Synthesis of 6-alkyl-4-[5-dialkylaminomethyl-4-(4-methyl-1,3-thiazol-2-yl)- 1H-pyrazol-3-yl]-1,3-benzenediols

Article abstract of DOI:10.1007/s10593-013-1250-0

6-Alkyl-2-dialkylaminomethyl-7-hydroxy-3-(4-methyl-1,3-thiazol-2-yl) -4H-chromen-4-ones recyclized into 6-alkyl-4-[5-dialkylaminomethyl-4-(4-methyl- 1,3-thiazol-2-yl)-1H-pyrazol-3-yl]-1,3-benzenediols under the influence of hydrazine hydrate.

Full text of DOI:10.1007/s10593-013-1250-0

Chemistry of Heterocyclic Compounds, Vol. 49, No. 2, May, 2013 (Russian Original Vol. 49, No. 2, February, 2013)
SYNTHESIS OF 6-ALKYL-4-[5-DIALKYLAMINOMETHYL-
4-(4-METHYL-1,3-THIAZOL-2-YL)-1H-PYRAZOL-3-YL]-
1,3-BENZENEDIOLS
T. V. Shokol1*, N. V. Gorbulenko1, A. V. Turov1, and V. P. Khilya1
6-Alkyl-2-dialkylaminomethyl-7-hydroxy-3-(4-methyl-1,3-thiazol-2-yl)-4H-chromen-4-ones recyclized
into 6-alkyl-4-[5-dialkylaminomethyl-4-(4-methyl-1,3-thiazol-2-yl)-1H-pyrazol-3-yl]-1,3-benzenediols
under the influence of hydrazine hydrate.
Keywords: 6-alkyl-4-[5-dialkylaminomethyl-4-(4-methyl-1,3-thiazol-2-yl)-1H-pyrazol-3-yl]-1,3-benzene-
diols,
2-dialkylaminomethyl-3-thiazolylchromones,
3-aryl-4-hetarylpyrazoles,
2-chloromethyl-
3-thiazolylchromones.
In the last 20 years there has been a steady growth in the number of publications devoted to the
synthesis and study of pyrazole derivatives, including the functionalized 3-aryl-4-aryl(hetaryl)pyrazoles. This is
explained by the broad spectrum of biological activity exhibited by these compounds and their potential use as
structural blocks in the design of pyrazole-containing condensed systems with valuable properties [1-3]. A
series of 3-aryl-4-aryl(hetaryl)pyrazole derivatives shows antiherpetic [4], antifungal, antibacterial [5],
fungicidal, herbicidal, and growth regulating activity [6, 7]. Some of these have been studied as potential drugs
for treatment of the nervous system (cerebral ischemia), diseases of the heart and gastrointestinal tract [8], they
possess anti-inflammatory, analgesic, hypotensive, antiarrhythmic, thrombocyte antiaggregative [9],
hypoglycemic, antiviral, and neuroleptic [4] effects. Derivatives of 3-(2,4-dihydroxyphenyl)-4-aryl(hetaryl)-
pyrazole are recognized as a new class of HSP90 inhibitors and may find use in the therapy of some types of
cancer [10, 11].
The reactions of 3-(het)arylchromones with hydrazines are applicable for the synthesis of pyrazoles and
have been used to prepare 2-(pyrazol-3-yl)phenol derivatives with het(aryl) substituents in position 4 and a
variety of substituents (H, CF3, Me, CO2Et, CO2H, CONHNH2, CONHAlk, NH2, (CH2)2CO2H) in position 5 of
the pyrazole ring [12, 13]. 2-(Pyrazol-3-yl)phenols with dialkylaminomethyl substituent in position 4 of the
pyrazole ring were synthesized by recyclization of 3-dialkylaminomethylchromones under the influence of
hydrazine hydrate [14].
In this paper, we present data on the assembly of pyrazolylthiazole bisheterocycles with
dialkylaminomethyl substituents in position 5 of the pyrazole ring by starting from the 3-(4-methyl-1,3-thiazol-
2-yl)chromone 2-dialkylaminomethyl derivatives 1a,c,d, 2a-c,e,f [15], or from the newly synthesized
_______
*To whom correspondence should be addressed, e-mail: shokol_tv@mail.univ.kiev.ua.
1Kyiv Taras Shevchenko National University, 60 Volodymirska St., Kyiv 01601, Ukraine.
________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, 351-356, February 2013. Original
article submitted May 29, 2012.
0009-3122/13/4902-0325©2013 Springer Science+Business Media New York
325

2-[4-(4-fluorophenyl)- and 2-[4-(3-chlorophenyl)piperazinomethyl]chromones 1f and 2g. The latter were
obtained by amination of 2-chloromethylchromones 3 and 4 with 1-(4-fluorophenyl)- and 1-(3-chloro-
phenyl)piperazines by known methods [15, 16].
On refluxing compounds 1a,c,d,f and 2a-c,e-g for 5 min in ethanol with an excess of hydrazine hydrate,
followed by dilution with water, the recyclization products 5a,c,d,f and 6a-c,e-g were isolated (Table 1).
X
X
O
HO
R
N
N
Cl
S
N
H
O
O
HO
R
Dioxane
O
N
S
Me
3, 4
1a,c,d,f
2a–c,e–g
Me
N2H4
EtOH 5 min

Me
Me
R
R
S
S
HO
HO
N
N
HO HN
N
OH
N
N
N
N
H
X
X
A
B
5a,c,d,f
6a–c,e–g
1a,c,d,f, 3, 5a,c,d,f R = Et; 2a–c,e–g, 4, 6a–c,e–g R = Pr;
a X = O, b X = CH2, c X = CHCH2Ph; d X = NMe,
N
Cl
N
O
N
e X =
, f X =
, g X =
O
F
Pyrazoles 5a,c,d,f and 6a-c,e-g were colorless crystalline compounds, insoluble in water, readily soluble
in 2 N NaOH, and gave a characteristic blue color with an ethanolic solution of FeCl3 as a result of chelate
complex formation with the phenolic hydroxyl, suitably located close to the pyrazole ring nitrogen atom.
1
Characteristically, the H NMR spectra of compounds 5a,c,d,f and 6a-c,e-g recorded in DMSO-d6
contained three downfield singlets which exchanged with D2O. The pyrazole ring NH proton gave the furthest
downfield signal (12.58-13.13 ppm), while the hydroxyl protons gave signals at 9.11-10.18 ppm (Table 2).
These signals were broadened as a result of proton exchange (interconversion of tautomers A and B). There was
a doubling of NH proton signals (12.77 (A) and 13.13 ppm (B)) and the 3-OH proton signals (9.38 (B) and 9.44
ppm (A)) in the 1H NMR spectrum of compound 6a. The assignment of the tautomers A and B was based on the
chemical shifts of the NH and 3-OH protons and their integrated intensities. The downfield signal among the
two NH protons we assigned to the tautomer B because of its participation in an intramolecular hydrogen bond
with the hydroxyl group oxygen atom, which is always associated with a paramagnetic shift. It followed from
the integrated peak intensities that the 3-OH proton signal of the tautomer A was located downfield. The ratio of
tautomers A and B was 7:3.
The methylene group signals from the aminomethyl substituent in pyrazoles 5a,c,d,f and 6a-c,e-g was
shifted upfield by 0.5 ppm in comparison with the analogous signal in the starting 2-dialkylaminochromones
1a,c,d,f and 2a-c,e-g.
326

Table 1. Physicochemical Characteristics of Pyrazoles 5a,c,d,f and 6a-c,e-g
Found, %
Calculated, %
——————
Com-
pound
Empirical
formula
Mp, °С
Yield, %
75
С
Н
N
S
C20H24N4O3S
59.68
59.98
6.19
6.04
13.69
13.99
7.74
8.01
125-126
5a
C28H32N4O2S
C21H27N5O2S
C26H28FN5O2S
C21H26N4O3S
C22H28N4O2S
C29H34N4O2S
C29H33N5O4S
C27H30FN5O2S
C27H30ClN5O2S
68.77
68.82
61.15
60.99
63.15
63.27
60.57
60.85
64.35
64.05
68.99
69.29
63.38
63.60
63.63
63.89
6.90
6.60
6.45
6.58
5.99
5.72
6.53
6.32
6.76
6.84
6.92
6.82
6.12
6.07
6.20
5.96
11.47
11.47
16.77
16.93
14.17
14.19
13.51
13.52
13.68
13.58
11.09
11.15
12.57
12.79
13.58
13.80
6.55
6.56
7.48
7.75
6.35
6.50
7.70
7.73
7.55
7.77
6.34
6.38
5.77
5.85
6.24
6.32
119-120
134-135
114-115
114-115
120-121
105-106
126-127
115-116
94-95
82
81
92
90
97
67
97
73
78
5c
5d
5f
6a
6b
6c
6e
6f
61.59
61.88
5.95
5.77
13.56
13.36
5.94
6.12
6g
The majority of the aromatic proton signals in compounds 5 and 6 were unequivocally assigned from
their multiplicity. Less definite is the assignment of the two close singlets with chemical shifts of 6.93 and 6.85
ppm in the pyrazole 5c and also the aliphatic proton signals of the amine group. For clear assignments we
acquired the COSY-90 spectrum (Fig.1 and 2).
Fig.1. Fragment of the COSY spectrum, corresponding to the aliphatic proton signals of compound 5c.
The correlations in the COSY-90 spectrum differed in intensity. The greatest peak area corresponded to
the geminal spin-spin coupling constants. The intensity of the correlated peaks decreased as the value of the
spin-spin coupling constant decreased. This rule could be used to refine the assignments. For example, the
signal at 2.89 ppm had one intense correlation with the signal of the geminal proton at 1.95 ppm and two
correlations of lesser intensity with the vicinal proton signals at 1.55 and 1.21-1.25 ppm. The analogous
consideration of all the other correlations permitted the full assignment of the signals (Fig.2).
327

The low intensity correlation between the aromatic proton signal at 6.93 ppm and the signal of the
methyl protons at 2.40 ppm reflected the spin-spin coupling over four chemical bonds between the 4-methyl
group of the thiazole ring and the neighboring H-5 proton (Fig. 2).
2.40
CH3
9.13
HO
10.18
OH
6.93
6.37
6.85
N
S
2.41H2C
CH3
2.H89
3.62
1.95
N
H
H
N
1.55
N
1.06
12.70H
H 1.24
7.12
7.20
1.40
H
2.50
7.07
Fig. 2. Correlations found in the COSY spectrum of compound 5c.
Thus, the synthesis of 6-alkyl-4-[5-dialkylaminomethyl-4-(4-methyl-1,3-thiazol-2-yl)-1H-pyrazol-3-yl]-
1,3-benzenediols, potentially biologically active compounds, was carried out by the recyclization of 6-alkyl-2-
di-alkylaminomethyl-7-hydroxy-3-(4-methyl-1,3-thiazol-2-yl)-4H-chromen-4-ones under the influence of
hydrazine hydrate.
EXPERIMENTAL
1
The H NMR spectra were acquired on a Varian Mercury 400 (400 MHz) instrument for DMSO-d6
solutions with TMS as internal standard. A 4048×4048 matrix was used in the COSY-90 experiment. Elemental
analyses were performed with a Perkin-Elmer CHN analyzer. Melting points were determined on a Boetius hot
stage apparatus with a VEB Analytic PHMK 0.5 viewing adapter. The course of reactions and the purity of the
obtained compounds were monitored by TLC on Silufol UV-254 plates with 9:1 CHCl3–MeOH as eluent.
6-Ethyl-2-[4-(4-fluorophenyl)piperazinomethyl]-7-hydroxy-3-(4-methyl-1,3-thiazol-2-yl)-4H-chro-
men-4-one (1f). 1-(4-Fluorophenyl)piperazine (0.36 g, 2 mmol) was added to a solution of 2-chloro-methyl-
6-ethyl-7-hydroxy-3-(4-methyl-1,3-thiazol-2-yl)-4H-chromen-4-one (3) (0.33 g, 1 mmol) in dioxane (10 ml).
The mixture was refluxed for 40 min, maintained for 1 day at room temperature. The solvent was evaporated,
the residue was triturated in water (50 ml), the precipitate was filtered off and recrystallized. Yield 0.40 g
(83%). Mp 169-170°C (dioxane). 1H NMR spectrum, δ, ppm (J, Hz): 1.23 (3H, t, J = 7.2, CH2CH3); 2.48 (3H, s,
CH3); 2.67 (2H, q, J = 7.2, CH2CH3); 2.73 (4H, br. s, CH2NCH2); 3.04 (4H, br. s, CH2N(Ar)CH2); 4.31 (2H, s,
2-CH2N); 6.80-6.91 (5H, m, H-8, NC6H4F); 7.15 (1H, s, H-5'); 7.81 (1H, s, H-5); 10.67 (1H, s, 7-OH). Found,
%: C 65.07; H 5.68; N 8.97; S 6.42. C26H26FN3O3S. Calculated, %: C 65.12; H 5.46; N 8.76; S 6.69.
2-[4-(3-Chlorophenyl)piperazinomethyl]-7-hydroxy-3-(4-methyl-1,3-thiazol-2-yl)-6-propyl-4H-chromen-
4-one (2g) was obtained analogously from 2-chloromethyl-7-hydroxy-3-(4-methyl-1,3-thiazol-2-yl)-6-propyl-
4H-chromen-4-one (4) and 1-(3-chlorophenyl)piperazine. Yield 0.41 g (79%). Mp 157-158°C (EtOAc).
1H NMR spectrum, δ, ppm (J, Hz): 0.99 (3H, t, J = 7.2, (CH2)2CH3); 1.65-1.68 (2H, m, CH2CH2CH3); 2.49 (3H,
s, CH3); 2.64 (2H, t, J = 7.2, CH2CH2CH3); 2.72 (4H, br. s, CH2NCH2); 3.15 (4H, br. s, CH2N(Ar)CH2); 4.31
(2H, s, 2-CH2N); 6.71 (1H, d, J = 7.6, H-6"); 6.78 (1H, d, J = 7.6, H-4"); 6.81 (1H, s, H-2"); 6.90 (1H, s, H-8);
328

Table 2. 1H NMR Spectra of Compounds 5a,c,d,f and 6a-c,e-g
Com-
pound
Chemical shifts, , ppm (J, Hz)
1.03 (3H, t, 3J = 7.2, CH2CH3); 2.32 (3H, s, CН3); 2.37 (2H, q, 3J = 7.2, CH2CH3);
5a
2.49 (4H, br. s, CH2NCH2); 3.53 (4H, br. s, CH2OCH2); 3.76 (2H, s, 5'-CH2N);
6.43 (1H, s, H-2); 6.84 (1H, s, H-5); 7.05 (1H, s, H-5''); 9.45 (1H, br. s, 3-OH);
9.69 (1H, br. s, 1-OH); 12.77 (1H, br. s, NH)
5c*
1.06 (3H, t, 3J = 7.2, CH2CH3); 1.21-1.25 (2H, m, CHeqCHCHeq);
1.38-1.43 (1H, m, CHCH2Ph); 1.55 (2Н, d, 2J = 12.8, CHaxCHCHax);
1.95 (2H, t, 2J = 12.8, CHeqNCHeq); 2.40-2.48 (7H, m, CН3, CH2CH3, CH2Ph);
2.89 (2H, d, 2J = 10.4, CHaxNCHax); 3.62 (2H, s, 5'-CH2N); 6.37 (1H, s, H-2);
6.85 (1H, s, H-5); 6.93 (1H, s, H-5''); 7.07 (2H, d, 3J = 7.6, H-2''',6''');
7.12 (1H, t, 3J = 7.6, H-4'''); 7.20 (2H, t, 3J = 7.6, H-3''',5'''); 9.13 (1H, br. s, 3-OH);
10.18 (1H, br. s, 1-OH); 12.70 (1Н, br. s, NH)
1.03 (3H, t, 3J = 7.2, CH2CH3); 2.12 (3H, s, NCH3); 2.32 (3H, s, 4''-CH3);
2.39-2.50 (10H, m, CH2CH3, 4CH2 piperazine); 3.73 (2H, s, 5'-CH2N); 6.42 (1H, s, H-2);
6.84 (1H, s, H-5); 7.06 (1H, s, H-5''); 9.47 (1H, br. s, 3-OH); 9.76 (1H, br. s, 1-OH);
12.78 (1H, br. s, NH)
1.04 (3H, t, 3J = 7.2, CH2CH3); 2.35 (3H, s, CH3); 2.41 (2H, q, 3J = 7.2, CH2CH3);
2.63 (4H, br. s, CH2NCH2); 3.05 (4H, br. s, CH2N(Ar)CH2); 3.86 (2H, s, 5'-CH2N);
6.45 (1H, s, H-2); 6.87 (1H, s, H-5); 6.93-7.07 (5H, m, H-5'', C6H4F);
9.48 (1H, br. s, 3-OH); 9.74 (1H, br. s, 1-OH); 12.81 (1H, br. s, NH)
5d
5f
0.84 (3H, t, 3J = 7.2, (CH2)2CH3); 1.46-1.49 (2H, m, CH2CH2CH3);
2.33-2.44 (9H, m, CH3, CH2CH2CH3, CH2NCH2); 3.54 (4H, br. s, CH2OCH2);
3.77 (2H, s, 5'-CH2N); 6.43 (1H, s, H-2); 6.82 (1H, s, H-5); 7.06 (1H, s, H-5'');
9.38 (0.3H, br. s, 3-OH (B)); 9.44 (0.7H, br. s, 3-OH (A)); 9.67 (1H, br. s, 1-OH);
12.77 (0.7H, br. s, NH (A)); 13.13 (0.3H, br. s, NH (B))
6a
0.87 (3H, t, 3J = 7.2, (CH2)2CH3); 1.41-1.52 (8H, m, CH2CH2CH3, 3,4,5-CH2 piperidine);
2.39-2.42 (9H, m, CH2CH2CH3, CH3, CH2NCH2); 3.60 (2H, s, 5'-CH2N); 6.37 (1H, s, H-2);
6.78 (1H, s, H-5); 6.95 (1H, s, H-5''); 9.11 (1H, br. s, 3-OH); 10.12 (1H, br. s, 1-OH);
12.58 (1H, br. s, NH)
6b
6c
0.84 (3H, t, 3J = 7.2, (CH2)2CH3); 1.17 (2H, m, CHeqCHCHeq);
1.44-1.48 (5H, m, CH2CH2CH3, CHCH2Ph, CHaxCHCHax); 1.95 (2H, t,2J = 13.4, CHeqNCHeq);
2.30-2.32 (5H, m, CН3, CH2Ph); 2.46 (2Н, t,3J = 7.2, CH2CH2CH3);
2.87 (2H, br. s, CHaxNCHax); 3.69 (2H, s, 5'-CH2N); 6.42 (1H, s, H-2); 6.82 (1H, s, H-5);
7.07 (1H, s, H-5''); 7.13-7.17 (3H, m, H-2''',6''',4'''); 7.26 (2H, t, 3J = 7.6, H-3''',5''');
9.39 (1H, br. s, 3-OH); 9.76 (1H, br. s, 1-OH); 12.73 (1H, br. s, NH)
0.83 (3H, t, 3J = 7.2, (CH2)2CH3); 1.42-1.46 (2H, m, CH2CH2CH3);
2.31-2.45 (11H, m CH3, CH2CH2CH3, CH2NCH2, NCH2Ar);
6e
6f
3.32 (4H, br. s, CH2N(CH2Ar)CH2); 3.74 (2H, s, 5'-CH2N); 5.97 (2H, s, OCH2);
6.43 (1H, s, H-2); 6.71 (1H, d,3J = 6.4, H-7'''); 6.81-6.82 (3H, m, H-5,4''',6''');
7.05 (1H, s, H-5''); 9.43 (1H, br. s, 3-OH); 9.74 (1H, br. s, 1-OH); 12.74 (1H, br. s, NH)
0.83 (3H, t, 3J = 6.8, (CH2)2CH3); 1.42-1.45 (2H, m, CH2CH2CH3);
2.32-2.34 (5H, m, CH3, CH2CH2CH3); 2.61 (4H, br. s, CH2NCH2);
3.03 (4H, br. s, CH2N(Ar)CH2); 3.84 (2H, s, 5'-CH2N); 6.45 (1H, s, H-2);
6.82 (1H, s, H-5); 6.90-7.04 (5H, m, H-5'', C6H4F); 9.48 (1H, br. s, 3-OH);
9.69 (1H, br. s, 1-OH); 12. 81 (1H, br. s, NH)
0.89 (3H, t, 3J = 7.2, (CH2)2CH3); 1.46-1.49 (2H, m, CH2CH2CH3);
2.36 (2H, t, 3J = 7.2, CH2CH2CH3); 2.40 (3H, s, CH3); 2.65 (4H, br. s, CH2NCH2);
3.16 (4H, br. s, CH2N(Ar)CH2); 3.78 (2H, s, 5'-CH2N); 6.39 (1H, s, H-2);
6.68 (1H, d, 3J = 8.0, H-6'''); 6.77 (1H, d, 3J = 8.0, H-4'''); 6.80 (1H, s, H-5);
6.84 (1Н, s, Н-5''); 6.90 (1Н, s, Н-2'''); 7.12 (1H, t,3J = 8.0, H-5''');
9.11 (1H, br. s, 3-OH); 9.93 (1H, br. s, 1-OH); 12. 61 (1H, br. s, NH)
6g
_______
*Spin-spin coupling constants with values less than 4.0 Hz were not
successfully measured because of the width of the signals.
7.14 (1H, t, J = 7.6, H-5"); 7.19 (1H, s, H-5'); 7.81 (1H, s, H-5); 10.33 (1H, br. s, 7-OH). Found, %: C 63.76;
H 5.28; N 8.54; S 6.26. C27H28ClN3O3S. Calculated, %: C 63.58; H 5.53; N 8.24; S 6.29.
6-Alkyl-4-[5-dialkylaminomethyl-4-(4-methyl-1,3-thiazol-2-yl)-1H-pyrazol-3-yl]-1,3-benzenediols
5a,c,d,f and 6a-c,e-g (General Method). Hydrazine hydrate (0.1 g, 3.2 mmol) was added to a solution of
6-alkyl-2-dialkylaminomethyl-7-hydroxy-3-(4-methyl-1,3-thiazol-2-yl)-4H-chromen-4-one 1a,c,d,f or 2 a-c,e-g
329

(0.3 mmol) in EtOH (1 ml). The mixture was refluxed for 5 min, cooled, diluted with water (10 ml), then the
precipitate was filtered off and recrystallized from aqueous EtOH.
REFERENCES
1.
2.
3.
4.
T. V. Shokol, V. A. Turov, V. V. Semenyuchenko, N. V. Krivokhizha, and V. P. Khilya, Khim.
Geterotsikl. Soedin., 571 (2006). [Chem. Heterocycl. Compd., 42, 500 (2006).]
S. L. Bogza, V. I. Dulenko, S. Yu. Zinchenko, K. I. Kobrakov, and I. V. Pavlov, Khim. Geterotsikl.
Soedin., 1737 (2004). [Chem. Heterocycl. Compd., 40, 1506 (2004).]
Yu. M. Volovenko, T. A. Volovnenko, and A. V. Stel'makh, in: Abstr. XXI Ukrain. Konf. Org.. Khim.,
[in Ukrainian], Chernigiv (2007), p. 144.
N. V. Gorbulenko, T. V. Shokol, V. P. Khilya, and V. M. Kovalyov, in: Abstr. III Mizhnar. Nauk. prakt.
Conf. "Current Problems of Biology, Ecology, and Chemistry" [in Ukrainian], Zaporizhzhya (2012), p.
308.
5.
6.
T. I. El-Emary and E. A. Banhite, Pharmazie, 54, 106 (1999); Chem. Abstr., 130, 232289 (1999).
T.-L. Liu, S.-L. Yu, and A.-M. Yu, Gaodeng Xuexiao Huaxue Xuebao, 19, 232 (1998); Chem. Abstr.,
128, 192588 (1998).
7.
Z.-N. Huang and Z.-M. Li, Gaodeng Xuexiao Huaxue Xuebao, 16, 1888 (1995); Chem. Abstr., 124,
317062 (1996).
8.
9.
H. Obara, T. Igarashi, K. Sakurai, and T. Oshii, JP Pat. Appl. 10306077
O. Bruno, A. Ranise, F. Bondavalli, P. Schenone, M. D'Amico, A. Filippelli, W. Filippelli, and F. Rossi,
Farmaco, 48, 949 (1993).
10.
K.-M. J. Cheung, T. P. Matthews, K. James, M. G. Rowlands, K. J. Boxall, S. Y. Sharp, A. Maloney, S.
M. Roe, C. Prodromou, L. H. Pearl, G. W. Aherne, E. McDonald, and P. Workman, Bioorg. Med.
Chem. Lett., 15, 3338 (2005).
11.
12.
A. Kreusch, S. Han, A. Brinker, V. Zhou, H.-S. Choi, Y. He, S. A. Lesley, J. Caldwell, and H.-J. Gu,
Bioorg. Med. Chem. Lett., 15, 1475 (2005).
V. P. Khilya, I. P. Kupchevskaya, and L. G. Grishko, in: Chemistry and Biological Activity of Synthetic
and Natural Compounds. Nitrogen Heterocycles and Alkaloids [In Russian], Vol. 1, Iridium Press,
Moscow (2001), p. 147.
13.
B. W. Dymock, X. Barril, P. A. Brough, J. E. Cansfield, A. Massey, E. McDonald, R. E. Hubbard,
A. 4212 (2005).
14.
15.
M.-C. Sacquet, M-.C. Fargeau-Bellassoued, and B. Graffe, J. Heterocycl. Chem., 28, 667 (1991).
T. V. Shokol, N. V. Gorbulenko, A. V. Turov, and V. P. Khilya, Khim. Geterotsikl. Soedin., 1266
(2012). [Chem. Heterocycl. Compd., 48, 1181 (2012).]
16.
T. V. Shokol, N. V. Gorbulenko, and V. P. Khilya, Khim. Geterotsikl. Soedin., 1568 (2011). [Chem.
Heterocycl. Compd., 47, 1298 (2011).]
330