Design, synthesis and antimicrobial evaluation of novel 1-benzyl 2-butyl-4-chloroimidazole embodied 4-azafluorenones via molecular hybridization approach

Article abstract of DOI:10.1016/j.bmcl.2012.10.042

A series of novel 1-benzyl-2-butyl-4-chloroimidazole embodied 4-azafluorenone hybrids, designed via molecular hybridization approach, were synthesized in very good yields using one pot condensation of 1-benzyl-2-butyl-4-chloroimidazole-5-carboxaldehyde, 1

Full text of DOI:10.1016/j.bmcl.2012.10.042

Bioorganic & Medicinal Chemistry Letters 22 (2012) 7475–7480
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Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Design, synthesis and antimicrobial evaluation of novel 1-benzyl
2-butyl-4-chloroimidazole embodied 4-azafluorenones via molecular
hybridization approach
Dinesh Addla a, Bhima b, Balasubramanian Sridhar c, Anjana Devi d, Srinivas Kantevari a,
⇑
a Organic Chemistry (CPC) Division-II, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India
b Department of Microbiology, Osmania University, Hyderabad 500 007, India
c Laboratory of X-ray Crystallography, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India
d Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of novel 1-benzyl-2-butyl-4-chloroimidazole embodied 4-azafluorenone hybrids, designed via
molecular hybridization approach, were synthesized in very good yields using one pot condensation of
1-benzyl-2-butyl-4-chloroimidazole-5-carboxaldehyde, 1,3-indanedione, aryl/heteroaryl methyl ketones
and ammonium acetate. All the synthetic derivatives were fully characterized by spectral data and eval-
uated for antimicrobial activity by disc diffusion method against selected bacteria and fungal strains.
Among the 15 new compounds screened, 4-(1-benzyl-2-butyl-4-chloro-1H-imidazol-5-yl)-2-(furan-2-
yl)-5H-indeno[1,2-b]pyridin-5-one(10k) has pronounced activity with higher zone of inhibition (ZoI)
against Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Aspergillus flavus and
Candida albicans. Also 4-(1-benzyl-2-butyl-4-chloro-1H-imidazol-5-yl)-2-(dibenzo[b,d]thiophen-2-yl)-
5H-indeno [1,2-b]pyridin-5-one (10n) and 4-(1-benzyl-2-butyl-4-chloro-1H-imidazol-5-yl)-2-(3-tosyl-
3H-inden-1-yl)-5H-indeno[1,2-b]pyridin-5-one (10o) showed selective higher inhibitory activity against
Aspergillus flavus and Candida albicans. The results demonstrated potential importance of molecular
hybridization in the development of 10k as potential antimicrobial agent.
Received 31 August 2012
Revised 5 October 2012
Accepted 9 October 2012
Available online 24 October 2012
Keywords:
Molecular hybridization
Azafluorenone
Imidazole
Natural product
Antimicrobial
Ó 2012 Elsevier Ltd. All rights reserved.
With the emergence and development of resistant, multidrug
resistant and even extremely drug resistant microbial strains, the
battle of humankind against infections is never ending in this
‘Plethora of microbes’.1,2 This has created an urgent need to devote
our continuous efforts for the discovery and development of new
antimicrobials with broader spectrum of activity and lower toxic-
ity. Many structural frameworks have been described as privileged
structures3 and in particular the five member heterocyclic imidaz-
ole nucleus is endowed with various biological activities due to the
presence of ring nitrogens.4,5 The valuable therapeutic properties
of the imidazole related drugs have encouraged the medicinal
chemists to synthesize a large number of novel chemotherapeutic
agents such as ketoconazole, miconazole, tioconazole, clotrimazole
and sulconazole etc.6 However, with the emergence of resistance
mechanisms, there is a need for newer antimicrobial agents to
combat resistance developed against widely used antimicrobial
drugs.1,6
Polyalthia debilis (Pierre) belonging to the family of Annonaceae, the
root water decoction of which has been traditionally used for
treatment of antimicrobial infections.7–16 The isolated compound
Onychine (1) with azafluorenone architecture is active against
Candida albicans in micro molar concentrations.8 In addition, 1 also
exhibited antimicrobial activity against Staphylococcus aureus,
Bacillus subtilis, Escherichia coli, and Saccharomyces in the range of
50–100 l
M. concentration.9
Other 4-azafluorenone derivatives 2–5 are found to exhibit
antimalarial, adenosine A2a receptor binding and phosphodiester-
ase inhibiting activities for the treatment of neurodegenerative dis-
orders, calcium antagonistic agents and inflammation related
diseases.11–16 The unique structural feature of these bioactive nat-
ural and synthetic analogs.17,18 (Fig. 1 is due the presence of 4-aza-
fluorenone moiety playing a vital role exhibiting wide spectrum
pharmacological properties.
We therefore envisaged that integrating natural 4-azafluore-
none and pharmacophoric imidazole moieties in one molecular
platform (molecular hybridization)19,20 could generate potential
new scaffolds for biological evaluation. The choice of 1-benzyl-
2-butyl-4-chloroimidazole as pharmacophore for modification
arises from recent reports, wherein 2-butyl-4-chloroimidazole
was conjugated to isoxazolidine, which exhibited enhanced
4-Azafluorenones (5H-indeno[1,2-b]pyridin-5-one; Fig. 1) are
the naturally occurring alkaloids isolated from the root of the plant
⇑
Corresponding author. Tel.: +91 4027191437; fax: +91 4027198933.
E-mail addresses: kantevari@yahoo.com, kantevari@gmail.com (S. Kantevari).
0960-894X/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.bmcl.2012.10.042

7476
D. Addla et al. / Bioorg. Med. Chem. Lett. 22 (2012) 7475–7480
Table 1
O
Optimization of reaction conditionsa
H3C
R
O
H3C
Entry
Solventb
Reaction Temp (°C)
Time (h)
Product Yield (%)c
R
1
2
3
4
5
6
7
8
Methanol
Methanol
2-Propanol
2-Propanol
Glycol
Glycol
DMF
DMF
Acetonitrile
Water
40
Reflux
60
Reflux
60
120
60
120
Reflux
100
Reflux
120
100
110
130
8
8
8
8
8
8
8
3
8
8
8
8
3
3
3
20
42
25
46
30
74
48
82
54
15
28
64
76
82
84
N
N
OCH3
HO
R=H; Onychine (1)
R=H; Isoursuline (3)
R=OH; (4)
R=OCH3; 7-methoxyonychine (2)
O
9
10
11
12
13
14
15
THF
Neat
DMF
DMF
N
N
O
N
H
DMF
5
a
1-Benzyl-2-butyl-4-chloroimidazole carboxaldehyde 7 (1 mmol), 1,3-indane-
dione (1 mmol), acetophenone (1 mmol) and ammonium acetate (2.5 mmol).
Figure 1. Examples of bioactive natural (1–4) and synthetic (5) azafluorenones.
b
The volume of solvent is 5 mL.
Isolated yield.
c
antimicrobial activity.21–23 As a part of our ongoing research aim-
ing on the development of novel bioactive hybrid molecules
through one-pot multicomponent reactions,24–26 we report herein
one-pot synthesis and antimicrobial evaluation of novel 1-benzyl-
2-butyl-4-chloroimidazole embodied 4-azafluorenones. Antimi-
crobial evaluation of these new derivatives resulted in the
identification of 4-(1-benzyl-2-butyl-4-chloro-1H-imidazol-5-yl)-
2-(furan-2-yl)-5H-indeno[1,2-b]pyridin-5-one 10k as most active
antimicrobial agent. 4-(1-Benzyl-2-butyl-4-chloro-1H-imidazol-
5-yl)-2-(dibenzo[b,d]thio phen-2-yl)-5H-indeno[1,2-b]pyridin-5-one
and temperatures ranging from 60 °C to 130 °C by modifying the
related literature protocols,29,30 After a series of experiments
(Table 1), the reaction was found to be most efficient when 7
was reacted with equimolar amounts of 1,3-indanedione (8), ace-
tophenone (9a) and 2.5 equiv of ammonium acetate in DMF at
120 °C to give 4-azafluorenone 10a in very good yield (82%;
Scheme 1).
Further, to expand the series, imidazole embodied 4-azafluore-
none analogs 10a–o were prepared through one-pot condensation
between 1-benzyl-2-butyl-4-chloroimidazole carboxaldehyde (7),
aryl/heteroaryl methyl ketones 9a–o (Fig. 3), 1,3-Indanedione (8)
and ammonium acetate (Scheme 1 and Table 2).31 All the reactions
proceeded well in 3.0–4.0 h to give products in very good yields
(77–86%). The results also revealed that aryl methyl ketones bear-
ing electron withdrawing groups (entry 5) gave slightly higher
yield compared with aryl methyl ketones bearing electron releas-
ing groups (entries 4 and 6). The reactions are also progressed well
with heterocyclic methyl ketones (entries 9–15) to give 4-azafluor-
enone derivatives 10i–o in very good yields. All the compounds
were purified through silica gel column chromatography and were
fully characterized by IR, 1H NMR, 13C NMR, Electrospray ionization
(ESI) and High resolution mass spectral (HRMS) analysis.32 The
single crystal X-ray diffraction studies of 10h unambiguously
confirmed the structure (Fig. 4).33 A plausible mechanism for the
formation of 4-azafluorenones 10 is depicted in Figure 5. Based
on the above data and literature precedents,30 initially, 1-benzyl-
2-butyl-4-chloroimidazole carboxaldehyde 7 condenses with 1,3-
indanedione to form intermediate 11 which further undergoes
in situ Michael addition with 1-arylethenamine 12, obtained by
reacting aromatic ketone with ammonium acetate, to yield
intermediate 13, which then cyclized and subsequently dehydro-
genated to afford 4-azafluorenone 10.
(10n)
and
4-(1-benzyl-2-butyl-4-chloro-1H-imidazol-5-yl)-
2-(3-tosyl-3H-ind en-1-yl)-5H-indeno[1,2-b]pyridin-5-one (10o)
also exhibited selective higher inhibitory activity against fungal
strains Aspergillus flavus and Candida albicans.
The design strategy adopted here for library generation is based
on most recent molecular hybridization approach.19,20 Molecular
hybridization is a strategy of rational design based on the recogni-
tion of pharmacophoric sub-units in the molecular structure of two
or more known bioactives. The adequate fusion of these sub-units,
lead to the design of new hybrid architecture that maintain pre-se-
lected characteristics of the original template (Fig. 2). Considering
antimicrobial Onychine 1 as a basic bioactive unit of natural
4-azafluorenone, the modifications were introduced on 4-azafluor-
enone nucleus through hybridization with chosen imidazole
pharmacophore (1-benzyl-2-butyl-4-chloroimidazole).
As a starting point for the study, 2-butyl-4-chloroimidazole-
5-carboxaldehyde 6 was prepared from valeronitrile by following
the procedure developed in our laboratory.25,27 N-Benzylation of
6 using benzyl bromide, K2CO3 in DMF gave benzyl derivative 7
in very good yield (92.0%).28 Compound 7 was characterized by
1H NMR and mass spectral analysis.28 With requisite imidazole
derivative 7 in hand, initially, it was reacted with 1,3-indane-
dione, acetophenone and ammonium acetate in various solvents
(methanol, 2-propanol, acetonitrile, THF, water, DMF and glycol)
O
Cl
Cl
N
Natural product Fragment
N
N
CHO
N
CH3
N
O
N
Aromatic or heterocyclic units
R
Fragment from Drug molecule
Figure 2. Illustration of design strategy for library generation.

D. Addla et al. / Bioorg. Med. Chem. Lett. 22 (2012) 7475–7480
7477
O
O
Cl
CHO
Cl
O
N
N
N
NH4OAc
R1
CH3
+
+
N
R
DMF
Reflux
3.0-4.0h
O
9a-o
8
N
10a-o
6,
7,
R=H
R1
R=Bn
Scheme 1. Synthesis of 4-azafluorenone hybrids 10a–o.
H3COC
COCH3
COCH3
COCH3
COCH3
COCH3
COCH3
COCH3
H3CO
OCH3
OCH3
9f
Br
9c
9h
COCH3
OCH3
9d
NO2
9e
9a
COCH3
9b
9g
COCH3
COCH3 COCH3
O
COCH3
N
COCH3
S
S
N
S
O
O
O
S
Br
Br
9l
9j
9k
9i
9n
9m
9o
Figure 3. Aryl/heteroayl methyl ketones 9a–o used in the present study.
Table 2
Synthesis of 2-butyl-4-chloro-1-benzylimidazole derived 4-azaflourenone 10a–o
Entry
Ketones 9
Reaction time (h)
Product 10
Yield (%)a
1
2
3
4
5
6
7
8
9a
9b
9c
9d
9e
9f
9g
9h
9i
9j
9k
9l
9m
9n
9o
3.0
3.5
4.0
4.0
3.0
4.0
3.5
3.5
3.5
3.5
4.0
3.5
3.5
4.0
4.0
10a
10b
10c
10d
10e
10f
10g
10h
10i
10j
10k
10l
10m
10n
10o
82
80
81
79
86
77
84
85
86
84
85
83
81
86
85
9
10
11
12
13
14
15
a
Isolated yield.
Fifteen newly synthesized 1-benzyl-2-butyl-4-chloroimidazole
embodied 4-azafluorenones 10a–o were evaluated for their
in vitro antibacterial activity against two gram positive bacteria
namely Bacillus subtilis (MTCC 121) and Staphylococcus aureus
(MTCC 1430) and three gram negative bacteria namely Escherichia
coli (MTCC 1573), Klebsiella pneumoniae (MTCC 618) and Pseudo-
monas aeruginosa (MTCC 2453) by disc diffusion method,34,35 using
gentamicin as the reference drug. The results were recorded for
Figure 4. ORTEP representation of compound 10h with thermal displacement
ellipsoids drawn at the 30% probability.33
each tested compound (10 lg/disc) as an average diameter of zone
of inhibition (ZoI) in millimeters (zone lacking the bacterial
growth) surrounding the disc. Antibacterial evaluation data
revealed that, in general all the tested compounds 10a–o (10 lg/
disc) possessed good deal of antibacterial activity against selected
gram positive (Staphylococcus aureus) and gram negative bacteria
(Klebsiella pneumoniae and Pseudomonas aeruginosa) as compared
to the standard drug gentamicin (Table 3). On the basis of zone
of inhibition (ZoI) against test bacterium S. aureus, nine compounds
10a, 10c, 10f, 10g, 10h, 10j, 10k, 10l and 10n (10 lg/disc) exhib-
ited good activity with higher zone of inhibition P12.0 mm as
compared to standard gentamicin which showed ZoI of 15.0 mm.
It is noteworthy that, among the nine active compounds one
compound 10k was found to be the most potent member produc-
ing ZoI of 15.0 mm against S. aureus equal to that of the standard
antibiotic gentamicin (Table 3).

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D. Addla et al. / Bioorg. Med. Chem. Lett. 22 (2012) 7475–7480
O
O
Cl
Cl
CHO
O
Cl
N
N
N
N
N
O
N
O
NH2
13
O
11
Ar
NH
O
NH4OAc
-H2O
O
H2N
Ar
12
Ar
Ar
CH3
Cl
Ar
Cl
O
N
N
N
-2H
N
NH
N
10
Ar
Figure 5. Plausible mechanism for the formation of 4-azafluorenone 10.
Table 3
Inhibitory action of 10a-o against the selected bacterial strains (gram positive and gram negative bacteria) and fungal strains determined as zone of inhibition (in mm) by the disc
diffusion methoda
Compounds
Gram positive bacteria1
B. subtilis S. aureus
Gram negative bacteria
Fungal strains
C. albicans
E. coli
P. aeruginosa
K. pneumoniae
A. flavus
10a
10b
10c
10d
10e
10f
10g
10h
10i
10j
10k
10l
10m
10n
10o
Gentamicin
Nystatin
DMSO
8
8
9
9
10
9
10
9
10
9
8
8
9
9
7
14
—
—
12
10
12
10
10
12
12
12
10
12
15
12
11
12
10
15
—
9
9
9
8
8
9
9
8
9
8
8
9
9
8
8
12
—
—
10
8
6
9
10
7
11
11
12
11
10
11
12
12
10
12
15
9
13
11
12
19
—
8
7
7
6
6
6
5
6
5
10
10
10
12
11
10
12
10
10
9
13
11
10
14
13
—
6
13
11
13
14
12
13
7
7
10
9
7
10
11
—
9
7
15
—
—
8
—
—
—
—
A. flavus: Aspergillus flavus, B. subtilis: Bacillus subtilis, S. aureus: Staphylococcus aureus, C. albicans: Candida albicans E. coli: Escherichia coli, P. aeruginosa: Pseudomonas
aeruginosa, K. pneumoniae: Klebsiella pneumoniae.
— indicates no activity.
a
The experiment was carried out in triplicate and the values represent average zone of inhibition.
Similarly, based on the measurement of ZoI at a concentration
of 10 g/disc, five compounds 10h, 10j, 10k, 10l and 10m were
K. pneumoniae with higher ZoI comparable to standard drug
gentamicin.
l
found to be most effective against gram negative bacteria P. aeru-
ginosa showing maximum ZoI P 12 mm compared to the zone of
inhibition of standard drug gentamicin (15 mm). Here also, 10k
was found to be most active compound producing ZoI of
14.0 mm. In case of Klebsiella pneumoniae, all the compounds
except 10e, 10i and 10l, exhibited moderate to good activity with
ZoI in the range of 11–15 mm. Among them, compound 10k
showed maximum zone of inhibition (15 mm) when compared to
standard drug gentamicin (19 mm) and resulted as the most active
compound in the series against K. pneumoniae. However, all the
compounds 10a–o showed lower antibacterial activity against
the bacteria; Bacillus subtilis (a gram positive bacteria) and E. coli
(gram negative bacteria) producing ZoI 6 10 as shown in Table 3.
On the whole among all the compounds evaluated against gram
positive and gram negative bacteria, 10k exhibited significantly
greater antibacterial activity against S. aureus, P. aeruginosa and
1-Benzyl-2-butyl-4-chloroimidazole embodied 4-azafluorenon-
es 10a–o were also evaluated for their in vitro antifungal activity
against two fungal strains namely Aspergillus flavus (MTCC 8188)
and Candida albicans (MTCC 7253) by disc diffusion method. Nysta-
tin was used as the reference antifungal drug for comparison. Re-
sults of the in vitro antifungal activity (Table 3) for the tested
compounds (10 lg/disc) showed that 10d, 10e, 10f, 10g, 10h
(ZoI 6 6), 10b, 10c, 10j, 10m (ZoI = 7), 10a (ZoI = 8), and 10k, 10l,
10n and 10o (ZoI P 9) produced moderate to higher antifungal
activity against Aspergillus flavus compared to standard drug as
described in Table 3. However, all the compounds tested against
another fungal strain, Candida albicans showed greater inhibitory
activity than the standard drug Nystatin (ZoI = 8). Among them,
three compounds 10k, 10n, 10o (ZoI P13) were found to be most
potent members showing higher zone of inhibition against Candida
albicans even greater than standard drug Nystatin (ZoI = 8 mm,

D. Addla et al. / Bioorg. Med. Chem. Lett. 22 (2012) 7475–7480
7479
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Table 3). Together with antibacterial and antifungal evaluations,
10k was found to be the most potent antimicrobial agent with
higher inhibitory activity against bacterial and fungal strains: S.
aureus, P. aeruginosa, K. pneumoniae, A. flavus and C. albicans. The
compounds 10n and 10o also showed higher selective antifungal
activity against fungal strains A. flavus and C. albicans.
In summary, a series of novel 1-benzyl-2-butyl-4-chloroimidaz-
ole embodied 4-azafluorenone hybrids, designed via molecular
hybridization approach, were prepared in very good yields using
one pot condensation of 1-benzyl-2-butyl-4-chloroimidazole-
5-carboxaldehyde, 1,3-indanedione, aryl/hetero aryl methyl ketones
and ammonium acetate. Antimicrobial evaluation data revealed
that, in general all the tested compounds 10a–o (10 lg/disc) pos-
sessed good deal of antibacterial activity against selected gram po-
sitive (Staphylococcus aureus), gram negative bacteria (Klebsiella
pneumoniae and Pseudomonas aeruginosa) and antifungal activity
against fungal strains (A. flavus and C. albicans) as compared to
the standard drugs. On the whole among all the compounds tested,
compound 10k exhibited significantly greater antibacterial activity
among the tested series against S. aureus, P. aeruginosa and K. pneu-
moniae with higher zone of inhibition comparable to standard drug
Gentamicin and anti fungal activity against A. flavus and C. albicans
with an inhibitory activity even greater than standard drug Nysta-
tin. Compounds 10n and 10o also exhibited significantly higher
antifungal activity against A. flavus and C. albicans with greater
zone of inhibition than the reference drug. Since Staphylococcus
aureus, Pseudomonas aeruginosa and Candida albicans are well
known opportunistic pathogens and known to cause severe noso-
comial and/or secondary infections, the compounds can be tested
in combination with the known antibiotics in vitro for effective
treatment to avoid development of resistance mechanisms by
these microbes.
26. Patpi, S. R.; Pulipati, L.; Yogeeswari, P.; Sriram, D.; Jain, N.; Sridhar, B.; Murthy,
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28. 1-Benzyl-2-butyl-4-chloroimidazole
carboxaldehyde
(7).
2-Butyl-4-
chloroimidazole carboxaldehyde 627 (5.0 g, 26.9 mmol) in DMF was added
potassium carbonate (4.08 g, 29.56 mmol) and benzyl bromide (3.15 mL,
26.9 mmol) with stirring at 0 °C for 1 h and then at RT for 3 h. The reaction
mixture was poured in ice cold water, extracted with ethyl acetate (3 Â 25 mL),
combined organic extract was dried over anhydrous sodium sulphate and
evaporated under vacuum. The crude residue thus obtained was
chromatographed over silica gel (hexane/ethyl acetate, 9:1) to give 1-benzyl-
2-butyl-4-chloroimidazole carboxaldehyde
7 (6.53 g, 92%) as pale yellow
syrup. 1H NMR (300 MHz, CDCl3) d 9.74(s, 1H), 7.29 (m, 3H), 7.01 (d, J = 8.3 Hz,
2H), 5.53 (s, 2H), 2.59 (t, J = 7.5Hz, 2H), 1.60-1.70 (m, 2H), 1.25-1.37 (m, 2H),
0.88(t, J = 7.5Hz, 3H). MS (ESI) m/z 277 [M+H]+.
29. Tu, S.; Jiang, B.; Jiang, H.; Zhang, Y.; Jia, R.; Zhang, J.; Shao, Q.; Li, C.; Zhou, D.;
Cao, L. Tetrahedron 2007, 63, 5406.
30. Tu, S.; Jiang, B.; Jia, R.; Zhang, J.; Zhang, Y. Tetrahedron Lett. 2007, 48, 1369.
31. General procedure for the synthesis of 4-(1-benzyl-2-butyl-4-chloro-1H-imidazol-
5-yl)-2-substituted-5H-indeno[1,2-b]pyridin-5-one (10a–o). 1-Benzyl-2-butyl-4-
chloroimidazole carboxaldehyde 7 (0. 250 g, 0.90 mmol), acetophenones 9a–o
Acknowledgments
(0.906 mmol), 1,3-indanedione
8 (0.132 g, 0.906 mmol) and ammonium
acetate (0.174 g, 2.26 mmol) in DMF (5 mL) was heated at 120 °C for 3.0–
4.0 h. After completion (by tlc), the reaction mixture was cooled to room
temperature, poured in ice cold water, filtered and washed with water
(2 Â 5 mL) to give crude solid residue. Column chromatography over silica gel
(hexane/ethyl acetate, 8:2) gave 10a–o as pale yellow solids.
Authors are thankful to Director, IICT and Dr. V. J. Rao, Head of
CPC Division, IICT, Hyderabad for encouragement, support and
financial assistance from Network (NWP) and MLP projects. D.A.
(SRF) is thankful to CSIR for fellowship.
32. 4-(1-Benzyl-2-butyl-4-chloro-1H-imidazol-5-yl)-2-phenyl-5H-indeno[1,2-b]
pyridine -5-one (10a). Mp:110–113 °C; 1H NMR (300 MHz, CDCl3) d 7.95–8.01
(m, 3H), 7.70 (d, J = 7.55 Hz, 1H), 7.60 (t, J = 7.55 Hz, 1H), 7.42–7.48 (m, 6H),
7.14–7.22 (m, 2H), 6.80 (d, J = 7.55 Hz, 2H), 5.11 (d, J = 16.6 Hz, 1H), 4.93 (d,
J = 16.6 Hz, 1H), 2.58–2.69 (m, 2H), 1.66–1.85 (m, 2H), 1.33–1.46 (m, 2H), 0.93
(t, J = 6.79 Hz, 3H). 13C NMR (75 MHz, CDCl3) d 190.1, 166.2, 161.5, 149.7, 143.3,
137.9, 136.4, 135.5, 134.9, 134.5, 131.1, 130.3, 128.9, 128.8, 127.8, 127.5, 126.0,
123.9, 121.8, 121.2, 48.9, 29.7, 27.2, 22.5, 13.9. IR (KBr) 2924, 2860, 1710, 1556,
1454, 1253, 1169, 1078, 748, 692 cmÀ1. MS (ESI) m/z 504 [M+H]+; HR-MS (ESI)
Supplementary data
Supplementary data associated with this article can be found, in
online version, at http://dx.doi.org/10.1016/j.bmcl.2012.10.042.
Copies of 1H, 13C NMR and mass (ESI-MS and HR-MS) spectra of
all the new compounds. CCDC 885580 (for 10h) contain the crys-
tallographic data and can be obtained free of charge from the Cam-
bridge Crystallographic Data centre via www.ccdc.cam.ac.uk/
data_request/cif.
Calcd for
butyl-4-chloro-1H-imidazol-5-yl)-2-p-tolyl-5H-indeno[1,2-b]pyridin-5-one (10b)
Mp:122–125 °C; 1H NMR (300 MHz, CDCl3)
7.76–7.91 (m, 3H), 7.62 (t,
C
32H27N3OCl [M+H]+: 504.1842, found: 504.1857. 4-(1-Benzyl-2-
d
J = 7.55 Hz, 1H), 7.49–7.56 (m, 1H), 7.35–7.42 (m, 2H), 7.11–7.21 (m, 5H), 6.78
(d, J = 7.55 Hz, 2H), 5.17 (d, J = 16.6 Hz, 1H), 4.91 (d, J = 16.6 Hz, 1H), 2.50–2.65
(m, 2H), 2.38 (s, 3H), 1.64–1.79 (m, 2H), 1.32–1.45 (m, 2H), 0.90 (t, J = 7.55 Hz,
3H). 13C NMR (75 MHz, CDCl3) d 190.1, 166.1, 161.4, 149.5, 143.1, 140.3, 136.2,
135.3, 134.9, 134.7, 134.2, 130.9, 129.4, 128.8, 127.7, 125.9, 123.6, 122.9, 121.1,
121.0, 48.7, 29.6, 27.0, 22.3, 21.4, 13.8. IR (KBr) 2922, 2852, 1704, 1561, 1452,
1340, 1248, 1174, 917, 826, 750, 730 cmÀ1. MS (ESI) m/z 518 [M+H]+; HR-MS
(ESI) Calcd for C33H29N3OCl [M+H]+: 518.1999, found: 518.2011. 4-(1-Benzyl-2-
butyl-4-chloro-1H-imidazol-5-yl)-2-(4-bromophenyl)-5H-indeno[1,2-b]pyridin-
5-one (10c) Mp: 133–135 °C; 1H NMR (300 MHz, CDCl3) d 7.92 (d, J = 7.55 Hz,
1H), 7.84 (d, J = 8.30 Hz, 2H), 7.68 (d, J = 7.55 Hz, 1H), 7.56–7.61 (m, 3H), 7.41–
7.47 (m, 2H), 7.15–7.24 (m, 3H), 6.79 (d, J = 6.80 Hz, 2H), 5.11 (d, J = 17.3 Hz,
1H), 4.90 (d, J = 17.3 Hz, 1H), 2.54–2.66 (m, 2H), 1.60–1.80 (m, 2H), 1.34–1.44
(m, 2H), 0.92 (t, J = 7.55 Hz, 3H). 13C NMR (75 MHz, CDCl3) d 189.9, 166.2,
160.1, 149.9, 143.0, 136.6, 136.3, 135.4, 134.9, 134.5, 131.9, 131.5, 131.2, 130.7,
128.9, 128.9, 127.9, 125.9, 125.8, 125.1, 123.9, 121.4, 121.2, 48.8, 29.7, 27.1,
22.4, 13.9. IR (KBr) 2922, 2851, 1711, 1562, 1493, 1455, 1381, 1261, 1071,
1007, 916, 832, 749 cmÀ1. MS (ESI) m/z 582 [M+H]+; HR-MS (ESI) Calcd for
C32H26N3OClBr [M+H]+: 582.0947, found: 582.0976. 4-(1-Benzyl-2-butyl-4-
chloro-1H-imidazol-5-yl)-2-(4-methoxyphenyl)-5H-indeno [1,2-b]pyridin-5-one
(10d) Mp: 139–141 °C; 1H NMR (300 MHz, CDCl3) d 7.88–7.95 (m, 3H), 7.64
(d, J = 7.36 Hz, 1H), 7.54 (t, J = 7.36 Hz, 1H), 7.36–7.40 (m, 2H), 7.10–7.20 (m,
3H), 6.90 (d, J = 8.68Hz, 2H), 6.80 (d, J = 6.79Hz, 2H), 5.09 (d, J = 16.9 Hz, 1H),
4.93 (d, J = 16.9 Hz, 1H), 3.83 (s, 3H), 2.51–2.67 (m, 2H), 1.65–1.83 (m, 2H),
References and notes
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7480
D. Addla et al. / Bioorg. Med. Chem. Lett. 22 (2012) 7475–7480
1.34–1.46 (m, 2H), 0.91 (t, J = 7.36 Hz, 3H). 13C NMR (75 MHz, CDCl3) d 190.3,
166.2, 161.8, 161.2, 149.6, 143.1, 136.3, 135.4, 134.8, 134.3, 131.0, 130.3, 128.9,
(ESI) m/z 494 [M+H]+; HR-MS (ESI) Calcd for C30H25N3O2Cl [M+H]+: 494.1635,
found:494.1654. 4-(1-Benzyl-2-butyl-4-chloro-1H-imidazol-5-yl)-2-(6-
bromopyridin-2-yl)-5H-indeno[1,2-b]pyridin-5-one (10l). Mp: 161–163 °C; 1H
NMR (300 MHz, CDCl3) 8.52 (d, J = 7.74 Hz, 1H), 8.23 (s, 1H), 7.87 (d,
128.8, 127.8, 125.9, 123.7, 122.1, 121.0, 120.7, 114.2, 55.3, 48.8, 29.7, 27.1,
22.4, 13.8. IR (KBr) 2925, 2854, 1703, 1562, 1454, 1256, 1170, 1028, 917, 831,
752 cmÀ1. MS (ESI) m/z 534 [M+H]+; HR-MS (ESI) Calcd for C33H29N3O2Cl
[M+H]+: 534.1948, found:534.1971. 4-(1-Benzyl-2-butyl-4-chloro-1H-imidazol-
5-yl)-2-(4-nitrophenyl)-5H-indeno[1,2-b]pyridin-5-one (10e) Mp: 163–166 °C;
1H NMR (300 MHz, CDCl3) d 8.23–8.32 (m, 2H), 8.12 (d, J = 9.06 Hz, 2H), 7.95–
8.02 (m, 2H), 7.70–7.82 (m, 1H), 7.65 (t, J = 7.55Hz, 1H), 7.46–7.51(m, 2H),
7.19–7.34(m, 2H), 6.84 (d, J = 6.79Hz, 2H), 5.17 (d, J = 16.6 Hz, 1H), 4.96 (d,
J = 16.6 Hz, 1H), 2.60–2.72 (m, 2H), 1.63–1.85 (m, 2H), 1.34–1.48 (m, 2H), 0.84–
0.95 (m, 3H). 13C NMR (75 MHz, CDCl3) d 189.7, 166.2, 158.4, 155.0, 150.2,
148.6, 143.3, 142.6, 136.1, 135.2, 134.7, 131.5, 129.6, 129.4, 128.9, 128.0, 127.9,
127.5, 125.8, 124.0, 123.8, 122.5, 121.2, 48.8, 29.6, 27.0, 22.3, 13.7. IR (KBr)
2922, 2851, 1715, 1593, 1516, 1452, 1344, 1275, 1253, 1083, 916, 862,
750 cmÀ1. MS (ESI) m/z 549 [M+H]+; HR-MS (ESI) Calcd for C32H20N4O3Cl
[M+H]+: 549.1693, found:549.1687. 4-(1-Benzyl-2-butyl-4-chloro-1H-imidazol-
5-yl)-2-(3,4,5-trimethoxyphenyl)-5H-indeno[1,2-b]pyridin-5-one (10f) Mp: 143–
d
J = 7.36 Hz, 1H), 7.67 (t, J = 7.36 Hz, 2H), 7.57 (t, J = 7.55 Hz, 1H), 7.49 (d, J =
7.93 Hz, 1H), 7.43 (t, J = 7.36 Hz, 1H), 7.08–7.21 (m, 3H), 6.83 (d, J = 7.17 Hz,
2H), 5.09 (d, J = 16.6 Hz, 1H), 4.97 (d, J = 16.6 Hz, 1H), 2.54–2.65 (m, 2H), 1.64–
1.81 (m, 2H), 1.33–1.45 (m, 2H), 0.91 (t, J = 7.17 Hz, 3H). 13C NMR (75 MHz,
CDCl3) d 193.5, 165.7, 160.0, 158.0, 155.7, 149.8, 142.9, 141.9, 138.9, 136.0,
135.4, 134.9, 131.2, 129.0, 127.9, 126.0, 124.0, 122.8, 121.0, 120.7, 48.3, 29.6,
27.2, 22.5, 13.9. IR (KBr) 2954, 2854, 1713, 1605, 1562, 1495, 1426, 1378, 1272,
1181, 1126, 917, 799, 734 cmÀ1. MS (ESI) m/z 583 [M+H]+; HR-MS (ESI) Calcd
for C31H25N4OClBr [M+H]+: 583.0900, found:583.0891. 4-(1-Benzyl-2-butyl-4-
chloro-1H-imidazol-5-yl)-2-(dibenzo[b,d]furan-2-yl)-5H-indeno[1,2-b]pyridin-5-
one (10m) Mp: 197–198 °C; 1H NMR (300 MHz, CDCl3) d 8.59 (d, J = 1.51Hz,
1H), 7.96 (m, 3H), 7.72 (d, J = 7.55Hz, 1H), 7.46–7.66 (m, 6H), 7.35–7.42 (m,
1H), 7.18–7.25 (m, 3H), 6.87 (d, J = 7.55Hz, 2H), 5.15 (d, J = 16.6 Hz, 1H), 4.99 (d,
J = 16.6 Hz, 1H), 2.63–2.70 (m, 2H), 1.68–1.87 (m, 2H), 1.35–1.47 (m, 2H), 0.85–
0.95 (m, 3H). 13C NMR (75 MHz, CDCl3) d 190.4, 166.3, 161.4, 157.5, 156.7,
149.9, 142.9, 136.1, 135.0, 134.3, 132.7, 131.2, 128.9, 127.8, 127.6, 126.8, 125.9,
123.8, 123.0, 121.5, 121.1, 120.9, 119.9, 111.9, 111.8, 48.8, 29.6, 27.1, 22.4,
13.7. IR (KBr) 2924, 2853, 1710, 1596, 1560, 1451, 1420, 1256, 1198, 1120, 917,
749, 731 cmÀ1. MS (ESI) m/z 594 [M+H]+; HR-MS (ESI) Calcd for C38H29N3O2Cl
[M+H]+: 594.1948, found: 594.1969. 4-(1-benzyl-2-butyl-4-chloro-1H-imidazol-
5-yl)-2-(dibenzo[b,d]thiophen-2-yl)-5H-indeno[1,2-b]pyridin-5-one (10n) Mp:
181–183 °C; 1H NMR (300 MHz, CDCl3) d 8.77 (s, 1H), 8.23 (t, J = 3.77Hz,1H),
8.00–8.04 (m, 2H), 7.81–7.88 (m, 2H), 7.69 (d, J = 7.55Hz, 1H), 7.57–7.63 (m,
2H), 7.42–7.49(m, 4H), 7.14–7.23(m, 2H), 6.83 (d, J = 6.79Hz, 2H), 5.13 (d,
J = 16.6 Hz, 1H), 4.95 (d, J = 16.6 Hz, 1H), 2.55–2.70 (m, 2H), 1.66–1.86 (m, 2H),
1.36–1.46 (m, 2H), 0.94 (t, J = 6.79Hz, 3H). 13C NMR (75 MHz, CDCl3) d 190.2,
166.4, 161.4, 149.8, 143.1, 141.8, 139.8, 135.5, 135.4, 134.9, 134.5, 134.3, 131.8,
128.9, 127.9, 127.1, 126.0, 125.7, 124.6, 123.9, 121.6, 121.3, 48.9, 29.7, 27.2,
22.5, 13.9. IR (KBr) 2922, 2851, 1705, 1604, 1557, 1451, 1349, 1247, 1080,
1022, 916, 878, 780, 726 cmÀ1. MS (ESI) m/z 610 [M+H]+; HR-MS (ESI) Calcd for
144 °C; 1H NMR (300 MHz, CDCl3)
d 7.96 (d, J = 7.36 Hz, 2H), 7.71 (d,
J = 7.36 Hz, 1H), 7.62 (q, J = 7.36 Hz, J = 7.36 Hz, 2H), 7.43–7.53 (m, 1H), 7.38
(s, 1H), 7.23 (s, 2H), 6.81 (d, J = 6.79 Hz, 3H), 5.11 (d, J = 16.9 Hz, 1H), 4.95 (d,
J = 16.9 Hz, 1H), 3.95 (s, 6H), 3.89 (s, 3H), 2.58–2.66 (m, 2H), 1.67–1.80 (m, 2H),
1.34–1.47 (m, 2H), 0.88–0.96 (m, 3H). 13C NMR (75 MHz, CDCl3) d 189.9, 166.1,
161.2, 153.6, 149.6, 143.1, 136.4, 135.5, 134.7, 134.5, 133.1, 132.1, 131.1, 128.9,
128.8, 127.9, 124.0, 123.9, 121.4, 121.2, 105.1, 60.7, 56.2, 48.9, 29.7, 27.2, 22.4,
13.9. IR (KBr) 2924, 2854, 1715, 1542, 1446, 1377, 1256, 1174, 1088, 1020, 812,
750, 664 cmÀ1. MS (ESI) m/z 594 [M+H]+; HR-MS (ESI) Calcd for C35H33N3O4Cl
[M+H]+: 594.2159, found: 594.2151. 4-(1-Benzyl-2-butyl-4-chloro-1H-imidazol-
5-yl)-2-(naphthalen-1-yl)-5H-indeno[1,2-b]pyridin-5-one (10g) Mp: 138–
139 °C; 1H NMR (300 MHz, CDCl3)
d 8.05 (d, J = 7.55 Hz, 1H), 7.87 (t,
J = 7.55 Hz, 3H), 7.70 (d, J = 6.79 Hz, 1H), 7.61 (d, J = 6.79 Hz, 1H), 7.35–7.57
(m, 6H), 7.12–7.19 (m, 3H), 6.77 (d, J = 7.55 Hz, 2H), 5.12 (d, J = 16.6 Hz, 1H),
4.97 (d, J = 16.6 Hz, 1H), 2.56–2.70 (m, 2H), 1.65–1.85 (m, 2H), 1.34–1.46 (m,
2H), 0.92 (t, J = 6.79 Hz, 3H). 13C NMR (75 MHz, CDCl3) d 190.4, 166.0, 163.7,
149.8, 143.2, 137.0, 136.2, 135.0, 134.0, 133.9, 131.1, 130.8, 129.9, 128.8, 127.9,
127.8, 126.8, 126.7, 126.0, 125.3, 125.1, 123.8, 123.1, 121.8, 121.3, 48.8, 29.7,
27.1, 22.3, 13.8. IR (KBr) 2927, 2859, 1712, 1563, 1454, 1352, 1256, 1152, 1048,
967, 916, 823, 755, 717 cmÀ1. MS (ESI) m/z 554 [M+H]+; HR-MS (ESI) Calcd
for C36H29N3OCl [M+H]+: 554.1999 found: 554.1977. 4-(1-Benzyl-2-butyl-4-
chloro-1H-imidazol-5-yl)-2-(naphthalen-2-yl)-5H-indeno[1,2-b]pyridin-5-one (10h);
Mp: 130–131 °C; 1H NMR (300 MHz, CDCl3) d 8.44 (s, 1H), 8.10 (d, J = 8.30 Hz,
1H), 8.02 (d, J = 7.17 Hz, 1H), 7.81–7.89 (m, 3H), 7.70 (d, J = 7.17 Hz, 1H), 7.61
(s, 2H), 7.42–7.51 (m, 3H), 7.11–7.25 (m, 3H), 6.83 (d, J = 6.42 Hz, 2H), 5.13 (d,
J = 16.6 Hz, 1H), 4.95 (d, J = 16.6 Hz, 1H), 2.55–2.69 (m, 2H), 1.65–1.83 (m, 2H),
1.33–1.48 (m, 2H), 0.94 (t, J = 7.17 Hz, 3H). 13C NMR (75 MHz, CDCl3) d 190.2,
161.4, 149.8, 143.2, 136.3, 135.5, 135.1, 134.9, 134.5, 134.3, 133.3, 131.1, 129.0,
128.6, 127.9, 127.7, 127.5, 127.2, 126.5, 126.0, 124.5, 123.9, 122.0, 121.3, 48.9,
29.7, 27.2, 22.5, 13.9. IR (KBr) 2927, 2859, 1712, 1563, 1454, 1352, 1256, 1154,
1048, 967, 916, 823, 755, 717 cmÀ1. MS (ESI) m/z 554 [M+H]+; HR-MS (ESI)
Calcd for C36H29N3OCl [M+H]+: 554.1999, found 554.1998. 4-(1-Benzyl-2-butyl-
4-chloro-1H-imidazol-5-yl)-2-(thiophen-2-yl)-5H-indeno[1,2-b]pyridin-5-one
(10i) Mp: 153–155 °C; 1H NMR (300 MHz, CDCl3) d 7.94 (d, J = 7.36 Hz, 1H),
7.68 (d, J = 7.17 Hz, 1H), 7.57–7.61 (m, 2H), 7.39–7.52 (m, 3H), 7.35 (s, 1H),
7.14–7.22 (m, 2H), 7.11 (t, J = 4.91 Hz, 1H), 6.80(d, J = 6.79 Hz, 2H), 5.12 (d,
J = 16.8 Hz, 1H), 4.93 (d, J = 16.8 Hz, 1H), 2.54–2.68 (m, 2H), 1.66–1.84 (m, 2H),
1.35–1.44 (m, 2H), 0.93 (t, J = 7.17 Hz, 3H). 13C NMR (75 MHz, CDCl3) d 191.5,
165.8, 16.08, 158.4, 155.0, 148.8, 142.0, 141.0, 136.5, 135.5, 134.5, 130.1, 129.0,
127.9, 126.9, 126.4, 126.0, 123.8, 123.6, 121.4, 119.7, 48.9, 29.8, 27.2, 22.5,
13.9. IR (KBr) 2924, 2852, 1716, 1561, 1432, 1381, 1256, 1159, 916, 786, 747,
728 cmÀ1. MS (ESI) m/z 510 [M+H]+; HR-MS (ESI) Calcd for C30H25N3OSCl
[M+H]+: 510.1406, found: 510.1399. 4-(1-Benzyl-2-butyl-4-chloro-1H-imidazol-
5-yl)-2-(5-bromothiophen-2-yl)-5H-indeno [1,2-b]pyridin-5-one (10j) Mp: 162–
C
38H29N3OSCl [M+H]+: 610.1719, found:610.1692. 4-(1-Benzyl-2-butyl-4-
chloro-1H-imidazol-5-yl)-2-(3-tosyl-3H-inden-1-yl)-5H-indeno[1,2-b]pyridin-5-
one (10o) Mp: 148–150 °C; 1H NMR (300 MHz, CDCl3) d 8.31 (d, J = 6.79Hz, 1H),
8.05 (s, 1H), 7.94–8.00 (m, 2H), 7.82 (d, J = 8.30Hz, 2H), 7.70 (d, J = 7.17Hz, 1H),
7.57–7.65 (m, 1H), 7.43–7.53(m, 1H), 7.30–7.39 (m, 2H), 7.18–7.25 (m, 6H),
6.83 (d, J = 6.42Hz, 2H), 5.13 (d, J = 16.9 Hz, 1H), 4.94 (d, J = 16.6 Hz, 1H), 2.55–
2.67 (m, 2H), 2.36 (s, 3H), 1.66–1.83 (m, 2H), 1.33–1.46 (m, 2H), 0.83–0.91 (m,
3H). 13C NMR (75 MHz, CDCl3) d 188.6, 166.1, 157.4, 149.8, 145.1, 143.0, 135.9,
135.4, 135.1, 134.8, 132.1, 131.1, 130.1, 130.0, 128.9, 128.7, 128.0, 127.6, 127.0,
126.0, 125.9, 125.2, 124.1, 123.8, 122.4, 121.9, 121.1, 113.5, 48.8, 29.7, 27.1,
22.7, 21.6, 13.8. IR (KBr) 2952, 2855, 1712, 1568, 1450, 1382, 1348, 1256, 1103,
909, 753, 734 cmÀ1. MS (EI) m/z 661 [M-35]+; Calcd for C41H34N4O3SCl.
33. Sheldrick G.M. A short history of SHELX, Acta Crystallogr. 2008 A64, 112. Bruker
(2001) SAINT (Version 6.28a)
&
SMART (Version 5.625). Bruker AXS Inc.,
36H28ClN3O, M = 554.06,
triclinic, space group P1, a = 8.5222(8) Å, b = 12.0029 (11) Å, c = 14.2893(13) Å,
= 80.268(2)°, b = 87.545(2)°,
= 84.525(2)°, V = 1433.5(2) Å3, Z = 2,
Dcalcd = 1.284 mg mÀ3 = 0.168 mmÀ1
T = 294(2) K, F(000) = 580,
Madison, Wisconsin, USA. Crystal data for 10h:
C
ꢀ
a
c
,
l
,
k = 0.71073 Å. Data collection yielded 13815 reflections resulting in 5014
unique, averaged reflections, 3866 with I>2(I). Full-matrix least-squares
refinement led to a final R = 0.0421, wR = 0.1130 and GOF = 1.033.
34. Cruikshank, R.; Duguid, J. P.; Marion, B. P.; Swain, R. H. A. Medicial Microbiology,
12th ed.; Churchill Livingstone: London, 1975, Vol. II, 196–202. Collins A. H.,
Eds., Microbiology Methods, 2nd ed. Butterworth: London, 1976.
35. Evaluation of in vitro antimicrobial activity: For evaluation of antibacterial
activity, a standard inoculum of 0.5Mac Farland was introduced on to the
surface of nutrient agar plates and evenly distributed with the aid of a sterile L-
Shaped glass spreader. Discs of 5mm diameter were prepared from Whatmann
No1 filter paper and sterilized by dry heat in a hot air oven at 160 °C for 2 h.
These sterile discs with the test compounds in DMSO at a concentration of
164 °C; 1H NMR (300 MHz, CDCl3)
d 7.89 (d, J = 7.36 Hz, 1H), 7.68 (d,
J = 7.36 Hz, 1H), 7.60 (t, J = 7.36 Hz, 1H), 7.37–7.47 (m, 2H), 7.15–7.28 (m,
3H), 7.06 (d, J = 3.77 Hz, 1H), 6.93(dd, J = 3.96 Hz, J = 3.71 Hz, 1H), 6.79 (d,
J = 7.55 Hz, 2H), 5.09 (d, J = 16.05 Hz, 1H), 4.89 (d, J = 16.05 Hz, 1H), 2.58–2.65
(m, 2H), 1.62–1.82 (m, 2H), 1.37–1.47 (m, 2H), 0.93 (t, J = 7.17 Hz, 3H). 13C NMR
(75 MHz, CDCl3) d 191.2, 162.8, 158.4, 153.0, 149.9, 143.8, 142.6, 134.8, 134.7,
130.7, 129.0, 126.6, 126.0, 124.7, 123.9, 121.4, 119.0, 115.6, 49.0, 29.8, 27.2,
22.5, 14.0. IR (KBr) 2922, 2851, 1715, 1566, 1435, 1273, 1082, 915, 807, 749,
729 cmÀ1. MS (ESI) m/z 588 [M+H]+; HR-MS (ESI) Calcd for C30H24N3OSClBr
[M+H]+:588.0511, found:588.0502. 4-(1-Benzyl-2-butyl-4-chloro-1H-imidazol-
5-yl)-2-(furan-2-yl)-5H-indeno[1,2-b]pyridin-5-one (10k); Mp: 137–138 °C; 1H
NMR (300 MHz, CDCl3) d 7.92 (d, J = 7.55 Hz, 1H), 7.69 (d, J = 7.55 Hz, 1H),
7.56–7.62 (m, 2H), 7.42–7.49 (m, 2H), 7.28 (d, J = 3.77 Hz, 1H), 7.13–7.21 (m,
3H), 6.79 (d, J = 6.75 Hz, 2H), 6.57(dd, J = 1.51 Hz, J = 1.51 Hz, 1H), 5.07 (d,
J = 16.6 Hz, 1H), 4.93 (d, J = 16.6 Hz, 1H), 2.53–2.69 (m, 2H), 1.66–1.83 (m, 2H),
1.33–1.46 (m, 2H), 0.92 (t, J = 7.55 Hz, 3H). 13C NMR (75 MHz, CDCl3) d 189.8,
166.4, 153.0, 152.8, 149.8, 144.7, 142.8, 136.2, 135.5, 134.8, 134.6, 131.2, 128.9,
127.8, 126.0, 123.8, 119.4, 112.7, 112.4, 48.9, 29.7, 27.2, 22.4, 13.9. IR (KBr)
2954, 2869, 1715, 1560, 1483, 1277, 1256, 1054, 912, 882, 748, 728 cmÀ1. MS
10 lg/disc, were gently placed onto the nutrient agar plates. The plates were
then incubated for 24 h at 37 °C. Gentamicin was used as a reference standard
for antibacterial evaluation. The zones of inhibition were measured in triplicate
in each case and compared with that of control and standard drug. Table 3
summarizes the results of the in vitro antibacterial activities of the compounds
10a–10o expressed as Zone of inhibition in mm. Similarly, antifungal activity
was determined using standard procedure in which a loopful of each of the
fungal strain was made as a suspension in saline and transferred to Yeast
extract potato dextrose agar plates. Nystatin was used as a reference standard
for antifungal evaluation. The inoculum was evenly distributed with the aid of
a
sterile glass spreader. The sterile discs (5 mm diameter) with the test
compounds in DMSO at a concentration of 10 g/disc, were gently placed onto
l
the Yeast extract potato dextrose agar plates. The plates were then incubated
for 2–3 days at room temperature. The zones of inhibition were measured in
each case and compared with that of control and standard drug. Table 3
summarizes the results of the in vitro antifungal activities of the compounds
10a–10o expressed as Zone of inhibition in mm.