Synthesis of some N-[4-(benzothiazole-2yl) phenyl]-2-aryloxyacetamide derivatives and their anticancer activities

Article abstract of DOI:10.3109/14756366.2011.599030

In this study, some N-[4-(Benzothiazole-2-yl) phenyl]-2-aryloxyacetamide derivatives were prepared by reacting N-[4-(benzothiazole-2yl)phenyl]-2- chloroacetamide and different substituent phenol or thiophenol derivatives. The anticancer activities of the

Full text of DOI:10.3109/14756366.2011.599030

Journal of Enzyme Inhibition and Medicinal Chemistry, 2012; 27(4): 515–520
© 2012 Informa UK, Ltd.
ISSN 1475-6366 print/ISSN 1475-6374 online
DOI: 10.3109/14756366.2011.599030
rEsEarch artIclE
Synthesis of some N-[4-(benzothiazole-2yl) phenyl]-2-
aryloxyacetamide derivatives and their anticancer activities
Funda Tay1, Leyla Yurttaş2, and Şeref Demirayak3
1Department of Chemistry, Faculty of Arts & Sciences, Eskisehir Osmangazi University, Eskisehir, Turkey,
2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskisehir, Turkey, and
3Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medipol University, İstanbul, Turkey
abstract
In this study, some N-[4-(Benzothiazole-2-yl) phenyl]-2-aryloxyacetamide derivatives were prepared by reacting
N-[4-(benzothiazole-2yl)phenyl]-2-chloroacetamide and different substituent phenol or thiophenol derivatives. The
anticancer activities of the compounds obtained were investigated. It was observed that some of the compounds,
namely 25 and 38, showed notable anticancer activity.
Keywords: Benzothiazole, antitumour, non-small cell lung cancer, prostate cancer
Introduction
2ˊ-(3-aminophenyl)-and2ˊ-(4-aminophenyl)benzothiaz-
Cytotoxic agents conventionally used in cancer treatment
(conventional phase-specific purine, pyrimidine bases and
non-phase-specific alkylating agents) are known to be toxic
and have been criticized because of this, but will continue
to be used until the introduction of less harmful agents.
Another limitation of cancer treatment is that resistance
to anticancer agents develops in tumor cells during clini-
cal use. In addition to the aforementioned drugs, intensive
investigationcontinuesintonewcompoundstargetingcan-
cer-specific proteins and affecting different mechanisms,
oles were prepared as building blocks and their inhibitory
activities were determined on kinase by initially testing
in vitro13. In addition, other notable structures in terms of
anticancer activity are compounds of aryloxy-acetamido-
thiazole II residue. ese compounds were reported to be
effective therapeutic agents in prostate cancer14.
such as topoisomerase and telomerase inhibition1–3
.
In previous studies, 2-(4-aminophenyl) benzothiazole
derivatives I were shown to have high antitumor activity
in vitro and in vivo4–6, mainly against breast, renal, colon,
ovarian, lung and prostate cancers, despite their simple
structures7–10. Analysis of structure-activity relationships
showedthatbenzothiazoleresidueswereessentialforhigh
activity. A phenyl ring on the 2-position of benzothiazole
and alkyl and halogen residues on the 3-position were
shown to be effective in increasing activity10. e bind-
ing of aminophenyl benzothiazoles to β-amyloid using
for has been used for imaging and therapy in Alzheimer’s
disease.11–12 e several differentially-substituted
In this study, 2-(aminoaryl)benzothiazole and aryloxy-
acetamide residues were combined in a single structure
in the light of the data above, N-[4-(Benzothiazole-2-yl)
phenyl]-2-aryloxyacetamide compounds were obtained
and their effects were evaluated against nine cancer types
comprised of approximately sixty cell-lines.
Experimental
Chemistry
e synthesis of 2-(4-aminophenyl)benzothiazole mol-
ecules was done using Milestone microwawe reaction
Address for Correspondence: Funda Tay, Department of Chemistry, Faculty of Arts & Sciences, Eskisehir Osmangazi University, 26480,
Eskisehir, Turkey. Fax: +90 222 2393578. E-mail: ftay@ogu.edu.tr
(Received 22 February 2011; revised 17 June 2011; accepted 18 June 2011)
515

516 F. Tay et al.
apparatus. Melting points were determined by using
an Electrothermal IA9000 digital melting point appara-
tus. Spectroscopic data were recorded on the following
instruments: a Bruker Tensor 27 IR spectrophotometer;
a H-NMR (nuclear magnetic resonance) Bruker DPX-
400 FT-NMR spectrophotometer, and an MS (mass
spectroscopy) Agilent 1100 MSD spectrophotometer.
Analyses for C, H and N were within 0.4% of the theo-
retical values. 4-(benzothiazole-2-yl)phenylamine and
N-(4-benzothiazole-2-yl)phenyl-2-chloroacetamide
were prepared according to the methods described in the
literatüre1,4. Some characteristics of the compounds are
given in Table 1 and the processes for their synthesis are
shown in Scheme 1.
1
Table 1. Some characteristic of the compounds.
Analyses calc./found
Comp.
3
R
R’
X
mp (°C)
174
Yield (%)
70
Molecular Formula
C21H16N2O2S.1/2H2O
(%) C H N
H
H
O
68.29 4.34
7.59
7.60
6.81
6.77
6.81
6.77
6.81
6.77
7.17
7.15
7.17
7.15
7.17
7.15
6.54
6.52
6.54
6.52
6.54
6.52
6.79
6.77
6.63
6.55
6.63
6.55
6.63
6.55
6.53
6.52
6.53
6.52
6.53
6.52
6.46
6.42
6.46
6.42
6.46
6.42
7.17
7.15
6.93
6.91
6.46
(Continued)
68.19 4.33
61.21 3.67
61.01 3.63
61.21 3.67
61.01 3.63
61.21 3.67
61.01 3.63
67.6 4.65
4
5
H
4-Cl
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
222
233
207
176
160
132
198
222
159
92
78
74
72
75
71
68
73
69
67
73
76
74
71
78
75
70
73
69
64
62
61
66
C21H15ClN2O2S.H2O
C21H15ClN2O2S.H2O
C21H15ClN2O2S.H2O
C22H18N2O3S
H
3-Cl
6
H
2-Cl
7
H
4-OCH3
3-OCH3
2-OCH3
4-CH3
3-CH3
2-CH3
H
67.5 4.63
8
H
C22H18N2O3S
67.6 4.65
67.5 4.63
9
H
C22H18N2O3S
67.6 4.65
67.5 4.63
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
H
C22H18N2O2S.3H2O
C22H18N2O2S.3H2O
C22H18N2O2S.3H2O
C21H15ClN2O2S.H2O
C22H17ClN2O2S. H2O
C22H17ClN2O2S. H2O
C22H17ClN2O2S. H2O
C21H14Cl2N2O2S
61.67 4.20
61.80 4.17
61.67 4.20
61.80 4.17
61.67 4.20
61.80 4.17
61.38 3.68
61.01 3.63
61.94 4.02
61.82 3.98
61.94 4.02
61.82 3.98
61.94 4.02
61.82 3.98
58.75 3.29
58.71 3.29
58.75 3.29
58.71 3.29
58.75 3.29
58.71 3.29
60.90 3.92
60.79 3.91
60.90 3.92
60.79 3.91
60.90 3.92
60.79 3.91
67.67 4.65
67.63 4.61
68.30 4.98
68.27 4.97
60.90 3.92
H
H
3-Cl
3-Cl
3-Cl
3-Cl
3-Cl
3-Cl
3-Cl
3-Cl
3-Cl
3-Cl
2-OCH3
2-OCH3
2-OCH3
4-CH3
3-CH3
2-CH3
4-Cl
266
259
186
204
214
224
161
149
162
167
174
181
3-Cl
C21H14Cl2N2O2S
2-Cl
C21H14Cl2N2O2S
4-OCH3
3-OCH3
2-OCH3
H
C22H17ClN2O3S.1/2H2O
C22H17ClN2O3S.1/2H2O
C22H17ClN2O3S.1/2H2O
C22H18N2O3S
4-CH3
4-Cl
O
O
C23H20N2O3S
C22H17ClN2O3S.1/2H2O
Journal of Enzyme Inhibition and Medicinal Chemistry

N-[4-(benzothiazole-2yl) phenyl]-2-aryloxyacetamide derivatives 517
Table 1. (Continued).
Analyses calc./found
Comp.
26
R
R’
4-OCH3
H
X
O
O
O
O
O
O
O
O
S
mp (°C)
152
186
157
200
185
203
208
162
94
Yield (%)
63
Molecular Formula
C23H20N2O4S
(%) C H N
60.79 3.91
6.42
6.66
6.68
7.48
7.51
7.21
7.19
7.21
7.19
6.85
6.83
6.85
6.83
6.93
6.92
6.93
6.92
7.18
7.10
6.82
6.81
6.50
6.47
6.82
6.79
5.93
5.91
6.07
6.05
2-OCH3
2-CH3
2-CH3
2-CH3
2-CH3
2-CH3
2-CH3
2-CH3
H
65.70 4.79
65.67 4.80
70.57 4.85
70.49 4.81
71.11 5.19
71.08 5.08
71.11 5.19
71.08 5.08
64.62 4.19
64.59 4.19
64.62 4.19
64.59 4.19
68.30 4.98
68.25 4.95
68.30 4.98
68.25 4.95
64.42 4.25
63.95 4.06
61.38 3.68
61.34 3.68
61.90 4.22
61.89 4.19
61.38 3.68
61.35 3.67
53.35 2.96
53.28 2.95
57.27 3.69
57.25 3.65
27
65
C22H18N2O2S
28
4-CH3
2-CH3
4-Cl
64
C23H20N2O2S
29
62
C23H20N2O2S
30
68
C22H17ClN2O2S
C22H17ClN2O2S
C23H20N2O3S
31
2-Cl
63
32
4-OCH3
2-OCH3
H
65
33
61
C23H20N2O3S
34
60
C21H16N2OS2.H2O
C21H15ClN2OS2
C22H18N2OS2.2H2O
C21H15ClN2OS2
C21H14Cl2N2OS2.3/2H2O
C22H17ClN2OS2. 2H2O
35
H
4-Cl
S
211
115
123
102
105
67
36
H
4-CH3
H
S
63
37
3-Cl
S
67
38
3-Cl
4-Cl
S
74
39
3-Cl
4-CH3
S
69
Scheme 1. Synthesis of compounds 3–39. Reagents and conditions: (a) PPA/MW, 125°C, 35 minutes (b) DMF/Et3N (c) acetonitril, K2CO3,
heating at reflux.
© 2012 Informa UK, Ltd.

518 F. Tay et al.
General method for the preparation of N-[4-
(benzothiazole-2-yl)phenyl)-2-phenoxyacetamide
and N-[4-(benzothiazole-2-yl)phenyl)-2-
result and discussion
Chemistry
N-[4-benzothiazole-2-yl]phenyl]-2-aryloxyacetamide
derivatives were synthesized using the sequence of
reactions depicted in Scheme 1. e initial compounds,
2-(4-aminophenyl)benzothiazoles 1a-d, were prepared
via polyphosphoric acid mediated oxidative condensa-
tion of 2-aminothiophenol with 4-aminobenzoic acid in
microwave conditions.
N-[4-(benzothiazole-2-yl)phenyl]-2-chloroacetamide
compounds 2a-d were prepared by reacting 2-(4-amin-
ophenyl)benzothiazole and chloroacetyl chloride in tri-
ethylamine and DMF to produce the halides.
thiophenoxyacetamide derivatives 3–33 and 34–39
A mixture of N-[4-benzothiazole-2-yl)phenyl]-2-chloro-
acetamide (1.65 mmol, 0.5 g), the appropriate substitue
phenol or thiophenol derivatives (1.98 mmol) and K2CO3
(1.98 mmol, 0.3 g) in acetonitril was refluxed for 6 hours.
e cooled mixture was filtered and recrystallized from
DMSO/alcohol.
e characterization of compounds (25 and 38) show-
ing high activity are given below. e remaining final
compounds characterization are given as supporting
data.
e two groups of final compounds are N-[4-
(benzothiazole-2-yl)phenyl)-2-phenoxyacetamide
derivatives and N-[4-(benzothiazole-2-yl)phenyl)-2-
(phenylthio) acetamide derivatives, derivative numbers
3–33 and 34–39 respectively. N-[4-(benzothiazole-
2-yl)phenyl)-2-phenoxyacetamide derivatives 3–33,
were synthesized by reacting N-[4-(benzothiazole-
2-yl)phenyl]-2-chloro acetamide and appropriate
substituent phenols in acetonitrile solvent. e other
derivatives, 34–39, were synthesized by reacting N-[4-
benzothiazole-2-yl)phenyl]-2-chloro acetamide and
appropriate substituent thiophenols in acetonitrile
solvent. e structures of the compounds obtained
were elucidated using spectral data. In the IR spec-
tra, characteristic amide carbonyl functions were
observed in the 1709-1670 cm−1 region, both separately
and as a single band. e NMR spectra of compounds
3–33 exhibited singlets resulting from resonances
of the N-[4-(benzothiazole-2-yl)phenyl)-2-phenoxy-
acetamide residue assigned to −O-CH2-protons at
4.7-4.8 ppm, and N-H protons at 9.3–10.92 ppm. N-[4-
(benzothiazole-2-yl)phenyl]-2-phenylthio) acetamide
derivative residue was assigned to −S-CH2-protons at
3.85-3.94 ppm and N-H protons at 9.61–10.70 ppm. For
the other compounds, the same protons were taking
part in multiplets, because they were overlapping with
aromatic and benzothiazole protons.
25: IR(KBr)υmax (cm−1): 3399 (N-H), 3050 (aromatic
C-H), 2904 (aliphatic C-H), 1689 (C=O), 1605, 1539, 1499
(C=C, C=N), 1300-1000 (C-N), 1245 (C-O-C), 596 (C=C-S),
664 (C-S) NMR(400 MHz)(DMSO-d6) δ (ppm): 3.72 (3H,
s, OCH3) 4.8 (2H, s, (-O-CH2-)), 6.89 (2H, d, J:8.78 Hz,
Ar-H), 7.05 (2H, d, J:8.34 Hz, Ar-H), 7.44 (1H, dt, J:7.62
Hz, J:7.52Hz, benzothiazole, C6-H), 7.55 (1H, dt, J:7.64
Hz, J:7.49Hz, benzothiazole,C5-H), 7.78 (1H, dd, J: 1.66
Hz, J: 1.64 Hz, Ar-H), 7.82 (1H, s, Ar-H), 8.12 (1H, d, J: 7.67
Hz, benzothiazole C7-H), 8.21 (1H, d, J:7.68 Hz, Ar-H),
8.38 (1H, d, J: 8.29 Hz, benzothiazole C4-H), 9.36 (1H, s,
NH) MS (ES+): 425.1 (100%) M+1, 426.1 (26%) M+2, 427.1
(40.3%) M+3, 428.1 (10%) M+4.
38:IR(KBr)υmax(cm−1):3249(N-H),3079(aromaticC-H),
2916 (aliphatic C-H), 1683 (C=O), 1600, 1531, 1477 (C=C,
1
C=N), 1300-1000 (C-N), 734 (C=C-S) H-NMR(400 MHz)
(DMSO-d6) δ (ppm): 3.94 (2H, s, (-S-CH2-)), 7.5 (5H, m,
Ar-H, benzothiazole, C6-H), 7.59 (1H, dt, J:8.26 Hz, J: 8.26
Hz, benzothiazole C5-H) 7.64 (1H, dd, J:2.11 Hz, J: 2.05
Hz, Ar-H), 8.02 (1H, d, J:2.04 Hz, Ar-H), 8.1 (1H, d, J:8.03
Hz, benzothiazole C7-H), 8.19 (1H, d, J:7.81 Hz Ar-H), 8.27
(1H, d, J: 8.69 Hz, benzothiazole C4-H), 10.70 (1H, s, NH)
MS (ES+): 445(100%) M+1, 446 (27%) M+2, 447 (74%)
M+3, 448(19%) M+4, 449 (20%) M+5.
Anticancer activity
e cyctotoxic and/or growth inhibitory effects of the
compounds were evaluated in vitro against approxi-
mately 60 human tumor cell lines derived from nine
neoplastic diseases, namely: leukemia (L), non-small
cell lung cancer (NSCLC), colon cancer (CC), central
nervous system cancer (CNSC), melanoma (M), ovar-
ian cancer (OC), renal cancer (RC), prostate cancer (PC)
and breast cancer (BC). e evaluation of anticancer
activity was performed at the National Cancer Institute
(NCI), Bethesda, USA. e in vitro screening program
was based upon the use of multiple panels of 60 human
tumor cell lines, against which our compounds were
tested at 10-fold dilutions of five concentrations ranging
from 10−4 to 10−8 M. e percentage growth was evaluated
spectrophotometrically against controls not treated with
test agents. A 48-hour continuous drug exposure proto-
col was followed and a sulforhodamine B (SRB) protein
assay was used to estimate cell growth15.
Anticancer activity
In the first step, compounds 3, 7, 13, 17, 20, 25, 26, 35
and 38 were selected by NCI for the anticancer tests.
e selected compounds were evaluated in vitro against
60 human tumor cell lines derived from nine neoplastic
diseases and the test results were determined as growth
percentage values for 10−5 M concentration. e obtained
growth percent values are shown in Table 2.
Compounds 25 and 38 showed notably low growth
of 29.64% and 30.93%, respectively, against CNSC and
PC cell lines. With respect to mean values, the same two
compounds exhibited the lowest growth percent values
of 50.94 and 59.73%, respectively. As required by the
test methods, the compounds with a growth percentage
lower than 75% were accepted for the further screening
test. us, compounds 25 and 38 were used in the second
Journal of Enzyme Inhibition and Medicinal Chemistry

N-[4-(benzothiazole-2yl) phenyl]-2-aryloxyacetamide derivatives 519
Table 2. Anticancer activity of some compounds as % growth.
Comp.
3
L
NSCLC
87.51
96.37
90.05
96.11
83.30
40.58
76.34
91.88
49.54
CC
CNSC
96.22
96.22
98.10
103.08
89.58
29.64
72.16
92.57
62.01
M
OC
RC
PC
BC
Mean
91.70
99.36
98.51
103.04
91.53
50.94
80.99
93.50
59.73
81.18
88.17
106.10
101.52
87.84
77.14
92.33
84.81
49.23
97.78
106.39
105.47
105.79
100.15
62.38
82.77
99.23
51.77
98.48
111.31
102.18
111.04
102.33
64.12
86.91
107.2
82.98
97.75
101.84
93.60
98.62
88.74
36.06
81.18
91.83
60.39
90.17
97.97
101.25
108.34
94.60
46.04
81.74
93.84
54.65
96.00
100.56
100.07
101.85
92.80
65.94
89.83
79.57
30.93
81.00
89.87
90.65
98.19
81.53
43.81
68.77
80.56
67.05
7
13
17
20
25
26
35
38
Table 3. Mean logGI50 values of compounds 25 and 38 and control anticancer agents.
Comp.
L
NSCLC
–5.42
–5.38
–5.17
–6.20
CC
CNSC
–5.11
–5.22
–5.12
–6.18
M
OC
RC
PC
BC
MG_MID
–5.14
25
38
A
–4.32
–5.32
–5.48
–6.39
–4.91
–5.45
–5.11
–6.14
–5.21
–5.25
–5.08
–6.08
–5.26
–5.34
–5.18
–6.45
–5.33
–5.26
–5.17
–5.41
–4.79
–6.05
–5.41
–4.99
–6.17
–5.62
–4.49
–6.41
–5.36
–5.09
B
–6.20
A: Melphalan, B: Cisplatin.
stage of the study, in which the selected compounds were
tested at 10-fold dilutions of five concentrations ranging
from 10−4 to 10−8 M. e results are given as logGI50 (GI50:
growth inhibition of 50%). e detailed test results are
given in Table 3.
acknowledgements
is work was supported by the Commission of Scientific
Research Projects of Eskisehir Osmangazi University
(ESOGU/200819010). e authors gratefully acknowl-
edge the financial support by Eskişehir Osmangazi
University. Authors also would like to thank to National
Cancer Institue (NCI), Bethesda, MD, USA for in vitro
screening of our compounds in human cancer cell lines.
e test method stated that compounds having logGI50
values greater than −4 are considered as inactive. It can
be seen that the logGI50 values for the compounds are
less than −4. erefore, we may conclude that the two
compounds under investigation provide a notable activ-
ity level. Melphalan and cisplatin (cis-diaminodichloro-
platinum) are two commonly used chemotherapeutic
agents and are used as control anticancer agents. When
the mean graph midpoint (MG-MID) values of the com-
pounds melphalan and cisplatin (i.e. −5.09 and −6.20,
respectively) are considered, it is observed that the two
compounds provide high activity levels. e MG-MID
values of the compounds are lower than that of the con-
trol compound, melphalan.
Declaration of interest
e authors report no conflicts of interest.
references
1. Prat WB, Ruddon RW, Ensminger WD, Maybaum J. e Anticancer
Drugs. 2nd Ed., Oxford: Oxford University Press, 1994.
2. Baguley BC, Kerr DJ. Anticancer Drug Development.New York:
Academic Pres, 2002.
e present study analyzed the effect levels of
2-(aminoaryl)benzothiazole and aryloxyacetamide, two
groups of compounds known to have an anticancer effect,
after their residues were combined in a single structure.
However, although the obtained compounds showed
relatively high activity values, they did not achieve the
same activity level as compounds containing both of the
residues separately within their structures.
Compound 25 contained R: 2-OCH3 and R’: 4-Cl as
a substituent and compound 38 contained R: 3-Cl and
R’: 4-Cl as substituents. Moreover, while compound
25 has an aryl ether structure, Compound 38 is an aryl
thioether. erefore, it is remarkable that the common
feature of these most effective two compounds is the
R’ group being 4-CI. Except for this feature, it does not
seem possible to establish a structure-activity relation-
ship according to the structure of the compounds and
substituents.
3. Adjei AA, Buolamwini JK. Novel Anticancer Agents, Strategies
for Discovery and Clinical Testing. New York: Elsevier Academic
Press, 2006.
4. Shi DF, Bradshaw TD, Wrigley S, McCall CJ, Lelieveld P,
Fichtner I et al. Antitumor benzothiazoles. 3. Synthesis of 2-(4-
aminophenyl)benzothiazoles and evaluation of their activities
against breast cancer cell lines in vitro and in vivo. J Med Chem
1996;39:3375–3384.
5. Chua MS, Shi DF, Wrigley S, Bradshaw TD, Hutchinson I,
Shaw PN et al. Antitumor benzothiazoles. 7. Synthesis of 2-(4-
acylaminophenyl)benzothiazoles and investigations into the role
of acetylation in the antitumor activities of the parent amines.
J Med Chem 1999;42:381–392.
6. Shi DF, Bradshaw TD, Chua MS, Westwell AD, Stevens MF.
Antitumour benzothiazoles. Part 15: e synthesis and physico-
chemicalpropertiesof2-(4-aminophenyl)benzothiazolesulfamate
salt derivatives. Bioorg Med Chem Lett 2001;11:1093–1095.
7. Tzanopoulou S, Sagnou M, Paravatou-Petsotas M, Gourni E,
Loudos G, Xanthopoulos S et al. Evaluation of Re and (99m)Tc
complexes of 2-(4’-aminophenyl)benzothiazole as potential breast
cancer radiopharmaceuticals. J Med Chem 2010;53:4633–4641.
© 2012 Informa UK, Ltd.

520 F. Tay et al.
8. Kashiyama E, Hutchinson I, Chua MS, Stinson SF, Phillips LR,
Kaur G et al. Antitumor benzothiazoles. 8. Synthesis, metabolic
formation, and biological properties of the C- and N-oxidation
products of antitumor 2-(4-aminophenyl)benzothiazoles. J Med
Chem 1999;42:4172–4184.
12. Serdons K, Verduyckt T, Cleynhens J, Terwinghe C, Mortelmans
L, Bormans G et al. Synthesis and evaluation of a (99m)Tc-BAT-
phenylbenzothiazole conjugate as a potential in vivo tracer for
visualization of amyloid beta. Bioorg Med Chem Lett 2007;17:
6086–6090.
9. Hutchinson I, Jennings SA, Vishnuvajjala BR, Westwell AD, Stevens
MF. Antitumor benzothiazoles. 16. Synthesis and pharmaceutical
properties of antitumor 2-(4-aminophenyl)benzothiazole amino
acid prodrugs. J Med Chem 2002;45:744–747.
13. Tasler S, Müller O, Wieber T, Herz T, Krauss R, Totzke F et al.
N-substituted 2’-(aminoaryl)benzothiazoles as kinase inhibitors:
hit identification and scaffold hopping. Bioorg Med Chem Lett
2009;19:1349–1356.
10. Hutchinson I, Chua MS, Browne HL, Trapani V, Bradshaw TD,
Westwell AD, Stevens MFG. Antitumor benzothiazoles.14.1
Synthesis and in vitro biological properties of fluorinated 2-
(4-aminophenyl)benzothiazoles. J Med Chem 2001;44:1447–1455.
11. Henriksen G, Hauser AI, Westwell AD, Yousefi BH, Schwaiger
M, Drzezga A et al. Metabolically stabilized benzothiazoles for
imaging of amyloid plaques. J Med Chem 2007;50:1087–1089.
14. Krasavin M, Karapetian R, Konstantinov I, Gezentsvey Y,
Bukhryakov K, Godovykh
E et al. Discovery and potency
optimization of 2-amino-5-arylmethyl-1,3-thiazole derivatives
as potential therapeutic agents for prostate cancer. Arch Pharm
(Weinheim) 2009;342:420–427.
15. Boyd MR. Status of the NCI preclinical antitumor drug discovery
screen principles and practice of oncology 1989;3:2.
Journal of Enzyme Inhibition and Medicinal Chemistry