New imidazole derivatives of 2(3H)-benzazolones as potential antifungal agents

Article abstract of DOI:10.1002/jhet.11

A series of new imidazole derivatives containing 2(3H)-benzoxazolone or 2(3H)-benzothiazolone ring were synthesized as analogues of the antifungal drug bifonazole. All compounds were tested in vitro against Candida albicans, Candida parapsilosis, and Cand

Full text of DOI:10.1002/jhet.11

44
New Imidazole Derivatives of 2(3H)-Benzazolones
as Potential Antifungal Agents
Vol 46
Ognyan Petrov,a* Mariana Gerova,a Katya Petrova,b and Yordanka Ivanovaa
aDepartment of Applied Organic Chemistry, Faculty of Chemistry, University of Sofia,
1164 Sofia, Bulgaria
bChemistry Department, Vanderbilt University, Nashville, Tennessee 37235-1822
*E-mail: opetrov@chem.uni-sofia.bg
Received May 13, 2008
DOI 10.1002/jhet.11
Published online 5 February 2009 in Wiley InterScience (www.interscience.wiley.com).
A series of new imidazole derivatives containing 2(3H)-benzoxazolone or 2(3H)-benzothiazolone ring
were synthesized as analogues of the antifungal drug bifonazole. All compounds were tested in vitro
against Candida albicans, Candida parapsilosis, and Candida krusli.
J. Heterocyclic Chem., 46, 44 (2009).
INTRODUCTION
as heterocyclic analogues of bifonazole, in which the
biphenyl moiety could be replaced with benzoxazole or
benzothiazole ring. A chlorine atom was introduced at
different position on benzene cycle.
In this article, we present the synthesis and the results
of the initial biological investigations of series bifona-
zole-like imidazole derivatives.
As a result of the dramatic increase in fungal infections,
in recent years serious attention has been directed toward
the discovery and development of new antifungal drugs.
Mostly caused by Candida albicans, these infections are
often spread through the use of broad-spectrum antibiot-
ics, immunosuppressive agents, anticancer, and anti-AIDS
drugs [1]. The main problem in the treatment of fungal
infections is the increasing prevalence of drug resistance
especially in patients chronically subjected to antimycotic
therapy such as persons infected with HIV [2].
Azoles (imidazole and triazole) are presented in many
effective antifungal drugs widely used for the treatment
of topical or inner mycoses, in particular AIDS-related
mycotic pathologies [3]. Their main effect is to block fun-
gal ergosterol biosynthesis by preventing the access of
natural substrate lanosterol to the active site of the cyto-
chrome P-450-dependent enzyme 14a-lanosterol demeth-
ylase [4,5]. Since the identification of clotrimazole in
1972 [6], a number of antifungal imidazole agents have
been studied and now are used in clinical practice: mico-
nazole, bifonazole, etc [7]. Fluconazole is one of the most
important drugs in the triazole family (Fig. 1).
In searching for new compounds with potential antifun-
gal activity, we synthesized a number of imidazole deriv-
atives, containing 2(3H)-benzoxazolone or 2(3H)-benzo-
thiazolone moiety. These compounds could be examined
Figure 1. The structures of azole antifungal drugs used in clinical practice.
C
V
2009 HeteroCorporation

January 2009
New Imidazole Derivatives of 2(3H)-Benzazolones as Potential Antifungal Agents
45
RESULTS AND DISCUSSION
case did not form the expect imidazole derivative. It
may be possible, instead of the desired compounds 10a–
o, imidazole-N-carboxylic ester intermediates are formed
[13]. Therefore, we followed the second approach: the
compounds 8a–o were converted to the corresponding
chlorides 9a–o by refluxing with thionyl chloride in tol-
uene. This reaction afforded sufficiently pure chlorides
9a–o, which were used without further purification. The
condensation of crude chlorides 9a–o with two equiva-
lents of 1H-imidazole provided target imidazole deriva-
tives 10a–o and the formation of imidazole hydrochlor-
ide as a by-product. Compounds 10a–o were isolated in
good yields (Table 1) and purified by recrystallization.
The imidazole derivatives 10a–o have one asymmet-
ric carbon atom; however, we did not make any efforts
for the separation of individual enantiomers in view of
the fact that both enantiomers of bifonazole have been
reported to possess the same antimycotic profile and po-
tency [15].
A series of new imidazole derivatives 10a–o with
2(3H)-benzoxazolone or 2(3H)-benzothiazolone moiety
were prepared as potential antifungal agents as shown in
Scheme 1.
The acylation of 3-methyl-2(3H)-benzoxazolone (4),
5-chloro-3-methyl-2(3H)-benzoxazolone (5), and 3-methyl-
2(3H)-benzothiazolone (6) was carried out in polyphos-
phoric acid (PPA) with unsubstituted and various chloro-
substituted benzoic acids and led to the corresponding
6-benzoyl derivatives 7a–o.
The acylation of 2(3H)-benzoxazolone and 2(3H)-ben-
zothiazolone was previously studied and was found to
proceed with high regioselectivity [8–10]. The precise
position of acylation was unequivocally assigned by X-
ray single-crystal diffraction in the case of 6-benzoyl-
2(3H)-benzoxazolone and 6-benzoyl-2(3H)-benzothiazo-
lone [11,12].
Compounds 8a–o were obtained in high yields and
purity by a sodium borohydride reduction of the corre-
sponding ketones 7a–o. The reaction was carried out at
room temperature in methanol and afforded the desired
hydroxyl derivatives, which were the starting materials
for the imidazole series.
The yields, melting points, and molecular formula of
imidazole derivatives 10a–o are listed in Table 1. All
spectral data are in accordance with the assumed struc-
1
tures. In addition to the signals for aromatic protons, H
NMR spectra of the compounds 10a–o reveal singlet at
3.39–3.47 ppm for the N-CH3 protons from 2(3H)-ben-
zoxazolone or 2(3H)-benzothiazolone ring. Furthermore,
the spectra show singlet for methyne proton at the asym-
metric carbon atom in range 6.53–6.92 ppm.
Two general approaches can be used for the synthesis
of imidazole derivatives 10a–o: by reaction of carbinols
8a–o with N,N0-carbonyldiimidazole (CDI) [13] or N,N0-
sulfinyldiimidazole (SDI) [14] or by conversion of cor-
responding hydroxyl derivatives 8a–o via their chlorides
to the desired heterocycles 10a–o. Our early experi-
ments showed that the use of the first method of
approach (CDI or SDI) brought low yields or in any
IR spectra of compounds 10a–o, containing 2(3H)-
benzoxazolone or 2(3H)-benzothiazolone ring showed
carbonyl bands at 1750–1795 cmꢀ1 and 1650–1680 cmꢀ1
respectively.
,
Scheme 1
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

46
O. Petrov, M. Gerova, K. Petrova, and Y. Ivanova
Vol 46
Table 1
Yields and physical data of compounds 10a-o.
Compd
X
R1
R2
R3
R4
Yield (%)
Mp (ꢁC)
Molecular formula
10a
10b
10c
10d
10e
10f
10g
10h
10i
O
O
O
O
O
O
O
O
O
O
S
H
H
H
Cl
H
H
H
Cl
H
H
H
H
Cl
H
H
H
H
Cl
H
H
H
H
80
82
60
68
50
69
70
55
52
53
64
84
78
75
70
144-145
143-144
124-125
108-110
167-168
195-196
189-190
232-234
119-121
208-210
132-133
182-184
149-150
188-189a
196-197
C18H15N3O2
C18H14ClN3O2
C18H14ClN3O2
C18H14ClN3O2
C18H13Cl2N3O2
C18H14ClN3O2
C18H13Cl2N3O2
C18H13Cl2N3O2
C18H13Cl2N3O2
C18H12Cl3N3O2
C18H15N3OS
H
H
H
H
Cl
Cl
H
H
Cl
H
Cl
H
Cl
Cl
Cl
Cl
Cl
H
H
H
H
Cl
Cl
H
10j
Cl
H
10k
101
10m
10n
10o
S
H
Cl
H
H
Cl
H
C18H14ClN3OS
C18H14ClN3OS
C18H14ClN3OS ꢂ HNO3
C18H13Cl2N3OS
S
S
H
H
H
Cl
Cl
S
H
a
Compound was isolated as a nitrate.
azole (0.68 g, 10 mmol) was added. The mixture was refluxed
for 6 h, until the chloride 9a was no longer detectable (TLC).
After cooling of the reaction mixture, 5% aqueous NaOH
(10 mL) was added. The organic layer was washed with water
and extracted with 10% HCl. The aqueous layer was neutral-
ized with 10% NaOH, extracted with dichloromethane, dried
(MgSO4), and evaporated under reduced pressure. The
obtained crude product 10a crystallized slowly. Yield 1.22 g
The new imidazole derivatives 10a–o were evaluated
in vitro against several pathogenic fungi responsible for
human diseases using the twofold agar dilution method
[16]. The results of this biological investigation did not
report any significant activity against yeast. The most
active compounds in the series showed weak antimicro-
bial activity against Candida albicans, Candida parapsi-
losis, and Candida krusli with MIC values 100–400 lM.
The results of the biological tests revealed that the
replacement of the biphenyl portion of the bifonazole
with 2(3H)-benzoxazolone or 2(3H)-benzothiazolone
moiety afforded heterocyclic analogues, which are inac-
tive as antimycotic agents toward Candida strains.
ꢁ
(80%), mp 144–145 C (ethyl acetate); ir (nujol): 1765 (C¼¼O)
cmꢀ1
;
1H NMR (CDCl3): d 3.41 (s, 3H, NCH3), 6.56 (s, 1H,
CH), 6.84–7.11 (m, 7H, ArH and ImH), 7.36–7.42 (m, 4H,
ArH and ImH). Anal. Calcd. for C18H15N3O2: C 70.81; H
4.95; N 13.76. Found: C 70.56; H 4.98; N 13.46.
6-[(2-Chlorophenyl)(1H-imidazol-1-yl)methyl]-3-methyl-
2(3H)-benzoxazolone (10b). This compound was obtained
according to the procedure for 10a, using compound 8b as a
starting material. Yield: 1.36 g (82%), mp 143–144 ꢁC (hex-
1
ane–ethyl acetate 1:1); ir (nujol): 1780 (C¼¼O) cmꢀ1; H NMR
EXPERIMENTAL
(CDCl3): d 3.43 (s, 3H, NCH3), 6.79–6.85 (m, 2H, ArH and
ImH), 6.92 (s, 1H, CH), 6.95–6.96 (m, 3H, ArH and ImH),
7.14 (s, 1H, ArH), 7.28 (dt, 1H, ArH, J ¼ 1.8 Hz, J ¼ 7.8
Hz), 7.35 (dt, 1H, ArH, J ¼ 1.8 Hz, J ¼ 7.8 Hz), 7.42 (s, 1H,
ImH), 7.45 (dd, 1H, ArH, J ¼ 1.8 Hz, J ¼ 7.8 Hz). Anal.
Calcd. for C18H14ClN3O2: C 63.63; H 4.15; N 12.37. Found:
C 63.90; H 4.18; N 12.44.
Melting points were determined on a Boetius hot-stage
microscope and are uncorrected. IR spectra (nujol) were
1
recorded on a Specord 71 spectrophotometer. H NMR spectra
were obtained on a Bruker DRX 300 spectrometer operating at
300 MHz in CDCl3. Chemical shifts were reported in d units
(ppm) relative to (CH3)4Si as internal standard. Coupling con-
stants (J) were reported in Hz. Elemental analyses (C, H, N,
S) for final compounds were performed on a Vario III micro-
analyzer. Obtained results were within 0.4% of theoretical val-
ues. Thin layer chromatography (TLC) was carried out on
Silica gel plates (Merck 60 F254) using toluene–chloroform–
ethyl acetate (3:1:1) and ethyl acetate–isopropanol (3:1) as
eluent.
Ketones 7a–o and corresponding alcohols 8a–o were pre-
pared according to the method described previously [17,18].
6-[(1H-Imidazol-1-yl)phenylmethyl]-3-methyl-2(3H)-benz-
oxazolone (10a). A solution of hydroxyl derivative 8a (1.28 g,
5 mmol) in toluene (10 mL) and thionyl chloride (1 mL,
14 mmol) was refluxed for 30 min and then the excess of thi-
onyl chloride was evaporated under reduced pressure. The
obtained oil of 9a was dissolved in toluene (15 mL) and imid-
6-[(3-Chlorophenyl)(1H-imidazol-1-yl)methyl]-3-methyl-
2(3H)-benzoxazolone (10c). This compound was obtained
according to the procedure for 10a, using compound 8c as a
starting material. Yield: 1.02 g (60%), mp 124–125 ꢁC (hex-
ane–ethyl acetate, 1:1); ir (nujol): 1780 (C¼¼O) cmꢀ1
;
1H
NMR (CDCl3): d 3.43 (s, 3H, NCH3), 6.54 (s, 1H, CH), 6.85
(s, 1H, ImH), 6.96–7.08 (m, 5H, ArH and ImH), 7.14 (s, 1H,
ArH), 7.33–7.36 (m, 2H, ArH), 7.44 (s, 1H, ImH). Anal.
Calcd. for C18H14ClN3O2: C 63.63; H 4.15; N 12.37. Found:
C 63.86; H 4.18; N 12.45.
6-[(4-Chlorophenyl)(1H-imidazol-1-yl)methyl]-3-methyl-
2(3H)-benzoxazolone (10d). This compound was obtained
according to the procedure for 10a, using compound 8d as a
ꢁ
starting material. Yield: 1.16 g (68%), mp 108–110 C (cyclo-
;
1H
hexane–ethyl acetate, 1:1); ir (nujol): 1760 (C¼¼O) cmꢀ1
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2009
New Imidazole Derivatives of 2(3H)-Benzazolones as Potential Antifungal Agents
47
ꢁ
NMR (CDCl3): d 3.43 (s, 3H, NCH3), 6.55 (s, 1H, CH), 6.84
(s, 1H, ImH), 6.95–6.96 (m, 3H, ArH and ImH), 7.02 (d, 2H,
ArH, J ¼ 8.4 Hz), 7.14 (s, 1H, ArH), 7.34 (d, 2H, ArH, J ¼
8.4 Hz), 7.44 (s, 1H, ImH). Anal. Calcd. for C18H14ClN3O2: C
63.63; H 4.15; N 12.37. Found: C 63.96; H 4.10; N 12.56.
6-[(2,4-Dichlorophenyl)(1H-imidazol-1-yl)methyl]-3-methyl-
2(3H)-benzoxazolone (10e). This compound was obtained
according to the procedure for 10a, using compound 8e as a
starting material. Yield: 0.94 g (50%), mp 167–168 ꢁC (ethyl
8j as a starting material. Yield: 1.04 g (53%), mp 208–210 C
1
(toluene); ir (nujol): 1780 (C¼¼O) cmꢀ1; H NMR (CDCl3): d
3.42 (s, 3H, NCH3), 6.61 (s, 1H, CH), 6.69 (d, 1H, ArH, J ¼
8.4 Hz), 6.79 (s, 1H, ImH), 7.09–7.15 (m, 3H, ArH and ImH),
7.27 (dd, 1H, ArH, J ¼ 2.1 Hz, J ¼ 8.4 Hz), 7.37 (s, 1H,
ImH), 7.49 (d, 1H, ArH, J ¼ 2.1 Hz). Anal. Calcd. for
C18H12Cl3N3O2: C 52.90; H 2.96; N 10.28. Found: C 52.79; H
3.22; N 10.33.
6-[(1H-Imidazol-1-yl)phenylmethyl]-3-methyl-2(3H)-benz-
othiazolone (10k). This compound was obtained according to
the procedure for 10a, using compound 8k as a starting mate-
rial. Yield: 1.03 g (64%), mp 132–133 ꢁC (ethyl acetate); ir
acetate); ir (nujol): 1750 (C¼¼O) cmꢀ1
;
1H NMR (CDCl3):
d 3.43 (s, 3H, NCH3), 6.7 (d, 1H, ArH, J ¼ 7.4 Hz), 6.81
(s, 1H, ImH), 6.85 (s, 1H, CH), 6.93–6.98 (m, 3H, ArH and
ImH), 7.15 (s, 1H, ArH), 7.27 (dd, 1H, ArH, J ¼ 2.0 Hz, J ¼
7.4 Hz), 7.39 (s, 1H, ImH), 7.48 (d, 1H, ArH, J ¼ 2.0 Hz).
Anal. Calcd. for C18H13Cl2N3O2: C 57.77; H 3.50; N 11.23.
Found: C 57.68; H 3.62; N 11.07.
5-Chloro-6-[(1H-imidazol-1-yl)phenylmethyl]-3-methyl-
2(3H)-benzoxazolone (10f). This compound was obtained
according to the procedure for 10a, using compound 8f as a
starting material. Yield: 1.17 g (69%), mp 195–196ꢁC (ethyl
(nujol): 1680 (C¼¼O) cmꢀ1; H NMR (CDCl3): d 3.44 (s, 3H,
1
NCH3), 6.54 (s, 1H, CH), 6.84 (s, 1H, ImH), 6.99–7.13 (m,
6H, ArH and ImH), 7.35–7.43 (m, 4H, ArH and ImH). Anal.
Calcd. for C18H15N3OS: C 67.23; H 4.70; N 13.07. Found: C
67.09; H 4.55; N 13.43.
6-[(2-Chlorophenyl)(1H-imidazol-1-yl)methyl]-3-methyl-
2(3H)-benzothiazolone (10l). This compound was obtained
according to the procedure for 10a, using compound 8l as a
starting material. Yield: 1.49 g (84%), mp 182–184 C (cyclo-
;
1H
NMR (CDCl3): d 3.47 (s, 3H, NCH3), 6.81–6.84 (m, 2H, ArH
and ImH), 6.91 (s, 1H, CH), 7.02–7.13 (m, 4H, ArH and
ImH), 7.29 (dt, 1H, ArH, J ¼ 1.8 Hz, J ¼ 7.8 Hz), 7.34 (dt,
1H, ArH, J ¼ 1.8 Hz, J ¼ 7.8 Hz), 7.39 (s, 1H, ImH), 7.45
(dd, 1H, ArH, J ¼ 1.8 Hz, J ¼ 7.8 Hz). Anal. Calcd. for
C18H14ClN3OS: C 60.76; H 3.97; N 11.81. Found: C 60.87; H
3.99; N 11.62.
acetate); ir (nujol): 1790 (C¼¼O) cmꢀ1
;
1H NMR (CDCl3):
ꢁ
d 3.41 (s, 3H, NCH3), 6.70 (s, 1H, CH), 6.81 (s, 1H, ImH),
6.91 (s, 1H, ArH), 7.05–7.07 (m, 3H, ArH and ImH), 7.13
(s, 1H, ArH), 7.34–7.40 (m, 4H, ArH and ImH). Anal. Calcd.
for C18H14ClN3O2: C 63.63; H 4.15; N 12.37. Found: C 63.88;
H 4.16; N 12.56.
hexane–ethyl acetate, 1:1); ir (nujol): 1670 (C¼¼O) cmꢀ1
5-Chloro-6-[(2-chlorophenyl)(1H-imidazol-1-yl)methyl]-3-
methyl-2(3H)-benzoxazolone (10g). This compound was
obtained according to the procedure for 10a, using compouꢁnd
8g as a starting material. Yield: 1.31 g (70%), mp 189–190 C
6-[(3-Chlorophenyl)(1H-imidazol-1-yl)methyl]-3-methyl-
2(3H)-benzothiazolone (10m). This compound was obtained
according to the procedure for 10a, using compound 8m as a
starting material. Yield: 1.39 g (78%), mp 149–150 ꢁC
(ethyl acetate); ir (nujol): 1780 (C¼¼O) cmꢀ1
;
1H NMR
(CDCl3): d 3.42 (s, 3H, NCH3), 6.63 (s, 1H, CH), 6.76 (dd,
1H, ArH, J ¼ 1.5 Hz, J ¼ 7.5 Hz), 6.81 (s, 1H, ImH), 7.10 (s,
1H, ArH), 7.15 – 7.17 (m, 2H, ArH and ImH), 7.23 (dt, 1H,
ArH, J ¼ 1.5 Hz, J ¼ 7.5 Hz), 7.33–7.39 (m, 2H, ArH and
ImH), 7.46 (dd, 1H, ArH, J ¼ 1.5 Hz, J ¼ 7.5 Hz). Anal.
Calcd. for C18H13Cl2N3O2: C 57.77; H 3.50; N 11.23. Found:
C 57.83; H 3.49; N 10.86.
(ethyl acetate); ir (nujol): 1670 (C¼¼O) cmꢀ1
;
1H NMR
(CDCl3): d 3.47 (s, 3H, NCH3), 6.53 (s, 1H, CH), 6.85 (s,
1H, ImH), 6.96–7.16 (m, 6H, ArH and ImH), 7.32–7.35 (m,
2H, ArH), 7.43 (s, 1H, ImH). Anal. Calcd. for
C18H14ClN3OS: C 60.76; H 3.97; N 11.81. Found: C 60.53;
H 4.02; N 11.81.
6-[(4-Chlorophenyl)(1H-imidazol-1-yl)methyl]-3-methyl-
2(3H)-benzothiazolone nitrate (10n). This compound was
obtained according to the procedure for 10a, using compound
8n as a starting material. The crude product 10n, obtained as a
viscous oily residue was dissolved in isopropanol and conc.
HNO3 was added. The obtained precipitate was collected by
filtration and washedꢁ with cold isopropanol. Yield: 1.57 g
(75%), mp 188–189 C (isopropanol); ir (nujol): 2770–2250
(NHþ), 1660 (C¼¼O) cmꢀ1. Anal. Calcd. for C18H14ClN3OS ꢂ
HNO3: C 51.62; H 3.61; N 13.38. Found: C 52.00; H 4.01; N
13.10.
5-Chloro-6-[(3-chlorophenyl)(1H-imidazol-1-yl)methyl]-3-
methyl-2(3H)-benzoxazolone (10h). This compound was
obtained according to the procedure for 10a, using compouꢁnd
8h as a starting material. Yield: 1.03 g (55%), mp 232–234 C
1
(toluene); ir (nujol): 1790 (C¼¼O) cmꢀ1; H NMR (CDCl3): d
3.39 (s, 3H, NCH3), 6.65 (s, 1H, CH), 6.81 (s, 1H, ImH), 6.89
(s, 1H, ArH), 6.93–6.96 (m, 1H, ArH), 7.04–7.15 (m, 3H, ArH
and ImH), 7.31–7.41 (m, 3H, ArH and ImH). Anal. Calcd. for
C18H13Cl2N3O2: C 57.77; H 3.50; N 11.23. Found: C 57.93; H
3.41; N 11.36.
5-Chloro-6-[(4-chlorophenyl)(1H-imidazol-1-yl)methyl]-3-
methyl-2(3H)-benzoxazolone (10i). This compound was
obtained according to the procedure for 10a, using compouꢁnd
8i as a starting material. Yield: 0.97 g (52%), mp 119–121 C
(cyclohexane–ethyl acetate, 2:1); ir (nujol): 1795 (C¼¼O)
6-[(2,4-Dichlorophenyl)(1H-imidazol-1-yl)methyl]-3-methyl-
2(3H)-benzothiazolone (10o). This compound was obtained
according to the procedure for 10a, using compound 8o as a
starting material. Yield: 1.37 g (70%), mp 196–197 ꢁC (ethyl
cmꢀ1 1H NMR (CDCl3): d 3.42 (s, 3H, NCH3), 6.67 (s, 1H,
;
CH), 6.80 (s, 1H, ImH), 6.88 (s, 1H, ArH), 6.99 (d, 2H, ArH,
J ¼ 7.0 Hz), 7.07 (s, 1H, ArH), 7.14 (s, 1H, ImH), 7.35–7.39
(m, 3H, ArH and ImH). Anal. Calcd. for C18H13Cl2N3O2: C
57.77; H 3.50; N 11.23. Found: C 58.09; H 3.72; N 11.27.
5-Chloro-6-[(2,4-dichlorophenyl)(1H-imidazol-1-yl)methyl]-
3-methyl-2(3H)-benzoxazolone (10j). This compound was
obtained according to the procedure for 10a, using compound
acetate); ir (nujol): 1650 (C¼¼O) cmꢀ1
;
1H NMR (CDCl3): d
3.47 (s, 3H, NCH3), 6.75 (d, 1H, ArH, J ¼ 8.4 Hz), 6.81 (s,
1H, ImH), 6.85 (s, 1H, CH), 7.02–7.16 (m, 4H, ArH and
ImH), 7.27 (dd, 1H, ArH, J ¼ 1.8 Hz, J ¼ 8.4 Hz), 7.38 (s,
1H, ImH), 7.48 (d, 1H, ArH, J ¼ 1.8 Hz). Anal. Calcd. for
C18H13Cl2N3OS: C 55.39; H 3.36; N 10.77. Found: C 55.78;
H 3.46; N 10.55.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

48
O. Petrov, M. Gerova, K. Petrova, and Y. Ivanova
Vol 46
[10] Petrov, O.; Antonova, A.; Kalcheva, V.; Daleva, L. Med
Chem Res 1995, 5, 442.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet