Synthesis of some thiazolyl-pyrazoline derivatives and preliminary investigation of their hypotensive activity

Article abstract of DOI:10.1016/S0223-5234(00)00152-5

Some 1-(4-arylthiazol-2-yl)-3,5-diaryl-2-pyrazoline derivatives were synthesized by reacting 1-thiocarbamoyl-3,5-diaryl-2-pyrazoline derivatives with phenacetylbromide in ethanol. The structural elucidation of the compounds were performed by IR, ¹H-NMR and Mass spectral data and elemental analyses. The hypotensive activities of 13 compounds were evaluated by using the tail-cuff method. All examined compounds showed appreciable hypotensive activities. Clonidine was used as reference substance in the pharmacological evaluation. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

Full text of DOI:10.1016/S0223-5234(00)00152-5

Eur. J. Med. Chem. 35 (2000) 635−641
© 2000 Éditions scientifiques et médicales Elsevier SAS. All rights reserved
S0223523400001525/SCO
635
Short communication
Synthesis of some thiazolyl-pyrazoline derivatives and preliminary investigation
of their hypotensive activity
Gülhan Turan-Zitounia*, Pierre Chevalletb, Fatma S. Kiliçc, Kevser Erolc
aAnadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 26470 Eskisehir, Turkey
bMontpellier University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, LAAP, CNRS-UMR 5810, 34000
Montpellier, France
cOsmangazi University, Faculty of Medicine, Department of Pharmacology, 26480 Eskisehir, Turkey
Received 9 March 1999; revised and accepted 22 December 1999
Abstract – Some 1-(4-arylthiazol-2-yl)-3,5-diaryl-2-pyrazoline derivatives were synthesized by reacting 1-thiocarbamoyl-3,5-diaryl-2-
pyrazoline derivatives with phenacetylbromide in ethanol. The structural elucidation of the compounds were performed by IR, 1H-NMR and
Mass spectral data and elemental analyses. The hypotensive activities of 13 compounds were evaluated by using the tail-cuff method. All
examined compounds showed appreciable hypotensive activities. Clonidine was used as reference substance in the pharmacological
evaluation. © 2000 Éditions scientifiques et médicales Elsevier SAS
thiazol / pyrazoline / thiazolyl-pyrazoline / chalcone / hypotensive activity
1. Introduction
Compounds including a pyrazole nucleus are known to
possess analgesic, anti-inflammatory, antipyretic, antiar-
rhythmic, tranquillizing, muscle relaxant, psychoanalep-
tic, anticonvulsant, hypotensive, monoamine oxidase in-
hibitor, antidiabetic and antibacterial activities [1–9].
Some thiazol derivatives have been reported to possess
tuberculostatic, antibacterial and antifungal activities
[10–14].
It was also reported that one of the modified forms of
clonidine I, thiazolo-imidazoline derivative II, is as
potent as clonidine itself [15]. This result encouraged us
to study several thiazolyl-pyrazoline derivatives III bear-
ing structural and isosteric relationships to I and II
(figure 1).
In this study, 39 1-(4-aryl-thiazol-2-yl)-3,5-diaryl-2-
pyrazoline derivatives were synthesized and the hypoten-
sive activities of 13 of them were studied in rats by using
tail-cuff method.
Figure 1. Structures of I–III.
2. Chemistry
The synthesis of the new compounds was carried out as
outlined in figure 2. 1-Thiocarbamoyl-3,5-diaryl-2-
pyrazoline derivatives III were synthesized by the reac-
* Correspondence and reprints: gzitouni@anadolu.edu.tr

636
Figure 2. Synthesis of 1-(4-arylthiazol-2-yl)-3,5-diaryl-2-pyrazoline.
tion of 1,3-diaryl-2-propen-1-ones (chalcones) I with
thiosemicarbazide II in accordance with the method
described in literature [16].
1-(4-Arylthiazol-2-yl)-3,5-diaryl-2-pyrazoline deriva-
tives 1–39 were obtained by reacting compounds III with
phenacetylbromide in ethanol (figure 2). Some character-
istics of the compounds are presented in table I.
conscious rats were measured by the tail-cuff method [17,
18] and using an indirect blood pressure recorder. The
blood pressure of each rat was measured before and
30 min after the intraperitoneal injection of the com-
pounds. Each compound was given at 20 mg/kg dose in
0.1 mL volume. The same volume of DMSO was admin-
istered to the animals in the control group. Clonidine
(0.5 mg/kg) was used as a reference drug. The reduction
of blood pressures between two measurements were
recorded as mm Hg. The results were expressed as mean
± SEM. Student’s t-test was used for statistical analysis
(table II).
3. Pharmacology
The hypotensive activity of 13 compounds chosen
randomly was determined in vivo. Albino rats of either
sex weighing 200 ± 10 g were used in this study. There
were seven animals in each group. The compounds were
dissolved in DMSO. The arterial blood pressures of the
The tested compounds showed hypotensive activity.
The magnitude of their effects after acute i.p. administra-
tion of single doses (20 mg/kg) was less pronounced than

637
Table I. Physico-chemical data of the compounds.
R1
R2
R3
R4
R5
R6
M.p. °C
Yield %
Mol. For.
1
2
3
4
5
6
7
8
H
H
H
H
H
Cl
Cl
Cl
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
OCH3
OCH3
H
H
H
H
H
H
H
H
H
H
H
H
H
H
OH
OH
H
H
H
H
OH
H
OH
OH
H
H
H
H
OH
OH
H
H
OH
H
H
H
H
H
H
H
NO2
H
H
H
H
H
NO2
H
H
H
H
H
H
H
H
H
H
NO2
H
H
H
H
H
H
H
NO2
H
H
H
H
H
H
NO2
H
H
H
NO2
H
H
OCH3
H
NO2
Cl
H
H
H
H
OCH3
H
NO2
Cl
CH3
H
OCH3
H
H
OCH3
H
NO2
Cl
OCH3
CH3
H
H
Cl
OCH3
OH
H
NO2
H
H
OCH3
Cl
215
233
217
219
227
186
251
189
207
222
213
212
220
191
235
166
197
214
192
237
184
192
201
228
179
222
181
207
225
226
191
83
72
81
80
75
72
72
75
68
74
75
77
71
65
82
77
73
70
65
62
78
60
62
70
74
68
68
70
76
73
67
75
65
74
77
75
68
67
60
58
C24H19N3S
C24H18N4O2S
C24H18N4O2S
C24H19N3OS
C25H21N3O2S
C24H18ClN3S
C24H17ClN4O2S
C24H17Cl2N3S
C24H17ClN4O2S
C24H18ClN3OS
C25H21N3OS
C25H21N3O2S
C26H23N3O3S
C26H22N3S
C26H22N4O2S
C26H21ClN3S
C27H24N3S
C26H22N3OS
C27H24N3O2S
C26H22N4O2S
C25H21N3OS
C26H23N3O3S
C27H23N3S
C27H22N4O2S
C27H22ClN3S
C28H25N3OS
C28H25N3S
C27H22N4O2S
C27H23N3OS
C27H22ClN3OS
C28H25N3O2S
C28H25N3OS
C28H25N3S
C28H24N4O2S
C28H24N4O2S
C28H25N3OS
C29H27N3O2S
C28H24N3ClOS
C29H27N3OS
9
Cl
Cl
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
OCH3
OCH3
OCH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
H
H
CH3
CH3
CH3
CH3
CH3
CH3
CH3
H
H
H
-(CH2)3-
-(CH2)3-
-(CH2)3-
-(CH2)3-
-(CH2)3-
-(CH2)3-
-(CH2)3-
-(CH2)3-
-(CH2)3-
-(CH2)3-
-(CH2)4-
-(CH2)4-
-(CH2)4-
-(CH2)4-
-(CH2)4-
-(CH2)4-
-(CH2)4-
H
OH
OH
OH
CH3
H
H
H
OH
OH
OH
CH3
191
186
197
224
184
208
88
H
H
H
H
H
H
H
H
OH
that of an optimal dosage of the reference drug clonidine
(0.5 mg/kg) in the same experimental conditions.
ring were seen as doublets of doublets at 3.10–3.30,
4.00–4.10 and 5.60–5.70 ppm (JAB = 17.07, JAX = 6.30,
JBX = 11.05 Hz), respectively. The protons belonging to
the aromatic ring and phenyl substituents were observed
at expected chemical shift and integral values. The 5-H
proton of thiazole was observed as a singlet between 7.20
and 7.70 ppm.
4. Results, discussion and conclusions
In the present work, 39 new compounds were synthe-
sized. The structures of all compounds were confirmed by
1
According to the results shown in table II an increase
in the hypotensive activity of the compounds 5, 19, 22
and 31 has been observed. It can be concluded that the
addition of a hydroxyl group to R4 and a methoxy group
IR, H-NMR, Mass spectra and elemental analyses. IR
spectra of the compounds showed C=N and C=C stretch-
ing bands at 1 630 cm–1 and 1 580 cm–1, respectively. In
1
the H-NMR spectra, HA, HB, HX protons of pyrazoline

638
Table II. Hypotensive activity of compounds.
aromatic protons), 7.80–8.00 (2H, two s, NH2), (JAB
17.94, JAX = 2.85, JBX = 11.30 Hz).
=
Compound
Reduction of arterial
blood pressure (mm Hg)
(X ± SEM)
n
Student’s t-test
5.1.2.3. 1-Thiocarbamoyl-3-(5′,6′,7′,8′
-tetrahydronaphthalene-2′-yl)-5-phenyl-2-pyrazoline
1
3
5
9
16
19
20
21
22
31
34
35
13.80 ± 3.45
12.29 ± 3.41
33.29 ± 6.23
8.57 ± 1.69
7
7
7
7
7
7
7
7
7
7
7
7
7
7
P < 0.05
P < 0.05
P < 0.05
P < 0.05
P < 0.05
P < 0.05
P < 0.05
P < 0.05
P < 0.05
P < 0.05
P < 0.05
P < 0.05
P < 0.05
P < 0.001
1H-NMR (DMSO-d6, δ, ppm): 1.70 (4H, s, CH2), 2.70
(4H, s, CH2), 3.10 (1H, dd, HA), 3.80 (1H, dd, HB), 5.90
(1H, dd, HX), 7.00–7.60 (8H, m, aromatic protons),
7.80–8.00 (2H, two s, NH2), (JAB = 18.00, JAX = 3.09,
JBX = 11.40 Hz).
16.29 ± 4.12
29.57 ± 9.43
34.29 ± 8.69
17.43 ± 4.05
35.57 ± 10.36
25.57 ± 7.15
16.57 ± 3.48
20.43 ± 6.17
16.14 ± 7.47
63.00 ± 4.56
5.1.2.4. Preparation of 1-(4-arylthiazol-
2-yl)-3,5-diaryl-2-pyrazoline derivatives 1–39
To a solution of III (0.01 mol) in ethanol (30 mL)
phenacetylbromide (or w-chloroacetyl substituted phe-
nol) (0.01 mol) was added. The resulting mixture was
refluxed for 1 h. After cooling, the solid which separated
was recrystallized from ethanol. 1–39: IR (KBr, cm–1);
1 630 (C=N), 1 580 (C=C).
36
Clonidine
(0.5 mg/kg)
Control
(DMSO)
3.86 ± 1.038
7
P < 0.05
5.1.2.5. 1-(4-Phenylthiazol-2-
yl)-3,5-diphenyl-2-pyrazoline 1
1H-NMR (DMSO-d6, δ, ppm): 3.20–3.40 (1H, m, HA),
4.10 (1H, dd, HB), 5.70 (1H, dd, HX), 7.20–7.80 (16H, m,
aromatic protons), (JAB = 17.05, JAX = 6.35, JBX = 11.08
Hz). MS (FAB+): M + 1: m/z: 382.
to R6 leads to an increase in the hypotensive activity of
the above compounds. Besides this, compound 20 shows
hypotensive activity due to the nitro group at R5.
5.1.2.6. 1-[4-(4′-Nitrophenyl)thiazol-
5. Experimental protocols
2-yl]-3,5-diphenyl-2-pyrazoline 2
1H-NMR (DMSO-d6, δ, ppm): 3.30 (1H, dd, HA), 4.00
(1H, dd, HB), 5.70 (1H, dd, HX), 7.20–8.50 (15H, m,
aromatic protons), (JAB = 17.25, JAX = 6.37, JBX = 11.88
Hz). MS (FAB+): M + 1: m/z: 427.
5.1. Chemistry
Melting points were determined by using a Gallen-
kamp apparatus. Spectroscopic data were recorded by the
following instruments: IR, Shimadzu IR-435 spectropho-
tometer; 1H-NMR, Bruker 250 MHz NMR spectrometer;
MS, fast atom bombardment mass spectra (MS-FAB+)
were obtained by VG Quattro Mass spectrometer; mi-
croanalyses, Leco CHNS elemental analyses apparatus.
5.1.2.7. 1-[4-(3′-Nitrophenyl)thiazol-
2-yl]-3,5-diphenyl-2-pyrazoline 3
1H-NMR (DMSO-d6, δ, ppm): 3.20–3.40 (1H, m, HA),
4.05 (1H, dd, HB), 5.70 (1H, dd, HX), 7.30–8.50 (15H, m,
aromatic protons), (JAB = 17.32, JAX = 6.34, JBX = 10.98
Hz). MS (FAB+): M + 1: m/z: 427.
5.1.2. General procedure
5.1.2.8. 1-[4-(2′-Hydroxyphenyl)thiazol-
5.1.2.1. Preparation of
2-yl]-3,5-diphenyl-2-pyrazoline 4
1H-NMR (DMSO-d6, δ, ppm): 3.10–3.30 (1H, m, HA),
4.15 (1H, dd, HB), 5.70 (1H, dd, HX), 7.10–7.70 (15H, m,
aromatic protons), 10.60 (1H, s, OH), (JAB = 17.15, JAX
= 6.45, JBX = 11.00 Hz). MS (FAB+): M + 1: m/z: 398.
1-thiocarbamoyl-3,5-diaryl-2-pyrazoline derivatives III
A mixture of chalcone (0.01 mol), thiosemicarbazide
(0.01 mol) and NaOH (0.025 mol) was refluxed in etha-
nol (25 mL) for 8 h. The solution was poured into
ice-water. The precipitate was filtered and crystallized
from methanol.
5.1.2.9. 1-[4-(2′-Hydroxy-4′-
methoxyphenyl)thiazol-2-yl]-3,5-diphenyl-2-pyrazoline 5
1H-NMR (DMSO-d6, δ, ppm): 3.30–3.50 (1H, m, HA),
3.75 (3H, s, OCH3), 3.95–4.10 (1H, m, HB), 5.70 (1H, dd,
HX), 6.30–7.70 (14H, m, aromatic protons), 10.75 (1H, s,
OH), (JAX = 6.35, JBX = 11.95 Hz).
5.1.2.2. 1-Thiocarbamoyl-3-
(3′,4′-dimethylphenyl)-5-phenyl-2-pyrazoline
1H-NMR (DMSO-d6, δ, ppm): 3.10 (1H, dd, HA), 3.80
(1H, dd, HB), 5.80 (1H, dd, HX), 7.00–7.60 (8H, m,

639
5.1.2.10. 1-(4-Phenylthiazol-2-yl)-
m, HB), 5.60 (1H, dd, HX), 6.30–7.70 (13H, m, aromatic
protons), 10.70 (1H, s, OH), (JAX = 6.20, JBX = 11.35
Hz).
3-(3″-chlorophenyl)-5-phenyl-2-pyrazoline 6
1H-NMR (DMSO-d6, δ, ppm): 3.20–3.40 (1H, m, HA),
4.00–4.10 (1H, m, HB), 5.70 (1H, dd, HX), 7.20–7.70
(15H, m, aromatic protons), (JAX = 6.72, JBX = 11.35
Hz). MS (FAB+): M + 1: m/z: 416.
5.1.2.18. 1-(4-Phenylthiazol-2-yl)-3-
(3′,4′-dimethylphenyl)-5-phenyl-2-pyrazoline 14
1H-NMR (DMSO-d6, δ, ppm): 2.25 (6H, s, CH3),
3.10–3.20 (1H, m, HA), 4.00 (1H, dd, HB), 5.60 (1H, dd,
HX), 6.80–7.70 (14H, m, aromatic protons), (JAX = 6.40,
JBX = 11.22 Hz) MS (FAB+): M + 1: m/z: 409.
5.1.2.11. 1-[4-(4′-Nitrophenyl)thiazol-
2-yl]-3-(3″-chlorophenyl)-5-phenyl-2-pyrazoline 7
1H-NMR (DMSO-d6, δ, ppm): 3.40–3.60 (1H, m, HA),
4.15 (1H, dd, HB), 5.70 (1H, dd, HX), 7.40–8.60 (14H, m,
aromatic protons), (JAB = 17.42, JAX = 6.57, JBX = 11.30
Hz). MS (FAB+): M + 1: m/z: 461.
5.1.2.19. 1-[4-(4′-Nitrophenyl)thiazol-2-yl]-3-
(3″,4″-dimethylphenyl)-5-phenyl-2-pyrazoline 15
1H-NMR (DMSO-d6, δ, ppm): 2.25 (6H, s, CH3),
3.20–3.30 (1H, m, HA), 4.20 (1H, dd, HB), 5.80 (1H, dd,
HX), 7.25–8.60 (13H, m, aromatic protons), (JAX = 6.55,
JBX = 10.42 Hz) MS (FAB+): M + 1: m/z: 455.
5.1.2.12. 1-[4-(4′-Chlorophenyl)thiazol-
2-yl]-3-(3″-chlorophenyl)-5-phenyl-2-pyrazoline 8
1H-NMR (DMSO-d6, δ, ppm): 3.30–3.50 (1H, m, HA),
4.05 (1H, dd, HB), 5.70 (1H, dd, HX), 7.10–7.90 (14H, m,
aromatic protons), (JAB = 17.22, JAX = 6.37, JBX = 11.00
Hz). MS (FAB+): M + 1: m/z: 450.
5.1.2.20. 1-[4-(4′-Chlorophenyl)thiazol-2-yl]-3-
(3″,4″-dimethylphenyl)-5-phenyl-2-pyrazoline 16
1H-NMR (DMSO-d6, δ, ppm): 2.25 (6H, s, CH3),
3.10–3.20 (1H, m, HA), 4.00–4.20 (1H, m, HB), 5.60 (1H,
5.1.2.13. 1-[4-(3′-Nitrophenyl)thiazol-
2-yl]-3-(3″-chlorophenyl)-5-phenyl-2-pyrazoline 9
1H-NMR (DMSO-d6, δ, ppm): 3.40–3.60 (1H, m, HA),
4.15 (1H, dd, HB), 5.80 (1H, dd, HX), 7.40–8.40 (14H, m,
aromatic protons), (JAB = 18.02, JAX = 6.45, JBX = 11.32
Hz). MS (FAB+): M + 1: m/z: 461.
dd, HX), 6.80–7.80 (13H, m, aromatic protons), (JAX
=
6.60, JBX = 11.53 Hz) MS (FAB+): M + 1: m/z: 443.
5.1.2.21. 1-[4-(4′-Methylphenyl)thiazol-2-yl]-3-
(3″,4″-dimethylphenyl)-5-phenyl-2-pyrazoline 17
1H-NMR (DMSO-d6, δ, ppm): 2.22 (3H, s, CH3), 2.25
(6H, s, CH3), 3.15–3.30 (1H, m, HA), 4.00–4.15 (1H, m,
HB), 5.70 (1H, dd, HX), 6.70–7.70 (13H, m, aromatic
protons), (JAX = 6.75, JBX = 12.03 Hz) MS (FAB+): M +
1: m/z: 423.
5.1.2.14. 1-[4-(2′-Hydroxyphenyl)thiazol-
2-yl]-3-(3″-chlorophenyl)-5-phenyl-2-pyrazoline 10
1H-NMR (DMSO-d6, δ, ppm): 3.30 (1H, dd, HA), 4.15
(1H, dd, HB), 5.70 (1H, dd, HX), 7.10–8.00 (14H, m,
aromatic protons) 11.00 (1H, s, OH), (JAB = 17.37, JAX
=
6.41, JBX = 11.77 Hz). MS (FAB+): M + 1: m/z: 432.
5.1.2.22. 1-[4-(2′-Hydroxyphenyl)thiazol-2-yl]-3-
(3″,4″-dimethylphenyl)-5-phenyl-2-pyrazoline 18
1H-NMR (DMSO-d6, δ, ppm): 2.25 (6H, s, CH3),
3.15–3.30 (1H, m, HA), 4.00–4.10 (1H, m, HB), 5.70 (1H,
dd, HX), 6.40–7.80 (13H, m, aromatic protons) 10.80
(1H, s, OH), (JAX = 6.70, JBX = 11.42 Hz) MS (FAB+):
M + 1: m/z: 425.
5.1.2.15. 1-(4-Phenylthiazol-2-yl)-3-
(3″-methoxyphenyl)-5-phenyl-2-pyrazoline 11
1H-NMR (DMSO-d6, δ, ppm): 3.30–3.50 (1H, m, HA),
3.65 (3H, s, OCH3), 3.90–4.10 (1H, m, HB), 5.60 (1H, dd,
HX), 6.60–7.70 (15H, m, aromatic protons), (JAX = 6.20,
JBX = 11.35 Hz).
5.1.2.23. 1-[4-(2′-Hydroxy-4′-methoxyphenyl)thiazol-2-
yl]-3-(3″,4″-dimethylphenyl)-5-phenyl-2-pyrazoline 19
1H-NMR (DMSO-d6, δ, ppm): 2.25 (6H, s, CH3),
3.10–3.30 (1H, m, HA), 3.75 (3H, s, OCH3), 4.00–4.10
(1H, m, HB), 5.60 (1H, dd, HX), 6.30–7.80 (12H, m,
5.1.2.16. 1-[4-(2′-Hydroxyphenyl)thiazol-
2-yl]-3-(3″-methoxyphenyl)-5-phenyl-2-pyrazoline 12
1H-NMR (DMSO-d6, δ, ppm): 3.20–3.45 (1H, m, HA),
3.55 (3H, s, OCH3), 3.95–4.10 (1H, m, HB), 5.60 (1H, dd,
HX), 6.75–7.80 (14H, m, aromatic protons), 10.80 (1H, s,
OH), (JAX = 6.20, JBX = 11.35 Hz) MS (FAB+): M + 1:
m/z: 428.
aromatic protons) 10.70 (1H, s, OH), (JAX = 6.40, JBX
=
11.22 Hz) MS (FAB+): M + 1: m/z: 455.
5.1.2.17. 1-[4-(2′-Hydroxy-4′-methoxyphenyl)thiazol-
2-yl]-3-(3″-methoxyphenyl)-5-phenyl-2-pyrazoline 13
1H-NMR (DMSO-d6, δ, ppm): 3.30–3.50 (1H, m, HA),
3.65 (3H, s, OCH3), 3.80 (3H, s, OCH3), 3.90–4.10 (1H,
5.1.2.24. 1-[4-(3′-Nitrophenyl)thiazol-2-yl]-3-
(3″,4″-dimethylphenyl)-5-phenyl-2-pyrazoline 20
1H-NMR (DMSO-d6, δ, ppm): 2.25 (6H, s, CH3),
3.20–3.30 (1H, m, HA), 4.20 (1H, m, HB), 5.80 (1H, dd,

640
HX), 7.25–8.60 (13H, m, aromatic protons), (JAX = 6.55,
JBX = 10.42 Hz) MS (FAB+): M + 1: m/z: 455.
dd, HA), 4.10 (1H, dd, HB), 5.70 (1H, dd, HX), 7.10–7.90
(13H, m, aromatic protons), (JAB = 17.85, JAX = 6.95,
JBX = 11.90 Hz) MS (FAB+): M + 1: m/z: 436.
5.1.2.25. 1-(4-Phenylthiazol-2-yl)-3-
phenyl-5-(4′-methoxyphenyl)-2-pyrazoline 21
5.1.2.32. 1-[4-(3′-Nitrophenyl)thiazol-
1H-NMR (DMSO-d6, δ, ppm): 3.25–3.50 (1H, m, HA),
3.70 (3H, s, OCH3), 4.00 (1H, dd, HB), 5.65 (1H, dd, HX),
6.50–7.90 (15H, m, aromatic protons), (JAB = 17.02, JAX
= 6.22, JBX = 11.09 Hz). MS (FAB+): M + 1: m/z: 412.
2-yl]-3-(indan-5″-yl)-5-phenyl-2-pyrazoline 28
1H-NMR (DMSO-d6, δ, ppm): 2.00–2.10 (2H, m,
CH2), 2.90 (4H, br, CH2), 3.30 (1H, dd, HA), 4.00 (1H,
dd, HB), 5.70 (1H, dd, HX), 7.20–8.50 (13H, m, aromatic
protons), (JAB = 17.18, JAX = 6.55, JBX = 11.86 Hz) MS
(FAB+): M + 1: m/z: 467.
5.1.2.26. 1-[4-(2′-Hydroxy-4′-methoxyphenyl)thiazol-
2-yl]-3-phenyl-5-(4″-methoxyphenyl)-2-pyrazoline 22
1H-NMR (DMSO-d6, δ, ppm): 3.25–3.50 (1H, m, HA),
3.65 (3H, s, OCH3), 3.80 (3H, s, OCH3), 4.00 (1H, dd,
HB), 5.60 (1H, dd, HX), 6.70–7.70 (13H, m, aromatic
protons), (JAB = 17.02, JAX = 6.22, JBX = 11.09 Hz),
10.80 (1H, s, OH), MS (FAB+): M + 1: m/z: 458.
5.1.2.33. 1-[4-(2′-Hydroxyphenyl)thiazol-
2-yl]-3-(indan-5″-yl)-5-phenyl-2-pyrazoline 29
1H-NMR (DMSO-d6, δ, ppm): 2.00–2.10 (2H, m,
CH2), 2.90 (4H, br, CH2), 3.30 (1H, dd, HA), 4.00 (1H,
dd, HB), 5.70 (1H, dd, HX), 6.80–7.70 (13H, m, aromatic
protons), 10.70 (1H, s, OH), (JAB = 17.17, JAX = 6.56,
JBX = 11.86 Hz).
5.1.2.27. 1-(4-Phenylthiazol-2-yl)-3-
(indan-5″-yl)-5-phenyl-2-pyrazoline 23
1H-NMR (DMSO-d6, δ, ppm): 2.00–2.10 (2H, m,
CH2), 2.90 (4H, br, CH2), 3.30 (1H, dd, HA), 4.00 (1H,
dd, HB), 5.70 (1H, dd, HX), 6.80–7.80 (14H, m, aromatic
protons), (JAB = 17.35, JAX = 6.65, JBX = 11.85 Hz) MS
(FAB+): M + 1: m/z: 422.
5.1.2.34. 1-[4-(2′-Hydroxy-4′-chlorophenyl)thiazol-
2-yl]-3-(indan-5″-yl)-5-phenyl-2-pyrazoline 30
1H-NMR (DMSO-d6, δ, ppm): 2.00–2.10 (2H, m,
CH2), 2.90 (4H, br, CH2), 3.30 (1H, dd, HA), 4.00 (1H,
dd, HB), 5.70 (1H, dd, HX), 7.00–7.90 (12H, m, aromatic
protons), 10.90 (1H, s, OH), (JAB = 17.22, JAX = 6.86,
JBX = 11.00 Hz).
5.1.2.28. 1-[4-(4′-Nitrophenyl)thiazol-
2-yl]-3-(indan-5″-yl)-5-phenyl-2-pyrazoline 24
1H-NMR (DMSO-d6, δ, ppm): 2.00–2.10 (2H, m,
CH2), 2.90 (4H, br, CH2), 3.30 (1H, dd, HA), 4.00 (1H,
dd, HB), 5.70 (1H, dd, HX), 7.20–8.40 (13H, m, aromatic
protons), (JAB = 17.65, JAX = 6.85, JBX = 11.80 Hz) MS
(FAB+): M + 1: m/z: 467.
5.1.2.35. 1-[4-(2′-Hydroxy-4′-methoxyphenyl)thiazol-
2-yl]-3-(indan-5″-yl)-5-phenyl-2-pyrazoline 31
1H-NMR (DMSO-d6, δ, ppm): 2.00–2.10 (2H, m,
CH2), 2.90 (4H, br, CH2), 3.30 (1H, dd, HA), 3.70 (3H, s,
OCH3), 4.00 (1H, dd, HB), 5.70 (1H, dd, HX), 6.80–7.70
(12H, m, aromatic protons), 10.70 (1H, s, OH), (JAB
=
5.1.2.29. 1-[4-(4′-Chlorophenyl)thiazol-
17.22, JAX = 6.86, JBX = 11.00 Hz) MS (FAB+): M + 1:
2-yl]-3-(indan-5″-yl)-5-phenyl-2-pyrazoline 25
1H-NMR (DMSO-d6, δ, ppm): 2.00–2.10 (2H, m,
CH2), 2.90 (4H, br, CH2), 3.30 (1H, dd, HA), 4.00 (1H,
dd, HB), 5.70 (1H, dd, HX), 6.90–7.60 (13H, m, aromatic
protons), (JAB = 17.35, JAX = 7.05, JBX = 12.00 Hz) MS
(FAB+): M + 1: m/z: 456.
m/z: 468.
5.1.2.36. 1-[4-(2′-Methyl-4′-hydroxyphenyl)thiazol-
2-yl]-3-(indan-5″-yl)-5-phenyl-2-pyrazoline 32
1H-NMR (DMSO-d6, δ, ppm): 2.00–2.10 (2H, m,
CH2), 2.23 (3H, s, CH3), 2.90 (4H, br, CH2), 3.30 (1H,
dd, HA), 4.10 (1H, dd, HB), 5.70 (1H, dd, HX), 6.70–7.50
5.1.2.30. 1-[4-(4′-Methoxyphenyl)thiazol-
(12H, m, aromatic protons), 10.70 (1H, s, OH), (JAB
=
2-yl]-3-(indan-5″-yl)-5-phenyl-2-pyrazoline 26
17.45, JAX = 7.06, JBX = 11.20 Hz) MS (FAB+): M + 1:
1H-NMR (DMSO-d6, δ, ppm): 2.00–2.10 (2H, m,
CH2), 2.90 (4H, br, CH2), 3.30 (1H, dd, HA), 3.65 (3H, s,
OCH3), 4.00 (1H, dd, HB), 5.70 (1H, dd, HX), 7.20–8.00
(13H, m, aromatic protons), (JAB = 17.28, JAX = 6.35,
JBX = 11.06 Hz) MS (FAB+): M + 1: m/z: 452.
m/z: 452.
5.1.2.37. 1-4-(Phenylthiazol-2-yl)-3-(5″,6″,7″,8″-
tetrahydronaphthalene-2″-yl)-5-phenyl-2-pyrazoline 33
1H-NMR (DMSO-d6, δ, ppm): 2.00–2.10 (4H, m,
CH2), 2.90 (4H, br, CH2), 3.20–3.40 (1H, m, HA), 4.00
(1H, dd, HB), 5.65 (1H, dd, HX), 7.20–7.80 (14H, m,
aromatic protons), (JAB = 17.41, JAX = 6.42, JBX = 11.45
Hz) MS (FAB+): M + 1: m/z: 436.
5.1.2.31. 1-[4-(4′-Methylphenyl)thiazol-
2-yl]-3-(indan-5″-yl)-5-phenyl-2-pyrazoline 27
1H-NMR (DMSO-d6, δ, ppm): 2.00–2.10 (2H, m,
CH2), 2.24 (3H, s, CH3), 2.90 (4H, br, CH2), 3.35 (1H,

641
5.1.2.38. 1-[4-(4′-Nitrophenyl)-
thiazol-2-yl]-3-(5″,6″,7″,8″-
5.1.2.43. 1-[4-(2′-Methyl-4′-
hydroxyphenyl)thiazol-2-yl]-3-(5″,6″,7″,8″-
tetrahydronaphthalene-2″-yl)-5-phenyl-2-pyrazoline 34
1H-NMR (DMSO-d6, δ, ppm): 2.00–2.10 (4H, m,
CH2), 2.90 (4H, br, CH2), 3.20–3.40 (1H, m, HA), 4.00
(1H, dd, HB), 5.70 (1H, dd, HX), 7.20–0–8.50 (13H, m,
aromatic protons), (JAB = 17.27, JAX = 6.32, JBX = 11.75
Hz) MS (FAB+): M + 1: m/z: 481.
tetrahydronaphthalene-2″-yl)-5-phenyl-2-pyrazoline 39
1H-NMR (DMSO-d6, δ, ppm): 2.00–2.15 (4H, m,
CH2), 2.25 (3H, s, CH3), 2.80 (4H, br, CH2), 3.10–3.30
(1H, m, HA), 4.00 (1H, dd, HB), 5.65 (1H, dd, HX),
7.20–8.20 (12H, m, aromatic protons), 10.80 (1H, s, OH),
(JAB = 17.27, JAX = 6.32, JBX = 11.75 Hz) MS (FAB+):
M + 1: m/z: 466.
5.1.2.39. 1-[4-(3′-Nitrophenyl)-
thiazol-2-yl]-3-(5″,6″,7″,8″-
tetrahydronaphthalene-2″-yl)-5-phenyl-2-pyrazoline 35
1H-NMR (DMSO-d6, δ, ppm): 2.00–2.10 (4H, m,
CH2), 2.90 (4H, br, CH2), 3.20–3.40 (1H, m, HA), 4.00
(1H, dd, HB), 5.70 (1H, dd, HX), 7.10–0–8.40 (13H, m,
aromatic protons), (JAB = 17.20, JAX = 6.42, JBX = 11.95
Hz) MS (FAB+): M + 1: m/z: 481.
References
[1] Polevoi L.G., Tr Nauchn Konf Aspir Ordin 1-yi Mosk Med. Inst.
Moscow (1966) 159–161; C.A.: 65: 19147 d.
[2] Batulin Y.M., Farmacol Toksicol 31 (1969) 533–536; C.A.: 70: 2236
a.
[3] Parmar S.S., Pandey B.R., Dwivedi C., Harbison R.D., J. Pharm.
5.1.2.40. 1-[4-(2′-Hydroxy-
phenyl)thiazol-2-yl]-3-(5″,6″,7″,8″-
Sci. 63 (1974) 1152–1155.
[4] Soni N., Pande K., Kalsi R., Gupta T.K., Parmar S.S., Barthwal J.P.,
tetrahydronaphthalene-2″-yl)-5-phenyl-2-pyrazoline 36
1H-NMR (DMSO-d6, δ, ppm): 2.00–2.10 (4H, m,
CH2), 2.90 (4H, br, CH2), 3.10–3.30 (1H, m, HA), 4.10
(1H, dd, HB), 5.65 (1H, dd, HX), 6.70–0–7.80 (13H, m,
aromatic protons), 10.90 (1H, s, OH), (JAB = 18.07, JAX
= 6.65, JBX = 11.65 Hz) MS (FAB+): M + 1: m/z: 452.
Res. Commun. Chem. Path. Pharm. 56 (1987) 129–132.
[5] Palaska E., Erol D., Demirdamar R., Eur. J. Med. Chem. 31 (1996)
43–47.
[6] Bruno O., Ranise A., Bondavalli F., Schenone F., D’Amico M.,
Filipelli A., Filipelli W., Francesco R., Farmaco 48 (1993) 949–966.
[7] Bondavalli F., Bruno O., Ranise A., Schenone F., Addonizio P., De
Novellis V., Loffreda A., Marmo E., Farmaco 43 (1988) 725–743.
[8] Bruno O., Ranise A., Bondavalli F., Schenone P., Farmaco 48 (1993)
5.1.2.41. 1-[4-(2′-Hydroxy-4′-
methoxyphenyl)thiazol-2-yl]-3-(5″,6″,7″,8″-
967–977.
[9] Mazzone G., Puglisi G., Corsaro A., Panico A., Bonina F., Amico-
Roxas M., Caruso A., Trombadore S., Eur. J. Med. Chem. 21 (1986)
277–284.
tetrahydronaphthalene-2″-yl)-5-phenyl-2-pyrazoline 37
1H-NMR (DMSO-d6, δ, ppm): 2.00–2.10 (4H, m,
CH2), 2.90 (4H, br, CH2), 3.10–3.30 (1H, m, HA), 3.65
(3H, s, OCH3), 4.15 (1H, dd, HB), 5.75 (1H, dd, HX),
6.80–0–7.90 (12H, m, aromatic protons), 11.05 (1H, s,
OH), (JAB = 17.80, JAX = 6.95, JBX = 11.85 Hz) MS
(FAB+): M + 1: m/z: 482.
[10] Taniyama H., Tanaka Y., J. Pharm. Soc. Japan (1953) 528–529;
C.A.: 48: 3347 a.
[11] Scherman W.R., Dickson D.E., J. Org. Chem. 27 (1952) 1351–1355.
[12] Usui Y., Ann. Rep. Takeda Res. Lab. 27 (1968) 130–143; C. A.: 70:
96686 x.
[13] Gursoy A., J. Fac. Pharm. Istanbul 9 (1973) 77–84; C. A.: 81: 3815
c.
5.1.2.42. 1-[4-(2′-Hydroxy-4′-
chlorophenyl)thiazol-2-yl]-3-(5″,6″,7″,8″-
[14] Turan-Zitouni G., Demirayak S., Chevallet P., Acta Pharmaceutica
Turcica, XXXIV (1992) 23–26; C.A.: 117: 191739 q.
[15] Van Zwieten P.A., Pharmacology 13 (1975) 352–354.
tetrahydronaphthalene-2″-yl)-5-phenyl-2-pyrazoline 38
1H-NMR (DMSO-d6, δ, ppm): 2.00–2.10 (4H, m,
CH2), 2.90 (4H, br, CH2), 3.10–3.30 (1H, m, HA), 4.15
(1H, dd, HB), 5.70 (1H, dd, HX), 6.85–0–7.80 (12H, m,
aromatic protons), 11.00 (1H, s, OH), (JAB = 17.80, JAX
= 6.95, JBX = 11.85 Hz) MS (FAB+): M + 1: m/z: 486.
[16] Bilgin A.A., Palaska E., Sunal R., Arzneim.-Forsch. 43 (1993)
1041–1044.
[17] Pruneau D., Roy F., Arzneim.-Forsch. 37 (1987) 416–418.
[18] Ashimori A., Ono T., Ohtaki Y., Ushida T., Fukaya C., Watanabe M.,
Yokoyama K., Chem. Pharm. Bull. 38 (1990) 2446–2458; C.A.: 114:
61893 n.