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360 Letters in Drug Design & Discovery, 2013, 10, 360-368
Certain 2-Furano-4(3H)-Quinazolinone Analogs: Synthesis, Characteriza-
tion and Pharmacological Evaluation
Varun Bhardwaj*
,a
, Poonam Sharma
a
, Malleshappa N. Noolvi
b
, Harun M. Patel
c
, Sumit Bansal
a
,
Sandeep Lohan
a
and Gaurav Badola
d
a
Department of Biotechnology, Bioinformatics and Pharmacy, Jaypee University of Information Technology, Wakna-
ghat, Solan, 173234 (Himachal Pradesh) India;
b
Department of Pharmaceutical Chemistry, Shree Dhanvantary Phar-
macy College, Kim (Surat) 394110, Gujarat, India.;
c
Department of Pharmaceutical Chemistry, R.C. Patel Institute of
Pharmaceutical Education and Research, Shirpur (Dhule) 425405, Maharashtra, India;
d
Department of Pharmaceutical
Chemistry, ASBASJSM College of Pharmacy, Bela, Ropar, 140111 (Punjab) India.
Abstract: A series of new of 2-furano-4(3H)-quinazolinone derivatives 5 (a-t) were synthesized. The compounds were
characterized by their IR,
1
H NMR,
13
C NMR, and Mass spectral data. The antimicrobial activity of newly anthranilic
acid-based compounds against various bacteria; S. aureus, Salmonella enterica, Vibrio cholerae, Bacillus subtilis, Proteus
mirabili, Escherichia coli V517, Mycobacterium smegmatics, Pseudomonas aeruginosa and fungi; C. albicans, were
evaluated with ampicillin and amphotericin B as standards. All compounds were also evaluated for antibacterial activity
against R. solanacearum along with Kocide 3000 as a commercialized reference. Compounds 5d, 5g, 5j, 5l, 5q, 5r, 5s,
and 5t exhibited good potential as antimicrobial.
Keyword: Synthesis; Quinazolinone; Diamide (open quinazoline ring); Antimicrobial activity.
1. INTRODUCTION
Substituted heterocyclic ring systems have emerged as
powerful scaffolds for many biological evaluations. Hetero-
cyclic compounds provide scaffolds on which pharmacopho-
res can arrange to yield potential and selective drugs [1,2].
Quinazolinones and quinazoline are very interesting mole-
cule and their pharmacological activities are well docu-
mented. It has been reported as antihypertensive [3], antimi-
crobial [4-8], antiviral [9,10], anti-HIV [11], anticonvulsant
[12,13], anti-inflammatory [14], antihypertensive [15], and
anticancer [16-18] activity, etc. The rapid rise in bacterial
resistance to the traditional antibiotics such as tetracycline
has encouraged a continuing search for new classes of com-
pounds with novel modes of antimicrobial activity. Even
controlling of plant bacterial diseases has also been a long
challenging mission in the agricultural sector, in particular,
heterocyclic structures from the basis of many pharmaceuti-
cal, agrochemical, and veterinary products. There had been
many methods and procedure for the formation of quinazoli-
none ring and also for substitutions over it [19,20]. Anthra-
nilic acid and its derivatives are well-precedent building
blocks for the synthesis of new analogs as potential candi-
dates [21]. Quinazolin-4(3H)-ones with substitution at posi-
tion 3, has been reported to have antimicrobial properties
[22-25]. Examples of these substitutions are; substituted
phenyl ring moieties [19,20], bridged phenyl rings, hetero-
cyclic rings, and aliphatic systems [19,22,23]. On the other
hand, diverse chemotherapeutic agents contain pharma-
cophores like Br, phenolic OH, and Cl substitutions, are re-
ported to possess antimicrobial activities [6,25].
*Address correspondence to this author at the Department of Biotechnology,
Bioinformatics and Pharmacy, Jaypee University of Information Technol-
ogy, Waknaghat, Solan, 173234 (Himachal Pradesh) India;
Tel: +91-94189-05865; Fax: +91-1792-245362;
E-mail: varunmilton@yahoo.com
In the present work, the open quinazoline analogs typi-
cally known as diamides were designed to contain a proper
side chain bearing group which are believed to contribute
biologically, furthermore with respect to amide containing
compounds, these have been developed and commercialized
for example, fluopicolide, boscalid, and benquinox Fig. (1).
In addition, attempts have been made for incorporation of
some heterocycles that are known to have antimicrobial ac-
tivity. The synthesis by different methods likely fusion
(without using solvent and frequently heating at high tem-
perature i.e. more than 200 °C) etc. and antimicrobial poten-
tial of the newly synthesized compounds are reported in this
paper.
2. EXPERIMENTAL
2.1. Material and Methods
All chemicals and solvents were supplied by Merck, Ald-
rich, and S.D. Fine Chemical Limited, Mumbai. The reac-
tions were monitored with thin-layer chromatography using
pre-coated aluminum sheets with GF
254
silica gel, 0.2 mm
layer thickness (E. Merck). Solvent systems of benzene-
acetone (9:1) or (8:2), toluene-ethylacetate-formic acid
(5:4:1), and chloroform-methanol (9:1), (9.5:0.5) were util-
ized. Melting points were recorded on the Veego (VMP-MP)
melting point apparatus. IR spectra were obtained on a Shi-
madzu Infra Red Spectrometer, (model FTIR-8400S). Both
1
H-NMR (DMSO) and
13
C NMR (DMSO) spectra were per-
formed with Bruker Avance-II 400 NMR Spectrometer op-
erating at 400 MHz for
1
H and 100 MHz for
13
C, respec-
tively, in SAIF, Panjab University (Chandigarh). Chemical
shifts are reported in parts per million (ppm) using
tetramethylsilane (TMS) as an internal standard. Mass spec-
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