Mono and bis-6-arylbenzimidazo[1,2-c]quinazolines: A new class of antimicrobial agents

Article abstract of DOI:10.1016/j.ejmech.2009.03.022

With the aim of obtaining novel biologically active compounds, we have synthesized a series of mono, bis-2-o-arylideneaminophenylbenzimidazoles and a second series of corresponding mono, bis-6-arylbenzimidazo[1,2-c]quinazolines respectively. The target be

Full text of DOI:10.1016/j.ejmech.2009.03.022

European Journal of Medicinal Chemistry 44 (2009) 3330–3339
Contents lists available at ScienceDirect
European Journal of Medicinal Chemistry
journal homepage: http://www.elsevier.com/locate/ejmech
Short communication
Mono and bis-6-arylbenzimidazo[1,2-c]quinazolines: A new class of
antimicrobial agents
,
,
a,
*
Rondla Rohini a, Kanne Shanker a, Puchakayala Muralidhar Reddya b, Yen-Peng Ho b , Vadde Ravinder
*
a Department of Chemistry, Kakatiya University, Warangal 506 009, Andra Pradesh, India
b Department of Chemistry, National Dong Hwa University, Hualien 974, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
With the aim of obtaining novel biologically active compounds, we have synthesized a series of mono,
bis-2-o-arylideneaminophenylbenzimidazoles and a second series of corresponding mono, bis-6-aryl-
benzimidazo[1,2-c]quinazolines respectively. The target benzimidazo[1,2-c]quinazoline compounds were
obtained by the condensation of 2-(o-aminophenyl)benzimidazole with mono and di carbonyl
compounds, followed by oxidative cyclisation of the resulting mono and bis-2-o-arylideneaminophe-
nylbenzimidazoles.All the products were characterized via IR, 1H NMR, 13C NMR, MS and elemental
analysis. The antimicrobial activities of all quinazolines against various bacteria and fungi were evalu-
ated. Among the compounds tested IVd, IVe exhibited good antibacterial and antifungal activities while
IIIb, IIIc also showed notable antimicrobial activity with reference to standard drugs Ampicillin and
Ketoconazole respectively.
Received 5 February 2009
Received in revised form
15 March 2009
Accepted 19 March 2009
Available online 27 March 2009
Keywords:
Mono, bis-6-arylbenzimidazo[1,2-
c]quinazolines
Synthesis
Antibacterial activity
Antifungal activity
Ó 2009 Elsevier Masson SAS. All rights reserved.
1. Introduction
bis-2-o-arylideneaminophenylbenzimidazoles (Ia–e & IIa–e) and
mono, bis-6-substituted benzimidazo[1,2-c]quinazolines (IIIa–e &
In the broad class of heterocyclic compounds, the nitrogen
heterocycles play an important role. Among them, quinazolines are
most important class of compounds and have received much
attention from synthetic as well as medicinal chemists, because of
the diverse range of their pharmacological properties [1–8] and
also in several areas as materials in electronics, in electrochemistry
as anticorrosive agents, as polymers or optical materials and fluo-
rescent tags in DNA sequencing [9–12]. Previous reports described
benzimidazo and benzothiazoloquinazoline derivatives as cyto-
toxic compounds with potential antitumoral [13–17] and particu-
larly, there is one report that describes the antitumor activity of
benzimidazo[1,2-c]quinazolines [17]. It was reported that benzi-
midazo[1,2-c]quinazoline derivatives show various therapeutic
activities, such as anticancer [14,16,17], antiviral [18,19], antimi-
crobial [20], anti-inflammatory [13,18] and anticonvulsants [21].
Based on the importance of these molecules, our attention was
attracted towards synthesis of novel quinazoline derivatives in
order to find more potent biologically active molecules. In this
paper, we describe the synthesis and characterization of both mono,
IVa–e). In addition, the antimicrobial activities of all synthesized
quinazolines against different bacteria and fungi were evaluated.
Among the compounds tested some of quinazolines were found to
be superior in inhibiting all the bacterial and fungal strains.
2. Chemistry
In the present investigation, the starting compound, 2-(o-ami-
nophenyl)benzimidazole (A) was prepared according to the proce-
dure described by Heins et al. [22]. The target compounds IIIa–e,
IVa–e were prepared by using the reaction sequence in Scheme 1.
Initially, we synthesized ten 2-o-arylideneaminophenylbenzimi-
dazoles (Ia–e & IIa–e) via the condensation between 2-(o-amino-
phenyl)benzimidazole (A) and various mono (Ar–CHO), di carbonyl
compounds (CHO–Ar–CHO). At last, we prepared mono, bis-6-
arylbenzimidazo[1,2-c]quinazolines through oxidative cyclisation
[23] of corresponding 2-o-arylideneaminophenylbenzimidazoles.
3. Pharmacology
3.1. Antibacterial activity
* Corresponding authors. Tel.: þ91 9390100594.
E-mail addresses: ypho@mail.ndhu.edu (Y.-P. Ho), ravichemku@rediffmail.com
(V. Ravinder).
All the quinazolines prepared herein were screened for their
potential biological activities such as, antibacterial activity against
0223-5234/$ – see front matter Ó 2009 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.ejmech.2009.03.022

R. Rohini et al. / European Journal of Medicinal Chemistry 44 (2009) 3330–3339
3331
BI
N
N
H
H2N
H2N
(A)
CHO-Ar-CHO
Ar-CHO
2:1
ethanol
1:1
ethanol
BI
BI
BI
CH
CH
N
HC
N
N
Ar
Ar
(IIa-e)
(Ia-e)
KMnO4, 60-80°c,
reflux, 40 min.
KMnO4, 40-80°c,
reflux, 30 min.
N
N
N
BIQ-Ar
BIQ-Ar-BIQ
N
N
N
N
N
Ar
N
Ar
(IVa-e)
(IIIa-e)
IIa, IVa. Ar = 1,2 phenyl
IIb, IVb. Ar = 1,3 phenyl
IIc, IVc. Ar = 1,4 phenyl
IId, IVd. Ar = 2,6 pyridyl
IIe, IVe. Ar = 2,5thienyl
Ia, IIIa. Ar = phenyl
Ib, IIIb. Ar = 2-pyridyl
Ic, IIIc. Ar = 2-thienyl
Id, IIId. Ar = 2-furyl
Ie, IIIe. Ar = 2-pyrrolyl
Scheme 1. Synthetic route of mono, bis-benzimidazo[1,2-c]quinazolines.
Staphylococcus aureus, Bacillus subtilis, Streptococcus pyogenes
(Gram positive) and Salmonella typhimurium, Escherichia coli,
Klebsiella pneumonia (Gram negative) bacterial strains by agar
diffusion method [29,30]. Ampicillin was used as a reference
standard. Preliminary screening for ten quinazolines was per-
four compounds IIIb, IIIc and IVd, IVe were found to be very
effective based on the obtained values of relative zone of inhibition.
The maximum inhibition was observed in IIIb and IIIc against all
the tested organisms except S. typhimurium and K. pneumonia. In
addition, the most potent activity was observed in bis-benzimi-
dazo[1,2-c]quinazolines (IVd and IVe) against all bacterial strains
when compared them with standard drug Ampicillin. The
minimum inhibitory concentration [31,32] of these quinazolines
(IIIb, IIIc and IVd, IVe) was also verified by the liquid dilution
formed at fixed concentrations of 1000 mg/ml. Screening results are
summarized in Table 1. The antibacterial screening revealed that all
the tested compounds IIIa–e and IVa–e showed moderate to good
inhibition towards all bacterial strains. Out of ten quinazolines, the
Table 1
Zone of inhibition of newly synthesized mono, bis-benzimidazo[1,2-c]quinazolines against different bacteria and fungi.
Compound (1000
mg/ml)
Zone of inhibition (mm)
Gram-positive bacteria
Gram-negative bacteria
Fungi
S. aureus
B. subtilis
S. pyogenes
S. typhimurium
E. coli
K. pneumonia
A. niger
C.albicans
T. viridae
IIIa
IIIb
IIIc
IIId
IIIe
IVa
IVb
IVc
IVd
IVe
Std
18
50
51
25
22
18
21
25
52
55
48a
14
42
45
21
18
14
18
19
45
50
39a
13
49
50
18
13
15
15
18
50
52
35a
12
38
40
15
14
12
15
14
46
46
45a
18
51
50
20
18
20
19
21
50
51
40a
16
35
36
12
12
15
18
18
49
50
45a
10
49
51
13
11
16
18
21
50
55
45b
10
48
48
11
9
13
15
16
50
51
40b
9
45
46
6
9
13
12
13
45
48
41b
a
Ampicillin.
Ketoconazole.
b

3332
R. Rohini et al. / European Journal of Medicinal Chemistry 44 (2009) 3330–3339
Table 2
MIC values potent mono, bis-benzimidazo[1,2-c]quinazolines and standard drugs.
Compound
Range of concentration (mg/ml)
Gram-positive bacteria
Gram-negative bacteria
Fungi
S. aureus
B. subtilis
S. pyogenes
S. typhimurium
E. coli
K. pneumonia
A. niger
C.albicans
T. viridae
IIIb
IIIc
IVd
IVe
Std
10
5
2.5
2.5
10a
20
15
15
10
20a
15
10
10
5
20
15
5
15
10
5
2.5
15a
20
15
5
10
5
2.5
2.5
15b
15
15
5
2.5
25b
15
10
10
5
5
5
25a
10a
10a
20b
a
Ampicillin.
Ketoconazole.
b
method in which the effectiveness was observed at lower
concentrations (Table 2).
was confirmed on the basis of elemental analysis, IR, NMR and mass
spectral analysis.
4.1. Infrared spectral analysis
3.2. Antifungal activity
IR spectra of compound
A showed absorption band at
All the above-mentioned quinazoline compounds were also
examined for antifungal activity against Aspergillus niger, Candida
albicans, Trichoderma viridae fungal strains. Ketoconazole was used
as standard drug for the comparison of antifungal results. The
fungal strains were grown and maintained on Sabouraud glucose
agar plates. Preliminary screening for ten quinazolines was per-
3350 cmꢂ1 assigned to aminophenyl ring and in the case of
compounds A, Ia–e and IIa–e, two absorption bands in the region
3150–3300 cmꢂ1 and 1420 cmꢂ1 were assigned to –NH stretching
and bending vibrations of imidazolyl ring, respectively [24,25]. The
absence of aminophenyl ring absorption at 3350 cmꢂ1 and
appearance of a strong intensity band in the IR spectra of
compounds (Ia–e, IIa–e) in the range of 1610–1655 cmꢂ1 attribut-
able to C]N provides a strong evidence for the condensation and
also confirms the formation of the azomethines Ia–e and IIa–e [26].
The oxidative cyclisation of compounds Ia–e, IIa–e to IIIa–e, IVa–e
was accompanied by the disappearance of the absorption maxima
at 3150–3300 cmꢂ1, which are ascribed to the vibrations of NH
group of the benzimidazole ring; at the same time the appearance
of a new maximum at 1360–1388 cmꢂ1, which is characteristic for
formed at fixed concentrations of 1000 mg/ml. The plates were
incubated at 26 ꢀC for 72 h and zones of inhibition formed were
measured [33]. The antifungal screening revealed that all the tested
compounds IIIa–e and IVa–e showed moderate to good inhibition.
The pyridyl and thienyl substituted quinazolines IIIb, IIIc and IVd,
IVe showed same trend in the case of fungal strains (Tables 1 and 2).
In general, the order of both antibacterial and antifungal activity
of the quinazolines is IVe ꢁ IVd ꢁ IIIc ꢁ IIIb ꢁ IVc ꢁ IIId ꢁ IVb ꢁ
IIIe ꢁ IVa ꢁ IIIa. Furthermore, the MIC values of potent compounds
IIIb, IIIc, IVd and IVe (Table 2 and Fig. 5) showing their superior
activity against bacterial and fungal strains than respective stan-
dard drugs Ampicillin and Ketoconazole.
benzimidazoquinazoline ring with
appears [21,27].
a tertiary nitrogen atom,
4.2. 1H & 13C NMR spectral analysis
4. Results and discussion
The 1H NMR spectra of the compound A as well as its deriv-
atives have been recorded in CDCl3/DMSO-d6 using TMS as
internal standard. In the spectra of 2-(o-aminophenyl) benz-
Formation of 2-o-arylideneaminophenylbenzimidazoles (Ia–e,
IIa–e) and 6-arylbenzimidazo[1,2-c]quinazolines (IIIa–e), (IVa–e)
imidazole (A), signals at 6.4
d and 8.25 d were appeared
Fig. 1. 1H NMR spectrum of compound IVb.

R. Rohini et al. / European Journal of Medicinal Chemistry 44 (2009) 3330–3339
3333
Fig. 2. 13C NMR spectrum of compound IVb.
corresponding to free amino and imidazolyl protons respectively
[24,26]. The aromatic protons of various environments present in
all compounds appeared as multiplets in the range of 6.50–
8.78 ppm [26,28]. 1H NMR spectra of compounds Ia–e, IIa–e
contain signals corresponding to CH]N protons in the range of
7.90–8.31 ppm suggesting the condensation of aromatic alde-
hydes with compound A. However, in the spectra of Ia–e and IIa–
azomethines. Finally, in the spectra of IIIa–e, IVa–e compounds
disappearance of signals corresponding to –NH of imidazolyl ring
and CH]N protons supports the benzimidazoquinazoline ring
structure [21,27].
13C NMR spectra of all the compounds contain signals in the
range of 141.1–168.3 ppm confirming the presence of carbon, which
is doubly bonded to nitrogen. The aromatic carbons of various
environments present in all the compounds appeared as signals in
the range of 110.3–156.2 ppm [28]. The 1H & 13C NMR spectra of
compound IVb are presented in Figs. 1 and 2 respectively.
e compounds the disappearance of signals at 6.4
d which is due to
NH2 protons of compound A supports the involvement of amino
group in condensation and confirms the formation of
Fig. 3. FAB mass spectrum of compound IIIb.

3334
R. Rohini et al. / European Journal of Medicinal Chemistry 44 (2009) 3330–3339
Fig. 4. FAB mass spectrum of compound IVb.
4.3. FAB mass analysis
(42.2%), 192 (100%), and 76 (18.6%), which indicate the fragmen-
tation pattern and their intensity gives an idea about the abun-
dance and stability of the fragments. The mass fragmentation
pattern of compounds IIIb and IVb as assigned on the basis of mass
spectra (Figs. 3 and 4) is presented in Schemes 2 and 3.
All the compounds showed a single peak in ESI-MS suggesting
the purity of the azomethines and quinazolines. The FAB mass
spectrum of compound (IIIb) shows a parent peak at m/z (Mþ) 296
(80.5%) corresponding to the molecular formula C19H12N4. The
mass spectrum shows major fragments at m/z values of 218 (40.2%),
193 (52.1%), 192 (100%), 180 (74.6%) and 76 (24.2%). The spectrum of
(IVb) shows a molecular ion peak (Mþ) at m/z 512 (65.4%), which
confirms the proposed formula (C34H20N6). The peaks have been
observed at m/z values 396 (80.2%), 294 (51.5%), 218 (30.8%), 193
5. Conclusion
Benzimidazo[1,2-c]quinazolines have been used widely in the
pharmaceutical industry and medicine because of their antimi-
crobial, antipyretic, anti-inflammatory, and anticancer properties.
We have described the synthesis, characterization and antimicro-
bial studies of several mono, bis-benzimidazo[1,2-c]quinazolines.
All are newly synthesized compounds, except one (IIIa) [23].
Furthermore, we have chosen six bacterial and three fungal strains
for microbial studies of these entire quinazoline compounds. From
this study it is evident that mono-benzimidazo[1,2-c]quinazoline
compounds are showing better activity when compared to Ampi-
cillin and Ketoconazole towards inhibiting all tested bacterial
strains (except S. typhimurium, K. pneumonia) and all fungal strains
respectively. Furthermore, the most potent activity was observed in
bis-benzimidazo[1,2-c]quinazolines (IVd and IVe) against all
bacterial and fungal strains when compared to respective standard
drugs Ampicillin and Ketoconazole. From the results it could be
deduced that among the compounds those containing pyridyl,
thienyl at the C6 position of the benzimidazo[1,2-c]quinazoline
moiety showed better activities against the test bacteria and fungi
than those containing other aromatic substituents. Especially, the
compounds with two quinazoline moieties (IVd, IVe) were more
active than all mono-benzimidazo[1,2-c]quinazolines. A possible
explanation for this result is that the antibacterial and antifungal
activity of compounds may be depending on the basic skeleton of
molecule as well as on the nature of substituents. Hence we
III b
III c
IV d
Ketoconazole
Ampicillin
IV e
30
25
20
15
10
5
0
E. coli
A. niger
T. viridae
S. aureus B. subtilis
C. albicans
S. pyogenes
S. typhimurium
K. pneumonia
Bacteria, Fungi and Standard drugs
Fig. 5. Comparison of MIC values (in
m
g/ml) of quinazolines and standard drugs against
different bacteria and fungi.

R. Rohini et al. / European Journal of Medicinal Chemistry 44 (2009) 3330–3339
3335
N
N
N
H
N
N
m/z 193
m/z 218
N
N
N
N
m/z 296
N
N
N
N
m/z 192
m/z 180
m/z76
Scheme 2. FAB mass fragmentation pattern of 6-(2-pyridyl)benzo[4,5]imidazo[1,2-c]quinazoline (IIIb).
conclude that although all quinazolines itself were observed active
6.2. Procedure for preparation of bis-2-o-(arylideneamino) phenyl
benzimidazoles (IIa–e)
the activity was further enhanced by the presence of basic bis-
benzimidazo[1,2-c]quinazoline structure and as well as pyridyl,
thienyl groups.
2-(o-Aminophenyl) benzimidazole (A, 0.837 g, 4 mmol) was
dissolved in 20 ml of ethanol. To this solution, 20 ml of CHO–Ar–
CHO solution (2 mmol, viz., 0.268 g of o-pthalaldehyde, 0.268 g of
m-pthalaldehyde, 0.268 g of p-pthalaldehyde, 0.270 g of 2,6-
diformyl pyridine or 0.280 g of 2,5-diformyl thiophene in ethanol)
and acetic acid (2–3 drops) were added. The reaction mixture was
refluxed under heat for 2 h after which the compound was
obtained. The product was filtered and recrystallized from
a dichloromethane–methanol mixture (2:1, v/v).
6. Experimental protocols
Analar grade reagents and freshly distilled solvents were used
throughout the investigations. Purity of the compounds was
checked by TLC using Merck 60F254 silica gel plates. Micro
analytical (C, N, H) data was obtained by using a Perkin–Elmer 2400
CHN elemental analyzer. The IR spectra were recorded in KBr
pellets on Perkin–Elmer-283 spectrophotometer. Brucker 400 MHz
and Brucker 67.93 MHz spectrometers were used for 1H NMR and
13C NMR measurements. ESI and FAB MS were used to obtain mass
spectra. Hot air oven (Instrument and equipment Pvt. Ltd., Mum-
bai), incubator (Instrument and equipment Pvt. Ltd., Mumbai),
laminar airflow unit (Clas laminar technologies Pvt. Ltd. Secun-
derabad), autoclave (Medica instrument Mfg. Co., Mumbai) were
used in the present investigations. Organisms like S. aureus,
B. subtilis, S. pyogenes (Gram positive), S. typhimurium, E. coli,
K. pneumonia (Gram negative) bacteria and A. niger, C. albicans,
T. viridae fungi were used in the present investigations.
6.3. Procedure for preparation of mono, bis-6-substituted
benzimidazo[1,2-c]quinazolines[BIQ–Ar and BIQ–Ar–BIQ] (IIIa–e
and IVa–e)
All the benzimidazo[1,2-c]quinazolines (IIIa–e and IVa–e) were
prepared from azomethines Ia–e and IIa–e through oxidative cyc-
lisation method reported by Davis and Mann [23]. Appropriate
amount of powdered potassium permanganate was added to
a solution of the azomethyne compound (Ia–e, IIa–e) in 50–75 ml
of acetone. The mixture was boiled under reflux for 30 min. it was
then filtered hot, and an equal volume of hot water added to the
filtrate. The quinazolines (IIIa–e and IVa–e) rapidly separated, and
6.1. Procedure for preparation of mono-2-o-(arylideneamino)
phenyl benzimidazoles (Ia–e)
was
collected
by
filtration
and
recrystalized
from
dimethylformamide.
2-(o-Aminophenyl) benzimidazole (A, 0.418 g, 2 mmol) was dis-
solved in 20 ml of ethanol. To this solution, 20 ml of Ar–CHO solution
(2 mmol, viz., 0.212 g of benzaldehyde, 0.214 g of 2-formyl pyridine,
0.224 g of 2-formyl thiophene, 0.192 g of 2-formyl furan or 0.190 g of
2-formyl pyrrole in ethanol) and acetic acid (2–3 drops) were added.
The reaction mixture was refluxed under heat for 2 h after which the
compound was obtained. The product was filtered and recrystallized
from a dichloromethane–methanol mixture (2:1, v/v).
6.3.1. N-[2-(1H-Benzo[d]imidazol-2-yl)phenyl]-N-[(E)-1-
phenylmethylidene]amine (Ia)
Yield 69%; mp 221–223 ꢀC (lit. mp 222 ꢀC); IR 3300, 1655, 1590,
1575, 1130 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d in ppm: 6.83 (t, 1H,
Ar, J ¼ 7.4 Hz), 7.05–7.09 (m, 2H, Ar), 7.12–7.18 (m, 2H, Ar), 7.22–
7.25 (m, 3H, Ar); 7.30–7.32 (m, 3H, Ar), 7.63 (d, 1H, Ar, J ¼ 7.3 Hz),
7.95 (d, 1H, Ar, J ¼ 7.3 Hz), 8.22 (s, 1H, CH]N), 8.89 (s, 1H,

3336
R. Rohini et al. / European Journal of Medicinal Chemistry 44 (2009) 3330–3339
N
N
m/z 192
m/z 76
-C21H12N4
-C21H12N4
N
N
N
N
-C14H8N3
-C7H4N2
N
N
N
N
N
N
N
N
N
m/z 294
m/z 396
m/z 512
-C21H11N4
N
-C20H12N3
N
N
N
H
N
m/z 193
m/z 218
Scheme 3. FAB mass fragmentation pattern of 6-(3-benzo[4,5]imidazo[1,2-c]quinazoline-6-ylphenyl)benzo[4,5]imidazo[1,2-c]quinazoline (IVb).
imidazolyl –NH); 13C NMR (67.93 MHz, CDCl3)
d
114.1, 118.2, 123.1,
71.29; H, 4.59; N, 13.80%. Calcd for C18H13N3S: C, 71.26; H, 4.32; N,
123.5, 126.2, 130.5, 130.8, 131.2, 132.2, 136.5, 141.2, 142,6, 143.8,
146.3, 165.7 (20C, Ar–C); Anal. Found: C, 81.08; H, 5.07; N, 14.15%.
Calcd for C20H15N3: C, 80.78; H, 5.08; N, 14.13%. MS: [M]þ at m/z
297.
13.85%. MS: [M]þ at m/z 303.
6.3.4. N-[2-(1H-Benzo[d]imidazol-2-yl)phenyl]-N-[(E)-1-(2-
furyl)methylidene]amine (Id)
Yield 78%; mp 214–216 ꢀC; IR 3300,1638,1605,1585,1128 cmꢂ1
;
6.3.2. N-[2-(1H-Benzo[d]imidazol-2-yl)phenyl]-N-[(Z)-1-(2-
pyridyl)methylidene]amine (Ib)
1H NMR (400 MHz, CDCl3)
d
in ppm 6.67 (dd,1H, Ar, J ¼ 3.62,1.81 Hz
furanyl C4H), 6.82 (t, 1H, Ar, J ¼ 7.4 Hz), 6.95 (d, 1H, J ¼ 3.62 Hz,
furanyl C3H), 7.36–7.42 (m, 3H, Ar), 7.44–7.48 (m, 3H, Ar), 7.63 (d,1H,
Ar, J ¼ 7.3 Hz), 7.94 (d, 1H, Ar, J ¼ 7.3 Hz), 8.02 (s, 1H, CH]N), 8.85 (s,
Yield 79%; mp 228–230 ꢀC; IR 3300, 1630, 1610, 1580,
1100 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
6.83 (t, 1H, Ar, J ¼ 7.4 Hz),
7.06–7.10 (m, 2H, Ar), 7.12–7.18 (m, 2H, Ar), 7.29–7.30 (m, 2H, Ar);
7.62 (d, 1H, Ar, J ¼ 7.3 Hz), 7.75–7.79 (m, 1H, Ar), 7.82 (t, 1H, Ar,
J ¼ 8.0 Hz), 7.94 (d, 1H, Ar, J ¼ 7.3 Hz), 8.24 (s, 1H, CH]N), 8.72 (d,
1H, J ¼ 5.25 Hz), 8.89 (s, 1H, –NH); 13C NMR (67.93 MHz, CDCl3)
1H, –NH); 13C NMR (67.93 MHz, CDCl3)
d 111.6, 114.0, 114.3, 121.6,
123.4, 123.5, 126.2, 130.5, 130.8, 131.1, 132.0, 141.1, 142,3, 143.5, 146.1,
154.2 (18C, Ar–C), Anal. Found: C, 76.02; H, 5.01; N,14.80%. Calcd for
C18H13N3O: C, 75.25; H, 4.56; N, 14.62%. MS: [M]þ at m/z 287.
d
114.1, 118.2, 123.1, 123.5, 126.2, 130.5, 130.8, 131.2, 132.2, 136.5,
141.2, 142,8, 143.5, 146.3, 149.40, 154.48, 166.1 (19C, Ar–C), Anal.
Found: C, 76.02; H, 5.07; N, 18.80%. Calcd for C19H14N4: C, 76.49; H,
4.73; N, 18.78%. MS: [M]þ at m/z 298.
6.3.5. N-[2-(1H-Benzo[d]imidazol-2-yl)phenyl]-N-[(E)-1-(1H-2-
pyrrolyl)methylidene] amine (Ie)
Yield 75%; mp 210–212 ꢀC; IR 3300, 3215, 1640, 1605, 1580,
1130 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d in ppm 5.93 (dd, 1H,
6.3.3. N-[2-(1H-Benzo[d]imidazol-2-yl)phenyl]-N-[(E)-1-(2-
thienyl)methylidene]amine (Ic)
J ¼ 3.94, 2.88 Hz, pyrrolyl C4–H), 6.63 (d, 1H, J ¼ 2.88 Hz, pyrrolyl
C5–H), 6.82 (t, 1H, Ar, J ¼ 7.4 Hz), 6.95 (d, 1H, J ¼ 3.94 Hz, pyrrolyl
C3–H), 7.36–7.42 (m, 3H, Ar), 7.43–7.49 (m, 2H, Ar), 7.63 (d, 1H, Ar,
J ¼ 7.3 Hz), 7.94 (d,1H, Ar, J ¼ 7.3 Hz), 7.98 (s,1H, CH]N), 8.85 (s,1H,
Yield 80%; mp 220–222 ꢀC; IR 3300, 1635, 1608, 1590, 1130,
695 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d in ppm 6.82 (t, 1H, Ar,
J ¼ 7.4 Hz), 7.27 (d, 2H, Ar, J ¼ 3.8 Hz), 7.36–7.43 (m, 4H, Ar), 7.45–
7.48 (m, 2H, Ar), 7.63 (d,1H, Ar, J ¼ 7.3 Hz), 7.94 (d,1H, Ar, J ¼ 7.3 Hz),
8.02 (s, 1H, CH]N), 8.89 (s, 1H, –NH); 13C NMR (67.93 MHz, CDCl3)
–NH), 9.77 (s, 1H, pyrrolyl NH); 13C NMR (67.93 MHz, CDCl3)
d 113.6,
114.4, 118.2, 121.7, 123.5, 126.2, 130.5, 130.8, 131.2, 132.5, 136.5, 141.1,
141.2, 144,8, 146.3, 149.40 (18C, Ar–C); Anal. Found: C, 75.49; H,
5.01; N, 19.55%. Calcd for C18H14N4: C, 75.51; H, 4.93; N, 19.57%. MS:
[M]þ at m/z 286.
d
114.2, 118.2, 121.1, 123.3, 126.2, 130.5, 131.2, 132.2, 132.4, 133.5,
141.1, 143.5, 146.5, 146.8, 147.40, 148.5 (18C, Ar–C); Anal. Found: C,

R. Rohini et al. / European Journal of Medicinal Chemistry 44 (2009) 3330–3339
3337
6.3.6. N1-(Z)-1-[2-([2-(1H-Benzo[d]imidazol-2-
l)phenyl]iminomethyl)phenyl]methylidene-2-(1H-
benzo[d]imidazol-2-yl)aniline (IIa)
(32C, Ar–C) Anal. Found: C, 73.59; H, 4.57; N, 16.29%. Calcd for
32H22N6S: C, 73.54; H, 4.24; N, 16.08%. MS: [M]þ at m/z 522.
C
Yield 75%; mp 224–225 ꢀC; IR 3300, 1640, 1605, 1585,
6.3.11. 6-Phenylbenzo[4,5]imidazo[1,2-c]quinazoline (IIIa)
1120 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
in ppm 6.81 (d, 2H, Ar,
Yield 81%; mp 241–242 ꢀC (lit. mp 242 ꢀC); IR 1621, 1585, 1529,
J ¼ 8.4 Hz), 6.83 (t, 2H, Ar, J ¼ 7.4 Hz), 7.05–7.09 (m, 4H, Ar), 7.12–
7.18 (m, 4H, Ar), 7.32 (t, 2H, Ar, J ¼ 7.6 Hz), 7.35–7.44 (m, 4H, Ar), 7.95
(d, 2H, Ar, J ¼ 7.3 Hz), 8.31 (s, 2H, CH]N), 8.89 (s, 2H, –NH); 13C
1457, 1380, 773, 741, 732 cmꢂ1 1H NMR (400 MHz, DMSO-d6)
; d in
ppm 6.65 (d, 1H, Ar, J ¼ 8.2 Hz), 6.81 (d, 1H, Ar, J ¼ 8.4 Hz), 6.83 (t,
1H, Ar, J ¼ 7.4 Hz), 7.17–8.03 (m, 9H, Ar), 8.75 (dd, 1H, J ¼ 6.9,
NMR (67.93 MHz, CDCl3)
d
114.1,118.2, 123.1, 123.5, 125.2, 127.3,
2.5 Hz); 13C NMR (67.93 MHz, DMSO-d6)
d 112.4, 120.1, 121.5, 122.4,
128.3, 130.5, 130.8, 131.2, 132.2, 133.5, 138.3, 141.1, 142,6, 144.2,
146.6, 158.2 (34C, Ar–C); Anal. Found: C, 80.08; H, 5.02; N, 16.02%.
Calcd for C34H24N6: C, 79.05; H, 4.68; N, 16.27%. MS: [M]þ at m/z
516.
125.8, 126.4, 129.3, 129.5, 130.7, 131.5, 132.6, 133.2, 145.6, 146.5,
146.8, 151.5, (20C, Ar–C) Anal. Found: C, 81.35; H, 4.58; N, 14.25%.
Calcd for C20H13N3: C, 81.34; H, 4.44; N, 14.23%. MS: [M]þ at m/z
295.
6.3.7. N1-(E)-1-[3-([2-(1H-Benzo[d]imidazol-2-yl)
phenyl]iminomethyl)phenyl]methylidene-2-(1H-benzo[d]imidazol-
2-yl)aniline (IIb)
6.3.12. 6-(2-Pyridyl)benzo[4,5]imidazo[1,2-c]quinazoline (IIIb)
Yield 67%; mp 228–230 ꢀC; IR 1621, 1610, 1524, 1459, 1378, 775,
744, 739 cmꢂ1; 1H NMR (400 MHz, DMSO-d6)
d in ppm 6.65 (d, 1H,
Yield 68%; mp 216–218 ꢀC; IR 3300, 1625, 1605, 1575, 1130 cmꢂ1
;
Ar, J ¼ 8.2 Hz), 6.81 (d, 1H, Ar, J ¼ 8.4 Hz), 6.83 (t, 1H, Ar, J ¼ 7.4 Hz),
7.03 (t, 1H, Ar, J ¼ 7.4 Hz), 7.20–8.03 (m, 6H, Ar), 8.75 (dd, 1H, J ¼ 6.9,
2.5 Hz) 8.80 (dd, 1H, J ¼ 4.93, 1.7 Hz); 13C NMR (67.93 MHz, DMSO-
1H NMR (400 MHz, CDCl3)
d
in ppm 6.81 (d, 2H, Ar, J ¼ 8.4 Hz), 6.83
(t, 2H, Ar, J ¼ 7.4 Hz), 7.05–7.09 (m, 4H, Ar), 7.12–7.18 (m, 4H, Ar),
7.35–7.42 (m, 2H, Ar), 7.62 (t, 2H, Ar, J ¼ 6.4 Hz), 7.93 (t, 2H, Ar,
J ¼ 8.8 Hz), 7.95 (d, 2H, Ar, J ¼ 7.3 Hz), 8.07 (s, 2H, CH]N), 8.89 (s,
d6) d 112.4, 120.3, 121.6, 122.8, 125.8, 126.4, 129.8, 130.7, 131.5, 133.3,
138.4, 143.1, 145.6, 146.5, 146.8, 150.2, 151.5, 152.4 (19C, Ar–C); Anal.
Found: C, 77.08; H, 5.02; N, 18.90%. Calcd for C19H12N4: C, 77.01; H,
4.08; N, 18.91%. MS: [M]þ at m/z 296.
2H, –NH); 13C NMR (67.93 MHz, CDCl3)
d 114.3, 114.4, 123.1, 123.4,
124.2, 126.4, 127.3, 128.3, 130.7, 130.9, 132.2, 134.3, 133.5, 135.3,
141.1, 142,6, 144.5, 146.6, 146.8, 168.2 (34C, Ar–C); Anal. Found: C,
80.08; H, 4.69; N, 16.15%. Calcd for C34H24N6: C, 79.05; H, 4.68; N,
16.27%. MS: [M]þ at m/z 516.
6.3.13. 6-(2-Thienyl)benzo[4,5]imidazo[1,2-c]quinazoline (IIIc)
Yield 74%; mp 232–234 ꢀC; IR 1640, 1605, 1580, 1459, 1385, 775,
745, 749, 690 cmꢂ1; 1H NMR (400 MHz, DMSO-d6)
d in ppm 6.62 (d,
6.3.8. N1-(E)-1-[4-([2-(1H-Benzo[d]imidazol-2-
yl)phenyl]iminomethyl)phenyl]methylidene-2-(1H-
benzo[d]imidazol-2-yl)aniline (IIc)
1H, J ¼ 3.63 Hz), 6.66 (d, 1H, Ar, J ¼ 8.2 Hz), 6.80 (d, 1H, Ar,
J ¼ 8.4 Hz), 6.83 (t, 1H, Ar, J ¼ 7.4 Hz), 7.08 (d, 1H, J ¼ 5.25 Hz), 7.20–
7.50 (m, 4H, Ar), 7.52 (d, 1H, J ¼ 5.25 Hz), 8.74 (dd, 1H, J ¼ 6.9,
Yield 71%; mp 220–222 ꢀC; IR 3300,1621,1600,1580,1130 cmꢂ1
;
2.5 Hz); 13C NMR (67.93 MHz, DMSO-d6)
d 111.4, 119.3, 121.6, 121.7,
1H NMR (400 MHz, CDCl3)
d
in ppm 6.80 (d, 2H, Ar, J ¼ 8.4 Hz), 6.82
123.0, 124.8, 125.4, 126.8, 130.7, 131.5, 132.3, 138.4, 143.6, 145.4,
146.1, 147.8, 149.2, (18C, Ar–C) Anal. Found: C, 71.76; H, 4.02; N,
13.95%. Calcd for C18H11N3: C, 71.74; H, 3.68 N, 13.94%. MS: [M]þ at
m/z 301.
(t, 2H, Ar, J ¼ 7.4 Hz), 7.05–7.09 (m, 4H, Ar), 7.13–7.18 (m, 4H, Ar),
7.39–7.40 (m, 2H, Ar), 7.42 (t, 4H, Ar, J ¼ 7.8 Hz), 7.95 (d, 2H, Ar,
J ¼ 7.3 Hz), 8.21 (s, 2H, CH]N), 8.87 (s, 2H, –NH); 13C NMR
(67.93 MHz, CDCl3)
d 114.1, 114.2, 123.1, 123.5, 125.2, 127.3,
128.3,130.5, 130.8, 131.2, 132.2, 137.3, 141.1, 142,6, 144.2, 146.6, 168.3
(34C, Ar–C); Anal. Found: C, 80.02; H, 5.07; N, 16.24%. Calcd for
C34H24N6: C, 79.05; H, 4.68; N, 16.27%. MS: [M]þ at m/z 516.
6.3.14. 6-(2-Furyl)benzo[4,5]imidazo[1,2-c]quinazoline (IIId)
Yield 81%; mp 225–227 ꢀC; IR 1638, 1615, 1575, 1465, 1380, 770,
742, 739 cmꢂ1; 1H NMR (400 MHz, DMSO-d6)
d in ppm 6.46 (d, 1H,
furyl C3–H, J ¼ 3.53 Hz), 6.55 (d, 1H, furyl C4–H, J ¼ 3.5 Hz), 6.65 (d,
1H, Ar, J ¼ 8.2 Hz), 6.80 (d, 1H, Ar, J ¼ 8.4 Hz), 6.83 (t, 1H, Ar,
J ¼ 7.4 Hz), 7.20–7.51 (m, 4H, Ar), 7.59 (s, 1H, furyl C5–H), 8.75 (dd,
6.3.9. N1-(E)-1-[6-([2-(1H-Benzo[d]imidazol-2-
yl)phenyl]iminomethyl)-2-pyridyl]methylidene-2-(1H-
benzo[d]imidazol-2-yl)aniline (IId)
1H, J ¼ 6.9, 2.5 Hz); 13C NMR (67.93 MHz, DMSO-d6)
d 111.5, 112.3,
Yield 81%; mp 255–257 ꢀC; IR 3300, 1640, 1605, 1580,
120.6,121.7,122.8,124.8,126.4,127.8,130.7,131.2,132.6,137.2,143.6,
145.6, 146.1, 147.8, 148.2, (18C, Ar–C) Anal. Found: C, 76.80; H, 3.92;
N, 14.90%. Calcd for C18H11N3O: C, 75.78; H, 3.89; N, 14.73%. MS:
[M]þ at m/z 285.
1130 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d in ppm 6.80 (d, 2H, Ar,
J ¼ 8.4 Hz), 6.82 (t, 2H, Ar, J ¼ 7.4 Hz), 7.05–7.09 (m, 4H, Ar), 7.13–
7.18 (m, 4H, Ar), 7.20 (d, 2H, Ar, J ¼ 7.8 Hz), 7.39–7.42 (m, 2H, Ar),
7.89 (t, 1H, Ar, J ¼ 7.8 Hz), 7.95 (d, 2H, Ar, J ¼ 7.3 Hz), 8.12 (s, 2H,
CH]N), 8.87 (s, 2H, –NH); 13C NMR (67.93 MHz, CDCl3)
d
114.2,
6.3.15. 6-(1H-2-Pyrrolyl)benzo[4,5]imidazo[1,2-c]quinazoline (IIIe)
114.4, 121.6, 123.5, 124.6, 127.3, 128.3,130.5, 131.8, 132.6, 141.8, 142,6,
144.2, 146.6, 146.8, 154.2, 168.4 (33C, Ar–C); Anal. Found: C, 76.59;
H, 4.52; N, 18.75%. Calcd for C33H23N7: C, 76.58; H, 4.48; N, 18.94%.
MS: [M]þ at m/z 517.
Yield 72%; mp 217–219 ꢀC; IR 3215, 1640, 1620, 1580, 1475, 1382,
770, 745, 739 cmꢂ1; 1H NMR (400 MHz, DMSO-d6)
d in ppm 5.73 (d,
1H, J ¼ 3.8 Hz), 6.38 (d, 1H, J ¼ 3.8 Hz), 6.65 (d, 1H, Ar, J ¼ 8.2 Hz),
6.80 (d, 1H, Ar, J ¼ 8.4 Hz), 6.83 (t, 1H, Ar, J ¼ 7.4 Hz), 7.14 (s, 1H),
7.21–7.54 (m, 4H, Ar), 8.74 (dd, 1H, J ¼ 6.9, 2.5 Hz) 10.6 (s, 1H, pyr-
6.3.10. N1-(Z)-1-[5-([2-(1H-Benzo[d]imidazol-2-
yl)phenyl]iminomethyl)-2-thienyl]methylidene-2-(1H-
benzo[d]imidazol-2-yl)aniline (IIe)
rolyl NH); 13C NMR (67.93 MHz, DMSO-d6)
d 111.6, 114.6, 119.6,
121.9, 122.8, 124.6, 125.4, 126.3, 129.7, 131.8, 132.5, 142.2, 143.6,
145.6, 146.1, 147.8, 149.2, (18C, Ar–C) Anal. Found: C, 76.08; H, 5.01;
N, 19.80%. Calcd for C18H12N4: C, 76.04; H, 4.25; N, 19.71%. MS: [M]þ
at m/z 284.
Yield 79%; mp 226–228 ꢀC; IR 3300, 1620, 1605, 1585, 1130,
698 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d in ppm 6.80 (d, 2H, Ar,
J ¼ 8.4 Hz), 6.82 (t, 2H, Ar, J ¼ 7.4 Hz), 7.05–7.09 (m, 4H, Ar), 7.13–
7.18 (m, 4H, Ar), 7.20 (s, 2H, thienyl –C3–H, C4–H), 7.39–7.42 (m, 2H,
Ar), 7.90 (s, 2H, CH]N), 7.95 (d, 2H, J ¼ 7.3 Hz), 8.87 (s, 2H, –NH);
6.3.16. 6-(2-Benzo[4,5]imidazo[1,2-c]quinazolin-6-
ylphenyl)benzo[4,5]imidazo[1,2-c]quinazoline (IVa)
Yield 78%; mp 235–237 ꢀC; IR 1635, 1605, 1460, 1380, 1130, 775,
13C NMR (67.93 MHz, CDCl3)
d 113.4, 114.1, 121.6, 123.4, 125.4, 126.3,
128.3,130.3,131.1,132.3,141.8,142,6,144.2,145.6,146.5,146.8,151.2,
740, 739 cmꢂ1 1H NMR (400 MHz, DMSO-d6)
; d 6.64 (d, 2H, Ar,

3338
R. Rohini et al. / European Journal of Medicinal Chemistry 44 (2009) 3330–3339
J ¼ 8.2 Hz), 6.81 (d, 2H, Ar, J ¼ 8.4 Hz), 6.82 (t, 2H, Ar, J ¼ 7.4 Hz),
a borer. The solutions of test compounds (1000 mg/ml) were added
7.20–7.85 (m, 10H, Ar), 8.70–8.78 (m, 4H, Ar); 13C NMR (67.93 MHz,
into each of the bores using a sterile tip with micropipette. A similar
plate was prepared by replacing quinazoline by Ampicillin. This was
taken as a standard against bacteria. The plates were then incu-
bated at 37 ꢀC for 24 h. The fungal strains were grown and main-
tained on Sabouraud glucose agar plates. A similar test compounds
and standard Ketoconazole plates were prepared for antifungal
screening. The plates were incubated at 26 ꢀC for 72 h. The zone of
the clearance around each bore after the incubation period,
confirms the antimicrobial activity of the respective quinazoline.
Each experiment was carried out in three replicates with each
replication consisting of three test tubes for quantitative analysis.
The clear zones formed around each bore were measured and
average diameter of the inhibition zone was calculated and
expressed in millimeter. It was used to determine the antimicrobial
activity of quinazolines. The results were analyzed using ANOVA
one way at p ꢃ 0.05.
DMSO-d6) d 113.0, 114.7, 120.5, 121.4, 122.7, 125.4, 126.3, 128.7, 131.8,
133.5, 135.5, 142.2, 143.5, 144.2, 145.1, 152.5, 154.2, (34C, Ar–C) Anal.
Found: C, 80.08; H, 4.07; N, 16.15%. Calcd for C34H20N6: C, 79.67; H,
3.93; N, 16.40%. MS: [M]þ at m/z 512.
6.3.17. 6-(3-Benzo[4,5]imidazo[1,2-c]quinazolin-6-
ylphenyl)benzo[4,5]imidazo[1,2-c]quinazoline (IVb)
Yield 71%; mp 242–244 ꢀC; IR 1620, 1610, 1459, 1385, 1128, 779,
758, 740 cmꢂ1 1H NMR (400 MHz, DMSO-d6)
; d 6.63 (d, 2H, Ar,
J ¼ 8.2 Hz), 6.81 (d, 2H, Ar, J ¼ 8.4 Hz), 6.83 (t, 2H, Ar, J ¼ 7.4 Hz),
7.19–7.28 (m, 4H, Ar), 7.53 (d, 2H, Ar, J ¼ 7.6 Hz), 7.81 (t, 2H,
J ¼ 7.6 Hz), 8.10–8.25 (m, 4H, Ar), 8.76 (dd, 2H, J ¼ 6.9, 2.5 Hz); 13C
NMR (67.93 MHz, DMSO-d6) d 113.0, 114.5, 120.4, 121.9, 122.4, 124.6,
126.5, 128.7, 131.7, 133.5, 142.2, 143.5, 144.2, 145.1, 152.2, 156.2, (34C,
Ar–C); Anal. Found: C, 81.08; H, 4.07; N, 16.21%. Calcd for C34H20N6:
C, 79.67; H, 3.93; N, 16.40%. MS: [M]þ at m/z 512.
The minimum inhibitory concentration required was also found
when a series of dilutions were tested. The minimum inhibitory
concentration at which no growth was observed was taken as the
MIC values.
6.3.18. 6-(4-Benzo[4,5]imidazo[1,2-c]quinazolin-6-
ylphenyl)benzo[4,5]imidazo[1,2-c]quinazoline (IVc)
Yield 75%; mp 280–282 ꢀC; IR 1625, 1601, 1457, 1388, 1125, 779,
773, 732 cmꢂ1 1H NMR (400 MHz, DMSO-d6)
; d 6.65 (d, 2H, Ar,
6.5. Determination of minimum inhibitory concentration (MIC)
J ¼ 8.2 Hz), 6.80 (d, 2H, Ar, J ¼ 8.4 Hz), 6.83 (t, 2H, Ar, J ¼ 7.4 Hz),
7.20–8.02 (m, 8H, Ar), 8.38 (s, 4H, Ar), 8.74 (dd, 2H, J ¼ 6.9, 2.5 Hz);
The minimum inhibitory concentration [31,32] of IIIb, IIIc and
IVd, IVe against S. aureus, B. subtilis, S. pyogenes, S. typhimurium, E.
coli, K. pneumonia (bacterial strains), A. niger, C. albicans, T. viridae
(fungal strains) was determined by liquid dilution method. Stock
solutions of tested compounds with 2.5, 5, 10, 15, 20, 25, 30, 35, 40,
13C NMR (67.93 MHz, DMSO-d6)
d 112.3, 120.3, 121.7, 122.8, 124.3,
126.9, 129.7, 131.3, 133.4, 135.2, 138.4, 141.2, 143.8, 145.2, 149.1,
152.2, 156.2, (34C, Ar–C); Anal. Found: C, 79.81; H, 4.02; N, 16.45%.
Calcd for C34H20N6: C, 79.67; H, 3.93; N, 16.40%. MS: [M]þ at m/z
512.
45 and 50 mg/ml concentrations were prepared with appropriate
solvent. The solutions of standard drugs, Ampicillin and Ketoco-
nazole were prepared in the same concentrations. Inoculums of the
bacterial and fungal culture were also prepared. To a series of tubes
containing 1 ml each of quinazoline compound solution with
different concentrations and 0.2 ml of the inoculum was added.
Further 3.8 ml of the sterile water was added to each of the test
tubes. These test tubes were incubated for 24 h and observed for
the presence of turbidity. This method was repeated by changing
quinazoline compounds with standard drug Ampicillin (in the case
of bacteria) and with Ketoconazole (in the case of fungi) for
comparison. The minimum inhibitory concentration at which no
growth was observed was taken as the MIC values.
6.3.19. 6-(6-Benzo[4,5]imidazo[1,2-c]quinazolin-6-yl-2-
pyridyl)benzo[4,5]imidazo[1,2-c]quinazoline (IVd)
Yield 72%; mp 354–356 ꢀC; IR 1625, 1605, 1590, 1380, 1130, 747,
738, 732 cmꢂ1 1H NMR (400 MHz, DMSO-d6)
; d 6.64 (d, 2H, Ar,
J ¼ 8.2 Hz), 6.81 (d, 2H, Ar, J ¼ 8.4 Hz), 6.82 (t, 2H, Ar, J ¼ 7.4 Hz),
7.12–7.82 (m, 10H, Ar), 7.90 (t, 1H, Ar, J ¼ 7.8 Hz) 8.74 (dd, 2H, J ¼ 6.9,
2.5 Hz); 13C NMR (67.93 MHz, DMSO-d6)
d 111.2, 112.2, 120.3, 121.5,
122.8, 123.3, 124.3, 126.6, 129.7, 132.3, 133.3, 135.2, 138.4, 141.2,
143.8, 145.2, 147.7, 151.1, 153.2, 156.2, (33C, Ar–C); Anal. Found: C,
77.17; H, 3.91; N, 18.75%. Calcd for C33H19N7: C, 77.18; H, 3.73; N,
19.09%. MS: [M]þ at m/z 513.
6.3.20. 6-(5-Benzo[4,5]imidazo[1,2-c]quinazolin-6-yl-2-
thienyl)benzo[4,5]imidazo[1,2-c]quinazoline (IVe)
References
Yield 73%; mp 314–316 ꢀC; IR 1635, 1608, 1457, 1388, 1129, 775,
742, 731, 693 cmꢂ1; 1H NMR (400 MHz, DMSO-d6)
d 6.65 (d, 2H, Ar,
[1] Y. Zhang, Z. Chen, Y. Lou, Y. Yu, Eur. J. Med. Chem. 44 (2009) 448–452.
[2] A. Kumar, C.S. Rajput, Eur. J. Med. Chem. 44 (2009) 83–90.
[3] R. Arienzo, S. Cramp, H.J. Dyke, P.M. Lockey, D. Norman, A.G. Roach, P. Smith,
M. Wong, S.P. Wren, Bioorg. Med. Chem. Lett. 17 (2007) 1403–1407.
[4] P. Kung, M.D. Casper, K.L. Cook, L.W. Lingardo, L.M. Risen, T.A. Vickers,
R. Ranken, L.B. Blyn, J.R. Wyatt, P. Dan Cook, D.J. Ecker, J. Med. Chem. 42 (1999)
4705–4713.
J ¼ 8.2 Hz), 6.80 (d, 2H, Ar, J ¼ 8.4 Hz), 6.83 (t, 2H, Ar, J ¼ 7.4 Hz), 6.95
(s, 2H, Ar) 7.17–8.01 (m, 8H, Ar), 8.74 (dd, 2H, J ¼ 6.9, 2.5 Hz); 13C
NMR (67.93 MHz, DMSO-d6)
d 110.3, 111.8, 112.5, 119.6, 120.7, 121.5,
123.3, 124.7, 126.2, 129.7, 130.3, 132.8, 133.5, 138.2, 141.2, 143.3,
145.2, 147.7, 150.1, 152.3 (32C, Ar–C); Anal. Found: C, 75.08; H, 4.02;
N, 16.15%. Calcd for C32H18N6S: C, 74.11; H, 3.50; N, 16.21%. MS: [M]þ
at m/z 518.
[5] A.R. Genady, Eur. J. Med. Chem. 44 (2009) 409–416.
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