.42 g, 73%); white solid, m.p. 138–139 °C. IR
(KBr, cm-1): 2926 (mCH, w), 1748(mC=O, s), 1589, 1515
(mC=C, mC=N, m), 1205 (mC–O–C, s). 1H NMR (CDCl3,
400 MHz): d8.89 (s, 1H, quinoline-H), 8.40(d, 1H,
J = 8.4 Hz, quinoline-H), 7.83 (d, 1H, J = 7.6 Hz, quin-
oline-H), 7.56–7.63 (m, 2H, quinoline-H), 7.47–7.49 (m,
1H, quinoline-H), 3.08(s, 3H, CH3 of 1,2,3-thiadiazole
ring), HRMS calcd. for C13H9N3O2S (M??H): 272.0488;
Found: 272.0492.
CH3
O
CH3
N
N
N
Et3N
Cl
O
R
N
R-OH
+
S
S
CH2Cl2, r. t.
O
1
2
R = 8-quinolyl, 2a; 2-nitrophenyl, 2b
Scheme 1 Synthesis route of the title compound 2
esters were synthesized for biological screening [20]. In this
paper, two new 1,2,3-thiadiazole compounds, quinolin-8-yl
4-methyl-1,2,3-thiadiazole-5-carboxylate, 2a, and 2-nitro-
phenyl 4-methyl-1,2,3-thiadiazole-5-carboxylate, 2b were
synthesized and characterized. Their synthetic route was
showed in Scheme 1.
2-Nitrophenyl 4-methyl-1,2,3-thiadiazole-5-carboxylate
(2b). (0.35 g, 62%); white solid, m.p. 78–79 °C. IR (KBr,
cm-1): 3096, 2852 (mCH, w), 1760(mC=O, s), 1592, 1532
(mC=C, mC=N, m), 1199(mC–O–C, s). 1H NMR (400 MHz,
CDCl3): d8.23 (d, 1H, J = 8.4 Hz, Ph-H), 7.77 (t, 1H,
J = 7.8 Hz, Ph-H), 7.54 (t, 1H, J = 7.8 Hz, Ph-H), 7.40
(d, 1H, J = 8.4 Hz, Ph-H), 3.04 (s, 3H, CH3 of 1,2,3-
thiadiazole ring). HRMS calcd. for C10H7N3O4S (M??H):
266.0230; Found: 266.0224.
Experimental Procedures
Reagents and Measurements
Crystal Data and Structure Determination
All starting materials and solvents (A. R. grade) were
purchased from J&K Scientific Ltd. (China) and used
without further purification. The melting point was deter-
mined on an XT-4A apparatus and the thermometer was
uncorrected. Infrared spectra were recorded on a Bruker
A single crystal of 2a with dimensions of 0.24 mm 9
0.20 mm 9 0.18 mm was selected for X-ray diffraction
studies. The data were collected on a Bruker Smart 1000
CCD diffractometer equipped with a graphite-monochro-
1
˚
matic Mo-Ka radiation (k = 0.71073 A) at 113(2) K. A
Equinox 55 Spectrophotometer by a KBr pellet press. H
total of 5678 reflections including 2043 independent ones
(Rint = 0.0344) were collected within the range of
2.50 B h B 25.01° by using an x scan mode, of which
1951 observed reflections with I [ 2r(I) were considered
as observed and used in the succeeding refinements.
The ranges of h, k, l are -9 B h B 9, -9 B k B 9,
-11 B l B 11, respectively.
NMR spectra were measured on a Bruker AC-P500
Instrument (400 MHz) with CDCl3 as the solvent and TMS
as the internal standard. High-resolution mass spectrometry
(HRMS) data were obtained on an FTICR-MS Varian 7.0T
FTICR-MS instrument. The single-crystal structure was
determined on a Bruker SMART 1000 CCD diffractome-
ter. The equipment was operated using Mo-Ka radiation
˚
A single crystals of 2b of dimensions 0.18 mm 9
0.16 mm 9 0.12 mm was chosen for X-ray diffraction
studies on the same instrument at 116(2) K. A total of 4075
reflections including 1933 independent ones (Rint = 0.0292)
were collected within the range of 2.02 B h B 25.02° by
using a u and x scan mode, of which 1614 observed
reflections with I [ 2r(I) were considered as observed and
used in the succeeding refinements. The ranges of h, k, l are
-8 B h B 8, -8 B k B 9, -12 B l B 12, respectively.
Both structures were solved by direct methods using the
program SHELXS-97 [21]. Refinements were done by the
full-matrix least-squares on F2 with SHELXL-97 [22].
Non-hydrogen atoms were refined with anisotropic dis-
placement parameters. The hydrogen atoms were placed in
calculated positions and refined using a riding model, with
(k = 0.71073 A).
Synthesis of the Title Compounds 2a and 2b
The 4-methyl-1,2,3-thiadiazole-5-carbonyl chloride 1 was
synthesized according to reference [3].
To a mixture of phenol (2.1 mmol) and triethylamine
(3.1 mmol) in dichloromethane (20 mL) stirred at room
temperature, 4-methyl-1,2,3-thiadiazole-5-carbonyl chlo-
ride 1 (2.5 mmol) in dichloromethane (10 mL) was added
dropwise within 20 min. The reaction mixture was stirred
for 6 h at room temperature and then washed with water
(30 mL) followed by brine (30 mL). The organic layer was
dried over Na2SO4 and then evaporated under reduced
pressure after filtration. The product was purified by col-
umn chromatography on silica gel [eluent: petroleum ether/
acetic ether 4:1 (v/v)].
Uiso(H) = 1.2 Ueq(C) and Uiso (H) = 1.5 Ueq (C). The
details of crystal data and refinement are given in Table 1.
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Table 1 Crystal data and
structure refinement for
2a and 2b
Empirical formula
Formula weight
T/K
C13H9N3O2S (2a)
271.29
C10H7N3O4S (2b)
265.25
113(2)
116(2)
˚
Radiation, k/A
0.71073
0.71073
Crystal system, Space group
Triclinic, P-1
a = 7.957(7)
b = 8.378(7)
c = 10.097(10)
b = 112.742(17)
604.0(10)
Triclinic, P-1
a = 7.134(4)
b = 8.154(4)
c = 10.254(5)
b = 91.311(7)
552.5(5)
˚
Unit cell dimensions/A and °
3
˚
Volume/A
Z
2
2
Calculated density/g cm-3
Absorption coefficient/mm-1
F(000)
1.492
1.594
0.269
0.304
280
272
Crystal size/mm
0.24 9 0.20 9 0.18
2.50 to 25.01
0.18 9 0.16 9 0.12
2.02 to 25.02
Theta range/°
Index ranges
-9 B h B 9, -9 B k B 9,
-11 B l B 11
5678
-8 B h B 8, -8 B k B 9,
-12 B l B 12
4075
Reflections collected
Independent reflections
2043 [R(int) = 0.0344]
96.4%
1933 [R(int) = 0.0292]
98.9%
Completeness to h max.
Max. and min. transmission
Observed data/restraints/parameters
Goodness-of-fit on F2
0.9533 and 0.9384
2043/0/173
0.9644 and 0.9473
1933/0/164
1.207
1.101
Final R indices [I [ 2r(I)]
R1 = 0.0696
R1 = 0.0313
wR2 = 0.1612
R1 = 0.0707
wR2 = 0.0839
R1 = 0.0362
R indices (all data)
wR2 = 0.1625
0.573 and -0.743
wR2 = 0.0857
0.229 and -0.274
-3
Largest diff. peak and hole/e-
˚
A
Biological Screening
corresponding control. Fungi used in this study included
Alternaria solani (AS), Botrytis cinerea (BC), Cercospora
arachidicola (CA), Gibberella zeae (GZ), Phytophthora
infestans (Mont) de Bary (PI), Physalospora piricola (PP),
Pellicularia sasakii (PS), Sclerotinia sclerotiorum (SS), and
Rhizoctonia cerealis (RC). Precision toxicity studies were
conducted according to the above methods by determina-
tion of growth inhibition of specific fungi using the same
compound by five to seven different concentrations; the
EC50 and EC90 were calculated by the linear regression of
logarithm of the concentration with probability of the
corresponding growth inhibition by Excel [6].
Fungicide Screening
Preliminary screening was conducted by fungi growth
inhibition method according to the reference using potato
dextrose agar (PDA) as cultivation medium [3, 5]. A stock
solution of each compound was prepared at 500 lg/mL
using sterilized water containing two drops of N,N-
dimethylformamide (DMF) as a solvent, then 1 mL of the
stock solution was transferred into a 10 cm diameter of
Petri dish, 9 mL of PDA was then added to prepare the
plate containing 50 lg/mL of the test compound. Before
the plate solidification, the PDA was thoroughly mixed by
turning around the Petri dish in the sterilized operation
desk five times to scatter the compound in PDA evenly.
Then, 4 mm of diameter of fungi cake was inoculated on
the plate and cultured in the culture tank at 24–26 °C. The
diameter of fungi spread was measured 2 days later.
Growth inhibition was then calculated using the
Systemic Acquired Resistance Screening
Systemic acquired resistance of the target compounds was
detected using tobacco against the tobacco mosaic virus
(TMV) system as described in ref [1, 3, 7]. The induction
activity was evaluated using the antivirus inhibition ratio,
which was calculated by the average number of viral
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J Chem Crystallogr (2011) 41:1348–1354
1351
Fig. 1 Molecular plot of the
asymmetric units of
C13H9N3O2S (2a) and
C10H7N3O4S (2b) showing the
labeling scheme of the non-H
atoms and their displacement
ellipsoids at the 50% probability
level
˚
inflammations on the inoculated leaves with the corre-
sponding control accordingly. Tiadinil (TDL) and ribavirin
were chosen as positive control and negative control,
respectively, and all compounds tested were conducted at
500 and 100 lg/mL, respectively.
Protective, inactivation and curative effects of the target
compounds against TMV in Vivo were detected according
to the description of ref [1]. TMV concentration was
5.88 9 10-2 lg/mL, and the concentrations of test com-
pounds were 500 and 100 lg/mL, respectively. Before the in
vivo test, the in vitro activity determination was conducted
by traditional half juicy robbing method at 500 lg/mL as
described in ref [3, 7, 20]. TDL, ribavirin and Ningnanmycin
were chosen as corresponding control.
Table 2 Selected bond lengths (A) and bond angles (°) for the
title compounds
2a
S(1)–N(2)
S(1)–C(3)
O(2)–C(4)
O(2)–C(5)
O(1)–C(4)
N(1)–N(2)
C(1)–C(2)
C(2)–C(3)
C(4)–C(3)
C(2)–N(1)
2b
1.672 (2)
1.700(3)
1.358(3)
1.416(3)
1.208(3)
1.299(3)
1.497(3)
1.383(3)
1.474(3)
1.371(3)
N(2)–S(1)–C(3)
N(2)–N(1)–C(2)
O(1)–C(4)–O(2)
O(1)–C(4)–C(3)
O(2)–C(4)–C(3)
N(1)–C(2)–C(3)
C(2)–C(3)–S(1)
C(4)–C(3)–S(1)
N(1)–C(2)–C(1)
N(1)–N(2)–S(1)
92.71(12)
114.4(2)
124.33(19)
125.4(2)
110.21(18)
112.5(2)
108.43(17)
123.69(17)
119.4(2)
111.89(18)
The anti-TMV activities were calculated by the average
number of viral inflammations on the inoculated leaves
with the corresponding control according to Eq. 1.
S(1)–N(2)
S(1)–C(3)
O(2)–C(4)
O(2)–C(5)
O(1)–C(4)
N(1)–N(2)
C(1)–C(2)
C(2)–C(3)
C(4)–C(3)
N(1)–C(2)
1.6635(16)
1.6923(19)
1.3714(18)
1.3959(19)
1.195(2)
N(2)–S(1)–C(3)
N(2)–N(1)–C(2)
N(1)–N(2)–S(1)
N(1)–C(2)–C(3)
N(1)–C(2)–C(1)
C(2)–C(3)–S(1)
C(4)–C(3)–S(1)
O(1)–C(4)–O(2)
O(1)–C(4)–C(3)
O(2)–C(4)–C(3)
92.77(8)
113.96(15)
111.98(12)
112.53(16)
119.44(16)
108.76(13)
124.33(12)
124.28(15)
126.50(14)
109.23(14)
CK ꢁ A
Y ¼
ꢂ 100%
ð1Þ
CK
1.305(2)
where Y is the antivirus inhibition ratio (%), CK is the
average number of viral inflammations on the control
leaves, and A is the average number of viral inflammations
on the target compound treated leaves.
1.482(2)
1.376(2)
1.469(2)
1.371(2)
Results and Discussion
conjugation between thiadiazole ring and C(4)=O(1) bond,
˚
the bond lengths of C(2)=C(3) (1.383(3) A in 2a and
Crystallographic Structure
˚
1.376(2) A in 2b) and N(1)=N(2) (1.299(3) in 2a and
˚ ˚
1.305(2) A in 2b) A) are slightly longer than that of typical
The molecular structure of compounds 2a and 2b are
shown in Fig. 1, and selected bond lengths and angles are
listed in Table 2.
˚
C=C bond (1.34 A) [25] and N=N bond (1.24 A) [26],
˚
respectively, and the bond lengths of C(3)–C(4) (1.474(3)
˚
A in 2a and 1.469(2)A in 2b) and C(2)–N(1) (1.371(3) A)
˚
in 2a and 1.371(2) A) in 2b) are slightly shorter than
˚
˚
Bond lengths and bond angles within the thiadiazole of
2a and 2b agree well with the values reported [23]. In both
compounds, the angles of O(1)–C(4)–C(3), O(1)–C(4)–
O(2) and O(2)–C(4)–C(3) are 360°, this indicates the sp2
hybridization state of C(4) atom.
˚
˚
typical C–C bond (1.54 A) [27] and C–N bond (1.47 A)
[28].
The torsion angles of C(2)–C(3)–C(4)–O(1) and S(1)–
C(3)–C(4)–O(2) in compound 2a are -2.8(4)° and
-0.2(3)°, respectively, this indicates that the ester group
and the thiadiazole ring are basically coplanar; while, the
similar torsion angles in compound 2b are -7.6(3)° and
-9.1(2)°, respectively, this proves that the ester group has
In the two title compounds, because of the P–p conju-
˚
gate effect, the C(4)–O(2) bond (1.358(3) A in 2a and
˚
1.3714(18) A in 2b) is obviously shorter than the typical
˚
C–O bond (1.43 A) [24] and normal C(5)–O(2) bond
˚
(1.416(3) A in 2a and 1.3959(19) A in 2b); due to the
˚
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J Chem Crystallogr (2011) 41:1348–1354
hydrogen bond C(7)–H(7)ꢀꢀꢀO(4), forming a one-dimen-
sional chain structure which can be seen in Fig. 3. No
direct p–p interactions are observed among all aromatic
rings in the unit cell of the two compounds.
Table 3 Intermolecular hydrogen bonds of the title compounds
˚
˚
˚
Compd. D–HꢀꢀꢀA
dD–H/A dHꢀꢀꢀA/A dDꢀꢀꢀA/A \DHA/(8)
2a
C(6)–H(6) 0.95
ꢀꢀꢀN(1)i
C(8)–H(8) 0.95
2.61
2.57
2.51
3.375(4) 138.4
3.286(4) 132.6
3.421 (4) 166.0
ꢀꢀꢀO(1)ii
C(7)–H(7) 0.93
2b
Biological Activities
ꢀꢀꢀO(4)iii
Symmetry codes: (i) -x, 2 - y, 1 - z; (ii) -1/2 - x, 1 - y, -z; (iii)
x, -1 ? y, z
Fungicidal Activity
The nine fungi representing typical disease commonly
occurring in the Chinese agro-ecosystem including AS,
BC, CA, SS, RC, GZ, PI, PP and PS were chosen for
screening. The preliminary bioassay results indicated that
the title compound 2a completely inhibited all the nine
fungi tested at 50 lg/mL. Precession toxicological studies
showed that, the EC50 were detected as from 2.99 to
28.35 lg/mL, while the EC90 were detected as from 21.04
to 175.17 lg/mL (Table 4). The title compound 2b had
26.3, 67.7, 0, 58.0, 55.1, 16.7, 20.8, 43.3 and 42.1% of
inhibition against AS, BC, CA, SS, RC, GZ, PI, PP and PS
at 50 lg/mL, respectively. The bioassay results indicated
that quinolyl ester had much better fungicide activity than
phenyl ester.
Anti-TMV Activity In Vitro and In Vivo
Tiadinil, ribavirin and Ningnanmycin were used as three
positive controls. The results of activity screening by half-
leaf juice-robbing method against tobacco mosaic virus
(TMV) indicated that (Table 5) the two title compounds
showed a good direct inhibition activities against TMV in
vitro. Compounds 2a and 2b had inhibition activities of
50% at 100 lg/mL and 58% at 500 lg/mL, respectively,
which were significantly higher than those of three positive
control agents.
Fig. 2 View of the bidimensional self-arrangement of 2a cemented
by C(6)–H(6)ꢀꢀꢀN(1)i and C(8)–H(8)ꢀꢀꢀO(1)ii non-classical H bonds
[symmetry code (i) -x, 2 - y, 1 - z; (ii) -1/2 - x, 1 - y, -z]
little deviation from the thiadiazole ring. This difference is
caused by the steric hindrance between nitro and ester
group in 2b. The dihedral angle between thiadiazole and
quinolin in 2a, thiadiazole and benzene in 2b are 79.4° and
78.1°, respectively.
There are no classic hydrogen bonds in the two struc-
tures, but weak C–HꢀꢀꢀN and C–HꢀꢀꢀO intramolecular
interactions are observed, as detailed in Table 3.
The in vivo antivirus activity of two title compounds
including protection, inactivation, curative effect, and the
inductive activities were also evaluated. The results listed
in Table 5 indicated that, the two compounds had good
inactivation activity against TMV. Compounds 2a and 2b
had inactivation activities of 62 and 64% at 500 lg/mL,
respectively, and 52 and 50% at 100 lg/mL, respectively,
which were equal to or better than those of the three
positive control agents. Moreover, compounds 2b had
The neighboring molecules of compound 2a form a
bidimensional chain structure using non-classical C(6)–
H(6)ꢀꢀꢀN(1) and C(8)–H(8)ꢀꢀꢀO(1) hydrogen bonds which
can be seen in Fig. 2. The neighboring molecules of
compound 2b are connected together with intermolecular
Fig. 3 View of the one-
dimensional chain structure of
2b cemented by C(7)–
H(7)ꢀꢀꢀO(4)iii non-classical H
bonds [symmetry code (iii) x,
-1 ? y, z]
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J Chem Crystallogr (2011) 41:1348–1354
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Table 4 EC50 and EC90
determination of the title
compound 2a
Name of Fungi
Regression equation
R2
EC50 (lg/mL)
EC90 (lg/mL)
PI
y = 1.6184x ? 2.6492
y = 1.3898x ? 3.4258
y = 0.8510x ? 4.5954
y = 1.0685x ? 4.0245
y = 2.0189x ? 2.6304
y = 1.5386x ? 4.2467
y = 1.9089x ? 3.3645
y = 1.3598x ? 3.3954
y = 1.4954x ? 3.2208
0.9836
0.9322
0.952
28.35
13.57
2.99
175.17
113.16
95.40
CA
PP
BC
SS
RC
PS
AS
GZ
0.9094
0.9021
0.9938
0.9421
0.9494
0.898
8.18
129.09
64.23
14.92
3.09
21.04
7.19
33.68
15.14
15.48
132.23
111.11
Table 5 Activity against TMV of the title compounds 2a and 2b
Compd.
Concentration Half leaf
(lg/mL)
Inactivation
Curative
Induction
Protection
activity SD (%) activity SD (%) activity SD (%) activity SD (%) activity SD (%)
2a
500
100
500
100
500
100
500
100
45
50
58
36
39
36
43
36
49
39
2
7
4
4
4
2
3
4
4
6
62
52
64
50
39
2
2
4
1
1
48
32
55
43
49
36
60
59
72
56
0
8
2
4
4
4
9
2
1
2
51
32
31
53
58
3
3
6
5
7
53
28
59
29
56
21
47
6
6
5
4
2
5
6
2b
Ribavirin
Tiadinil
31 10
51 10
57
37
58
51
3
8
7
2
51
59
40
59
3
4
6
5
49 13
Ningnanmycin 500
100
56
58
2
2
2011BAE06B05) and the Foundation of Achievements Transforma-
tion and Spreading of Tianjin Agricultural Science and Technology
(No. 201002250), the Key Laboratory of Pesticide Chemistry and
Application, Ministry of Agriculture (MOA) (No. MOAPCA200903),
and the Russian Foundation for Basic Research (grant numbers RFBR
08-03-00376a and RFBR/NNSF 08-03-92208 a) for support of this
crystallographic investigation and biological activity determination.
protection activity of 59% at 500 lg/mL, which was also
higher than that of the three positive control agents.
Therefore, apart from introducing F atom [18, 29],
introducing quinolyl moiety can also improved the bio-
logical activity of the 1,2,3-thiadiazoles.
Supplementary Information
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