Exploration of antimicrobial and antioxidant potential of newly synthesized 2,3-disubstituted quinazoline-4(3H)-ones

Article abstract of DOI:10.1016/j.bmcl.2011.05.031

A series of 2-(chloromethyl)-3-(4-methyl-6-oxo-5-[(E)-phenyldiazenyl]-2- thioxo-5,6-dihydropyrimidine-1(2H)-yl)quinazoline-4(3H)-ones 9a-j was synthesized by treating 2-(chloroacetyl)amino benzoic acid with 3-amino-6-methyl-5-[(E)-phenyldiazenyl]-2-thioxo

Full text of DOI:10.1016/j.bmcl.2011.05.031

Bioorganic & Medicinal Chemistry Letters 21 (2011) 4353–4357
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Exploration of antimicrobial and antioxidant potential of newly synthesized
2,3-disubstituted quinazoline-4(3H)-ones
⇑
Ashok Kumar , Pratibha Sharma, Prerna Kumari, Bhagwan Lal Kalal
School of Chemical Sciences, Devi Ahilya University, Takshashila Campus, Khandwa Road, Indore 452001, M.P., 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 2-(chloromethyl)-3-(4-methyl-6-oxo-5-[(E)-phenyldiazenyl]-2-thioxo-5,6-dihydropyrimi-
Received 22 February 2011
Revised 22 April 2011
Accepted 10 May 2011
Available online 15 May 2011
dine-1(2H)-yl)quinazoline-4(3H)-ones 9a–j was synthesized by treating 2-(chloroacetyl)amino benzoic
acid with 3-amino-6-methyl-5-[(E)-phenyldiazenyl]-2-thioxo-2,5-dihydropyrimidine-4(3H)-one 8a–j
and was screened for in vitro antibacterial activities against a representative panel of Gram-positive
and Gram-negative bacteria. The compounds were synthesized in excellent yields and the structures
were corroborated on the basis of IR, 1H NMR, Mass and elemental analysis data. All the synthesized com-
pounds elicited the potent inhibitory action against all the tested bacterial stains. Furthermore, in order
to explore the antioxidant potential of newly synthesized compounds, the free radical scavenging activity
measurement were performed by the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay method. It is revealed
from the antioxidant screening results that the compounds 9c and f manifested profound antioxidant
potential.
Keywords:
Quinazoline-4(3H)-ones
Antibacterial activity
Antioxidant activity
DPPH
Ó 2011 Elsevier Ltd. All rights reserved.
The quinazolin-4(3H)-one structural motifs have attracted a
great deal of interest due to their ready accessibility, diverse chem-
ical reactivity and wide gamut of biological activities like anti-
fungal,1 antitumour,2 hypotensive,3 anticancer,4,5 antiHIV,6
antiinflammatory,7 antibacterial,8 antifolate,9 and antitumor10 etc.
Quinazoline derivatives acts as powerful inhibitors of epidermal
growth factor (EGF) receptors of tyrosine kinase,11 and some of them
show remarkable activity as anticancer,12 antiviral,13 and antituber-
cular agents.14 Quinazolinones are excellent reservoir of bioactive
substances. Several bio-active natural products such as febrifugine
and isofebrifugine contain quinazolinone moieties with potential
antimalarial activity.
Free radicals and oxygen derivatives are constantly generated
in vitro both by accident of chemistry and specific metabolic pur-
poses.15 The generation of free radicals during the metabolic pro-
cess is now observed to be responsible for wide range of human
conditions such as aging, cancer, atherosclerosis, arthritis, viral
infection stroke, myocardial infraction, pulmonary condition,
inflammatory bowel disease, neurogenerative disease and others
may be produced by reactive oxygen species, for example, hydro-
gen peroxide scavenging (H2O2); hypochlorous acid scavenging
(HOCl); hydroxyl radical scavenging (HO radical); peroxyl radical
scavenging (ROO radical). The action of free radicals is counter-
acted by free radicals endogenous or exogenous or synthetic route.
Reactive oxygen species (ROS) such as superoxide anions, hydro-
gen peroxide, hydroxyl, and nitric oxide radicals, play an important
role in oxidative stress related to the pathogenesis of various
important diseases. Antioxidants act as a major defense against
radical mediated toxicity by protecting the damages caused by free
radicals. Antioxidative agents are effective in the prevention and
treatment of complex diseases, like atherosclerosis, stroke, diabe-
tes, Alzheimer’s disease and cancer.
Nowadays, antioxidants that exhibit DPPH radical scavenging
activity are increasingly receiving attention.16 They have been re-
ported to have interesting anticancer, anti-aging, and antiinflamma-
tory activities. It is revealed from the literature survey that a very
littleattention has beenput inviewto exploretheantioxidantactivity
of substituted quinazoline derivatives. In the present study, efforts
have been laid down to evaluate the inherent antioxidant property
of the synthesized compounds along with the exploration of their
antimicrobial potential. Accordingly, syntheses of novel 2-(chloro-
methyl)-3-(4-methyl-6-oxo-5-[(E)-phenyldiazenyl]-2-thioxo-5,6-
dihydropyri-midine-1(2H)-yl)quinazoline-4(3H)-ones derivatives
was carried out as potential antioxidants with a view to support
new drug development programme to curb various diseases. The
model of scavenging of the stable DPPH radical is extensively used
to evaluate radical scavenging activities in a very short span of time
in comparison to other methods. Compound under investigation re-
acts with DPPH, which is nitrogen centered radical (Fig. 1) with a
characteristic absorption at 517 nm, and convert it to stable diamag-
netic molecule 1,1-diphenyl-picryl hydrazine, due to its hydrogen
donating ability at a very rapid rate.17 When this electron becomes
paired off, the absorption decreases stoichiometrically with respect
to thenumber of electrons taken up. Such a change in the absorbance
produced in this reaction has been widely applied to test the
⇑
Corresponding author.
E-mail address: drashoksharma2001@yahoo.com (A. Kumar).
0960-894X/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2011.05.031

4354
A. Kumar et al. / Bioorg. Med. Chem. Lett. 21 (2011) 4353–4357
O N
2
O N
2
A-H
.
NH
N
NO
N
N
NO
2
+
A
2
O N
O N
2
2
Figure 1. DPPH, chemical structure and its reaction with a scavenger, indicated by A–H.
O
COOH
NH2
COOH
O
i
NHCOCH
Cl
ii
2
Cl
CH2
N
(1)
(2)
(3)
R
1
+
-
R
O
CH3
N
N
Cl
2
OO
R1
2
iii
R2
+
O
N
3
H C
R
OEt
3
(6)
(4)
(5)
CH3
3
R
H
N
2
NH
NH
2
iv
(7)
S
R1
R2
R3
Entry
O
NH2
OH
OH
H
H
CH3
H
R2
9a
9b
9c
N
R1
N
S
CH3
OH
H
R3
N
N
OH
Cl
H3C
9d OH
(8a-j)
V
9e
9f
9g
9h
9i
H
NO2
H
OH
OH
(3)
OH
H
H
OH
H
N
O
CH
3
S
OH
Cl
O
N
H
OH
OCH3
R
N
N
N
1
9j
R
H
H
H
2
N
Cl
(9a-j)
R
3
Scheme 1. Synthesis of 2-(chloromethyl)-3-(4-methyl-6-oxo-5-[(E)-phenyldiazenyl]-2-thioxo-5,6-dihydropyrimidine-1(2H)-yl)quinazoline-4(3H)-ones (9a–j). Reagants and
conditions (i) chloroacetyl chloride, benzene. (ii) H2SO4. (iii) Sodium acetate and ethanol at 0-5°C. (iv) Sodium ethoxide. (v) Dry pyridine for 6-10 h.
capacity of numerous molecules to act as free radical scavengers.18
In this way, the scavenging effects of all the synthesized compounds
on the DPPH free radical were evaluated.
Moreover, pyrimidine analogues are used as chemotherapeutic
agents for the treatment of diseases resulting from different micro-
organisms and now there has been a major expansion in the num-
ber of pyrimidine derivatives as drugs. The design of pyrimidine
analogues as antimetabolites involves changes in the substituents
on the ring, isosteric replacement of rings, changes in ring size, at-
tached sugars and phosphate residues, etc. Many useful drugs con-
taining pyrimidine analogues with diverse biological activities
have now emerged possessing antifungal, antibacterial,19–21 anti-
inflammatory and antioxidant activities. Thus keeping in view
the biological activities displayed by pyrimidine system, it was
our endeavor to develop efficacious antimicrobial vis-à-vis antiox-
idant agents containing pyrimidine ring, coupled to quinazoline

A. Kumar et al. / Bioorg. Med. Chem. Lett. 21 (2011) 4353–4357
4355
system. Moreover, it was considered worthy of interest to investi-
gate the influence of substituents as the structural variants on the
anticipated biological activities.
Buoyed from these findings and in view of the fact that quinazoline-
ones and pyrimidine derivatives possess useful antimicrobial and
antioxidant activities, we designed and synthesized a number of 2-
(chloromethyl)-3-(4-methyl-6-oxo-5-[(E)-phenyldiazenyl]-2-
thioxo-5,6-dihydropyrimidine-1(2H)-yl)quinazoline-4(3H)-ones and
evalu ated their antimicrobial and antioxidant potentials.
Anthranilic acid 1 was reacted with chloroacetyl chloride to ob-
tain 2-[(chloroacetyl)amino]benzoic acid22 2 in the presence of ben-
zeneatroomtemperature. Compound2ontreatmentwithsulphuric
acid has been cyclized23 to yield 2-chloromethyl benzo[d][1,3]oxa-
zin-4-one 3. The synthesis of 3-amino-6-methyl-5-[(E)-phen-
yldiazenyl]-2-thioxo-2,5-dihydropyrimidine-4(3H)-one 8 was
performed by reaction of ethyl 3-oxo-2-[(E)phenyldiazenyl]butano-
ate 6 with thiosemicarbazide in presence of freshly prepared sodium
ethoxide as per the route depicted in Scheme 1. The final step of this
route involves condensation between 3 and 8 in dry pyridine for 6–
10 h to afford the product 9. The probable mechanism of the reaction
involves the ring opening of 2-chloromethyl benzo[d][1,3]oxazin-4-
one 3 by the attack of 3-amino-6-methyl-5-[(E)-phenyldiazenyl]-2-
thioxo-2,5-dihydropyrimidine-4(3H)-one 8. The ring-opening step
is followed by the ring closure after the removal of water molecule
so as to give the title compound 9.
enhancement in the potency of the synthesized analogues as anti-
bacterial agents. The data presented in Table 1 indicated that the
substitution in phenyl ring exerted significant influence on the anti-
bacterial profile. Interestingly, compounds 9a, b, i, with methoxy
and methyl-substituted ring are found to be more active molecules
in the respective series compared to the compounds bearing other
electron donating or with drawing groups (9c, d, e, f). In general,
meta-derivatives are more active than the corresponding para-
substituted derivatives. It has also been observed that the Gram po-
sitive bacteria are more susceptible towards the newly synthesized
series of quinazoline-4(3H)-ones 9a–j. This may be due to the ab-
sence of a unique outer membrane of peptidoglycan in Gram-
positive bacteria and hence, the wall of Gram-positive bacteria is
permeable to these derivatives. Generally, the Gram-positive bacte-
ria are more susceptible having only an outer peptidoglycan layer
which is not an effective permeability barrier25 whereas the Gram-
negative bacteria possess an outer phospholipidic membrane carry-
ing the structural lipopolysaccharide components. This makes the
cell wall impermeable to drug constituents.26 Percent inhibition (%
inhibition) of antibacterial activity for different derivatives over
control drug, was calculated using following formula:
% inhibition ¼ ð
a
ꢀ bÞ=
a
ꢁ 100
a
and b stands for zone of inhibition of control drug and synthesized
compounds, respectively.
Further, upon close inspection of results depicted in Figure 2
pertaining to the in vitro screening of synthesized compounds, it
has been inferred that all these compounds gives promising results
compared to the reference drug ampicillin against the tested bac-
terial strains. The negative% inhibition values of 9a, b, i for some
bacterial strains are suggestive of the better activity profile of these
derivatives as compared to the standard drug.
All the synthesized compounds were characterized by their
physical, analytical and spectral data. In general, the IR spectrum
of compound 8 exhibited NH2 stretching absorption bands at
3427 cmꢀ1 (NHasym) and 3252 cmꢀ1 (NHsym), whereas the C@S
absorption band is visible at 1075 cmꢀ1. Compounds 9a–j showed
disappearance of these bands in their IR spectrum owing to the con-
version of free amino group into cyclic nitrogen. Halogen containing
compounds 9c and d exhibit characteristic bands at 550–650 cmꢀ1
(C–X stretching). The EI-MS and 1H NMR spectral data of all the syn-
thesized compounds are in confirmation to the structural
assignment.
All the synthesized compounds to be examined for antibacterial
activity24 were evaluated in vitro against an assortment of two
Gram-positive bacteria Bacillus subtilis, Staphylococcus aureus, and
two Gram-negative bacteria Pseudomonas aeruginosa and Escherichia
coli. Screening results are summarized in Table 1. The newly gener-
ated compounds 9a–j has exerted significant inhibitory activity
against the growth of tested bacterial strains. The data also revealed
that derivatization of the parent molecule had produced the marked
Antioxidant assay27 is based on the measurements of the scav-
enging ability of compounds towards the stable 2,2-diphenyl-1-pic-
rylhydrazyl radical (DPPH). The disappearance of this commercially
available radical is measured spectrophotometrically at 517 nm in a
methanolic solution. The antioxidant activity was expressed as the
50% inhibitory concentration (IC50) based on the amount of com-
pound required for a 50% decrease of the initial DPPH radical
concentration.
As presented in Table 2, the quinazoline-4(3H)-ones (9a–j)
with IC50 values in the range of 1.4–8.6 lM showed higher radi-
cal-scavenging activities in comparison to ascorbic acid which
was attributed to presence of hydroxyl aryl moiety of quinazo-
Table 1
Antibacterial screening data for 2-(chloromethyl)-3-(4-methyl-6-oxo-5-[(E)-phen-
yldiazenyl]-2-thioxo-5,6-dihydropyrimidine-1(2H)-yl)quinazoline-4(3H)-ones (9a–j)
Compound no.
R1
R1
R1
Zone of inhibition (mm)
Gram-positive Gram-negative
BSa
SAb
PAc
ECd
9a
9b
9c
9d
9e
9f
9g
9h
OH
OH
H
OH
H
OH
H
OH
H
H
CH3
H
OH
Cl
OH
OH
OH
H
OCH3
H
33.0
36.5
27.0
29.0
20.0
24.5
18.5
31.5
42.1
16.2
40.0
39.0
44.5
31.5
33.0
29.0
30.0
27.0
33.5
47.5
24.5
36.0
22.0
23.5
16.0
18.5
12.0
13.5
10.0
21.5
28.0
7.0
25.0
27.5
17.5
20.5
14.0
15.5
13.5
20.9
30.0
11.5
28.0
CH3
OH
H
NO2
H
H
Cl
OH
H
—
9i
9j
H
—
Ampicillin
—
20.0
a
b
c
BS: Bacillus subtilis.
SA: Staphylococcus aureus.
PA: Pseudomonas aeruginosa.
EC: Escherichia coli.
d
Figure 2. Antibacterial activity for compounds 9a–j over control drug.

4356
A. Kumar et al. / Bioorg. Med. Chem. Lett. 21 (2011) 4353–4357
Table 2
Inhibition of DPPH radical by synthesized compound
S
N
N
CH
3
O
N
1
N
R
N
N
2
R
O
Cl
3
R
Compound
aIC50
Compound
aIC50
9a
9b
9c
9d
5.1
3.5
1.4
7.0
8.6
9.2
9f
9g
9h
9i
9j
—
2.1
5.4
8.3
3.0
NA
—
Figure 4. Graphical representation of
compounds 9a–j as a function of time.
% DPPH radical scavenging activity of
9e
Ascorbic acid
NA–not available.
a
IC50 values were determined by linear regression analysis using at least five
different concentrations in triplicate.
inhibition after 20, 30, 45, 60, 90, and 120 min was plotted against
concentration, and the equation for the line was used to obtain the
IC50 value. A lower IC50 value indicates greater antioxidant activity.
The entire synthesized compounds scavenged DPPH radical sig-
nificantly in a concentration-dependent manner. Their comparable
scavenging activities were expressed in IC50 (concentration re-
line-4(3H)-ones (that can donate hydrogen atoms) and governs
the main factor behind their ability to be scavenged by DPPH.
After donating a hydrogen atom, compounds exist in its radical
form, and the electron conjugation effect in the structure stabi-
lizes the radical which favors the reaction to occur (Fig. 3).
The difference in activity amongst compounds 9a–j was due to
the difference in the stability of the oxygen centered radical
formed in these compounds. Amongst them, compounds 9c and f
with two hydroxy substituents showed highest hydrogen donor
quired for 50% inhibition of 60 lM DPPH concentration) value. In
compound 9c both the hydroxy groups are ortho to each other,
therefore, radical ion resulted from the abstraction of either H atom
(ortho/meta hydroxy group with respect to azo group) by DPPH
would stabilize by other hydroxy group. Moreover, the radical ion
resulted from the abstraction of para hydroxyl group would also
be stabilized by azo group, para to it through extended conjugation.
While in compound 9f both the hydroxy groups are meta to each
other, therefore the radical ion resulted from the abstraction of H
atom would not be stabilized from either hydroxy group. Thus, com-
pound 9c shows better scavenging effect as compare to compound
9f. Compound 9i is less active compared to 9f due to the presence
of single hydroxy group but, also it shows better antioxidant activity
compared to 9b due to presence of methoxy group (i.e., the presence
of the electron donating OCH3 group at the ortho position enhanced
the stabilization of the resulting oxygen centered radical as the
number of conjugating structure is more than that without the
OCH3 group) which is absent in the later case. Compound 9a shows
lesser activity compared to 9b since it has methyl and hydroxy meta
to each other (because meta positions do not participate in reso-
nance stabilization). Compound 9g is less active compared to 9a be-
cause of absence of any electron releasing group which otherwise
stabilize the radical ion. But it shows higher activity compared to
compound 9d and h due to the presence of electron withdrawing
chloro groups in them which would destabilize the ring. Also com-
pound 9g provides better stability of the nitrogen centered radical
by extended conjugation resulting in para quinonoid structure
which has more stabilization than the ortho quinonoid structure
formed for compound 9d or h. The difference in activity among
the compounds 9d and h is due to the different positions of chloro
group. Compound 9h shows lesser radical scavenging activity as it
has chloro group ortho to hydroxy group, that is, a strong electron
with drawing group is situated on ortho position which destabilize
the radical ion while in compound 9d, chloro group is situated at
meta position which therefore neither stabilize nor destabilize the
ring, thus latter shows more antioxidant activity compared to for-
mer. Similarly, compound 9e shows lowest activity due to the pres-
ence of strong electron withdrawing effect (which would
destabilize the ring).
ability to DPPH radical (IC50 values were 1.4 and 2.1 lM, respec-
tively). Since the corresponding IC50 values for all synthesized
compounds after 60 min were lower than after 30 min, DPPH anti-
radical scavenging activity was also time-dependent (Fig. 4). The
radical-scavenging activity of the tested samples, expressed as per-
centage inhibition of DPPH, was calculated according to the
formula:
IC ð%Þ ¼ ½ðA0 ꢀ AtÞ n A0ꢂ ꢁ 100
where, At is the absorbance value of the tested sample and A0 is the
absorbance value of blank sample, at a particular time. Percentage
Figure 3. Graphical representation of
% DPPH radical scavenging activity of
compounds 9a–j as a function of concentration.

A. Kumar et al. / Bioorg. Med. Chem. Lett. 21 (2011) 4353–4357
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Calculated physico-chemical parameters of synthesized quinazoline-4(3H)-ones
using HyperChem software
Compounds Heat of formation
(kcal/mol)
Hydration energy of
molecule (kcal/mol)
Dipole
(Debyes)
9a
9b
9c
9d
9e
9f
9g
9h
9i
ꢀ117666.43
ꢀ117664.86
ꢀ120986.71
ꢀ121164.63
ꢀ131799.40
ꢀ120992.19
ꢀ114214.4
ꢀ13.65
ꢀ11.54
ꢀ23.67
ꢀ31.15
ꢀ31.11
ꢀ18.42
ꢀ17.39
ꢀ12.48
ꢀ18.12
ꢀ9.55
3.99
4.32
4.10
4.88
5.72
5.00
5.05
7.40
2.78
5.14
ꢀ121071.49
ꢀ124425.14
ꢀ106594.35
9j
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24. The antibacterial activity was investigated by the disc diffusion method using
nutrient agar medium.29–31 The agar medium was autoclaved for 30 min at a
pressure of 1.5 kg cmꢀ3 and cooled to 37 °C. It was inoculated with 0.5 mL fresh
subculture of all the corresponding microorganisms aseptically, and mixed
well by gentle shaking to get the homogenous suspension. 20 mL of this
medium was poured under aseptic conditions in each sterilized Petri dish and
allowed to set. Sterile 6 mm filter paper discs, impregnated with the solution of
test compound (200 mg mLꢀ1 in DMSO) were then placed at 37 °C for 24 h for
bacterial growth. For comparison, the solvent control (DMSO) and standard
drug ampicillin were also screened under similar conditions. The diameter of
inhibition zone (in mm) was measured at successive intervals during the
incubation period. Duplicate sets were used for each treatment.
25. Scherrer, R.; Gerhardt, P. J. Bacteriol. 1971, 107, 718.
The physico-chemical parameters, including heat of formation
DHf), dipole, and hydration of molecule were calculated using
(
HyperChem molecular modeling software. Some physico-chemical
parameters of the quinazoline-4(3H)-ones under investigation
were calculated using the HyperChem molecular modeling soft-
ware (Table 3). A QSAR28 model could be derived to calculate the
redox potential (i.e., a direct measure of the antioxidant property)
of phenolic compounds using calculated parameters such as the
heat of formation (
ing parent phenols. A combination of
D
Hf) of phenoxyl radicals and their correspond-
Hf and other calculated
D
parameters were found to be quite satisfactory for predicting the
antioxidant activities, or redox potentials of new phenolic antioxi-
dants. However, a model to predict the antioxidant activity from
the data on quinazoline-4(3H)-ones and its derivatives is presently
being developed.
In conclusion, the synthesized new compounds 9a–j has ex-
erted significant action on the growth of both Gram-positive and
Gram-negative bacteria, which render them as potential antimi-
crobial agents. Compounds 9c and f are very good antioxidants
due to the presence of two hydroxyl groups in them and could
be rendered for future antimitotic screening. Hence in view to cater
the needs associated with ever increasing demand of newer anti-
bacterial and antioxidant agents, exploration of these findings
can envisage these compounds as powerful antibacterial and anti-
oxidative agents.
26. Betoni, J. E. C.; Mantovani, R. P.; Barbosa, L. N.; Di stasi, L. C.; Fernandes, J. A.
Memorias do Instituto Oswaldo, Rio de Janeiro 2006, 101, 387.
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28. DPPH was dissolved in MeOH (100 mL) to obtain a concentration of 60 lM.
Acknowledgment
Serial dilutions were carried out with stock solutions (4 mmol) of the
compounds in methanol to obtain final concentrations of 0.012, 0.01, 0.008,
0.006, 0.004, 0.002, 0.0005 mmol in cuvette. Diluted solutions (2 mL each)
were mixed with DPPH (2 mL) and allowed to stand for 120 min for any
reaction to occur. The absorbance was recorded at 517 nm using a Perkin–
Elmer Lambda 25 UV–vis spectrophotometer. The experiment was performed
in triplicate and the average absorbance was noted for each concentration. The
IC50 value, which is the concentration of the test compound that reduces 50% of
We are grateful to Central Drug Research Institute, Lucknow, In-
dia for providing spectroanalytical facilities.
Supplementary data
Supplementary data (1H NMR, IR, mass, and elemental analysis)
associated with this article can be found, in the online version, at
doi:10.1016/j.bmcl.2011.05.031.
the initial free radical concentration, was calculated in lM. Ascorbic acid was
used as reference standard, at the same concentrations in methanol as were
used for the tested compounds.
29. Sharma, P.; Kumar, A.; Upadhyay, S.; Sahu, V.; Singh, J. Eur. J. Med. Chem. 2009,
44, 251.
30. Sharma, P.; Sharma, S.; Rane, N. Bioorg. Med. Chem. 2004, 12, 3135.
31. Sharma, P.; Kumar, A.; Sharma, S.; Rane, N. Bioorg. Med. Chem. Lett. 2005, 15,
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References and notes
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2. Bradly, D. S. Tetrahedron Lett. 2001, 42, 1851.