Regioselective synthesis of novel [n-(4-oxo-3-(2-phenyl-1,8-naphthyridin-3-yl)-thiazolidin-2-ylidene)]acetamide/benzamides and their biological activity

Article abstract of DOI:10.14233/ajchem.2019.21881

In an attempt to discover the new antibacterial agents to fight the bacterial infections, a series of 1,8-naphthyridine based 2-iminothiazolidin-4-one derivatives was synthesized by a straight-forward regioselective synthesis. 2-Phenyl-1,8-naphthyridin-3-

Full text of DOI:10.14233/ajchem.2019.21881

Asian Journal of Chemistry; Vol. 31, No. 6 (2019), 1246-1250
A
SIAN
J
OURNAL OF HEMISTRY
C
https://doi.org/10.14233/ajchem.2019.21881
Regioselective Synthesis of Novel [N-(4-Oxo-3-(2-phenyl-1,8-naphthyridin-3-yl)-
thiazolidin-2-ylidene)]acetamide/benzamides and their Biological Activity
1,
1,*,
2,
RAMALINGAM KUNDENAPALLY , RAMESH DOMALA
and B. SREENIVASULU
1Department of Chemistry and Pharmaceutical Sciences, Mahatma Gandhi University, Nalgonda-508254, India.
2Centre for Chemical Sciences and Technology, Insitute of Science & Technology, Jawaharlal Nehru Technological University, Hyderabad-
500085, India
*Corresponding author: E-mail: synchemram@gmail.com
Received: 18 December 2018;
Accepted: 22 January 2019;
Published online: 29 April 2019;
AJC-19363
In an attempt to discover the new antibacterial agents to fight the bacterial infections, a series of 1,8-naphthyridine based 2-iminothiazolidin-
4-one derivatives was synthesized by a straight-forward regioselective synthesis. 2-Phenyl-1,8-naphthyridin-3-amine (2) was reacted with
acetyl or aroyl isothiocyantes to give the corresponding N-[(2-phenyl-1,8-naphthyridin-3-yl)carbamothioyl)]acetamide or benzamides
(3a-e). Finally, the target compounds [N-(4-oxo-3-(2-phenyl-1,8-naphthyridin-3-yl)thiazolidin-2-ylidene)]acetamide or benzamides (4a-e)
were obtained by the reaction of thiourea (3a-e) with chloroacetyl chloride in presence of pyridine. All the synthesized products were
formed in good yields and their structures were characterized by spectral (IR, EI-MS and NMR) and physical data. The biological activity
of title compounds was evaluated against the bacterial strains and found to be more potent.
Keywords: 1,8-Naphthyrdine, Aroyl thiourea, Aroyl isothiocyanate, Iminothiazolidin-4-one, Antibacterial activity.
antithrombotic [11] antibacterial [12], anticancer [13] activities,
etc.
INTRODUCTION
A large number of organo-sulphur compounds have been
successfully utilized for the treatment of various diseases and
also found in many natural and synthetic products. These are
increasingly important with a broad range of applications in
biological profiles. Therefore, many researchers have more
concentrated to develop the sulphur-containing architectures
and investigated their pharmacological properties.
Our current efforts are focused in identifying newer structural
elements consisting of both 1,8-naphthyridine and 2-imino-
thiazolidin-4-ones. The 1,8-naphthyridine scaffold is a centre
of attention in all the nitrogen containing heterocycles due to
their biological importance. The significant activities of these
compounds have been reported such as antibacterial [1], anti-
fungal and antitumor [2], antihypertensive [3], HIV-1 integrase
mutant [4], antiplatelet [5], antidepressant [6], DNA stabilizing
[7], antiallergic [8] activities, etc. Moreover, 2-iminothiazoli-
dinone is a privileged moiety in five-membered heterocyclic
system and its derivatives exhibited a large range of interesting
bioactivities like antibiofilm [9], S1P1 receptor agonist [10],
The synthesis of 1,8-naphthyridine derivatives containing
thiazolidin-4-one core is also reported in the literature [14]. In
continuation of our studies, a 1,8-naphthyridine based acyl/
aroyl thiourea intermediates (3a-e) from 2-phenyl-1,8-naphth-
yridin-3-amine (2) in appreciable yields is excuted. In next
step, compounds 3a-e underwent a regioselective reaction with
chloroacetyl chloride in presence of a base to afford the highly
functionalized [N-(4-oxo-3-(2-phenyl-1,8-naphthyridin-3-
yl)thiazolidin-2-ylidene)]acetamide or benzamides (4a-e). The
final compounds were assayed for their biological efficacy
against the microorganisms.
EXPERIMENTAL
All the reagents and solvents were obtained from the comm-
ercial sources. Melting points were reported by open end capil-
laries method and are uncorrected. The IR spectra were measured
by employing the KBr pellets technique on a Shimadzu FT-IR
instrument. NMR spectra were obtained on Bruker spectro-
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Vol. 31, No. 6 (2019)
Regioselective Synthesis of Novel 1,8-Naphthyridine Derivatives and their Biological Activity 1247
meter at 300 MHz for 1H NMR, and 100 MHz for 13C NMR,
where the solvent is DMSO-d6 or CDCl3. The chemical shifts
are reported in δ ppm scale and TMS as reference. MS determi-
nations were conducted by the ESI method on waters Alliance
mass spectroscopic instrument. Elemental analyses were reported
by using a ElementarVario Micro Cube analyser. The reactions
and purity were checked by TLC plates (silica gel 60F254,
Merck) and the spots visualized under UV irradiation.
Spectral data
2-Phenyl-1,8-naphthyridin-3-amine (2): IR (KBr, νmax
,
cm-1): 3462, 3298 (NH2), 3186, 1616, 1544, 1429; 1H NMR
(DMSO-d6) δ ppm: 5.51 (s, 2H, -NH2, D2O exchange), 7.40-7.43
(m, 2H), 7.49-7.58 (m, 3H), 7.79 (d, J = 7.0 Hz, 2H), 8.13-8.15
(dd, J = 8.1, 1.3 Hz, 1H), 8.70 (d, J = 2.3 Hz, 1H,); 13C NMR
(DMSO-d6) δ ppm: 114.71, 122.01, 123.62, 128.51, 128.81,
134.42, 138.18, 140.68, 148.33, 149.72, 152.03; MS (ESI) m/z:
222 [M+H]+; Elemental analysis (%) found (calcd.): C 76.00
(76.03); H 5.01 (5.02); N 18.99 (19.03).
General procedure for the synthesis of 2-phenyl-1,8-
naphthyridin-3-amine (2): A mixture of compound 1 (0.01
mol) and hydrazine monohydrate (0.011 mol) in EtOH (35
mL) was stirred under reflux until the completion of reaction.
At the end of this period, the obtained solid was suspended in
dilute HCl followed by refluxing again for 0.5 h, solution was
cooled and filtered. The filtrate was basified (pH 8-9) with a
solution of 4 N NaOH. The formed product was extracted twice
by CHCl3 and the organic layers were washed successively
with brine and water. The dried extract was evaporated, and the
collected crude was recrystallized from the mixture of EtOAc-
EtOH (1:2) to furnish pure product 2 as yellow crystals.
General procedure for the synthesis of N-[(2-phenyl-
1,8-naphthyridin-3-yl)carbamothioyl]acetamide or N-[(2-
phenyl-1,8-naphthyridin-3-yl)carbamothioyl]benzamides
(3a-e): Acetyl chloride or substituted benzoyl chloride (0.01
mol) was gradually added during 15 min to a stirred solution
of KSCN (0.01 mol) in dry acetone (20 mL) at room temperature.
The mixture was refluxed for 20 min, cool and followed by
addition of 2-phenyl-1,8-naphthyridin-3-amine (2) (0.01 mol)
in dry acetone (20 mL) along with stirring. The resulting mixture
refluxed for 2-3 h (monitored byTLC) and poured onto an excess
of cold water and stirred another 10 min. The formed product
was extracted twice by chloroform. The dried organic extract
was evaporated and recrystallized by the mixture of dichloro-
methane and ethanol (2:1) to furnish the desired products
3a-e.
Synthesis N-(4-oxo-3-(2-phenyl-1,8-naphthyridin-3-
yl)thiazolidin-2-ylidene) acetamide or benzamides (4a-e):
To a suspension of compounds 3a-e (0.01 mol) and pyridine
(0.011 mol) in dry acetonitrile (10 mL) with constant stirring
at 0 ºC and followed by dropwise addition of a solution of chloro-
acetyl chloride (0.011 mol) in dry acetonitrile (5 mL) under
the nitrogen. Then, the reaction mixture was stirred at room
temperature for 30 min and was refluxed for 4-5 h (TLC moni-
tored). The content was concentrated to half of the volume and
treated with ice-cold water.The resulting brown solid was filtered,
dried and purified by using silica gel column chromatography
(hexane-EtOAc, 7:3) (Scheme-I).
N-[(2-Phenyl-1,8-naphthyridin-3-yl)carbamothioyl]-
acetamide (3a): IR (KBr, νmax, cm-1): 3225 (NH), 3009, 1692
(carbonyl), 1531 1243; 1H NMR (DMSO-d6) δppm: 2.11 (s, 3H),
7.48-7.51 (m, 3H), 7.66-7.69 (dd, 1H, J = 8.1, 4.2 Hz), 7.74-
7.76 (m, 2H), 8.53-8.56 (dd, 1H, J = 8.2, 2.0 Hz), 8.70 (s, 1H),
9.13 (s, 1H), 11.53 (s, 1H, NH), 12.34 (s, 1H, NH); 13C NMR
(DMSO-d6) δ ppm: 23.51, 121.02, 122.75, 123.81, 128.63,
128.89, 133.98, 136.84, 137.00, 153.84, 158.37, 167.49 (C=O),
177.84 (C=S); MS (ESI) m/z: 323 [M+H]+. Elemental analysis
(%) found (calcd.): C 63.33 (63.38); H 4.38 (4.39); N 17.38
(17.41); O 4.96 (4.99); S 9.95 (9.97).
N-[(2-phenyl-1,8-naphthyridin-3-yl)carbamothioyl]-
benzamide (3b): IR (KBr, νmax, cm-1): 3136(NH), 3061, 3003,
1658 (carbonyl), 1537, 1269; 1H NMR (CDCl3) δ ppm: 7.50-
7.55 (m, 6H), 7.63-7.67 (t, J = 7.44 Hz, 1H), 7.81-7.85 (m,
4H), 8.27-8.30 (dd, J = 8.14, 1.78 Hz, 1H), 9.14-9.16 (dd, J =
5.23, 2.88 Hz, 2H), 9.24 (s, 1H, NH), 12.68 (s, 1H, NH); 13C
NMR (CDCl3) δ ppm: 121.53, 122.50, 127.60, 128.01, 128.40,
128.51, 128.59, 129.19, 129.46, 129.68, 130.03, 130.68, 131.22,
133.51, 133.90, 136.71, 137.00, 153.98, 155.21, 158.48, 166.60
(C=O), 179.40 (C=S). MS (ESI) m/z: 385 [M+H]+. Elemental
analysis (%) found (calcd.): C 68.73 (68.77); H 4.19 (4.22); N
14.57 (14.58); O 4.16 (4.19); S 8.34 (8.37).
2-Chloro-N-((2-phenyl-1,8-naphthyridin-3-yl)carbamo-
thioyl)benzamide (3c): IR (KBr, νmax, cm-1): 3284 (NH), 3085,
1
1660 (carbonyl), 1544, 1262; H NMR (DMSO-d6): δ ppm:
7.49-7.58 (m, 5H), 7.65-7.82 (m, 5H), 8.34-8.37 (dd, J = 8.07,
1.65 Hz, 1H), 9.10-9.12 (dd, J = 4.83, 1.92 Hz, 2H), 9.23 (s,
13
1H, NH), 12.60 (s, 1H, NH); C NMR (DMSO-d6) δ ppm:
121.58, 125.32, 127.15, 128.37, 128.40, 128.83, 128.91, 129.28,
129.74, 130.51, 130.68, 132.14, 134.66, 136.37, 139.04, 143.23,
151.81, 155.35, 157.18, 166.74 (C=O), 178.28 (C=S); MS (ESI)
m/z: 419 [M+H]+. Elemental analysis (%) found (calcd.): C
63.08 (63.11); H 3.61 (3.62); Cl 8.46 (8.50); N 13.37 (13.38);
O 3.82 (3.84); S 7.65 (7.69).
N-(4-Oxo-3-(2-phenyl-1,8-naphthyridin-3-yl)thiazoli-
din-2-ylidene)acetamide (4a): IR (KBr, νmax, cm-1): 3059 (ring
O
O
H
S
R
O
N
N
NH
Ph
NH2
b
c
a
N
N
O
S
R
N
N
Ph
N
N
O
N
N
Ph
N
N
Ph
4a-e
3a-e
2
1
Reagents and conditions: (a) N2H4.H2O/ethanol, reflux (b) KSCN/RCOCl, acetone, reflux
(c) Chloroacetyl chloride, Py, ACN, Reflux; 3a-e and 4a-e: R = methyl, phenyl,2-chlorophenyl,
4-nitrophenyl, 4-methoxyphenyl
Scheme-I: Regioselective synthesis of compounds 4a-e

1248 Kundenapally et al.
Asian J. Chem.
CH2), 1732 (carbonyl), 1644 (carbonyl), 1520 (C=N), 1165
(C-S); H NMR (DMSO-d6) δ ppm: 2.14 (s, 3H), 3.75-3.94
RESULTS AND DISCUSSION
1
A reaction of 2-(2-phenyl-1,8-naphthyridin-3-yl)isoindo-
line-1,3-dione (1) with hydrazine monohydrate in alcohol to
give 2-phenyl-1,8-naphthyridin-3-amine (2). The intermediates
of N-[4-oxo-3-(2-phenyl-1,8-naphthyridin-3-yl)thiazolidin-2-
ylidene]acetamide or benzamides (3a-e) were obtained by the
reaction of compound 2 with acid chlorides and potassium
thiocyanate in anhydrous acetone. It is found that compounds
3a-e can react with chloroacetyl chloride or ethyl chloroacetate
in presence of base under reflux to give the regioselective
product N-[4-oxo-3-(2-phenyl-1,8-naphthyridin-3-yl)thiazo-
lidin-2-ylidene]acetamide or benzamides (4a-e) in high yield.
In the final step, the optimized reaction conditions were described
under the varying solvent, base, model reagents and compound
3b was chosen as the model compound (Table-1). In our preli-
minary observations based on the formation of compound 4b,
triethylamine and potassium carbonate bases (entry 5, 6, 7)
gave poor results. The solvents DMF, ethanol and dioxane
(entry 1, 3, 4) were also provided low yields. Thus, the model
reaction was carried out at refluxing acetonitrile in presence
of pyridine (entry 2), leading to the cyclized product (4b) in
(dd, J = 56.88, 18.45 Hz, 2H, CH2), 7.45-7.50 (m, 3H), 7.66-
7.76 (m, 3H), 8.49-8.52 (dd, J = 8.17, 2.03 Hz, 2H), 9.13-9.15
(d, J = 8.17 Hz, 1H ); 13CNMR (DMSO-d6) δ ppm: 23.51, 33.25,
121.22, 122.81, 123.59, 128.74, 128.68, 133.05, 135.77, 137.12,
148.61, 153.47, 156.29, 167.60 (C=O), 170.85 (C=O); MS (ESI)
m/z: 363 [M+H]+. Elemental analysis (%) found (calcd.): C
62.97 (63.00); H 3.89 (3.94); N 15.46 (15.49); O 8.83 (8.86);
S 8.85 (8.89).
N-[4-Oxo-3-(2-phenyl-1,8-naphthyridin-3-yl)thiazoli-
din-2-ylidene]benzamide (4b): IR (KBr, νmax, cm-1): 3059 (ring
CH2), 1732 (carbonyl), 1644 (carbonyl), 1514 (C=N), 1168
(C-S); 1H NMR (DMSO-d6) δ ppm: 3.75-3.94 (dd, J = 56.88,
18.45 Hz, 2H, CH2), 7.31-7.38 (m, 5H), 7.47-7.54 (m, 3H),
7.80-7.92 (m, 3H), 8.29-8.34 (dd, J = 12.96, 6.41 Hz, 2H),
9.15-9.17 (d, J = 8.17 Hz, 1H); 13CNMR (DMSO-d6) δ ppm:
33.23, 121.15, 122.39, 125.62, 127.57, 128.41, 128.73, 128.81,
128.99, 129.34, 129.46, 129.68, 131.18, 133.67, 135.21, 137.43,
148.38, 151.53, 154.72, 156.14, 167.61 (C=O), 170.88 (C=O).
MS (ESI) m/z: 425 [M+H]+. Elemental analysis (%) found
(calcd.): C 67.91 (67.96); H 3.80 (3.83); N 13.20 (13.21); O
7.54 (7.58); S 7.55 (7.59).
TABLE-1
2-Chloro-N-(4-oxo-3-(2-phenyl-1,8-naphthyridin-3-
yl)thiazolidin-2-ylidene)benzamide (4c): IR (KBr, νmax, cm-1):
3064 (ring CH2), 1735 (carbonyl), 1649 (carbonyl), 1518 (C=N),
1162 (C-S); 1H NMR (DMSO-d6) δ ppm: 3.79-3.98 (dd, J =
56.88, 18.45 Hz, 2H, CH2), 7.35-7.61 (m, 7H), 7.70-7.91 (m,
3H), 8.24-8.29 (dd, J = 12.87, 6.31 Hz, 2H), 9.11-9.13 (d, J =
8.15 Hz, 1H); 13CNMR (DMSO-d6) δppm: 33.16, 121.35, 122.25,
124.89, 127.45, 128.12, 128.64, 128.90, 129.07, 129.37, 129.81,
129.93, 131.59, 133.35, 135.47, 137.61, 148.49, 150.82, 153.48,
155.10, 158.23, 167.60 (C=O), 170.85 (C=O). MS (ESI) m/z:
459 [M+H]+. Elemental analysis (%) found (calcd.): C 62.81
(62.85); H 3.29 (3.31); Cl 7.73 (7.76); N 12.21 (12.25); O
6.97 (7.00); S 6.99 (7.02).
OPTIMIZED REACTION CONDITIONS
FOR THE SYNTHESIS OF 4a-e
Yield
(%)a
tracesb
71
49
35
Reflux
time (h)
Entry
Solvent
Reagent*
Base
1
2
3
4
5
6
7
EtOH
ACN
DMF
A/B
A/B
A
Py
Py
Py
8-9
4
4
Dioxane
ACN
DMF
A
A
A
A
Py
8
3
3
6
TEA
TEA
K2CO3
44
31
DMF
tracesb
a
A = Chloroacetyl chloride B = Ethyl chloroacetate; Isolated yields,
bReaction was not completed; Reaction conditions: Compound 3b (1
eq.), A or B (1.1 eq), base (1.1 eq) and solvent (15 mL).
O
Cl
Cl
O
O
O
S
S
N
O
S
Cl
R'
N
R
R
R'
N
N
H
-Py, HCl
R'
N
H
N
O
N
-Py, HCl
H
R
(I)
4
Py
3
Py
Cl
O
S
O
O
O
S
Cl
R
Cl
O
R'
O
S
R
-Py, HCl
R'
N
N
N
-Py, HCl
R'
N
N
H
H
H
R
Py
3
Py
(II)
R =
R' = CH3, substituted phenyls
N
N
Ph
Scheme-II: Probable mechanism for the formation of compound 4 series

Vol. 31, No. 6 (2019)
Regioselective Synthesis of Novel 1,8-Naphthyridine Derivatives and their Biological Activity 1249
good yields. Consequently, the best reaction conditions were
optimized in acetonitrile and the using pyridine as base at
refluxing temperature. The titled products (4a-e) were produced
by initially, S-alkylation followed by cyclization with N1 or
N2 and the plausible mechanism is described in Scheme-II.
The physico-chemical data of the synthesized compounds
(2, 3a-e and 4a-e) are depicted in Table-2. All the synthetic
products were identified in this study by physical, spectral,
analytical data, which are in good agreement with the assigned
structures.
molecular weight. In addition, 2-imino-thiazolidin-4-one deriv-
atives 4a-e were investigated for their antibacterial activity
and showed remarkable results.
The mechanism involves the sulphur attack to α-carbon
of chloroacetyl chloride to generate an acyclic intermediate I
or II (Scheme-II) followed by cyclization of carbonyl with
nitrogen (1 or 2) to afford the products 4a-e. In this case, regio-
selectivity was played a key role in product formation, but
only one regioisomer has been formed under the present reaction
conditions. The formation of -CO-CH2-S- linkage in acyclic
intermediate-I is supported by the spectral data. The 1H NMR
spectra results found that the signal disappearance of NH-1 at
12.40 ppm, whereas the 9.0 ppm signal of NH-2 was intact
and a new peak was also displayed at 4.05 ppm for methylene
group in intermediate-I. Consequently, predominant product
was obtained from an intermediate I over II, also supported
by the available literature [15,16]. Finally, all the compounds
4a-e were obtained as a single regioisomer from compounds
3a-e.
Biological evaluation: Antibacterial activity of the final
analogues 4a-e was screened against the several bacteria such
as Staphylococcus aureus, Bacillus subtilis, Escherichia coli
and Psuedomonas auroginosa by cup plate agar diffusion method
[17]. The test results were compared with reference drug ampicilin
and using DMSO as control. The compounds were evaluated
at a concentration of 50 µg/mL stock solution in DMSO. The
minimum inhibition zone was measured in mm and the bioassay
results are summarized in Table-3. The preliminary results of
antibacterial activity indicated that compound 4c was most
potent and 4a was exhibited least activity as comparable to
ampicillin, and the remaining compounds showed moderate
activity against the bacterial strains.
TABLE-2
PHYSICO-CHEMICAL DATA OF COMPOUNDS 2-4
m.p.
(°C)
Yield
(%)a
R
m.f.
C14H11N3
C17H14N4OS
C22H16N4OS
C22H15ClN4OS
C22H15N5O3S
1
2
3
4
5
6
7
8
9
–
238-240
216-218
203-205
252-254
197-199
224-226
190-192
185-187
230-232
241-243
208-210
62
83
84
80
77
79
65
73
71
68
62
2
Methyl
Phenyl
3a
3b
3c
3d
3e
4a
4b
4c
4d
4e
2-Chlorophenyl
4-Nitrophenyl
4-Methoxyphenyl C23H18N4O2S
Methyl
Phenyl
C19H14N4O2S
C24H16N4O2S
C24H15ClN4O2S
C24H15N5O4S
2-Chlorophenyl
4-Nitrophenyl
10
11
4-Methoxyphenyl C25H18N4O3S
aIsolated yields after purification.
IR spectra frequencies obtained at 3298-3205 cm-1 indicated
the appearance of amine function (-NH2) in compound 2. The
characteristic bands for amine (NH), carbonyl (C=O) and thio-
carbonyl (C=S) in aroyl/acoylthioureas (3a-e) were found at
the region of 3225-3300, 1692-1658 and 1265-1242 cm-1,
respectively. The lack of NH frequencies and the appearance
of additional C=O and C=N bands for 2-iminothizolidn-4-one
(4a-e) were observed at 1735-1732 and 1520-1514 cm-1, respec-
tively.
TABLE-3
ANTIBACTERIAL ACTIVITY OF
THE SYNTHETIC COMPOUNDS 4a-e
Microorganism inhibition zone (mm)
In 1H NMR spectra, compound 2 displayed a peak of 5.51
ppm as singlet and confirmed for the amine function (-NH2)
with D2O exchange. The characteristic singlets for NH (1) and
NH (2) functions were appeared at around 9.24-11.53 and
12.60-12.68 ppm in compounds 3a-e and 13C NMR of comp-
ounds 3a-e was showed most deshielded thiocarbonyl (C=S)
at about 177.84-179.40 ppm and carbonyl carbon (C=O) reso-
nated at around 166.60-167.49 ppm, respectively. It was evidently
indicated that the formation of acyl or aroyl thiourea core in
compounds 3a-e.
Gram-positive bacteria Gram-negative bacteria
Entry
S.
aureus
10
P.
B.
subtilis
E.
coli
aeruginosa
05
10
14
09
05
12
14
27
32
21
25
30
02
08
11
05
08
10
4a
4b
4c
4d
4e
25
27
22
10
Ampicillin (std.)
30
The methylene protons (ring -CH2-) of compounds 4a-e
was observed as a doublet of doublet at the region of 3.75-
3.98 ppm in 1H NMR due to deshielded by the adjacent sulphur
atom and carbonyl function. In 13C NMR, the methylene and
carbonyl carbon signals of compounds 4a-e were displayed at
33.16-33.25 ppm and 167.60-170.88 ppm region, respectively.
The aromatic protons in all the compounds were found at the
region 7.31-9.17 ppm in 1H NMR, which was assigned to the
peaks of phenyl and 1,8-naphthyridine system. In 13C NMR,
the other carbon signals appeared in their expected region.
In mass spectra, all the compounds furnish the corres-
ponding [M+1]+ peaks, which were matched with the calculated
Conclusion
In this work, 2-phenyl-1,8-naphthyridin-3-amine was effici-
ently prepared and converted into various acyl or aroyl thiourea
derivatives (3a-e) bearing 1,8-naphthyridine skeleton.A series
of [N-(4-oxo-3-(2-phenyl-1,8-naphthyridin-3-yl)thiazolidin-2-
ylidene]acetamide or benzamides (4a-e) were prepared by the
cyclization of 3a-e with chloroacetyl chloride in the presence
of pyridine in good yields. The new synthetic products were
successfully characterized and their biological results exhibited
that most of the 1,8-naphthyridine derivatives have shown signi-
ficant antibacterial activity against the microorganisms.

1250 Kundenapally et al.
ACKNOWLEDGEMENTS
Asian J. Chem.
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One of the authors (K.R.) is gratified to the CSIR-UGC,
New Delhi, India for the award of junior research fellowship.
The authors are indebted toVice-Chancellor, Mahatma Gandhi
University, Nalgonda, India for providing the research facilities
and constant support.
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CONFLICT OF INTEREST
https://doi.org/10.1016/j.bmcl.2010.03.013.
The authors declare that there is no conflict of interests
regarding the publication of this article.
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