Antidiabetic potential and enzyme kinetics of benzothiazole derivatives and their non-bonded interactions with α-glucosidase and α-amylase

Article abstract of DOI:10.1007/s00044-016-1520-3

Benzothiazole derivatives were synthesized and their antidiabetic potential evaluated using α-glucosidase, α-amylase, non-enzymatic glycosylation of hemoglobin and advanced glycation end product inhibition assays. Compound 3l showed low IC₅₀ va

Full text of DOI:10.1007/s00044-016-1520-3

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MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res
DOI 10.1007/s00044-016-1520-3
ORIGINAL RESEARCH
Antidiabetic potential and enzyme kinetics of benzothiazole
derivatives and their non-bonded interactions with a-glucosidase
and a-amylase
Ninad V. Puranik1 Hemalata M. Puntambekar1 Pratibha Srivastava1
•
•
Received: 6 May 2015 / Accepted: 29 January 2016
Ó Springer Science+Business Media New York 2016
Abstract Benzothiazole derivatives were synthesized
and their antidiabetic potential evaluated using a-glucosi-
dase, a-amylase, non-enzymatic glycosylation of hemo-
globin and advanced glycation end product inhibition
assays. Compound 3l showed low IC50 values of 0.31, 0.98,
0.59 and 0.19 mM in a-amylase, a-glucosidase, non-en-
zymatic glycosylation of hemoglobin and AGE inhibition
assays, respectively, and outperformed the standard acar-
bose. Enzyme kinetic studies revealed that it has a Ki of
0.39 and 1.5 mM for a-amylase and a-glucosidase,
respectively. The non-bonded interactions of 3l with a-
amylase (3OLD) and a-glucosidase (2ZE0) showed that it
binds in the active site pocket and is surrounded by resi-
dues Asp197, Glu233, Asp300 in 3OLD and Asp199,
Glu256, Asp326 in 2ZE0.
PI3Ks
PPHG
pNPG
SBG
Phosphoinositide 3-kinases
Postprandial hyperglycemia
p-Nitrophenyl glucopyranoside
Sugar beet glucosidase
Introduction
Diabetes is a very serious health problem that develops
because of insulin resistance or improper function of the
pancreas and widely affects millions of people worldwide
(Shaw et al., 2010). Diabetes is categorized into two main
types, Type I and Type II. The more prevalent, Type II
diabetes, or non-insulin-dependent diabetes mellitus
(NIDDM), is a metabolic syndrome characterized by a high
blood glucose level and generally occurs because of hectic
lifestyles and oxidative stress. The treatment of Type II
diabetes is quite complex because of the many symptoms
associated with the disease, among which elevated post-
prandial hyperglycemia (PPHG) is a major risk factor (Gin
and Rigalleau, 2000). Elevated PPHG is due to the action
of glucosidases, a class of enzymes that helps breakdown
complex carbohydrates into simple sugars such as maltose
and glucose. Glucosidase and a-amylase inhibitors play an
important role in controlling elevated PPHG in diabetic
patients. These inhibitors slow the action of enzyme,
reducing starch hydrolysis and having a beneficial effect on
glycemic index management in diabetic patients (Notkins,
2002).
Keywords AGE inhibition Á a-Amylase Á
Benzothiazole derivatives Á a-Glucosidase Á
Non-bonded interactions
Abbreviations
AGE
Advanced glycation end products
Adenosine 50-monophosphate-activated
protein kinase
AMPK
CAZY
GH
Carbohydrate active enzymes database
Glycoside hydrolases
GH31AG Glycoside hydrolases 31 alpha glucosidase
NIDDM Non-insulin-dependent diabetes mellitus
& Pratibha Srivastava
psrivastava@aripune.org;
psriyns27@gmail.com
Human pancreatic a-amylase is an enzyme from family
13 of the glycoside hydrolases (GH13a), an extremely
diverse enzyme family with members that display distinct
substrate and product specificities as reflected by the 26
1
Bioprospecting Group, Agharkar Research Institute,
G. G. Agarkar Road, Pune, Maharashtra 411004, India
123

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Med Chem Res
different EC numbers found in this family including: gly-
coside hydrolases (EC 3.2.1.X, the most abundant), gly-
coside transferases (EC 2.4.1.X) and even isomerases (EC
5.4.99.15 and EC 5.4.99.16) (Henrissat and Bairoch, 1996;
Henrissat et al., 1995; Stam et al., 2006). The a-glucosi-
dase members characterized to date are found in two major
families, GH13 and GH31, and two minor families, GH4
and GH97, according to the CAZY classification system
(Henrissat and Davies, 1997). They can hydrolyze 1, -4- or
1, -6- bonds of a-D-glucosides at the non-reducing ends
with release of a-D-glucose (EC 3.2.1.20) and retention of
configuration at the anomeric carbon (Ly and Withers,
1999; McCarter and Withers, 1996).
Experimental section
Materials and methods
a-Amylase was purchased from Himedia, and hemoglobin
solution was used as Coral Hemocor D purchased from
Coral Clinical System, Goa, India. Glucobay tablets
(acarbose tablets) from Bayer Zydus Pharma were used as
standard in place of acarbose. Bovine serum albumin,
aldehydes and 2-aminothiophenol were used which is
obtained from Sigma-Aldrich. a-Glucosidase, p-nitro-
phenyl glucopyranoside (pNPG) and starch were purchased
from Sisco Research Laboratory. Glucose, fructose, mal-
tose and organic solvents were purchased from Molychem.
1HNMR and 13CNMR spectra were recorded at room
temperature on Varian 400 MHz and Bruker 100 MHz
spectrophotometer, respectively. Chemical shift values
were reported relative to TMS that was used as an internal
standard. The samples were prepared by dissolving the
synthesized compounds in DMSO-d6. Chemical shifts were
expressed in d (ppm) and coupling constants (J) in hertz.
The splitting pattern abbreviations are as follows: s, singlet;
d, doublet; t, triplet; q, quartet; m, unresolved multiplet due
to the field strength of the instrument; dd, doublet of
doublet. Column chromatography was performed on Merck
silica gel 60 (230–400 mesh; Merck, Darmstadt, Germany).
Thin-layer chromatography was carried out on precoated
Merck silica gel 60F254 (Merck) sheets using UV absorp-
tion and iodine physical adsorption for visualization. Dis-
covery studio Visualizer, client version, was used for non-
bonded interaction study.
Although many pharmaceutical treatments for diabetes
(Abbatecola et al., 2008) are available, there is still no
complete cure for this chronic metabolic disorder. Patients
have to tolerate the side effects (Stang et al., 1999) of
medication as well as post-diabetic complications such as
hypertension, nephrotoxicity and vision problem (Kirk
et al., 2005; de Groot et al., 2001; Spiller and Quadrani,
2004). Therefore, there is still a great need for the devel-
opment of safe and efficacious antidiabetic molecules.
Heterocycles are gold mines in medicinal chemistry. Most
drugs used in modern medicine possess a heterocyclic
nucleus (Gomtsyan, 2012). One interesting heterocycle is
benzothiazole, whose importance in the field of medicinal
chemistry is undeniable because of its association with
diverse pharmacological activities (Keri et al., 2015).
Researchers have reported that benzothiazoles activate the
enzyme adenosine 50-monophosphate-activated protein
kinase (AMPK) (Meltzer-Mats et al., 2013), which is
involved in the regulation of the glucose transport in skeletal
muscle (Fujii et al., 2006) and as an inhibitor of phospho-
inositide 3-kinases (PI3Ks, D’Angelo et al., 2011). Medici-
nal chemists’ attention was particularly drawn to this core
motif when the clinically available drug riluzole (Miller
et al., 2007) was found to act as an anticonvulsant. The
diverse nature of this molecule in the field of medicinal
chemistry prompted us to evaluate the antidiabetic
potential of benzothiazole derivatives. Although there are
references in the literature for antidiabetic benzothiazoles
(Mariappan et al., 2012; Pattan et al., 2005; Meltzer-Mats
et al., 2013), the antidiabetic activity of the benzothia-
zoles studied in this paper has not previously been
explored. Therefore, in this paper, we report the synthesis
of benzothiazole derivatives, their effects on enzyme
kinetics, and an exploration of their antidiabetic potential
using a-amylase, a-glucosidase, non-enzymatic glycosy-
lation and advanced glycation end product (AGE) inhi-
bition assays. A computational study to understand the
non-bonded interactions of the molecules with glucosi-
dases from the families GH13 (2ZE0) and GH31 (3W38)
and an amylase (3OLD) was carried out.
General procedure for the synthesis of 2-substituted
benzothiazoles
Synthesis of benzothiazole derivatives(3 a-p) was carried
out according to the procedure reported by Kenny and
Mashelkar (2006). Different benzaldehydes (2, 5.5 mmol)
and 2-aminothiophenol (1, 5 mmol) were taken in a round-
bottom flask containing 7 ml of acetic acid. The reaction
mixture was refluxed for 5–6 h (Scheme 1). The reaction
was monitored by TLC. After completion of the reaction,
the reaction mixture was cooled to room temperature and
decomposed over ice–water mixture. The solid thus
obtained was collected by filtration. The crude product was
purified either by crystallization using ethanol or by col-
umn chromatography using hexane: ethyl acetate as sol-
vent. All the synthesized compounds were characterized by
spectroscopic methods.
2-(Cyanomethyl)-1,3-benzothiazole (3a) Compound 3a
was obtained as yellowish powder in 75 % yield, Mp
98–100 °C; IR (KBr) mmax: 3061, 2252, 1556, 1433,
123

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Med Chem Res
NH2
N
Acetic acid
Reflux
R
O
R
+
S
SH
3 (a-p)
1
2
R1
1'
R2
3'
1'
X
3
4
3
4
3
4
7
3'
N
4'
6'
2'
3a
3a
7a
S
5'
4'
3a
5
5
6
N
5
6
2'
2'
R3
5'
2
2
2
4'
6
N
7a
S
X
S
3'
7a
7
7
1
1
6'
5'
1
X= N
X= S, O
3
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
R
CH2CN CH2Cl 4-OCH3C6H4
3-OCH3C6H4 3,4- OCH3C6H3 4-ClC6H4 3,4-ClC6H3 4-FC6H4 2-OH C6H4 4-OH C6H4 2,3 -OH C6H3
4-(NMe2) C6H4 C5H4N C4H3O C4H3S 3-NO2C6H4
Scheme 1 Synthesis of benzothiazole derivatives
1307 cm-1; 1H NMR (DMSO-d6, 400 MHz): d = 8.2 (1H,
d, J = 8.0 Hz, H-7), 8.1 (1H, d, J = 8.0, H-4), 7.55 (1H, t,
J = 7.4 Hz, H-5), 7.45 (1H, t, J = 7.4 Hz, H-6), 4.88 (2H,
s, CH2); 13C NMR (DMSO-d6, 100 MHz): d = 160.4 (C,
C-2), 152.2 (C, C-3a), 135.0 (C, C-7a), 126.4 (CH, C-7),
125.5 (CH, C-6), 122.5 (CH, C-5), 122.2 (CH, C-4), 116.4
(CN, C-20), 22.3 (CH2, C-10); EIMS: m/z 174 [M?]; Anal.
Calcd for C9H6N2S: C, 62.04; H, 3.47; N, 16.07 Found: C,
62.11; H, 3.39, N, 16.13.
C-7), 114.9 (CH, C-50), 114.9 (CH, C-30), 55.5 (C,
–OCH3); EIMS: m/z 243 (12.5), 242 (38), 241 [M?] (100),
226 (15.8); Anal. Calcd for C14H11NOS: C, 69.68; H, 4.59;
N, 5.80 Found: C, 69.62; H, 4.64; N, 5.73.
2-(3-Methoxyphenyl)-1,3-benzothiazole (3d) Compound
3d was obtained as pale yellow powder in 75 % yield, Mp
120–122 °C; IR (KBr) mmax: 3059, 2962, 2933, 2835, 1604,
1
1581, 1471, 1431, 987, 761 cm-1; H NMR (DMSO-d6,
400 MHz): d = 8.18(1H, d, J = 8.0 Hz, H-7), 8.12 (1H, d,
J = 8.0 Hz, H-4), 7.41–7.71 (5H, m, H-5, H-6, H-20, H-50,
H-60), 7.18 (1H, d, J = 8.0 Hz, H-40), 3.9 (3H, s, OCH3);
13C NMR (DMSO-d6, 100 MHz): d = 167.8 (C, C-2),
159.6 (C, C-30), 153.9 (C, C-3a), 135 (C, C-7a), 134.8 (CH,
C-60), 129.9 (CH, C-20), 126.2 (CH, C-5), 125.1 (CH, C-6),
123.2 (C, C-10), 121.5 (CH, C-7), 120.1 (CH, C-4), 117.2
(CH, C-50), 112.0 (CH, C-40), 55.5 (C, –OCH3); EIMS: m/z
241 [M?] (13.73), 211.1 (9.57), 108.1 (22.84); Anal. Calcd
for C14H11NOS: C, 69.68; H, 4.59; N, 5.80. Found: C,
69.58; H, 4.61, N, 5.71.
2-(Chloromethyl)-1,3-benzothiazole (3b) Compound 3b
was obtained as greenish powder in 58 % yield, Mp 34 °C;
IR (KBr) mmax: 3088, 2999, 1514, 1431, 1263, 760 cm-1
;
1H NMR (DMSO-d6, 400 MHz): d = 7.1 (1H, d, J = 7.8,
H-7), 7.0 (1H, d, J = 7.8, H-4), 6.7 (1H, t, J = 7.2 Hz,
H-5), 6.4 (1H, t, J = 7.2 Hz, H-6), 5.4 (2H, s, CH2); 13C
NMR (DMSO-d6, 100 MHz): d = 166.7 (C, C-2), 152.8
(C, C-3a), 135.8 (C, C-7a), 127.8 (CH, C-7), 125.4 (CH,
C-6), 123.4 (CH, C-5), 121.7 (CH, C-4), 42.1 (CH2, C-10);
EIMS: m/z 183 [M?] (49), 148 (100), 108 (31.6); Anal.
Calcd for C8H6ClNS: C, 52.32; H, 3.29; N, 7.62 Found: C,
52.27; H, 3.34; N, 7.56.
2-(3,4-Dimethoxyphenyl)-1,3-benzothiazole (3e) Com-
pound 3e was obtained as pink powder in 80 % yield,
Mp 132–134 °C; IR (KBr) mmax: 2964, 2939, 2841, 1598,
2-(4-Methoxyphenyl)-1,3-benzothiazole (3c) Compound
3c was obtained as pale yellow powder in 80 % yield, Mp
134 °C; IR (KBr) mmax: 3021, 2835, 1604, 1591, 1485,
1521, 1481, 1431, 1338, 808, 763 cm-1
;
1H NMR
(DMSO-d6, 400 MHz): d = 8.10 (1H, d, J = 8.0 Hz,
H-7), 8.02 (1H, d, J = 8.0 Hz, H-4), 7.60–7.64 (2H, m,
H-20, H-60), 7.52 (1H, t, J = 7.4 Hz, H-5), 7.42(1H, t,
J = 7.4 Hz, H-6), 7.12 (1H, d, J = 8.0 Hz, H-50), 3.89
(3H, s, OCH3), 3.85 (3H, s, OCH3); 13C NMR (DMSO-
d6, 100 MHz): 168.2 (C, C-2), 154.1 (C, C-3a), 151.9
(C, C-30), 149.6 (C, C-40),. 134.9 (C, C-7a), 126.7 (C,
C-10), 126.5 (CH, C-5), 125.2 (CH, C-6), 123.0 (CH,
C-7), 121.7 (CH, C-4), 121.4 (CH, C-60), 111.2 (CH,
833 cm-1
;
1H
NMR
(DMSO-d6,
400 MHz):
d = 7.95–8.15 (4H, m, H-4, H-7, H-20, H-60), 7.52 (1H, t,
J = 7.6 Hz, H-5), 7.4 (1H, t, J = 7.6 Hz, H-6), 7.1 (2H, d,
J = 8.0 Hz, H-30. H-50), 3.85 (3H, s, OCH3); 13C NMR
(DMSO-d6, 100 MHz): d = 167.22 (C, C-2), 161.95 (C,
C-40), 153.87(C, C-3a), 134.43 (C, C-7a), 129.04 (CH,
C-60), 129.04(CH, C-20), 126.67 (CH, C-5), 125.71 (C,
C-10), 125.25 (CH, C-6), 122.64 (CH, C-4), 122.33 (CH,
123

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C-20), 110.0 (CH, C-50), 56.4 (C, –OCH3), 56.3 (C,
–OCH3); EIMS: 271[M?] (100); Anal. Calcd for C15-
H13NO2S: C, 66.39; H, 4.82; N, 5.16 Found: C, 66.31;
H, 4.88, N, 5.04.
715 cm-1; 1H NMR (DMSO-d6, 400 MHz): d = 11.6 (1H,
s, OH); 8.17–8.20 (2H, m, H-7, H-60), 8.08 (1H, d,
J = 8.0 Hz, H-4), 7.39–7.6 (3H, m, H-40, H-50, H-6), 7.1
(1H, d, J = 8.0 Hz, H-30), 7.0 (1H, t, J = 7.4 Hz, H-5);
13C NMR (DMSO-d6, 100 MHz): d = 169.23 (C, C-2),
157.84, (C, C-3a), 151.68 (C, C-20), 132.6 (C, C-7a),
132.45 (CH, C-40), 128.27 (CH, C-60), 126.52 (CH, C-5),
125.37 (CH, C-6), 122.0 (CH, C-50), 121.34 (C, C-10),
119.36 (CH, C-4), 117.73 (CH, C-7) 116.65 (CH, C-30);
EIMS: 227 [M?] (89); Anal. Calcd for C13H9NOS: C,
68.69; H, 3.99; N 6.16. Found: C, 68.58; H, 3.91; N, 6.03.
2-(4-Chlorophenyl)-1,3-benzothiazole (3f) Compound 3f
was obtained as pale yellow powder in 75 % yield, Mp
114–116 °C; IR (KBr) mmax: 3055, 1589, 1435, 1315, 1288,
1089, 966, 756 cm-1 1H NMR (DMSO-d6, 400 MHz):
;
d = 8.16 (1H, d, J = 8.0 Hz, H-7), 8.11 (2H, d, J = 8.0 Hz,
H-30, H-50), 8.07 (1H, d, J = 8.0 Hz, H-4), 7.64 (2H, d,
J = 8.0 Hz, H-20,H-60), 7.56 (1H, t, J = 7.4 Hz, H-5), 7.48
(1H, t, J = 7.4 Hz, H-6); 13C NMR (DMSO-d6, 100 MHz):
d = 166.6 (C, C-2), 154.1 (C, C-3a), 137.0 (C, C-7a), 135.0
(C, C-10), 132.1 (C, C-40), 129.3 (CH, C-30), 129.3 (CH, C-50),
128.7 (CH, C-20) 128.7 (CH, C-60), 126.5 (CH, C-5), 125.4
(CH, C-6), 123.3(CH, C-4), 121.6(CH, C-7)EIMS:245 [M?]
(100), 108 (30), 137 (70), 111(13); Anal. Calcd for C13H8-
ClNS: C, 63.54; H, 3.28; N, 5.70. Found C, 63.62; H, 3.14; N
5.62.
2-(4-Hydroxyphenyl)-1,3-benzothiazole (3j) Compound
3j was obtained as yellowish powder in 70 % yield. Mp
220–224 °C; IR (KBr) mmax: 3053, 2997, 1606, 1454 cm-1
;
1H NMR (DMSO-d6, 400 MHz): d = 10.2 (1H, s, OH), 8.1
(1H, d, J = 8.0 Hz, H-7), 7.9 (3H, dd, J = 8.0 Hz, H-4,
H-20, H-60), 7.5 (1H, t, J = 7.4 Hz, H-5), 7.4 (1H, t,
J = 7.4 Hz, H-6), 6.9 (2H, d, J = 8.2 Hz, H-30, H-50); 13C
NMR (DMSO-d6, 100 MHz): d = 169.2 (C, C-2), 160.8
(C, C-40), 153.8 (C, C-3a), 134.5 (C, C-7a), 129.1 (CH,
C-20), 129.1 (CH, C-60), 126.3 (CH, C-5), 124.9 (CH, C-6),
124.8 (CH, C-4), 121.9 (C, C-10), 121.6 (CH, C-7), 115.8
(CH, C-30) 115.8 (CH, C-50); EIMS: 227 [M?] (100); Anal.
Calcd for C13H9NOS: C, 68.69; H, 3.99; N, 6.16. Found: C,
68.59; H, 3.89; N 6.07.
2-(3,4-Dichlorophenyl)-1,3-benzothiazole
(3g) Com-
pound 3g was obtained as white powder in 90 % yield. Mp
118–119 °C; IR (KBr) mmax: 3062, 1500, 1462, 1433, 1375,
1
786 cm-1; H NMR (DMSO-d6, 400 MHz): d = 8.3 (1H,
s, H-20), 8.2 (1H, d, J = 8.0 Hz, H-50), 8.18 (1H, d,
J = 8.0 Hz, H-60), 8.1 (1H, d, J = 8.0 Hz,H-7), 7.82 (1H,
d, J = 8.0 Hz, H-4), 7.59 (1H, t, J = 7.2 Hz, H-6), 7.42
(1H, t, J = 7.2 Hz, H-5); 13C NMR (DMSO-d6,
100 MHz): d = 164.9 (C, C-2), 154.6 (C, C-3a), 135.6 (C,
C-7a), 135.0 (C, C-40), 133.9 (C, C-30), 133.7 (CH, C-20),
131.0 (CH, C-50), 129.3 (CH, C-60), 126.8 (C, C-10) 126.6
(CH, C-5), 125.8 (CH, C-6), 124, (CH, C-4), 121.8 (CH,
C-7). EIMS: 283 (14), 282 (11), 281 (67), 280 [M?] (20),
279 (100); Anal. Calcd for C13H7Cl2NS: C, 55.73; H, 2.51;
N, 4.99. Found: C, 55.61; H, 2.42; N 4.86.
2-(2,3-Dihydroxyphenyl)-1,3-benzothiazole (3k) Com-
pound 3k was obtained as white powder in 75 % yield, Mp
217 °C; IR (KBr) mmax: 3491, 2702, 1601, 1439, 1277,
1182, 905, 756 cm-1 1H NMR (DMSO-d6, 400 MHz):
;
d = 11.2 (1H, broad s, OH), 9.61 (1H, broad s, OH), 8.2
(1H, d, J = 8.0 Hz, H-7), 8.05 (1H, d, J = 8.0 Hz, H-4),
7.5–7.6 (2H, m, H-60, H-5), 7.41 (1H, t, J = 7.4 Hz, H-6),
6.95 (1H, d, J = 8.0 Hz, H-40), 6.85 (1H, t, J = 7.4 Hz,
H-50); 13C NMR (DMSO-d6, 100 MHz): d = 166.4 (C,
C-2), 151.4 (C, C-3a), 146.3 (C, C-30), 145.1 (C, C-20),
133.9 (C, C-7a), 126.6 (CH, C-5), 125.2 (CH, C-6), 122.1
(CH, C-7), 122.0 (CH, C-4), 119.5 (CH, C-50), 118.5 (CH,
C-60), 118.4 (C, C-10), 117.7 (CH, C-40); EIMS: m/z 243
[M?] (79); Anal Calcd for C13H9NO2S: C, 64.18; H, 3.72;
N 5.75. Found: C, 64.08; H, 3.79; N 5.81.
2-(4-Fluorophenyl)-1,3-benzothiazole (3h) Compound
3h was obtained as yellowish powder in 82 % yield. Mp
101–103 °C; IR (KBr) mmax: 3057, 1556, 1519, 1350, 1284,
1157, 758, 696 cm-1 1H NMR (DMSO-d6, 400 MHz):
;
d = 8.15–8.18 (3H, m, H-7, H-30, H-50), 8.06 (1H, d,
J = 8.0 Hz, H-4), 7.55 (1H, t, J = 7.4 Hz, H-5), 7.48 (2H,
d, J = 8.0 Hz, H-20, H-60), 7.42 (1H, t, J = 7.4, H-6); 13C
NMR (DMSO-d6, 100 MHz): d = 163.2 (C, C-2), 161.3
(C, C-3a), 152.4 (C, C-7a), 142.5 (C, C-10), 130.3 (C, C-40),
127.2 (CH, C-30), 127.2 (CH, C-50), 124.3 (CH, C-20),
124.3 (CH, C-60), 123.8 (CH, C-5), 119.9 (CH, C-6), 117.0
(CH, C-4), 111.4 (CH, C-7); EIMS: 229 [M?] (100); Anal.
Calcd for C13H8FNS: C, 68.10; H, 3.51; N 6.11. Found: C,
68.18; H, 3.63; N, 6.03.
2-(4’-(N,N-Dimethylamino)phenyl)-1,3-benzothiazole (3l)
Compound 3l was obtained as yellowish powder in 90 %
yield, Mp 160–162 °C; IR (KBr) mmax: 3053, 2906, 1610,
1485, 1433, 1371, 1315, 752, 721 cm-1; 1H NMR (DMSO-
d6, 400 MHz): d = 8.05 (1H, d, J = 8.0 Hz, H-7),
7.85–7.95 (3H, m, H-20, H-60, H-4), 7.46 (1H, t,
J = 7.4 Hz, H-5), 7.35 (1H, t, J = 7.4 Hz, H-6), 6.8 (2H,
d, J = 8 Hz, H-30, H-50), 3.0 (6H, s, N-CH3); 13C NMR
(DMSO-d6, 100 MHz): d = 168.01 (C, C-2), 154.09 (C,
C-3a), 133.98 (C, C-7a), 128.65, (CH, C-20), 128.65 (CH,
C-60), 126.47 (CH, C-5), 124.64 (CH, C-6), 122.31 (CH,
2-(2-Hydroxyphenyl)-1,3-benzothiazole (3i) Compound
3i was obtained as yellowish powder in 60 % yield, Mp
127–128 °C; IR (KBr) mmax: 3059, 1487, 1438, 1220, 817,
123