Antimicrobial and antileishmanial studies of novel (2E)-3-(2-chloro-6- methyl/methoxyquinolin-3-yl)-1-(aryl)prop-2-en-1-ones

Article abstract of DOI:10.1248/cpb.58.301

Thirty eight heterocyclic chalcones were synthesized by condensing formylquinolines with diverse methyl arylketones. The target compounds were characterized by spectroscopic techniques (NMR, IR, MS) and elemental analysis. The X-ray crystallographic study of (2E)-3-(2-chloro-6-methylquinolin-3-yl)-1- (2,3-dihydro-1,4-benzodioxin-6-yl)prop-2-en-1-one (1p) was also performed for the structure confirmation. The title compounds were screened for anti-microbial and antileishmanial activities. The compounds 1c - e, 1g, 1j - m, 1p, 1r - s, 2g, 2j - p, and 2r - s were found potentially active antileishmanial agents, while 1f - i, 1l, 1o - p, 2f - i, 2l, and 2o - p showed remarkable antibacterial activity. Only compounds 1g and 2g - h exhibited significant antifungal activity.

Full text of DOI:10.1248/cpb.58.301

March 2010
Chem. Pharm. Bull. 58(3) 301—306 (2010)
301
Antimicrobial and Antileishmanial Studies of Novel (2E)-3-(2-Chloro-6-
methyl/methoxyquinolin-3-yl)-1-(Aryl)prop-2-en-1-ones
Syed Umar Farooq RIZVI,a Hamid Latif SIDDIQUI,*,a Masood PARVEZ,b Matloob AHMAD,a
d
Waseeq Ahmad SIDDIQUI,c and Muhammad Masoom YASINZAI
a Institute of Chemistry, University of the Punjab; Lahore-54590, Pakistan: b Department of Chemistry, The University of
Calgary; 2500 University Drive, NW, Calgary, Alberta T2N 1N4, Canada: c Department of Chemistry, Ibn-e-Sina Block,
University of Sargodha; Sargodha–40100, Pakistan: and d Institute of Biochemistry, Balochistan University; Quetta–8700,
Pakistan. Received July 11, 2009; accepted December 3, 2009; published online December 9, 2009
Thirty eight heterocyclic chalcones were synthesized by condensing formylquinolines with diverse methyl
arylketones. The target compounds were characterized by spectroscopic techniques (NMR, IR, MS) and elemen-
tal analysis. The X-ray crystallographic study of (2E)-3-(2-chloro-6-methylquinolin-3-yl)-1-(2,3-dihydro-1,4-ben-
zodioxin-6-yl)prop-2-en-1-one (1p) was also performed for the structure confirmation. The title compounds were
screened for anti-microbial and antileishmanial activities. The compounds 1c—e, 1g, 1j—m, 1p, 1r—s, 2g, 2j—p,
and 2r—s were found potentially active antileishmanial agents, while 1f—i, 1l, 1o—p, 2f—i, 2l, and 2o—p
showed remarkable antibacterial activity. Only compounds 1g and 2g—h exhibited significant antifungal activity.
Key words chalcone; antimicrobial activity; antileishmanial activity; formylquinoline; arylketone
Chalcones are a,b-unsaturated ketones which constitute sized chalcones were in full agreement with the proposed
an important group of natural products that serve as precur- structures. Configuration of the double bond (1a—s, 2a—s)
sors for the synthesis of various heterocyclic compounds like was confirmed by coupling constant in 1H-NMR.
pyrimidines, imidazoles,1) pyrazoles,2) 2-pyrazolines3,4) and
Antileishmanial Activity According to the results ob-
flavonoids.5,6) Chalcones, either natural or synthetic, are known tained, it is evident that unsubstituted thiophenyl derivatives
to exhibit various biological activities such as anti-inflamma-
tory,7,8) antifungal,9—12) antioxidant,13—16) antimalarial,17—20)
Table 1. Aryl Moiety (Ar) of Aromatic Ketones (a—s)
antituberculosis,21) analgesic,22) anti-human immunodefi-
ciency virus (HIV)23) and antitumor activities.23—25) Some of
them act as anticancer,26) antiviral27) and anti-AIDS agents.28)
Quinoline-based chalcones have been reported to possess
antimalarial activity.29) Chalcones as well as some quinoline
derivatives have already been recognized for their antimicro-
bial30,31) and antileishmanial activities.32—34) In the present
study, the quinoline nucleus and chalcone functionality have
been incorporated in a single molecule (1a—s, 2a—s) and
deliberated their antimicrobial and antileishmanial activities
with variation of substituents at different positions in the Ar
ring.
Ketones Ar
Ketones Ar
Ketones Ar
a
g
m
b
c
h
i
n
o
p
d
j
The two precursors, 2-chloro-6-methyl-3-formylquinoline
and 2-chloro-6-methoxy-3-formylquinoline, were prepared
by reported method.35) Synthesis of the title compounds
(1a—s, 2a—s), was based on Claisen–Schmidt condensa-
tion.36,37) For this purpose, the prepared formyl quinolines
were condensed with commercially available methyl arylke-
tones (Table 1), in the presence of sodium hydroxide. The E-
configuration was confirmed by X-ray structure of (1p) and
two more chalcones (1k, 1m) which were already reported.38)
Spectral data (IR, 1H-NMR and MS) of all the newly synthe-
e
f
k
l
q
r
s
Chart 1
∗ To whom correspondence should be addressed. e-mail: drhamidlatif@yahoo.com
© 2010 Pharmaceutical Society of Japan

302
Vol. 58, No. 3
Table 2. Antileishmanial Activity of the Series 1a—s and 2a—s (IC50)
Compounds
IC50 (mg/ml)
Compounds
IC50 (mg/ml)
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
0.58ꢁ0.02
0.75ꢁ0.05
0.27ꢁ0.02
0.34ꢁ0.06
0.16ꢁ0.19
0.78ꢁ0.07
0.23ꢁ0.50
0.81ꢁ0.45
0.57ꢁ0.01
0.42ꢁ0.62
0.31ꢁ0.03
0.33ꢁ0.06
0.37ꢁ0.10
0.84ꢁ0.58
0.87ꢁ1.25
0.26ꢁ0.08
0.91ꢁ1.69
0.21ꢁ0.04
0.29ꢁ0.03
0.56ꢁ0.20
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
0.59ꢁ0.01
0.82ꢁ1.25
0.84ꢁ0.35
0.61ꢁ0.05
0.93ꢁ0.08
0.68ꢁ0.56
0.23ꢁ0.50
0.69ꢁ0.06
0.79ꢁ0.78
0.32ꢁ0.62
0.41ꢁ0.03
0.33ꢁ0.06
0.27ꢁ0.10
0.29ꢁ0.03
0.22ꢁ0.19
0.46ꢁ0.08
0.57ꢁ0.02
0.31ꢁ0.04
0.39ꢁ0.03
0.56ꢁ0.20
Fig. 1. ORTEP-3 Diagram of Compound 1p with the Numbering Scheme
Displacement ellipsoids are drawn at the 50% probability level, H atoms are repre-
sented by circles of arbitrary radii.
(1a, 2a) are almost equally active (IC50ꢀ0.58ꢁ0.02 mg/ml
for 1a and IC50ꢀ0.59ꢁ0.01 mg/ml for 2a), comparable to the
standard, amphotericin B (IC50ꢀ0.56ꢁ0.20 mg/ml) while the
activity enhances considerably by the substitution of methyl
and halo groups at position 5 of thiophenyl ring (1d, 2d, 1g,
2g, 1j, 2j, 1k, 2k; Table 2). Among the compounds, deriva-
tized at position 5, chloro analogues (1g, 2g) are the most ac-
tive. However, incorporation of these functionalities at posi-
tion 3 of thiophenyl ring (1b, 2b, 1f, 2f, 1i, 2i) instead of po-
sition 5, deactivates the compounds except of bromo deriva-
1q
1r
1s
2q
2r
2s
Standard drug
MIC (mg/mlꢁS.D.)
(Amphotericin B)
Standard drug
MIC (mg/mlꢁS.D.)
(Amphotericin B)
tive (1i) perhaps due to electronic and steric reasons. Incor- 2m). In general, activity enhances by the substitution of aro-
poration of methyl group at position 4 (1c) in category 1 in- matic rings with electron withdrawing groups and is sup-
creases the activity than its analogue 1b, derivatized at posi- pressed by the incorporation of electron donating methyl
tion 3 (IC50ꢀ0.75ꢁ0.05 mg/ml for 1b and IC50ꢀ0.27ꢁ0.02 groups. No systematic change has been observed in antibac-
mg/ml for 1c), while no prominent difference in activities is terial activities for the rest of the compounds (Table 3).
observed by the same change in category 2 (2b, 2c respec-
Antifungal Activity Among the compounds under in-
tively, Table 2). Similarly, the replacement of two methyl vestigation, un-substituted thiophenyl derivatives (1a, 2a) are
groups at position 2 and 5 of thiophenyl ring (1e, 2e) by two found almost equivalent in their antifungal activities to the
chloro groups (1h, 2h), significantly decreases the activity standard. In general, activity decreases in the compounds
(by about 5 times) in category 1; reverse is observed in case having substitution at position 2, 3 and 5 by the incorpora-
of category 2. In case of furanyl derivatives, incorporation of tion of electron donating methyl groups at aromatic rings
a second methyl group at position 2 considerably decreases while it enhances by the substitution of electron withdrawing
the activity (1n) than of the mono substituted one (1m) in groups. Among the electron withdrawing groups, activity in-
category 1, whereas in category 2 no marked difference is creases with the electronegativity of the substituent. How-
observed whether one (2m) or two (2n) methyl groups are ever, such substitutions at position 4 (1c, 2c) displayed no
present on the furanyl ring. For the rest of the compounds, no marked difference in the activities. No systematic change has
systematic change in anti-leishmanial activities is observed been observed in antibacterial activities for the rest of the
(Table 2).
Antibacterial Activity Compounds 2h, and 2o—p,
from substituted heteroaryl derivatives have shown promis- Conclusion
compounds (Table 3).
ing antibacterial activities (almost equivalent to standard)
Amongst the compounds tested for antibacterial study,
against all the three bacterial strains i.e., Escherichia coli, 1f—i, 1l, 1o—p, 2f—i, 2l, and 2o—p showed remarkable
Micrococcus luteus and Staphylococcus aureus. Among the antibacterial activity. Especially, compounds 1h, 1l, 1o—p,
two series of compounds, unsubstituted thiophenyl deriva- 2h—i, and 2o—p showed significant activity against E. coli
tives (1a, 2a) exhibited almost equivalent antibacterial activi- and 1h—i, 2h—i and 2o against M. luteus while 1h—i, 1p,
ties to that of the standard (Table 3). Activity decreases con- 2g, 2h—i, 2l and 2p were found most active against S. au-
siderably by the substitution of methyl and halo groups at po- reus. Compunds 1g, and 2g—h displayed more antifungal
sition 5 of thiophenyl ring (1d, 2d, 1g, 2g, 1j, 2j, 1k, 2k; activity, against all the fungi, than the standard flucanazole.
Table 3). Incorporation of chlorine at position 5 of thio- As far as antileishmanial activity is concerned, the com-
phenyl ring (1g, 2g) enhanced the activity to a considerable pounds 1c—e, 1g, 1j—m, 1p, 1r—s, 2g, 2j—p, and 2r—s
extent; it is further increased by the incorporation of another exhibited marvelous antileishmanial activity, while others
chlorine atom at position 2 (1h, 2h). However, incorporation showed moderate activity.
of same groups at positions 3 and 4 (1b, 1c, 1f, 1i, 2b, 2c, 2f,
2i) exhibited no difference in activity except of bromo deriv-
atives. In case of furanyl derivatives, incorporation of a sec-
ond methyl group at position 2 (1n, 2n) considerably de-
creases the activity than of the mono substituted one (1m,
Experimental
General Melting points were obtained on Gallenkamp melting point
apparatus and were uncorrected. IR spectra were recorded in KBr pellets on
Perkin Elmer infrared spectrophotometer. 1H-NMR spectra were recorded in
CDCl3 on Brücker/XWIN NMR (400 MHz) and tetramethylsilane (TMS)

March 2010
303
Table 3. Antimicrobial Activity of Compounds (1a—s, 2a—s)
Antibacterial activity zone of inhibition in mm
Antifungal activity zone of inhibition in mm
Compound
E. coli
M. luteus
S. aureus
A. flaves
A. niger
C. lunata
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
1q
1r
1s
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
2q
2r
21
16
14
13
11
30
32
36
28
20
15
36
16
11
36
37
11
15
10
22
20
16
14
12
31
33
38
37
21
14
30
18
13
37
38
12
25
17
39
ꢄve
31
23
27
22
20
28
30
35
34
22
21
33
27
17
30
30
25
17
15
32
28
23
27
22
30
32
35
34
20
18
36
30
19
34
32
27
30
20
36
ꢄve
34
25
31
26
22
30
38
39
40
31
19
37
31
15
31
39
35
25
11
35
29
37
30
24
33
39
41
40
30
12
41
32
12
33
41
37
35
13
43
ꢄve
10
8
7
4
3
20
18
13
16
10
7
10
12
3
11
10
9
10
8
15
17
15
17
9
12
11
8
9
5
11
15
10
12
10
11
14
10
6
11
15
13
11
10
13
5
9
11
13
5
16
12
15
10
12
12
6
11
8
7
17
21
22
14
6
8
11
10
11
10
11
7
10
8
4
22
20
25
12
9
9
10
6
10
18
20
11
11
10
13
11
8
18
16
14
11
12
16
ꢄve
6
8
16
10
2
11
12
13
10
11
17
ꢄve
16
10
3
17
13
16
11
13
18
ꢄve
2s
Standarad
DMF
ꢄve indicates microbial growth. Control: DMF (0.01% solution in distilled water). Standard for antibacterial: Chloramphenicol (1.00 mmol/ml). Standard for antifungal: Flu-
canazole (1.00 mmol/ml).
was used as internal standard (chemical shifts, d in ppm). Mass spectra were
(2E)-3-(2-Chloro-6-methylquinolin-3-yl)-1-(3-methylthien-2-yl)prop-
2-en-1-one 1b 53% yield. Pale yellow solid. mp 172—173 °C. IR (KBr)
recorded on a Jeol MSRoute instrument. Phosphoryl chloride, aromatic ke-
tones, p-anisidine, p-toluidine and N,N-dimethylformamide (Aldrich and cmꢂ1: 1654 (CꢀO), 1594 (CꢀC). 1H-NMR (CDCl3) d: 2.45—2.66 (s,
Alpha Aesar) were used as received. Elemental analyses were performed by Meꢅ2), 7.02 (1H, d, H4ꢃ, Jꢀ4.9 Hz), 7.40 (1H, d, Ha, Jꢀ15.4 Hz), 7.49 (1H,
C.S.I.C., Madrid, Spain and were within ꢁ0.4% of predicted values for all d, H5ꢃ, Jꢀ4.9 Hz), 7.58 (1H, dd, H7, Jꢀ8.6 Hz), 7.64 (1H, s, H5), 7.90 (1H,
compounds.
d, H8, Jꢀ8.6 Hz), 8.18 (1H, d, Hb, Jꢀ15.4 Hz), 8.35 (1H, s, H4). MS (m/z):
General Procedure for the Synthesis of Chalcones 1a—s and 2a—s 327 (Mꢄ, 25.8%), 292 (MꢄꢂCl, 100%). Anal. Calcd for C18H14NOClS: C,
The two precursors, 6-methyl/methoxy-substituted 2-chloro-3-formylquino- 65.95; H, 4.30; N, 4.27. Found: C, 65.89; H, 4.29; N, 4.25.
lines, were synthesized according to the literature procedure. A mixture of
(2E)-3-(2-Chloro-6-methylquinolin-3-yl)-1-(4-methylthien-2-yl)prop-
formylquinoline (10 mmol) and an aromatic ketone (10 mmol) in methanol 2-en-1-one 1c 45% yield. White solid. mp 150 °C. IR (KBr) cmꢂ1: 1656
(50 ml) was stirred at room temperature, followed by dropwise addition of (CꢀO), 1593 (CꢀC). 1H-NMR (CDCl3) d: 2.25—2.48 (s, Meꢅ2), 7.18
aq. NaOH (4 ml, 10%). The stirring was continued for 2 h and the reaction
(1H, s, H5ꢃ), 7.31 (1H, s, H4ꢃ), 7.44 (1H, d, Ha, Jꢀ15.5 Hz), 7.48 (1H, dd,
mixture was then kept at 0 °C (24 h). Subsequently, it was poured onto ice- H7, Jꢀ8.6 Hz), 7.51 (1H, s, H5), 7.83 (1H, d, H8, Jꢀ8.5 Hz), 8.21 (1H, d, Hb,
cold water (200 ml). The precipitates were collected by filtration, washed Jꢀ15.6 Hz), 8.41 (1H, s, H4). MS (m/z): 328 (Mꢄ, 11.4%), 125
with cold water followed by cold MeOH. The resulting chalcones were re- (MꢄꢂC12H9NCl, 100%). Anal. Calcd for C18H14NOClS: C, 65.95; H, 4.30;
crystallised from CHCl3.
N, 4.27. Found: C, 65.87; H, 4.24; N, 4.26.
(2E)-3-(2-Chloro-6-methylquinolin-3-yl)-1-thien-3-ylprop-2-en-1-one
(2E)-3-(2-Chloro-6-methylquinolin-3-yl)-1-(5-methylthien-2-yl)prop-
1a 72% yield. Pale yellow solid. mp 183—185 °C. IR (KBr) cmꢂ1: 1648 2-en-1-one 1d 44% yield. Bright yellow solid. mp 198 °C. IR (KBr) cmꢂ1
:
(CꢀO), 1592 (CꢀC). H-NMR (CDCl3) d: 2.54 (3H, s, Me), 7.39 (1H, dd, 1652 (CꢀO), 1596 (CꢀC). 1H-NMR (CDCl3) d: 2.54—2.57 (s, Meꢅ2),
1
H4ꢃ, Jꢀ2.8 Hz), 7.44 (1H, d, Ha, Jꢀ15.7 Hz), 7.6 (1H, d, H7, Jꢀ8.6 Hz),
7.62 (1H, s, H5), 7.70 (1H, d, H5ꢃ, Jꢀ4.7 Hz), 7.91 (1H, d, H8, Jꢀ8.5 Hz),
6.87 (1H, d, H4ꢃ, Jꢀ3.6 Hz), 7.42 (1H, d, Ha, Jꢀ15.6 Hz), 7.58 (1H, dd, H7,
Jꢀ8.6 Hz), 7.62 (1H, s, H5), 7.71 (1H, d, H3ꢃ, Jꢀ3.8 Hz), 7.90 (1H, d, H8,
8.18 (1H, d, Hb, Jꢀ15.8 Hz), 8.20 (1H, dd, H2ꢃ, Jꢀ2.2 Hz), 8.36 (1H, s, H4). Jꢀ8.6 Hz), 8.18 (1H, d, Hb, Jꢀ15.6 Hz), 8.35 (1H, s, H4). MS (m/z): 327
MS (m/z): 313 (Mꢄ, 7.9%), 278 (MꢄꢂCl, 100%). Anal. Calcd for (Mꢄ, 12.1%), 292 (MꢄꢂCl, 100%). Anal. Calcd for C18H14NOClS: C,
C17H12NOClS: C, 65.07; H, 3.85; N, 4.46. Found: C, 65.02; H, 3.75; N, 4.41.
65.95; H, 4.30; N, 4.27. Found: C, 65.89; H, 4.27; N, 4.22.

304
(2E)-3-(2-Chloro-6-methylquinolin-3-yl)-1-(2,5-dimethylthien-3-
yl)prop-2-en-1-one 1e 67% yield. Pale yellw solid. mp 128—130 °C; IR
(KBr) cmꢂ1: 1648 (CꢀO), 1585 (CꢀC). 1H-NMR (CDCl3) d: 2.44—2.72
(s, Meꢅ3), 7.10 (1H, s, H4ꢃ), 7.33 (1H, d, Ha, Jꢀ15.7 Hz), 7.58 (1H, dd, H7,
Jꢀ8.6 Hz), 7.62 (1H, s, H5), 7.90 (1H, d, H8, Jꢀ8.6 Hz), 8.08 (1H, d, Hb,
Jꢀ15.7 Hz), 8.33 (1H, s, H4). MS (m/z): 341 (Mꢄ, 48.2%), 306 (MꢄꢂCl,
100%). Anal. Calcd for C19H16NOClS: C, 66.75; H, 4.72; N, 4.10. Found: C,
66.61; H, 4.63; N, 4.05.
(2E)-3-(2-Chloro-6-methylquinolin-3-yl)-1-(3-chlorothien-2-yl)prop-2-
en-1-one 1f 74% yield. Bright yellow solid. mp 184—186 °C. IR (KBr)
cmꢂ1: 1650 (CꢀO), 1592 (CꢀC). 1H-NMR (CDCl3) d: 2.53 (3H, s, Me),
7.07 (1H, d, H4ꢃ, Jꢀ5.2 Hz), 7.50 (1H, d, H5ꢃ, Jꢀ5.2 Hz), 7.59 (1H, dd, H7,
Jꢀ8.5 Hz), 7.64 (1H, s, H5), 7.82 (1H, d, Ha, Jꢀ15.6 Hz), 7.90 (1H, d, H8,
Jꢀ8.6 Hz), 8.22 (1H, d, Hb, Jꢀ15.5 Hz), 8.37 (1H, s, H4). MS (m/z): 347
(Mꢄ, 4.2%), 312 (MꢄꢂCl, 100%). Anal. Calcd for C17H11NOCl2S: C, 58.63;
H, 3.18; N, 4.02. Found: C, 58.54; H, 3.16; N, 3.99.
Vol. 58, No. 3
147 °C; IR (KBr) cmꢂ1: 1648 (CꢀO), 1596 (CꢀC). 1H-NMR (CDCl3) d:
2.29—2.62 (s, Meꢅ3), 6.34 (1H, s, H4ꢃ), 7.22 (1H, d, Ha, Jꢀ15.9 Hz), 7.58
(1H, dd, H7, Jꢀ8.6 Hz), 7.61 (1H, s, H5), 7.90 (1H, d, H8, Jꢀ8.6 Hz), 8.08
(1H, d, Hb, Jꢀ15.8 Hz), 8.31 (1H, s, H4). MS (m/z): 325 (Mꢄ, 38.1%), 290
(MꢄꢂCl, 100%). Anal. Calcd for C19H16NO2Cl: C, 70.05; H, 4.95; N, 4.30.
Found: C, 69.99; H, 4.94; N, 4.22.
(2E)-1-(1-Benzofuran-2-yl)-3-(2-chloro-6-methylquinolin-3-yl)prop-2-
en-1-one 1o 56% yield. Off white solid. mp 162 °C. IR (KBr) cmꢂ1: 1660
1
(CꢀO), 1592 (CꢀC). H-NMR (CDCl3) d: 2.47 (3H, s, Me), 7.28 (1H, t,
Ar-H), 7.36 (1H, d, Ha, Jꢀ15.8 Hz), 7.42—7.53 (4H, m, Ar-H), 7.62 (1H, s,
H5), 7.68 (1H, dd, H7, Jꢀ8.5 Hz), 7.83 (1H, d, H8, Jꢀ8.6 Hz), 8.04 (1H, d,
Hb, Jꢀ15.6 Hz), 8.11 (1H, s, H4). MS (m/z): 348 (Mꢄ, 12.5%), 313
(MꢄꢂCl, 100%). Anal. Calcd for C21H14NO2Cl: C, 72.52; H, 4.06; N, 4.03.
Found: C, 72.49; H, 3.98; N, 4.01.
(2E)-3-(2-Chloro-6-methylquinolin-3-yl)-1-(2,3-dihydro-1,4-benzodi-
oxin-6-yl)prop-2-en-1-one 1p 46% yield. Off white solid. mp 158—
160 °C. IR (KBr) cmꢂ1: 1658 (CꢀO), 1595 (CꢀC). 1H-NMR (CDCl3) d:
2.54 (3H, s, Me), 4.32 (4H, m, Dioxane Ring), 6.96 (1H, d, Ar-H,
Jꢀ8.8 Hz), 7.42 (1H, m, Ar-H), 7.55 (1H, d, Ha, Jꢀ15.7 Hz), 7.58 (1H, dd,
H7, Jꢀ8.6 Hz), 7.62 (1H, s, H5), 7.70 (1H, m, Ar-H), 7.90 (1H, d, H8, Jꢀ
8.6 Hz), 8.15 (1H, d, Hb, Jꢀ15.7 Hz), 8.36 (1H, s, H4). MS (m/z): 365 (Mꢄ,
24.1%), 330 (MꢄꢂCl, 100%). Anal. Calcd for C21H16NO3Cl: C, 68.95; H,
4.41; N, 3.83. Found: C, 68.91; H, 4.36; N, 3.79.
(2E)-3-(2-Chloro-6-methylquinolin-3-yl)-1-(5-chlorothien-2-yl)prop-2-
en-1-one 1g 89% yield. Bright yellow solid. mp 180 °C. IR (KBr) cmꢂ1
:
1656 (CꢀO), 1598 (CꢀC). 1H-NMR (CDCl3) d: 2.54 (3H, s, Me), 7.03 (1H,
d, H4ꢃ, Jꢀ4.0 Hz), 7.39 (1H, d, Ha, Jꢀ15.6 Hz), 7.60 (1H, dd, H7,
Jꢀ8.6 Hz), 7.63 (1H, s, H5), 7.68 (1H, d, H3ꢃ, Jꢀ4.0 Hz), 7.91 (1H, d, H8,
Jꢀ8.5 Hz), 8.21 (1H, d, Hb, Jꢀ15.6 Hz), 8.36 (1H, s, H4). MS (m/z): 347
(Mꢄ, 6.9%), 312 (MꢄꢂCl, 100%). Anal. Calcd for C17H11NOCl2S: C, 58.63;
H, 3.18; N, 4.02. Found: C, 58.57; H, 3.13; N, 3.99.
(2E)-3-(2-Chloro-6-methylquinolin-3-yl)-1-(1-naphthyl)prop-2-en-1-
one 1q 97% yield. Bright yellow solid. mp 138 °C. IR (KBr) cmꢂ1: 1659
(2E)-3-(2-Chloro-6-methylquinolin-3-yl)-1-(2,5-dichlorothien-3-
yl)prop-2-en-1-one 1h 53% yield. Pale yellow solid. mp 128 °C. IR (KBr)
cmꢂ1: 1664 (CꢀO), 1595 (CꢀC). 1H-NMR (CDCl3) d: 2.53 (3H, s, Me),
7.15 (1H, s, H4ꢃ), 7.46 (1H, d, Ha, Jꢀ15.7 Hz), 7.60 (1H, dd, H7, Jꢀ8.6 Hz),
7.63 (1H, s, H5), 7.90 (1H, d, H8, Jꢀ8.6 Hz), 8.14 (1H, d, Hb, Jꢀ15.7 Hz),
8.34 (1H, s, H4). MS (m/z): 383 (Mꢄ, 5.7%), 346 (MꢄꢂCl, 100%). Anal.
Calcd for C17H10NOCl3S: C, 53.35; H, 2.63; N, 3.66. Found: C, 53.22; H,
2.58; N, 3.62.
(2E)-1-(3-Bromothien-2-yl)-3-(2-chloro-6-methylquinolin-3-yl)prop-2-
en-1-one 1i 64% yield. Bright yellow solid. mp 189—191 °C; IR (KBr)
cmꢂ1: 1650 (CꢀO), 1591 (CꢀC). 1H-NMR (CDCl3) d: 2.54 (3H, s, Me),
7.16 (1H, d, H4ꢃ, Jꢀ5.16 Hz), 7.58 (1H, d, H5ꢃ, Jꢀ5.1 Hz), 7.59 (1H, dd, H7,
Jꢀ8.6 Hz), 7.65 (1H, s, H5), 7.83 (1H, d, Ha, Jꢀ15.5 Hz), 7.91 (1H, d, H8,
Jꢀ8.6 Hz), 8.22 (1H, d, Hb, Jꢀ15.5 Hz), 8.38 (1H, s, H4). MS (m/z): 393
(Mꢄ, 5.1%), 356 (MꢄꢂCl, 100%). Anal. Calcd for C17H11NOClSBr: C,
51.99; H, 2.82; N, 3.57. Found: C, 51.96; H, 2.79; N, 3.58.
(2E)-1-(5-Bromothien-2-yl)-3-(2-chloro-6-methylquinolin-3-yl)prop-2-
en-1-one 1j 55% yield. Pale brown solid. mp 160—161 °C. IR (KBr)
cmꢂ1: 1653 (CꢀO), 1588 (CꢀC). 1H-NMR (CDCl3) d: 2.54 (3H, s, Me),
7.10 (1H, d, H4ꢃ, Jꢀ4.0 Hz), 7.17 (1H, d, H3ꢃ, Jꢀ4.0 Hz), 7.38 (1H, d, Ha,
Jꢀ15.6 Hz), 7.60 (1H, dd, H7, Jꢀ8.5 Hz), 7.63 (1H, s, H5), 7.91 (1H, d, H8,
Jꢀ8.3 Hz), 8.21 (1H, d, Hb, Jꢀ15.6 Hz), 8.36 (1H, s, H4). MS (m/z): 393
(Mꢄ, 10.9%), 358 (MꢄꢂCl, 100%). Anal. Calcd for C17H11NOClSBr: C,
51.99; H, 2.82; N, 3.57. Found: C, 51.98; H, 2.77; N, 3.56.
1
(CꢀO), 1587 (CꢀC). H-NMR (CDCl3) d: 2.53 (3H, s, Me), 7.38 (1H, d,
Ha, Jꢀ15.9 Hz), 7.53—7.60 (5H, m, Ar-H), 7.85 (1H, d, Ar-H, Jꢀ6.8 Hz),
7.90 (1H, d, H7, Jꢀ8.6 Hz), 7.93 (1H, s, H5), 8.02 (1H, d, H8, Jꢀ8.1 Hz),
8.04 (1H, d, Hb, Jꢀ16.2 Hz), 8.37 (1H, s, H4), 8.39 (1H, d, Ar-H, Jꢀ8.3 Hz).
MS (m/z): 357 (Mꢄ, 17.2%), 322 (MꢄꢂCl, 100%). Anal. Calcd for
C23H16NOCl: C, 77.20; H, 4.51; N, 3.91. Found: C, 77.13; H, 4.47; N, 3.85.
(2E)-3-(2-Chloro-6-methylquinolin-3-yl)-1-(2-naphthyl)prop-2-en-1-
one 1r 65% yield. Off white solid. mp 138 °C. IR (KBr) cmꢂ1: 1654 (Cꢀ
1
O), 1589 (CꢀC). H-NMR (CDCl3) d: 2.53 (3H, s, Me), 7.35 (1H, d, Ha,
Jꢀ16.1 Hz), 7.53—7.56 (2H, m, Ar-H), 7.60 (1H, dd, H7, Jꢀ 8.1 Hz), 7.63
(1H, s, H5), 7.86—7.93 (4H, m, Ar-H), 8.03 (1H, dd, H8, Jꢀ8.6 Hz), 8.06
(1H, d, Hb, Jꢀ16.1 Hz), 8.44 (1H, s, H4), 8.46 (1H, s, Ar-H). MS (m/z): 357
(Mꢄ, 1.7%), 127 (MꢄꢂC13H9NOCl, 100%). Anal. Calcd for C23H16NOCl:
C, 77.20; H, 4.51; N, 3.91. Found: C, 77.18; H, 4.48; N, 3.91.
(2E)-1-(9-Anthryl)-3-(2-chloro-6-methylquinolin-3-yl)prop-2-en-1-one
1s 86% yield. Deep yellow solid. mp 232—233 °C. IR (KBr) cmꢂ1: 1662
1
(CꢀO), 1586 (CꢀC). H-NMR (CDCl3) d: 2.54 (3H, s, Me), 7.32 (1H, d,
Ha, Jꢀ16.1 Hz), 7.47—7.57 (4H, m, Ar-H), 7.60 (1H, dd, H7, Jꢀ8.5 Hz),
7.63 (1H, s, H5), 7.77 (1H, d, Hb, Jꢀ16.1 Hz), 7.84 (1H, d, H8, Jꢀ8.6 Hz),
7.92—7.95 (2H, m, Ar-H), 8.05—8.07 (2H, m, Ar-H), 8.31 (1H, s, H4), 8.56
(1H, s, Ar-H). MS (m/z): 407 (Mꢄ, 83%), 177 (MꢄꢂC13H9NOCl, 100%).
Anal. Calcd for C27H18NOCl: C, 79.50; H, 4.45; N, 3.43. Found: C, 7979.46;
H, 4.41; N, 3.39.
(2E)-3-(2-Chloro-6-methylquinolin-3-yl)-1-(5-iodothien-2-yl)prop-2-
(2E)-3-(2-Chloro-6-methoxyquinolin-3-yl)-1-thien-3-ylprop-2-en-1-
en-1-one 1k 87% yield. Pale yellow solid. mp 178 °C. IR (KBr) cmꢂ1
:
one 2a 82% yield. Yellowish grey solid. mp 182 °C. IR (KBr) cmꢂ1: 1648
1648 (CꢀO), 1596 (CꢀC). 1H-NMR (CDCl3) d: 2.54 (3H, s, Me), 7.36 (1H,
d, H4ꢃ, Jꢀ3.9 Hz), 7.37 (1H, d, Ha, Jꢀ15.5 Hz), 7.50 (1H, d, H3ꢃ, Jꢀ3.9 Hz),
7.59 (1H, dd, H7, Jꢀ8.7 Hz), 7.62 (1H, s, H5), 7.90 (1H, d, H8, Jꢀ8.5 Hz),
8.20 (1H, d, Hb, Jꢀ15.6 Hz), 8.35 (1H, s, H4). MS (m/z): 439 (Mꢄ, 12.6%),
404 (MꢄꢂCl, 100%). Anal. Calcd for C17H11NOClSI: C, 46.44; H, 2.52; N,
3.19. Found: C, 46.41; H, 2.45; N, 3.17.
1
(CꢀO), 1593 (CꢀC). H-NMR (CDCl3) d: 3.94 (3H, s, OMe), 7.11 (1H, d,
H5, Jꢀ2.6 Hz), 7.39 (1H, d, H4ꢃ, Jꢀ2.9 Hz), 7.45 (1H, d, Ha, Jꢀ15.7 Hz),
7.60 (1H, dd, H7, Jꢀ9.1 Hz), 7.69 (1H, d, H5ꢃ, Jꢀ4.6 Hz), 7.91 (1H, d, H8,
Jꢀ9.2 Hz), 8.17 (1H, d, Hb, Jꢀ15.9 Hz), 8.20 (1H, dd, H2ꢃ, Jꢀ2.2 Hz), 8.36
(1H, s, H4). MS (m/z): 329 (Mꢄ, 19.7%), 294 (MꢄꢂCl, 100%). Anal. Calcd
for C17H12NO2ClS: C, 61.91; H, 3.67; N, 4.25. Found: C, 61.90; H, 3.61; N,
4.23.
(2E)-3-(2-Chloro-6-methylquinolin-3-yl)-1-(1H-pyrrol-2-yl)prop-2-en-
1-one 1l 70% yield. Bright yellow solid. mp 214 °C. IR (KBr) cmꢂ1: 1654
(2E)-3-(2-Chloro-6-methoxyquinolin-3-yl)-1-(3-methylthien-2-
yl)prop-2-en-1-one 2b 64% yield. Greenish yellow solid. mp 180 °C. IR
1
(CꢀO), 1594 (CꢀC). H-NMR (CDCl3) d: 2.47 (3H, s, Me), 6.24 (1H, dd,
1
(KBr) cmꢂ1: 1654 (CꢀO), 1594 (CꢀC). H-NMR (CDCl3) d: 2.67 (3H, s,
H4ꢃ, Jꢀ3.5 Hz), 6.70 (1H, d, H3ꢃ, Jꢀ3.5 Hz), 7.05 (1H, d, H5ꢃ, Jꢀ4.2 Hz),
7.41 (1H, d, Ha, Jꢀ15.6 Hz), 7.57 (1H, dd, H7, Jꢀ8.6 Hz), 7.63 (1H, s, H5),
7.91 (1H, d, H8, Jꢀ8.6 Hz), 8.18 (1H, d, Hb, Jꢀ15.7 Hz), 8.35 (s, 1H, H4).
MS (m/z): 295 (Mꢄ, 8.5%), 260 (MꢄꢂCl, 100%). Anal. Calcd for
C17H13N2OCl: C, 68.81; H, 4.42; N, 9.44. Found: C, 68.72; H, 4.36; N, 9.40.
(2E)-3-(2-Chloro-6-methylquinolin-3-yl)-1-(5-methyl-2-furyl)prop-2-
Me), 3.94 (3H, s, OMe), 7.02 (1H, d, H4ꢃ, Jꢀ4.9 Hz), 7.13 (1H, d, H5, Jꢀ
2.6 Hz), 7.36 (1H, d, H8, Jꢀ9.2 Hz), 7.40 (1H, d, Ha, Jꢀ15.5 Hz), 7.49 (1H,
d, H5ꢃ, Jꢀ4.9 Hz), 7.58 (1H, dd, H7, Jꢀ8.6 Hz), 7.90 (1H, d, H8, Jꢀ9.2 Hz),
8.17 (1H, d, Hb, Jꢀ15.4 Hz), 8.33 (1H, s, H4). MS (m/z): 343 (Mꢄ, 63.5%),
308 (MꢄꢂCl, 100%). Anal. Calcd for C18H14NO2ClS: C, 62.88; H, 4.10; N,
4.07. Found: C, 62.75; H, 4.02; N, 4.03.
en-1-one 1m 95% yield. Deep yellow solid. mp 158 °C. IR (KBr) cmꢂ1
:
1664 (CꢀO), 1594 (CꢀC). 1H-NMR (CDCl3) d: 2.45—2.54 (s, Meꢅ2),
6.24 (1H, dd, H4ꢃ, Jꢀ3.4 Hz), 7.29 (1H, d, H3ꢃ, Jꢀ3.5 Hz), 7.45 (1H, d, Ha,
Jꢀ15.7 Hz), 7.58 (1H, dd, H7, Jꢀ8.6 Hz), 7.63 (1H, s, H5), 7.90 (1H, d, H8,
Jꢀ8.6 Hz), 8.22 (1H, d, Hb, Jꢀ15.8 Hz), 8.38 (1H, s, H4). MS (m/z): 311
(Mꢄ, 8.3%), 276 (MꢄꢂCl, 100%). Anal. Calcd for C18H14NO2Cl: C, 69.34;
H, 4.53; N, 4.49. Found: C, 69.32; H, 4.47; N, 4.48.
(2E)-3-(2-Chloro-6-methoxyquinolin-3-yl)-1-(4-methylthien-2-
yl)prop-2-en-1-one 2c 74% yield. Greenish yellow solid. mp 146 °C. IR
1
(KBr) cmꢂ1: 1656 (CꢀO), 1594 (CꢀC). H-NMR (CDCl3) d: 2.33 (3H, s,
Me), 3.94 (3H, s, OMe), 7.02 (1H, d, H4ꢃ, Jꢀ4.9 Hz), 7.12 (1H, d, H5, Jꢀ
2.5 Hz), 7.31 (1H, s, H5ꢃ), 7.40 (1H, dd, H7, Jꢀ9.3 Hz), 7.44 (1H, d, Ha, Jꢀ
15.6 Hz), 7.70 (1H, s, H3ꢃ), 7.91 (1H, d, H8, Jꢀ9.2 Hz), 8.19 (1H, d, Hb, Jꢀ
15.6 Hz), 8.35 (1H, s, H4). MS (m/z): 343 (Mꢄ, 21.4%), 308 (MꢄꢂCl,
100%). Anal. Calcd for C18H14NO2ClS: C, 62.88; H, 4.10; N, 4.07. Found:
(2E)-3-(2-Chloro-6-methylquinolin-3-yl)-1-(2,5-dimethyl-3-
furyl)prop-2-en-1-one 1n 92% yield. Deep yellow solid. mp 145—

March 2010
305
C, 62.79; H, 4.04; N, 4.04.
Hz), 7.44 (1H, d, Ha, Jꢀ15.5 Hz), 7.52 (1H, dd, H7, Jꢀ8.6 Hz), 7.12 (1H, d,
H5, Jꢀ2.7 Hz), 7.90 (1H, d, H8, Jꢀ8.6 Hz), 8.20 (1H, d, Hb, Jꢀ15.6 Hz),
8.34 (1H, s, H4). MS (m/z): 311 (Mꢄ, 13.3%), 276 (MꢄꢂCl, 100%). Anal.
Calcd for C17H13N2O2Cl: C, 65.28; H, 4.19; N, 8.96. Found: C, 65.27; H,
4.11; N, 8.92.
(2E)-3-(2-Chloro-6-methoxyquinolin-3-yl)-1-(5-methyl-2-furyl)prop-
2-en-1-one 2m 98% yield. Greenish yellow solid. mp 168 °C. IR (KBr)
cmꢂ1: 1664 (CꢀO), 1594 (CꢀC). 1H-NMR (CDCl3) d: 2.45 (3H, s, Me),
3.93 (3H, s, OMe), 6.24 (1H, dd, H4ꢃ, Jꢀ3.0 Hz), 7.29 (1H, d, H3ꢃ, Jꢀ3.4
Hz), 7.45 (1H, d, Ha, Jꢀ15.8 Hz), 7.40 (1H, dd, H7, Jꢀ9.1 Hz), 7.12 (1H, d,
H5, Jꢀ2.7 Hz), 7.90 (1H, d, H8, Jꢀ8.2 Hz), 8.22 (1H, d, Hb, Jꢀ15.8 Hz),
8.36 (1H, s, H4). MS (m/z): 327 (Mꢄ, 28.7%), 292 (MꢄꢂCl, 100%). Anal.
Calcd for C18H14NO3Cl: C, 65.96; H, 4.31; N, 4.27. Found: C, 65.94; H,
4.31; N, 4.26.
(2E)-3-(2-Chloro-6-methoxyquinolin-3-yl)-1-(2,5-dimethyl-3-
furyl)prop-2-en-1-one 2n 69% yield. Pale yellow solid. mp 122 °C. IR
(KBr) cmꢂ1: 1649 (CꢀO), 1596 (CꢀC). 1H-NMR (CDCl3) d: 2.27—2.61
(s, Meꢅ2), 3.93 (3H, s, OMe), 6.97 (1H, s, H4ꢃ), 7.11 (1H, d, H5, Jꢀ2.7 Hz),
7.24 (1H, d, Ha, Jꢀ15.9 Hz), 7.40 (1H, dd, H7, Jꢀ9.2 Hz), 7.90 (1H, d, H8,
Jꢀ9.2 Hz), 8.12 (1H, d, Hb, Jꢀ15.8 Hz), 8.36 (1H, s, H4). MS (m/z): 341
(Mꢄ, 22.5%), 306 (MꢄꢂCl,100%). Anal. Calcd for C19H16NO3Cl: C, 66.77;
H, 4.72; N, 4.10. Found: C, 66.74; H, 4.68; N, 4.09.
(2E)-3-(2-Chloro-6-methoxyquinolin-3-yl)-1-(5-methylthien-2-
yl)prop-2-en-1-one 2d 57% yield. Yellowish grey solid. mp 152—153 °C.
IR (KBr) cmꢂ1: 1648 (CꢀO), 1588 (CꢀC). H-NMR (CDCl3) d: 2.54 (3H,
1
s, Me), 3.93 (3H, s, OMe), 7.06 (1H, d, H4ꢃ, Jꢀ4.4 Hz), 7.11 (1H, d, H5, Jꢀ
2.6 Hz), 7.33 (1H, d, Ha, Jꢀ15.6 Hz), 7.42 (1H, dd, H7, Jꢀ9.2 Hz), 7.68
(1H, d, H3ꢃ, Jꢀ4.4 Hz), 7.90 (1H, d, H8, Jꢀ9.2 Hz), 8.12 (1H, d, Hb, Jꢀ
15.6 Hz), 8.36 (1H, s, H4). MS (m/z): 343 (Mꢄ, 29.6%), 308 (MꢄꢂCl,
100%). Anal. Calcd for C18H14NO2ClS: C, 62.88; H, 4.10; N, 4.07. Found:
C, 62.81; H, 4.03; N, 4.01.
(2E)-3-(2-Chloro-6-methoxyquinolin-3-yl)-1-(2,5-dimethylthien-3-
yl)prop-2-en-1-one 2e 94% yield. Off white solid. mp 116 °C. IR (KBr)
cmꢂ1: 1648 (CꢀO), 1585 (CꢀC). 1H-NMR (CDCl3) d: 2.44—2.72 (s, Meꢅ
2), 3.93 (3H, s, OMe), 7.09 (1H, s, H4ꢃ), 7.10 (1H, d, H5, Jꢀ2.9), 7.33 (1H,
d, Ha, Jꢀ15.7 Hz), 7.39 (1H, dd, H7, Jꢀ9.2 Hz), 7.90 (1H, d, H8, Jꢀ9.2 Hz),
8.07 (1H, d, Hb, Jꢀ15.7 Hz), 8.31 (1H, s, H4). MS (m/z): 357 (Mꢄ, 56.4%),
322 (MꢄꢂCl, 100%). Anal. Calcd for C19H16NO2ClS: C, 63.77; H, 4.51; N,
3.91. Found: C, 63.62; H, 4.44; N, 3.85.
(2E)-3-(2-Chloro-6-methoxyquinolin-3-yl)-1-(3-chlorothien-2-yl)prop-
2-en-1-one 2f 67% yield. Greyish green solid. mp 136—138 °C. IR (KBr)
cmꢂ1: 1651 (CꢀO), 1594 (CꢀC). H-NMR (CDCl3) d: 3.94 (3H, s, OMe),
1
7.08 (1H, d, H4ꢃ, Jꢀ5.2 Hz), 7.12 (1H, d, H5, Jꢀ2.7 Hz), 7.41 (1H, dd, H7,
Jꢀ9.2 Hz), 7.61 (1H, d, H5ꢃ, Jꢀ5.2 Hz), 7.83 (1H, d, Ha, Jꢀ15.5 Hz), 7.91
(1H, d, H8, Jꢀ9.2 Hz), 8.22 (1H, d, Hb, Jꢀ15.6 Hz), 8.36 (1H, s, H4).
MS (m/z): 363 (Mꢄ, 24.9%), 328 (MꢄꢂCl, 100%). Anal. Calcd for
C17H11NO2Cl2S: C, 56.06; H, 3.04; N, 3.84. Found: C, 56.02; H, 3.01; N,
3.78.
(2E)-1-(1-Benzofuran-2-yl)-3-(2-chloro-6-methoxyquinolin-3-yl)prop-
2-en-1-one 2o 62% yield. Off white solid. mp 158 °C. IR (KBr) cmꢂ1
:
1
1658 (CꢀO), 1587 (CꢀC). H-NMR (CDCl3) d: 3.87 (3H, s, OMe), 7.01
(1H, d, H5, Jꢀ2.7 Hz), 7.29 (1H, t, Ar-H) 7.36 (1H, d, Ha, Jꢀ15.8 Hz),
7.42—7.52 (4H, m, Ar-H), 7.67 (1H, d, H7, Jꢀ9.2 Hz), 7.82 (1H, d, H8, Jꢀ
9.2 Hz), 8.06 (1H, d, Hb, Jꢀ15.8 Hz), 8.10 (1H, s, H4). MS (m/z): 363 (Mꢄ,
10.5%), 328 (MꢄꢂCl, 100%). Anal. Calcd for C21H14NO3Cl: C, 69.33; H,
3.88; N, 3.85. Found: C, 69.31; H, 3.82; N, 3.81.
(2E)-3-(2-Chloro-6-methoxyquinolin-3-yl)-1-(5-chlorothien-2-yl)prop-
2-en-1-one 2g 95% yield. Yellowish grey solid. mp 178—180 °C. IR
(KBr) cmꢂ1: 1654 (CꢀO), 1594 (CꢀC). H-NMR (CDCl3) d: 3.91 (3H, s,
1
OMe), 6.95 (1H, d, H4ꢃ, Jꢀ4.1 Hz), 7.11 (1H, d, H5, Jꢀ2.7 Hz), 7.36 (1H,
dd, H7, Jꢀ9.2 Hz), 7.42 (1H, d, Ha, Jꢀ15.6 Hz), 7.50 (1H, d, H3ꢃ, Jꢀ
4.1 Hz), 7.89 (1H, d, H8, Jꢀ9.2 Hz), 8.12 (1H, d, Hb, Jꢀ15.6 Hz), 8.36 (1H,
s, H4). MS (m/z): 363 (Mꢄ, 13.7%), 328 (MꢄꢂCl, 100%). Anal. Calcd for
C17H11NO2Cl2S: 56.06; H, 3.04; N, 3.84. Found: C, 56.01; H, 2.98; N, 3.79.
(2E)-3-(2-Chloro-6-methoxyquinolin-3-yl)-1-(2,5-dichlorothien-3-
yl)prop-2-en-1-one 2h 96% yield. Greyish green solid. mp 144 °C. IR
(2E)-3-(2-Chloro-6-methoxyquinolin-3-yl)-1-(2,3-dihydro-1,4-benzodi-
oxin-6-yl)prop-2-en-1-one 2p 92% yield. Off white solid. mp 163—
164 °C. IR (KBr) cmꢂ1: 1658 (CꢀO), 1596 (CꢀC). 1H-NMR (CDCl3) d:
3.93 (3H, s, OMe), 4.34 (4H, m, Dioxane Ring), 6.94 (1H, d, Ar-H, Jꢀ
8.1 Hz), 7.12 (1H, d, H5, Jꢀ2.6 Hz), 7.36 (1H, d, Ar-H, Jꢀ3.9 Hz), 7.50 (1H,
d, Ha, Jꢀ15.6 Hz), 7.58 (1H, dd, H7, Jꢀ9.1 Hz), 7.70 (1H, m, Ar-H), 7.91
(1H, d, H8, Jꢀ9.2 Hz), 8.18 (1H, d, Hb, Jꢀ15.6 Hz), 8.35 (1H, s, H4). MS
(m/z): 381 (Mꢄ, 7.5%), 346 (MꢄꢂCl, 100%). Anal. Calcd for C21H16NO4Cl:
C, 66.06; H, 4.22; N, 3.67. Found: C, 66.02; H, 4.18; N, 3.63.
1
(KBr) cmꢂ1: 1664 (CꢀO), 1591 (CꢀC). H-NMR (CDCl3) d: 3.94 (3H, s,
OMe), 7.11 (1H, d, H5, Jꢀ2.7 Hz), 7.16 (1H, s, H4ꢃ), 7.41 (1H, dd, H7, Jꢀ
9.2 Hz), 7.46 (1H, d, Ha, Jꢀ15.7 Hz), 7.91 (1H, d, H8, Jꢀ9.2 Hz), 8.14 (1H,
d, Hb, Jꢀ15.7 Hz), 8.33 (1H, s, H4). MS (m/z): 397 (Mꢄ, 14.3%), 362 (Mꢄꢂ
Cl, 100%). Anal. Calcd for C17H10NO2Cl3S: C, 51.21; H, 2.53; N, 3.51.
Found: C, 51.19; H, 2.42; N, 3.46.
(2E)-3-(2-Chloro-6-methoxyquinolin-3-yl)-1-(1-naphthyl)prop-2-en-1-
one 2q 90% yield. Pale yellow solid. mp 162 °C. IR (KBr) cmꢂ1: 1659
1
(CꢀO), 1587 (CꢀC). H-NMR (CDCl3) d: 3.92 (3H, s, OMe), 7.09 (1H, d,
H5, Jꢀ2.7 Hz), 7.38 (1H, d, Ha, Jꢀ15.9 Hz), 7.40 (1H, dd, H7, Jꢀ9.2 Hz),
7.53—7.61 (3H, m, Ar-H), 7.83—7.92 (3H, m, Ar-H), 7.98 (1H, d, H8, Jꢀ
9.2 Hz), 8.03 (1H, d, Hb, Jꢀ16.1 Hz), 8.35 (1H, s, H4), 8.40 (1H, d, Ar-H,
Jꢀ8.3 Hz). MS (m/z): 373 (Mꢄ, 57.0%), 338 (MꢄꢂCl, 100%). Anal. Calcd
for C23H16NO2Cl: C, 73.90; H, 4.31; N, 3.75. Found: C, 73.87; H, 4.27; N,
3.72.
(2E)-1-(3-Bromothien-2-yl)-3-(2-chloro-6-methoxyquinolin-3-yl)prop-
2-en-1-one 2i 73% yield. Greyish green solid. mp 148—150 °C. IR (KBr)
1
cmꢂ1: 1650 (CꢀO), 1591 (CꢀC). H-NMR (CDCl3) d: 3.94 (3H, s, OMe),
7.12 (1H, d, H5, Jꢀ2.7 Hz), 7.16 (1H, d, H4ꢃ, Jꢀ5.1 Hz), 7.41 (1H, dd, H7,
Jꢀ9.2 Hz), 7.59 (1H, d, H5ꢃ, Jꢀ5.1 Hz), 7.83 (1H, d, Ha, Jꢀ15.6 Hz), 7.91
(1H, d, H8, Jꢀ9.2 Hz), 8.22 (1H, d, Hb, Jꢀ15.6 Hz), 8.36 (1H, s, H4).
MS (m/z): 408 (Mꢄ, 16.2%), 374 (MꢄꢂCl, 100%). Anal. Calcd for
C17H11NO2ClSBr: C, 49.96; H, 2.71; N, 3.43. Found: C, 49.92; H, 2.70; N,
3.33.
(2E)-3-(2-Chloro-6-methoxyquinolin-3-yl)-1-(2-naphthyl)prop-2-en-1-
one 2r 55% yield. Light grey solid. mp 140 °C. IR (KBr) cmꢂ1: 1659 (Cꢀ
1
O), 1586 (CꢀC). H-NMR (CDCl3) d: 3.95 (3H, s, OMe), 7.15 (1H, d, H5,
Jꢀ2.7 Hz), 7.41 (1H, dd, H7, Jꢀ9.2 Hz), 7.55—7.64 (2H, m, Ar-H), 7.73
(1H, d, Ha, Jꢀ15.7 Hz), 7.89—8.00 (4H, m, Ar-H), 8.11 (1H, dd, H8 Jꢀ
9.2 Hz), 8.23 (1H, d, Hb, Jꢀ15.7 Hz), 8.42 (1H, s, H4), 8.56 (1H, s, Ar-H).
MS (m/z): 373 (Mꢄ, 34.9%), 338 (MꢄꢂCl, 100%). Anal. Calcd for
C23H16NO2Cl: C, 73.90; H, 4.31; N, 3.75. Found: C, 73.88; H, 4.27; N, 3.71.
(2E)-1-(9-Anthryl)-3-(2-chloro-6-methoxyquinolin-3-yl)prop-2-en-1-
(2E)-1-(5-Bromothien-2-yl)-3-(2-chloro-6-methoxyquinolin-3-yl)prop-
2-en-1-one 2j 84% yield. Yellowish grey solid. mp 178 °C. IR (KBr)
1
cmꢂ1: 1654 (CꢀO), 1589 (CꢀC). H-NMR (CDCl3) d: 3.91 (3H, s, OMe),
6.95 (1H, d, H4ꢃ, Jꢀ4.1 Hz), 7.10 (1H, d, H5, Jꢀ2.6 Hz), 7.36 (1H, dd, H7,
Jꢀ9.2 Hz), 7.42 (1H, d, Ha, Jꢀ15.6 Hz), 7.45 (1H, d, H3ꢃ, Jꢀ4.1 Hz), 7.89
(1H, d, H8, Jꢀ9.2 Hz), 8.13 (1H, d, Hb, Jꢀ15.6 Hz), 8.36 (1H, s, H4). MS
(m/z): 409 (Mꢄ, 20.4%), 374 (MꢄꢂCl, 100%). Anal. Calcd for
C17H11NO2ClSBr: C, 49.96; H, 2.71; N, 3.43. Found: C, 49.87; H, 2.68; N,
3.41.
one 2s 97% yield. Deep yellow solid. mp 220—222 °C. IR (KBr) cmꢂ1
:
1
1660 (CꢀO), 1588 (CꢀC). H-NMR (CDCl3) d: 3.92 (3H, s, OMe), 7.11
(1H, d, H5, Jꢀ2.7 Hz), 7.40 (1H, d, Ha, Jꢀ16.1 Hz), 7.47—7.56 (4H, m, Ar-
H), 7.84 (1H, dd, H7, Jꢀ7.2 Hz), 7.90—7.93 (2H, m, Ar-H), 7.96 (1H, d, Hb,
Jꢀ16.1 Hz), 8.03 (1H, d, H8, Jꢀ7.4 Hz), 8.54 (1H, s, Ar-H), 8.06—8.08
(2H, m, Ar-H). MS (m/z): 423 (Mꢄ, 16.3%), 177 (MꢄꢂC13H9NO2Cl,
100%). Anal. Calcd for C27H18NO2Cl: C, 76.50; H, 4.28; N, 3.30. Found: C,
76.42; H, 4.27; N, 3.27.
(2E)-3-(2-Chloro-6-methoxyquinolin-3-yl)-1-(5-iodothien-2-yl)prop-2-
en-1-one 2k 91% yield. Yellowish grey solid. mp 184 °C. IR (KBr) cmꢂ1
:
1
1648 (CꢀO), 1594 (CꢀC). H-NMR (CDCl3) d: 3.91 (3H, s, OMe), 6.92
(1H, d, H4ꢃ, Jꢀ4.1 Hz), 7.10 (1H, d, H5, Jꢀ2.7 Hz), 7.36 (1H, dd, H7, Jꢀ
9.2 Hz), 7.43 (1H, d, Ha, Jꢀ15.5 Hz), 7.46 (1H, d, H3ꢃ, Jꢀ4.1 Hz), 7.89 (1H,
d, H8, Jꢀ9.2 Hz), 8.14 (1H, d, Hb, Jꢀ15.6 Hz), 8.36 (1H, s, H4). MS (m/z):
455 (Mꢄ, 11.2%), 237 (MꢄꢂC12H9NOCl, 100%). Anal. Calcd for
C17H11NO2ClSI: C, 44.81; H, 2.43; N, 3.07. Found: C, 44.75; H, 2.39; N,
3.02.
Antileishmanial Assay The title compounds (1a—s, 2a—s) were tested
for the antileishmanial activity using L. major promastigotes as parasites
for in vitro screening. Parasites were cultured at 24 °C in Shaking incubator
on M 199 medium containing foetal bovine serum (10%); N-2-hydroxy-
ethylpiperazine-Nꢃ-2-ethanesulfonic acid (HEPES) (25 mM), and penicillin
and streptomycin (0.22 mg each).39)
Each compound (1 mg) was dissolved in 1 ml of dimethyl sulfoxide
(DMSO) and Amphotericin B (1 mg) taken in DMSO (1 ml) was used as a
positive control. Parasites were taken from lag phase of their growth and
(2E)-3-(2-Chloro-6-methoxyquinolin-3-yl)-1-(1H-pyrrol-2-yl)prop-2-
en-1-one 2l 90% yield. Pale yellow solid. mp 172 °C. IR (KBr) cmꢂ1
1648 (CꢀO), 1596 (CꢀC). H-NMR (CDCl3) d: 2.47 (3H, s, OMe), 6.34
(1H, dd, H4ꢃ, Jꢀ3.4 Hz), 6.64 (1H, d, H3ꢃ, Jꢀ3.4 Hz), 7.0 (1H, d, H5ꢃ, Jꢀ4.0
:
1

306
Vol. 58, No. 3
H., Van Der Goot H., Eur. J. Med. Chem., 35, 449—457 (2000).
were centrifuged at 3000 rpm for 3 min. The parasite density was maintained
at 2ꢅ106 cells/ml by diluting with fresh culture medium. In 96-well plates, 17) Narender T., Shweta, Tanvir K., Rao M. S., Srivastava K., Puri S. K.,
180 ml of medium was added in different wells. The experimental compound
(20 ml) was added in medium and serially diluted. Parasite culture (100 ml) 18) Liu M., Wilairat P., Croft S. L., Tan A. L., Go M., Bioorg. Med.
was added in all wells. In negative controls, DMSO was serially diluted in Chem., 11, 2729—2738 (2003).
medium while the positive control contained varying concentrations of stan- 19) Wu X., Wilairat P., Go M., Bioorg. Med. Chem. Lett., 12, 2299—2302
dard antileishmanial compound i.e. Amphotericin B. The plates were incu- (2002).
bated for 72 h at 24 °C. The culture was examined microscopically on an im- 20) Ram V. J., Saxena A. S., Srivastava S., Chandra S., Bioorg. Med.
proved neubaur counting chamber and IC50 values of compounds possessing Chem. Lett., 10, 2159—2161 (2000).
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195 (2003).
ial activity against Escherichia coli, Micrococus luteus and Staphylococus 23) Tiwar N., Dwivedi B., Nizamuddin N., Boll. Chim. Farm., 128, 332—
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activity was investigated against Aspergillus flavus, Aspergillus niger and
Curvuliaria lunata using Flucanazole (1.00 mmol/ml) as standard. At the
335 (1989).
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was repeated thrice and the average of the three independednt determina-
tions was recorded. The results are summarized in Table 3.
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Acknowledgement The author is grateful to Higher Education Com-
mission, Pakistan and Institute of Chemistry, University of the Punjab, La-
hore, for financial assistance. We are also thankful to International Centre
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