Synthesis, characterization and antiamoebic activity of 1-(thiazolo[4,5-b]quinoxaline-2-yl)-3-phenyl-2-pyrazoline derivatives

Article abstract of DOI:10.1016/j.bmcl.2006.01.116

A new series of 1-N-thiocarboxamide-3-phenyl-2-pyrazolines 1-6 was synthesized by cyclization of different Mannich bases with unsubstituted thiosemicarbazide. The reaction of cyclized pyrazoline derivatives 1-6 with 2,3-dichloroquinoxaline afforded the title compounds 7-12. The structures of the new compounds were confirmed by elemental analyses as well as ¹H, ¹³C NMR, IR and electronic spectral data. The HM1:IMSS strain of Entamoeba histolytica parasite was cultured in vitro and the sensitivity of the parasite to the synthesized compounds was evaluated using the microdilution method. Among all the pyrazoline derivatives 1-6, none was found to be a better inhibitor as compared to the reference drug, metronidazole. The quinoxaline derivatives, 9, 11 and 12 were found to be potent inhibitors of E. histolytica.

Full text of DOI:10.1016/j.bmcl.2006.01.116

Bioorganic & Medicinal Chemistry Letters 16 (2006) 2812–2816
Synthesis, characterization and antiamoebic activity of
1-(thiazolo[4,5-b]quinoxaline-2-yl)-3-phenyl-2-pyrazoline derivatives
Mohammad Abid and Amir Azam*
Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
Received 9 June 2005; revised 27 January 2006; accepted 31 January 2006
Available online 21 February 2006
Abstract—A new series of 1-N-thiocarboxamide-3-phenyl-2-pyrazolines 1–6 was synthesized by cyclization of different Mannich
bases with unsubstituted thiosemicarbazide. The reaction of cyclized pyrazoline derivatives 1–6 with 2,3-dichloroquinoxaline affor-
ded the title compounds 7–12. The structures of the new compounds were confirmed by elemental analyses as well as 1H, 13C NMR,
IR and electronic spectral data. The HM1:IMSS strain of Entamoeba histolytica parasite was cultured in vitro and the sensitivity of
the parasite to the synthesized compounds was evaluated using the microdilution method. Among all the pyrazoline derivatives 1–6,
none was found to be a better inhibitor as compared to the reference drug, metronidazole. The quinoxaline derivatives, 9, 11 and 12
were found to be potent inhibitors of E. histolytica.
Ó 2006 Elsevier Ltd. All rights reserved.
Amoebiasis is a protozoan infection caused by Entamoe-
ba histolytica. The prevalence of amoebic colitis, brain
and liver abscess is greater in developing world.1,2
Amoebiasis is the second leading cause of death world-
wide.3 More than 50 million people are infected and up
to 110,000 of these die per annum.4 There are numerous
antiamoebic compounds used in medical practice such
as nitroimidazoles. Metronidazole [1(b-hydroxyethyl)-
2-methyl-5-nitroimidazole] is the drug of choice for the
treatment of anaerobic protozoan and bacterial infec-
tions.5–10 Treatment failures among patients with amoe-
biasis often raise the possibility of drug resistance.11
Therefore, it is desirable to search for new leads as
amoebicidal.
MeCys3,N-MeCys7]TANDEM.22 In view of the above
considerations and as part of our continuous efforts to-
wards the identification of more potent amoebicidal,23–
25 we report herein the synthesis of new 1-N-thiocarbox-
amide-3-phenyl-2-pyrazolines 1–6, their quinoxaline
derivatives, 1-(thiazolo[4,5-b]quinoxaline-2-yl)-3-phen-
yl-2-pyrazolines 7–12 and in vitro screening of these
compounds against HM1:IMSS strain of E. histolytica.
To the best of our knowledge, this is the first report of
cyclized pyrazoline derivative having a quinoxaline
moiety and showing very encouraging results as regards
in vitro activity against E. histolytica.
Mannich bases of different ketones (0.2 mol) were
prepared by the reaction with paraformaldehyde
(0.26 mol) and dimethylamine hydrochloride (0.26 mol)
under reflux in a mixture of 35 mL of ethanol and
0.5 mL of concd HCl. The reaction works best when a
minimum amount of ethanol and 2 mL of acid/mol ke-
tone are added. After cooling, 200 mL of acetone was
added. The crystals formed were collected, washed with
acetone and dried in vacuo. The methyl phenyl ketone
and ethyl phenyl ketone gave high yields of about 60–
90%, while the yields for 3-bromo and 3-chloro acetoph-
enone and propeophenone in the Mannich reaction were
lower in the range of 30–60%. The Mannich bases have
been reported earlier.23,26 Mannich reaction product
(0.5 mmol) was cyclized with unsubstituted thiosemicar-
bazide (0.5 mol) under basic conditions in methanol
(5 mL) to give 1-N-thiocarboxamide-3-phenyl-2-pyrazo-
Pyrazolines, bicyclic pyrazolines and quinoxalines are
nitrogen-containing heterocyclic compounds, well
known for their pronounced anti-inflammatory activi-
ty.12–20 These compounds have been developed as
non-steroidal anti-inflammatory drugs. They block the
formation of prostaglandins and have analgesic, antipy-
retic and anti-inflammatory activity.21 The quinoxaline
antibiotics are a family of drugs that include the natural-
ly occurring triostin A and the synthetic derivative [N-
Keywords: Mannich bases; Thiocarboxamide; Pyrazolines; Quinoxa-
line; Antiamoebic activity.
*
Corresponding author. Tel.: +91 11 26981717/3253; fax: +91 11
26980229/1232; e-mail: amir_sumbul@yahoo.co.in
0960-894X/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2006.01.116

M. Abid, A. Azam / Bioorg. Med. Chem. Lett. 16 (2006) 2812–2816
2813
lines 1–6. According to the currently accepted mecha-
nism27,28 the formation of the cyclized pyrazoline deriv-
atives is favoured via thiosemicarbazone formation,
which undergo cyclization under basic conditions to
form the desired pyrazoline ring in all the compounds.
The product mixture contained only unreacted starting
material and the cyclization product, which was purified
by column chromatography using silica gel 60 F254, elut-
ed with dichloromethane–methanol (98:2) to give crys-
talline solid compounds but in low yield. All the
cyclized pyrazoline compounds were obtained in
moderate yields (30–50%). The refluxing of 1-N-thio-
carboxamide-3-phenyl-2-pyrazolines 1–6 (0.01 mol)
with 2,3-dichloroquinoxaline (0.01 mol) in absolute eth-
anol (15 mL) gave the corresponding fused 1-(thiazolo-
1–6 showed additional sharp bands in the region
3197–3334 cmꢀ1 due to the m(NH)stretch. The electronic
spectra of the compounds 1–6 studied in the UV region
exhibited three absorption bands at 369.2–293.3, 274.6–
237 and 228–204 nm assignable to n !p*, p ! p* and
n ! r* transitions, respectively. The UV spectral data
of quinoxaline derivatives 7–12 were also studied which
showed the same type of transitions as observed in com-
pounds 1–6. They showed three spectral bands at 388.3–
299, 287–248 and 239–204 nm assigned to n ! p*,
p ! p* and n ! r* transitions of thiocarboxamide
group (C@S), aromatic ring and azomethine nitrogen,
respectively. In the 1H NMR spectra, the pyrazoline
protons at C4 and C5 carbons in compounds 1–3 and
7–9 appeared as broad triplets at 3.2–3.36 (J = 7.14–
9.0 Hz) and 4.18–4.42 (J = 6.87–9.0 Hz) ppm, respec-
tively. The CH2 protons of the pyrazoline ring in
compounds 4–6 and 10–12 were resonated as a pair of
doublets of doublets at 4.43–4.99 (J = 4.5–6.82, 8.5–
11.93 Hz) and 4.06–4.64 (J = 4.5–6.82, 8.5–11.9 Hz).
The CH proton of the pyrazoline ring in the same com-
pounds was observed as a multiplet at 3.5–3.87 ppm.
The strong deshielding of the C5 protons compared with
that of the C4 protons of the pyrazoline ring can be
assumed due to its conformation A.30
[4,5-b]quinoxaline-2-yl)-3-phenyl-2-pyrazolines
7–12
(Scheme 1). All the compounds were obtained in good
yields and are stable in the solid as well as in the solution
state. Analytical and spectral data (IR, electronic, and
1H and 13C NMR) are in good agreement with the com-
position of the compounds.29 Other analytical and phys-
icochemical data of the compounds are presented in
Table 1. The purity of the compounds was established
by thin-layer chromatography (TLC) and elemental
analyses. Selected diagnostic bands of the IR spectra
of 1-N-thiocarboxamide-3-phenyl-2-pyrazolines 1–6
and 1-(thiazolo[4,5-b]quinoxaline-2-yl)-3-phenyl-2-pyr-
azolines 7–12 were very informative and provided evi-
dence for the formation of the expected structures.
The compounds 1–6 showed intense bands at 1021–
1098 cmꢀ1 due to the m(C@S) stretch of the thiocarbox-
amide group, while the compounds 7–12 showed this
band at 991–1094 cmꢀ1. A strong band due to m(C@N)
stretch was observed in the compounds 1–6 at 1530–
1598 cmꢀ1 because of the ring closure. The compounds
7–12 showed two strong bands at 1558–1663 and
1507–1593 cmꢀ1 due to m(C@N) stretch of azomethine
nitrogen of pyrazoline ring and quinoxaline ring, respec-
tively. In addition, the absorption band at 1125–
1187 cmꢀ1 in compounds 1–6 and at 1140–1213 cmꢀ1
in compounds 7–12 was attributed to the m(C–N) stretch
vibrations, which also confirm the formation of desired
pyrazoline ring in all the compounds. The compounds
4
3
R
X
5
2
N
N 1
H2N
A
S
The CH3 protons at C4 carbon of the pyrazoline ring in
compounds 4–6 and 10–12 showed a doublet at 1.12–
1.36 (J = 5.01–6.66 Hz). The NH proton of thiocarbox-
amide group of the compounds (1–6) showed a singlet at
7.88–8.90 ppm. The protons belonging to the aromatic
ring and quinoxaline ring showed multiplet at 6.09–
8.23 ppm. In the 13C NMR spectra, the C4 and C5 car-
bons of the pyrazoline ring in compounds 1–12 resonate
at 42.8–53.2 and 71.2–77.4 ppm, respectively. The com-
R
R
NH2
HCl
.
CH3
CH3
N
N
i
N
C
O
X
S
H
N
NH2
1-6
H2N
X
S
N
Cl
ii
Cl
N
R
N
N
N
N
S
N
7-12
X
Scheme 1. Reagents and conditions: (i) methanol, NaOH, reflux; (ii) absolute ethanol, reflux.

2814
M. Abid, A. Azam / Bioorg. Med. Chem. Lett. 16 (2006) 2812–2816
Table 1. Analytical and physicochemical data of pyrazoline and quinoxaline derivatives (1–12)
S. No. Compound/stoichiometry
Colour
Yield (%) Mp (°C)
Found (Calcd)
H
C
N
1
2
3-Ph-2-Pz-1-TC/C10H11N3S
Dark yellow
Light yellow
Cream
45
38
35
51
118
141
175
97
58.49 (58.53) 5.37 (5.36) 20.62 (20.48)
42.29 (42.25) 3.47 (3.52) 14.62 (14.78)
50.15 (50.10) 4.15 (4.17) 17.48 (17.54)
60.54 (60.27) 5.88 (5.93) 18.97 (19.20)
44.35 (44.29) 4.11 (4.02) 14.01 (14.09)
52.19 (52.07) 4.47 (4.73) 16.62 (16.57)
65.29 (65.26) 3.81 (3.93) 21.08 (21.15)
52.55 (52.68) 2.91 (2.93) 17.02 (17.10)
59.06 (59.10) 3.22 (3.28) 19.14 (19.15)
66.11 (66.10) 4.29 (4.35) 20.22 (20.30)
53.69 (53.78) 3.32 (3.30) 16.45 (16.51)
60.05 (60.10) 3.61 (3.70) 18.39 (18.45)
3-3-BrPh-2-Pz-1-TC/C10H10N3SBr
3-3-ClPh-2-Pz-1-TC/C10H10N3SCl
3-Ph-4-Me-2-Pz-1-TC/C11H13N3S
3-3-BrPh-4-Me-2-Pz-1-TC/C11H12N3SBr
3-3-ClPh-4-Me-2-Pz-1-TC/C11H12N3SCl
3-Ph-2-Pz-1-Tz-Qz/C18H13N5S
3
4
Pale yellow
5
Brownish yellow 44
92
6
Light yellow
Pale yellow
38
70
107
117
174
167
147
179
184
7
8
3-3-BrPh-2-Pz-1-Tz-Qz/C18H12N5SBr
3-3-ClPh-2-Pz-1-Tz-Qz/C18H12N5SCl
3-Ph-4-Me-2-Pz-1-Tz-Qz/C19H15N5S
Creamish yellow 55
9
Dark brown
Yellow solid
49
63
46
41
10
11
12
3-3-BrPh-4-Me-2-Pz-1-Tz-Qz/C19H14N5SBr Light yellow
3-3-ClPh-4-Me-2-Pz-1-Tz-Qz/C19H14N5SCl Yellow
Table 3. In vitro antiamoebic activity of 1-(thiazolo[4,5-b]quinoxaline-
2-yl)-3-phenyl-2-pyrazolines derivatives against HM1:IMSS strain of
Entamoeba histolytica
pounds 1–6 showed a signal at 153.1–156.4 ppm was
assigned due to the azomethine carbon of pyrazoline
ring. The compounds 7–12 showed two signals at
151.1–155.9 and 141.7–146.2 ppm due to azomethine
carbon of the pyrazoline ring and quinoxaline ring,
respectively. Thiocarboxamide carbon (C@S) displayed
a signal at 169.2–181.2 ppm in all the compounds. The
signals from 120.2–140.4 ppm were assumed due to the
aromatic carbons in compounds 1–12.
R
N
N
N
N
S
N
X
Compound
X
R
IC50 (lM)
SDa
All the compounds (1–12) were screened in vitro for
antiamoebic activity against HM1:IMSS strain of E.
histolytica by the microdilution method.31 E. histolytica
trophozoites were cultured in TYIS-33 growth medium
as described previously in wells of 96-well microtitre
plate.32 All the compounds were dissolved in DMSO
(40 lL) at which level no inhibition of amoeba oc-
curs33,34 and the stock solutions of the compounds were
prepared freshly before use at a concentration of 1 mg/
mL. The IC50 values in lM are given in Tables 2 and
3. Metronidazole was used as the reference drug and
7
H
H
H
H
6.76
4.98
1.09
2.34
1.45
0.72
1.69
0.20
0.11
0.08
0.23
0.14
0.10
0.24
8
Br
Cl
H
9
10
CH3
CH3
CH3
11
12
Br
Cl
Metronidazole
a Standard deviation.
sponding dose–response curve. The pyrazoline deriva-
tives 1–6 showed an IC50 value in the range 17.2–
4.4 lM. Out of six compounds in pyrazoline series,
compound 5 with 3-bromo and 4-methyl substitution
and compound 6 with 3-chloro and 4-methyl substitu-
tion showed the low IC50 values (5, IC50 = 5.9 lM; 6,
IC50 = 4.4 lM). The conversion of compounds 1–6 into
quinoxaline derivatives 7–12 results in the increase of
their antiamoebic activity. They showed IC50 in the
range 6.76–0.72 lM. Among all the quinoxaline deriva-
had
a 50% inhibitory concentration (IC50 1.69–
1.82 lM) in our experiments. The results were estimated
as the percentage of growth inhibition compared with
the untreated controls and plotted as probit values as
a function of the drug concentration. The IC50 and
95% confidence limits were interpolated in the corre-
Table 2. In vitro antiamoebic activity of thiocarboxamide-3-phenyl-2-
pyrazolines derivatives against HM1:IMSS strain of Entamoeba
histolytica
tives, the compounds having 3-chloro (9, IC50
=
1.09 lM), 3-bromo-4-methyl (11, IC50 = 1.45 lM) and
3-chloro-4-methyl (12, IC50 = 0.72 lM) substitutions
on the pyrazoline ring were distinctly more potent.
The compound 12 is the most active among the series.
The results were statistically evaluated by analysis of
variance. The null hypothesis was tested using t test.
The significance of the difference between the IC50 val-
ues of metronidazole and the compounds 9, 11 and 12
was evaluated by t test. The values of the calculated t
were found to be higher than the table value of t at
5% level, thus concluding that the character under study
is said to be significantly influenced by the treatment. All
the 3-bromo and 3-chloro substituted cyclised pyrazo-
line derivatives were found to be more active than their
respective unsubstituted analogues. It was concluded
that the presence of 3-bromo or 3-chloro substituents
R
NH2
N
N
S
X
Compound
X
R
IC50 (lM)
SDa
1
H
H
17.2
13.2
8.7
0.15
0.18
0.04
0.11
0.65
0.37
0.31
2
Br
Cl
H
H
3
H
4
CH3
CH3
CH3
10.2
5.9
5
Br
Cl
6
Metronidazole
4.4
1.82
a Standard deviation.

M. Abid, A. Azam / Bioorg. Med. Chem. Lett. 16 (2006) 2812–2816
2815
24. Sharma, S.; Athar, F.; Maurya, M. R.; Naqvi, F.; Azam,
A. Eur. J. Med. Chem. 2005, 40, 557.
25. Singh, S.; Husain, K.; Athar, F.; Azam, A. Eur. J. Pharm.
Sci. 2005, 25, 255.
26. Du, X.; Guo, C.; Hansell, E.; Doyle, P. S.; Caffrey, C. R.;
Holler, T. P.; Mckerrow, J. H.; Cohen, F. E. J. Med.
Chem. 2002, 45, 2695.
on the phenyl ring and 4-methyl group on the pyrazoline
ring greatly effects antiamoebic activity. Detailed studies
of the toxicity, in vivo and mechanism of action of these
compounds are in progress.
27. Ferres, H.; Jackson, W. R. J. Chem. Soc., Chem. Commun.
1969, 261.
Acknowledgments
28. Wiley, R. H.; Jarboe, C. H.; Hayes, F. N.; Hansbury, E.;
Nielsen, J. T.; Callahan, P. X.; Sellars, M. C. J. Org.
Chem. 1958, 23, 732.
Mohammad Abid acknowledges Senior Research
Fellowship from Council of Scientific and Industrial
Research, New Delhi, India. The authors are thankful
to Prof. Alok Bhattacharya and Prof. Sudha Bhattach-
arya, School of Life Sciences and School of Environ-
mental Sciences, Jawaharlal Nehru University, New
Delhi, respectively, for providing laboratory facilities
for antiamoebic activities.
29. All the new compounds (1–12) gave satisfactory spectral
data consistent with their proposed structures. Selected
spectral data for compounds 1–12. Compound 1 kmax
(nm): 367.7, 231.6, 319.8, 227, 220.2, 208; mmax (cmꢀ1):
3273 (NH), 1588 (C@N), 1161 (C–N), 1096 (C@S); 1H
NMR (CDCl3): (d, ppm) 7.74 (s, 2H, NH2), 7.21–7.67 (m,
5H, Ar-H), 4.41 (t, 2H, CH2, J = 7.89 Hz), 3.35 (t, 2H,
CH2, J = 7.89 Hz); 13C NMR (CDCl3): (d, ppm) 181.2
(C@S), 155.5 (C@N), 135.4, 130.1, 127.7, 125.4, 123.8,
121.2 (Ar-C), 75.3 (CH2), 53.2 (CH2).
References and notes
Compound 2 kmax (nm): 324.7, 304, 237, 210.1; mmax
(cmꢀ1): 3334 (NH), 1570 (C@N), 1166 (C–N), 1071
(C@S); 1H NMR (CDCl3): (d, ppm) 7.88 (s, 2H, NH2),
7.26–7.75 (m, 4H, Ar-H), 4.42 (t, 2H, CH2, J = 8.45 Hz),
3.36 (t, 2H, CH2, J = 8.45 Hz); 13C NMR (CDCl3): (d,
ppm) 176.3 (C@S), 156.1 (C@N), 133.6, 130.3, 125.3–
122.9 (Ar-C), 77.4 (CH2), 48.4 (CH2).
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de-Amico, M. D.; Parrillo, C.; Rossi, F.; Marmo, E. Eur.
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Compound 3 kmax (cmꢀ1): 369.2, 328, 239, 227, 204; mmax
(cmꢀ1): 3267 (NH), 1565 (C@N), 1187 (C–N), 1098
(C@S); 1H NMR (CDCl3): (d, ppm) 7.96 (s, 2H, NH2),
7.21–7.77 (m, 4H, Ar-H), 4.31 (t, 2H, CH2, J = 6.87 Hz),
3.31 (t, 2H, CH2, J = 7.14 Hz); 13C NMR (CDCl3): (d,
ppm) 177.2 (C@S), 153.1 (C@N), 132.8, 131.3, 124.3–
120.2 (Ar-C), 75.3 (CH2), 49.1 (CH2).
Compound 4 kmax (cmꢀ1): 358, 326, 249, 228, 204; mmax
(cmꢀ1): 3289 (NH), 1530 (C@N), 1125 (C–N), 1021
(C@S); 1H NMR (CDCl3): (d, ppm) 8.54 (s, 2H, NH2),
7.26–7.74 (m, 4H, Ar-H), 4.43 (dd, 1H, CH, J = 4.5,
11.4 Hz), 4.19 (dd, 1H, CH, J = 4.5, 11.4), 3.82 (m, 1H,
CH), 1.36 (d,3H, CH3, J = 6.4); 13C NMR (CDCl3): (d,
ppm) 177.8 (C@S), 156.4 (C@N), 133.5, 132.3, 127.5,
124.8–122.9 (Ar-C), 77.4 (CH2), 51.2 (CH), 11.6 (CH3).
Compound 5 kmax (cmꢀ1): 341, 322.9, 307.9, 293.1, 274.6,
248.9, 228, 216, 206.1; mmax (cmꢀ1): 3197 (NH), 1597
1
(C@N), 1139 (C–N), 1094 (C@S); H NMR (CDCl3): (d,
ppm) 8.07 (s, 2H, NH2), 7.18–7.87 (m, 4H, Ar-H), 3.5–3.8
(m, 1H, CH), 4.93 (dd, 1H, CH, J = 5.07, 10.22 Hz), 4.21
(dd, 1H, CH, J = 5.07, 10.22 Hz), 1.12 (d, 3H, CH3,
J = 5.01 Hz); 13C NMR (CDCl3): (d, ppm) 177.4 (C@S),
155.2 (C@N), 131.8, 129.4, 127.8–122.2 (Ar-C), 71.2
(CH2), 42.8 (CH), 12.6 (CH3).
Compound 6 kmax (cmꢀ1): 349.8, 321, 308, 293.3, 274.6,
249, 228, 216, 206; mmax (cmꢀ1): 3205 (NH), 1598 (C@N),
1138 (C–N), 1078 (C@S); 1H NMR (CDCl3): (d, ppm)
8.90 (s, 2H, NH2), 7.20–7.84 (m, 4H, Ar-H), 3.5–3.78 (m,
1H, CH), 4.68 (dd, 1H, CH, J = 6.82, 11.93 Hz), 4.06 (dd,
1H, CH, J = 6.82, 11.93 Hz), 1.16 (d, 3H, CH3,
J = 6.66 Hz); 13C NMR (CDCl3): (d, ppm) 176.9 (C@S),
156.1 (C@N), 132.6, 129.7, 125.4–121.2 (Ar-C), 74.1
(CH2), 44.7 (CH), 11.4 (CH3).
Compound 7 kmax (nm): 388.3, 352.9, 309.8, 237.1, 213.8;
m
max/cmꢀ1: 3052 (arom. C–H), 1602 (C@N), 1534 (C@N),
1
21. Lombardino, G. Nonsteroidal Anti-inflammatory Drugs;
Wiley Interscience, John Wiley and Sons: New York,
1985.
22. Addess, K. J.; Feigon, J. Biochemistry 1994, 33, 12397.
23. Abid, M.; Azam, A. Bioorg. Med. Chem. 2005, 13, 2213.
1138 (C–N), 1077 (C@S); H NMR (CDCl3): d 7.04–8.06
(9H, m, aryl-H), 4.18 (2H, t, CH2, J = 7.5 Hz), 3.23 (2H, t,
CH2, J = 7.5 Hz); 13C NMR (CDCl3): (d, ppm) 176.3
(C@S), 155.9 (C@N), 144.2 (C@N), 136.2–122.8 (Ar-C),
77.4 (CH2), 48.4 (CH2).

2816
M. Abid, A. Azam / Bioorg. Med. Chem. Lett. 16 (2006) 2812–2816
Compound 8 kmax (nm): 338, 321, 244, 239, 225, 218,
(C@N), 1213 (C–N), 1094 (C@S); 1H NMR (CDCl3): d
7.16–7.93 (8H, m, aryl-H), 3.5–3.7 (m, 1H, CH), 4.95
(1H,dd, CH, J = 5.66, 8.5 Hz), 4.64 (1H, dd, CH, J = 5.66,
8.5 Hz), 1.12 (3H, d, CH3, J = 5.8 Hz); 13C NMR(CDCl3):
(d, ppm) 179.5 (C@S), 151.1 (C@N), 145.2 (C@N), 139.7–
122.1 (Ar-C), 72.2 (CH2), 48.3 (CH), 11.2 (CH3).
204;mmax/cmꢀ1: 3118 (arom. C–H), 1663 (C@N), 1593
(C@N), 1140 (C–N), 1078 (C@S); 1H NMR (CDCl3): d
6.09–7.90 (8H, m, aryl-H), 4.3 (2H, t, CH2, J = 9.0 Hz),
3.2 (2H, t, CH2, J = 9.0 Hz); 13C NMR (CDCl3): (d, ppm)
175.2 (C@S), 154.2 (C@N), 145.2 (C@N), 140.2-121.5
(Ar-C), 75.1 (CH2), 48.6 (CH2).
Compound 12 kmax (nm): 341, 308, 283, 258, 237, 214, 206;
Compound 9 kmax (nm): 357.1, 343, 299, 239.5, 209.5,
m
max/cmꢀ1: 3042 (arom. C–H), 1630 (C@N), 1584 (C@N),
206.8; mmax/cmꢀ1: 3118 (arom. C–H), 1620 (C@N), 1563
1179 (C–N), 991 (C@S); H NMR (CDCl3): d 7.27–8.05
(8H, m, aryl-H), 3.63-3.87 (m, 1H, CH), 4.99 (1H, dd, CH,
J = 5.6, 8.5 Hz), 4.21 (1H, dd, CH, J = 5.6, 8.5 Hz), 1.24
(3H, d, CH3, J = 4.8 Hz); 13C NMR (CDCl3): (d, ppm)
179.5 (C@S), 152.1 (C@N), 146.2 (C@N), 140.4–122.8
(Ar-C), 74.1 (CH2), 49.2 (CH), 10.5 (CH3).
1
1
(C@N), 1140 (C–N), 1080 (C@S); H NMR (DMSO-d6):
(d, ppm) 7.11–8.23 (8H, m, aryl-H), 4.3 (2H, t, CH2,
J = 8.17 Hz), 3.3 (2H, t, CH2, J = 8.17 Hz); 13C NMR
(DMSO-d6): (d, ppm) 170.4 (C@S), 152.2 (C@N), 141.7
(C@N), 138.2–120.8 (Ar-C), 72.3 (CH2), 46.5 (CH2).
Compound 10. kmax (nm): 336.2, 322.2, 211, 209; mmax
/
30. Wellinga, K.; Grosscurt, A. C.; Hes, R. V. J. Agric. Food
Chem. 1977, 25, 987.
31. Wright, C. W.; O’Neill, M. J.; Phillipson, J. D.; Warhurst,
D. C. Antimicrob. Agents Chemother. 1988, 32, 1725.
32. Diamond, L. S.; Harlow, D. R.; Cunnick, C. C. Trans. R.
Soc. Trop. Hyg. 1978, 72, 431.
cmꢀ1: 3042 (arom. C–H), 1622 (C@N), 1544 (C@N), 1147
1
(C–N), 1081 (C@S); H NMR (CDCl3): d 7.19–8.01 (8H,
m, aryl-H), 3.54–3.67 (m, 1H, CH), 4.92 (1H, dd, CH,
J = 5.5, 10.7 Hz), 4.64 (1H, dd, CH, J = 5.8, 10.7 Hz), 1.19
(3H, d, CH3, J = 6.6 Hz); 13C NMR (CDCl3): (d, ppm)
169.2 (C@S), 155.2 (C@N), 142.7 (C@N), 138.2–124.9
(Ar-C), 76.5 (CH2), 47.2 (CH), 12.3 (CH3).
33. Gillin, F. D.; Reiner, D. S.; Suffness, M. Antimicrob.
Agents Chemother. 1982, 342.
Compound 11 kmax (nm): 335, 321, 309, 287, 248, 226, 216,
34. Keen, A. T.; Harris, A.; Phillipson, J. D.; Warhurst, D. C.
Planta Med. 1986, 278.
207; mmax/cmꢀ1: 2973 (arom. C–H), 1558 (C@N), 1507