Substituted quinolinyl chalcones and quinolinyl pyrimidines as a new class of anti-infective agents

Article abstract of DOI:10.1016/j.ejmech.2008.10.011

Frequency of tuberculosis and malaria is progressively increasing worldwide. New emerging strain of bacterium and resistance to currently available drugs make this field more conscientious and alarming. In this connection a series of substituted quinoliny

Full text of DOI:10.1016/j.ejmech.2008.10.011

European Journal of Medicinal Chemistry 44 (2009) 2081–2091
Contents lists available at ScienceDirect
European Journal of Medicinal Chemistry
journal homepage: http://www.elsevier.com/locate/ejmech
Original article
Substituted quinolinyl chalcones and quinolinyl pyrimidines as a new class of
anti-infective agents
Moni Sharma a, Vinita Chaturvedi b, Y.K. Manju b, Shalini Bhatnagar b, Kumkum Srivastava c,
,
S.K. Puri c, Prem M.S. Chauhan a
*
a Division of Medicinal and Process Chemistry, Central Drug Research Institute, Lucknow 226001, India
b Anti-TB Screening Unit, Drug Target Discovery and Development, Central Drug Research Institute, Lucknow 226001, India
c Division of Parasitology, Central Drug Research Institute, Lucknow 226001, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Frequency of tuberculosis and malaria is progressively increasing worldwide. New emerging strain of
bacterium and resistance to currently available drugs make this field more conscientious and alarming. In
this connection a series of substituted quinolinyl chalcones and substituted quinolinyl pyrimidines were
synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis
H37RV and antimalarial activity against NF-54 strain of Plasmodium falciparum. A comparison of struc-
ture–activity relationship reveals that different physicochemical and structural requirements exist for
these two activities. Out of synthesized compounds, compound nos. 22 and 23 have shown antituber-
Received 28 July 2008
Received in revised form
7 October 2008
Accepted 10 October 2008
Available online 1 November 2008
Keywords:
Tuberculosis
Malaria
Chalcones
Pyrimidines
cular activity of MIC 3.12
m
g/mL and were nontoxic against VERO, MBMDM cell lines and compounds 54,
g/mL.
Ó 2008 Elsevier Masson SAS. All rights reserved.
55, and 56 have shown antimalarial activity of MIC 1
m
1. Introduction
impressive array of pharmacological activities like anti-protozoal
[12,13], anti-inflammatory [14] immunomodulatory [15]. On the
other hand pyrimidine scaffold was the base of many bioactive
molecule as antimalarial such as Pyrimethamine (Ib), Cycloguanil
{DHFR (DiHydroFolate Reductase) inhibitor} [16], antibacterial
(Trimethoprim, Iclaprim) [17], antitubercular agents (II) [18].
As our research is devoted to the synthesis of diverse hetero-
cycles as anti-infective agents, we identified the pyrimidine and
quinoline (separately) as good anti-infectious agents [19–29].
Keeping this in view we designed and synthesized new proto-
types by combining both pyrimidine and quinoline. In this
communication we described the synthesis of hybrid molecules
consisting of chalcones and pyrimidines along with quinoline
moiety and highlighted their in vitro antitubercular and antima-
larial activities.
Infectious diseases are influencing the world with their
morbidity and mortality, out of which tuberculosis and malaria are
major infectious diseases caused by Mycobacterium tuberculosis
[1,2] and Plasmodium falciparum [3,4] respectively, have become
more virulent now a days by claiming about three to four million
lives and infecting over ten million people annually [5–8]. The
current chemotherapy is based on age old drugs like Chloroquine
(Ia), Pyrimethamine-sulfadoxine for malaria [3,4] and Pyr-
azinamide, Isoniazid and Rifampin for tuberculosis [9]. The efficacy
of these drugs has been deteriorated by the emerging resistant
strains. More over the pathogenic synergy of HIV to these diseases
is alarming the world to develop new efficient chemotherapy for
infectious diseases [10].
The development of new drugs will be greatly facilitated by
a complete understanding of the molecular mechanism underlying
previously successful antimalarial drugs [11]. For structurally
simple group of compounds which act on more than one target site
are liable to be more active. The chalcones have displayed an
2. Chemistry
To synthesize oxo linked pyrimidines (32–43) and amino linked
pyrimidines (44–59), oxo linked chalcones (4–15) and amino linked
chalcones (16–31) were reacted with guanidine hydrochloride in
the presence of NaH in DMF. Chalcones (4–15) and (16–31) were
prepared by standard Claisen–Schmidt aldol condensation reaction
of intermediates (2) and (3) with different aldehydes in 10%
NaOH and MeOH. Intermediate (2) was synthesized by nucleophilic
* Corresponding author. Fax: þ91 522 2623405.
E-mail addresses: prem_chauhan_2000@yahoo.com, premsc58@hotmail.com
(P.M.S. Chauhan).
0223-5234/$ – see front matter Ó 2008 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.ejmech.2008.10.011

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M. Sharma et al. / European Journal of Medicinal Chemistry 44 (2009) 2081–2091
ipso-substitution of 4-chloro of 4,7-dichloroqinoline with 4-
hydroxy acetophenone in DMF in the presence of potassium
hydroxide at 120 ꢀC and intermediate (3) was synthesized by
nucleophilic substitution of 4-chloro of 4,7-dichloroquinoline with
4-amino acetophenone in MeOH (Scheme 1). All the synthesized
compounds as mentioned in Table 1 were well characterized by
spectroscopic methods such as IR, FAB, NMR and elemental analysis.
was spread on the surface of the medium and the tubes were
kept at 37 ꢀC for 4 weeks for the appearance of colonies. Tubes
containing no drug served as control. The minimum concentra-
tion of the drugs (INH and RFM)/compounds that completely
inhibited the growth of mycobacterium was recorded as
Minimum Inhibitory Concentration (MIC) with respect to the
used inoculums.
Cl
Cl
S
N
NH
N
2
HN
N
N
N
Cl
H2N
Cl
N
(Ia)
S
CN
(II)
(Ib)
R
O
C
X
N
CH CH R
N
X
N
N
NH2
Cl
Cl
(4-15), X=O
(16-13), X=NH
(32-43), X=O
(44-59), X=NH
3. Biological activity
3.1. Cytotoxic evaluation
Evaluation of in vitro antitubercular activity against M. tuber-
culosis H37Rv strain was carried out with recommended
protocol [30] using Middle Brook (MB) 7H10 agar medium. A
100 L of serial two fold dilutions of the stock (1.0 mg/mL in
(i) In VERO [31] cells {104 cells/well/0.1 mL MEM (Minimum
Essential Medium) containing antibiotics and 10% FBS (Fetal
Bovine Serum)} were seeded in 96 wells tissue culture plate.
After 24 h incubation (37 ꢀC, 5% CO2) medium was replaced
with fresh medium (5% FBS and no antibiotic) containing
different concentrations of test compound/known toxic
a
m
DMSO, dimethyl sulphoxide) of test compounds and standard
antitubercular drugs {isoniazid (INH) and rifampicin (RFM)} were
incorporated in the medium (final volume, 2 mL/tube) supple-
mented with OADC (oleic acid, albumin fraction IV, dextrose and
catalase). Compounds/drugs containing tubes were kept in
slanting position till the medium solidified. Culture of M. tuber-
culosis H37RV grown on Lowenstein–Jensen (L–J) was harvested in
N–saline containing 0.05% Tween-80. The culture was vigorously
agitated with glass beads to make a single cell suspension. A
compound/DMSO. After 24 h incubation (37 ꢀC, 5% CO2) 20
mL
MTS (Meyallothioneins) reagent (Promega Kit) is added and
absorbance is read after 2 h at 490 nm. Absorbance shown by
DMSO containing wells is taken as 100% survivors.
A
compound is considered toxic if it causes 50% inhibition at
concentration 10 fold higher than its MIC.
(ii) In Mouse Bone Marrow Derived Macrophages (MBMDM):
working inoculum (2 ꢁ 107 cfu/mL; 10
mL/tube) of mycobacterium
plated 105 cells/0.1 mL/well in DMEM (Dulbecco’s Minimum
Cl
COCH3
X
N
a
+
X
COCH3
R
CHO
+
(i), (ii)
N
X
Cl
Cl
X=O
X=NH2
(1)
2, X=O
3, X=NH
b
R
O
X
N
C
CH=CH
R
N
N
c
NH2
Cl
N
(32-43), X=O
Cl
(4-15), X=O
(16-31), X=NH
(44-59), X=NH
Scheme 1. Reagents and conditions: (a) (i) DMF, KOH, 120 ꢀC, 8 h and (ii) MeOH, 80 ꢀC, 8 h; (b) 10% NaOH, MeOH, 0 ꢀC r.t. 5 h; (c) Guanidine hydrochloride, DMF, NaH, 120 ꢀC, 10 h.

M. Sharma et al. / European Journal of Medicinal Chemistry 44 (2009) 2081–2091
2083
Essential Medium) (supplemented with antibiotics, 10% FBS,
15% (v/v) L-929 fibroblast conditioned supernatant and non-
essential amino acids) in 96 wells tissue culture plate. After 5
volume of 200
tained. The test compound in 20
tration (ranging between 0.25 g/mL and 50
m
L of medium RPMI-1640 was uniformly main-
L volume at required concen-
g/mL) in duplicate
m
m
m
days incubation (37 ꢀC, 5% CO2) 20
mL MTS reagent (Promega
wells was incubated with parasitized cell preparation at 37 ꢀC in
a candle jar. After 36–40 h incubation, the blood smears from each
well were prepared and stained with giemsa stain. The slides were
microscopically observed to record maturation of ring stage para-
sites into trophozoites and schizonts in the presence of different
concentrations of compounds. The tested concentration, which
inhibits the complete maturation into schizonts, was recorded as
the minimum inhibitory concentration Table 2.
Kit) was added and absorbance read after 2 h at 490 nm.
Absorbance shown by DMSO containing wells is taken as 100%
survivors. A compound is considered toxic if it causes 50%
inhibition at concentration 10 fold higher than its MIC.
The in vitro antimalarial assay was carried out in 96-well
microtitre plates according to the microassay of Rieckmann et al.
[32]. The culture of P. falciparum NF-54 strain is routinely being
maintained in medium RPMI-1640 supplemented with 25 mM
HEPES {4-(2-hydroxy ethyl)-1-piprazine ethane sulphonic acid}. 1%
4. Results and discussion
D
-Glucose, 0.23% sodium bicarbonate and 10% heat inactivated
human serum [33]. The asynchronous parasite of P. falciparum was
synchronized after 5% -sorbitol treatment to obtain parasitized
All the 56 synthesized compounds were screened against H37Rv
strains of the M. tuberculosis and NF-54 strains of P. falciparum. The
compounds of the series which have shown significant activity are
mentioned in Table 2. Among all, compounds of the first series
where 4-oxo linkage between quinoline and chalcone 4–15 and
D
cells harboring only the ring stage. For carrying out the assay, an
initial ring stage parasitemia of z1% at 3% haematocrit in a total
Table 1
All the synthesized compounds of the 4-oxo and 4- amino linked series.
aChalcones (oxo linked,
amino linked)
aPyrimidines
(oxo linked, amino linked)
R (oxo linked,
amino linked)
Chalcones (oxo linked,
amino linked)
Pyrimidines (oxo linked,
amino linked)
R (oxo linked,
amino linked)
Cl
4, 16
32, 44
12, 24
40, 52
Me
5, 17
6, 18
33, 45
34, 46
13, 25
14, 26
41, 53
42, 54
Cl
SMe
OMe
OMe
OMe
OMe
7, 19
35, 47
36, 48
15, 27
43, 55
N
OMe
OMe
8, 20
28b
56
MeO
9, 21
37, 49
38, 50
29
30
57
58
O
Br
MeO
OMe
10, 22
Br
OMe
11, 23
39, 51
31
59
NO2
MeO
a
First no. refers to oxo linked and second no. refers to amino linked compounds.
single set of no. only refers to amino linked compounds.
b

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M. Sharma et al. / European Journal of Medicinal Chemistry 44 (2009) 2081–2091
Table 3
pyrimidine 32–43 were found to be inactive, while their 4-amino
linked analogues 16–31 and 44–59 showed promising activity
against M. tuberculosis and P. falciparum strains. These results
immediately suggested the straightforward structure activity rela-
tionship of 4-amino linker over the 4-oxo linked compounds.
Activity of the resulting chalcones and hybrid of quinoline and
pyrimidines reveals that different physiochemical and structural
requirements exist for these two activities. The 2,3-dimethox-
yphenyl 22 and 2,5-dimethoxyphenyl 23 substituted derivatives of
chalcones were found to be active against Mtb having a MIC of
Cytotoxicity against VERO and MBMDM cell lines.
Compound No.
MIC (
m
g/mL)
VERO
MBMDMa
22
23
3.12
3.12
50
NT
NT
NT
NT
NT
NT
Pyrazinamide
a
MBMDM: mouse bone marrow derived macrophages; NT: nontoxic.
analogues of these compounds were found to be active against
malaria. On the basis of above observations, we will further modify
to improve the anti-infective activity of chalcones and pyrimidines.
3.12 mg/mL and are nontoxic against VERO and MBMDM cell lines
(Table 3), while their pyrimidine analogues were found to be inac-
tive against the same strain. Compound 24 having chloro-substi-
6. Experimental
tution at para-position of phenyl ring showed MIC of 6.25
The 3,4,5-trimethoxy substituted phenyl system 47 was found to be
active against Mtb have shown MIC of 12.5 g/mL as compared to
mg/mL.
IR spectra were recorded on Beckman Aculab-10, Perkin Elmer
881 and FTIR 8210 PC, Schimadzu spectrophotometers either on
KBr discs or in neat. Nuclear magnetic resonance spectra were
recorded on either Bruker Avance DRX-300 MHz or Bruker DPX 200
FT spectrometers using TMS as an internal reference. FAB mass
spectra were recorded on JEOL SX 102/DA 6000 mass spectrometer
using argon/xenon (6 Kv, 10 mA) as the FAB gas. Chemical analysis
was carried out on carlo-Erba-1108 instrument. The melting points
were recorded on an electrically heated melting point apparatus
and are uncorrected.
m
dimethoxy substituted phenyl systems 50 and 51 in pyrimidines, it
is because of the analogy of resulting compound with antibacterial
drug trimethoprim. Substitution with heterocyclic ring system did
not alter the activity of pyrimidines to any greater extent, however,
oxygen containing heterocycle 49 is found to be moderately active
having MIC of 12.5 mg/mL against Mtb over the nitrogen containing
heterocycle, 3-pyridyl substitution 55. Contrarily nitrogen con-
taining heterocycle compound 55 has shown significant activity
against P. falciparum having a MIC of 1
mg/mL compared to oxygen
containing heterocycle (furan) compound 49 having a MIC of 10
mg/
6.1. Synthesisof1-(4-(7-chloroquinolin-4-yloxy)phenyl)ethanone (2)
mL. None of the chalcones have shown activity in malaria while
their pyrimidine scaffolds were significantly active having MIC in
The mixture of 4,7-dichloroquinoline (1.0 equiv), 4-hydroxy
acetophenone (1.5 equiv) and KOH (1.5 equiv) in DMF was refluxed
for 6 h. Water was added into the reaction mixture, a solid started
separating out. The solid was filtered out and purified by column
chromatography to obtain compound 2 as white crystals.
the range of 1–2
56 was found to be moderately active having a MIC 6.25
the other hand same compounds 56 and 54 having 4-thiomethyl
substituted phenyl ring system were found to be active in malaria
m
g/mL. 4-Isopropyl substituted phenyl ring system
mg/mL. On
and having a MIC of 1
methoxy group reduced the activity of compound 46 to MIC of
g/mL. All the results of biological activity are shown in Table 2.
mg/mL. Substitution of phenyl ring with 4-
Yield: 65%; m.p. 165–168 ꢀC; MS: 298 (M þ 1); IR (KBr): 3073,
2350, 1648, 1610, 1573, 1526, 1430, 1354, 1210, 1072, 776, 670 cmꢂ1
;
2
m
1H NMR (300 MHz, CDCl3)
d
: 9.01 (d, 1H, J ¼ 8.7 Hz, Ar-Qn), 8.41 (d,
1H, J ¼ 9.0 Hz, Ar-Qn), 8.03 (d, 2H, J ¼ 8.4 Hz, Ar), 7.83 (d, 1H,
J ¼ 9.0 Hz, Ar-Qn), 7.71 (d, 1H, J ¼ 1.8 Hz, Ar-Qn), 7.19 (d, 2H,
J ¼ 8.7 Hz, Ar), 6.49 (d, 1H, J ¼ 8.4 Hz, Ar-Qn), 2.68 (s, 3H, –COCH3);
5. Conclusion
In conclusion, we have reported the systematic evaluation of the
structure–activity relationships of the synthesized quinolinyl
chalcones and quinolinyl pyrimidines. The in vitro screenings of
these compounds against M. tuberculosis and P. falciparum have
shown their promising activity. Out of the synthesized compounds,
six compounds have shown antitubercular activity with MIC in the
range of 3.12–12.5
MBMDM cell lines. Four compounds have shown antimalarial
activity with MIC ranging from 1 to 2 g/mL. The SAR of these
13C NMR (75 MHz, CDCl3)
d: 189.91, 160.64, 159.87, 155.21, 147.38,
135.83, 133.08, 130.21, 129.13, 128.91, 124.67, 120.91, 118.17, 107.32,
30.18; Anal. Calcd. for C17H12ClNO2: C 70.19, H 4.76, N 6.30; Found: C
70.0, H 4.90, N 6.78%.
6.2. 1-(4-(7-Chloroquinolin-4-ylamino)phenyl)ethanone (3)
mg/mL and are nontoxic against VERO and
The mixture of 4,7-dichloroquinoline (1.0 equiv) and 4-amino-
acetophenone (1.5 equiv) in MeOH was refluxed for 6 h. The solvent
was evaporated under vacuum and solid mass was obtained. The
solid was recrystallised from methanol to obtain compound 3 as
a yellow solid.
m
compounds showed that quinolinyl chalcones are antitubercular
agents while their pyrimidine analogues were moderately active
against the same strain. On the other hand the pyrimidine
Yield: 85%; m.p 160–162 ꢀC; MS: 297 (M þ 1); IR (KBr) 3435,
Table 2
3021, 2361, 1670, 1623, 1473, 1215, 1093, 761, 669 cmꢂ1 1H NMR
;
Biological activity of chalcones and trisubstituted pyrimidines.
(300 MHz, CDCl3 þ CD3OD): : 8.69 (d, 1H, J ¼ 9.1 Hz, Ar-Qn), 8.37
d
Compound no.
Mycobacterium tuberculosis
Plasmodium falciparum
(d, 1H, J ¼ 9.0 Hz, Ar-Qn), 8.19–8.12 (m, 3H, Ar, NH), 7.66 (d, 1H,
J ¼ 8.6 Hz, Ar-Qn), 7.62 (d, 1H, J ¼ 2.1 Hz, Ar-Qn), 7.47 (d, 2H,
J ¼ 8.4 Hz, Ar), 7.06 (d, 1H, J ¼ 8.3 Hz, Ar-Qn), 2.71 (s, 3H, –COCH3);
MIC (
m
g/mL)
MIC (mg/mL)
22
23
24
46
47
49
54
3.12
3.12
6.25
NA
NA
NA
NA
2
13C NMR (75 MHz, CDCl3 þ CD3OD):
d 191.03, 152.38, 150.79,148.36,
148.13, 135.63, 132.67, 130.16, 129.78, 125.13, 123.62, 120.62, 114.62,
110.07, 31.07; Anal. Calcd. for C17H13ClN2O: C 68.81, H 4.42, N 9.44;
Found: C 68.78, H 4.60, N 9.68%.
12.5
12.5
NA
NA
NA
1
55
56
NA
6.25
–
1
1
6.3. General procedure for synthesis of compounds 4–31
Chloroquine
Pyrazinamide
0.125
–
50
Method a: 1 equiv of substituted quinoline was added dropwise
to a cooled solution of 10% NaOH, and 1.5 equiv of liquid aldehydes
*Only active compounds are shown in table.

M. Sharma et al. / European Journal of Medicinal Chemistry 44 (2009) 2081–2091
2085
over a period of 30 min. The solution was maintained at 0 ꢀC for an
696 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d
8.74 (d, 1H, J ¼ 5.46 Hz, Ar-
hour then was allowed to stir at room temperature. After some
time, a solid started separating out. The solution was further stirred
for about 1 h. The solid was filtered out and recrystallised from
methanol or ethanol to afford crystals of the chalcone having yield
in the range 60–79%.
Method B: In case of solid aldehydes, the aldehydes (1.3 equiv)
were first dissolved in a minimum quantity of methanol and then
10% NaOH solution was added to it to give a clear solution. The
solution was cooled up to 0 ꢀC and 1 equiv of substituted quinoline
was added dropwise to it, in around 30 min. The solution was
maintained at 0 ꢀC for an hour then was allowed to stir at room
temperature. After some time, a solid started separating out. The
solution was further stirred for about 1 h. The solid was filtered out
and recrystallised from methanol or ethanol to afford crystals of the
chalcone having yield in the range 60–79%.
Qn), 8.28 (d, 1H, J ¼ 9.0 Hz, Ar-Qn), 8.17 (d, 2H, J ¼ 8.7 Hz, Ar), 8.14
(d, 1H, J ¼ 2.1 Hz, Ar-Qn), 7.80 (d, 1H, J ¼ 15.3 Hz, –CH]CH–), 7.59–
7.55 (dd, 1H, J ¼ 8.4 Hz, J ¼ 2.1 Hz, Ar-Qn), 7.43 (d, 1H, J ¼ 15.6 Hz,
–CH]CH–), 7.32 (d, 2H, J ¼ 9.0 Hz, Ar), 6.90 (s, 2H, Ar), 6.70 (d, 1H,
J ¼ 5.34 Hz, Ar-Qn), 3.95 (s, 6H, OCH3), 3.93 (s, 3H, OCH3); 13C NMR
(75 MHz, CDCl3): d 188.81, 160.78, 158.08, 153.53, 152.24, 150.41,
145.45, 140.68, 136.44, 135.57, 131.06, 130.18, 128.24, 127.49, 123.24,
120.79, 120.53, 119.98, 105.80, 105.62, 61.02, 56.26; Anal. Calcd. for
C27H22ClNO5: C 68.14, H 4.66, N 2.94; Found: C 68.39, H 4.46, N
2.78%.
6.3.5. 1-(4-(7-Chloroquinolin-4-yloxy)phenyl)-3-(2,3,4-
trimethoxyphenyl)prop-2-en-1-one (8)
Yield: 78%; m.p 160–162 ꢀC; MS: 476 (M þ 1); IR (KBr): 3061,
2998, 2867, 2364, 1655, 1592, 1479, 1379, 1210, 1136, 1038, 830, 756,
730, 690 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d
8.71 (d,1H, J ¼ 5.34 Hz,
6.3.1. 1-(4-(7-Chloroquinolin-4-yloxy)phenyl)-3-phenylprop-2-en-
1-one (4)
Ar-Qn), 8.28 (d, 1H, J ¼ 9.0 Hz, Ar-Qn), 8.11 (d, 2H, J ¼ 8.46 Hz, Ar),
8.07 (d, 1H, J ¼ 2.1 Hz, Ar-Qn), 7.81 (d, 1H, J ¼ 15.6 Hz, –CH]CH–),
7.63 (d, 1H, J ¼ 8.47 Hz, Ar-Qn), 7.55–7.51 (dd, 1H, J ¼ 8.7 Hz,
J ¼ 1.8 Hz, Ar-Qn), 7.45 (d, 1H, J ¼ 15.3 Hz, –CH]CH–), 7.37 (d, 2H,
J ¼ 9.0 Hz, Ar), 7.21 (d, 1H, J ¼ 8.34 Hz, Ar), 6.67 (d, 1H, J ¼ 5.34 Hz,
Yield: 65%; m.p 172–174 ꢀC; MS: 386 (M þ 1); IR (KBr) 3061,
2362,1663,1567,1492,1376,1215,1097, 979, 833, 749, 670 cmꢂ1; 1H
NMR (CDCl3, 300 MHz):
d
8.74 (d, 1H, J ¼ 5.34 Hz, Ar-Qn), 8.26 (d,
1H, J ¼ 9.0 Hz, Ar), 8.16 (d, 2H, J ¼ 8.7 Hz, Ar), 8.12 (d, 1H, J ¼ 1.8 Hz,
Ar-Qn), 7.86 (d,1H, J ¼ 15.6 Hz, –CH]CH–), 7.49–7.55 (m, 4H), 7.66–
7.69 (m, 2H, Ar), 7.52–7.58 (m, 2H, Ar-Qn, –CH]CH–), 7.41–7.45 (m,
2H, Ar), 7.26 (d, 2H, J ¼ 9.0 Hz, Ar), 7.16 (d, 1H, Ar), 6.69 (d, 1H,
Ar-Qn), 4.01 (s, 3H, OCH3), 3.99 (s, 3H, OCH3), 3.91 (s, 3H, OCH3); 13
C
NMR (75 MHz, CDCl):
d 189.26, 161.71, 159.23, 155.72, 153.23,
151.64, 147.72, 141.12, 140.62, 138.71, 136.47, 135.62, 132.06, 131.13,
128.71, 127.57, 123.49, 121.83, 120.68, 119.34, 105.83, 105.61, 63.26,
62.71, 58.19; Anal. Calcd. for C27H22ClNO5: C 68.14, H 4.66, N 2.94;
Found: C 68.29, H 4.56, N 2.78%.
J ¼ 5.4 Hz, Ar-Q); 13C NMR (75 MHz, CDCl3):
d 188.23,160.71,158.08,
152.06, 150.47, 145.21, 136.46, 135.55, 134.76, 131.03, 128.98, 128.47,
128.37, 127.48, 123.13, 121.34, 120.48, 119.92, 105.53, 96.15; Anal.
Calcd. for C24H16ClNO2: C 74.71, H 4.18, N 3.63; Found: C 74.69, H
4.36, N 3.38%.
6.3.6. 1-(4-(7-Chloroquinolin-4-yloxy)phenyl)-3-(furan-2-yl)prop-
2-en-1-one (9)
Yield: 72%; m.p 165–167 ꢀC; MS: 376 (M þ 1); IR (KBr): 3092,
6.3.2. 1-(4-(7-Chloroquinolin-4-yloxy) phenyl)-3-p-tolylprop-2-
en-1-one (5)
2926, 2361, 1662, 1603, 1495, 1378, 1223, 1168, 1018, 968, 833,
755 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d
8.73 (d, 1H, J ¼ 5.46 Hz, Ar-
Yield: 60%; m.p 160–162 ꢀC; MS: 400 (M þ 1); IR (KBr): 3045,
Qn), 8.26 (d, 1H, J ¼ 9.0 Hz, Ar-Qn), 8.18 (d, 2H, J ¼ 8.76 Hz, Ar), 8.13
(d, 1H, J ¼ 2.1 Hz, Ar-Qn), 7.65 (d, 1H, J ¼ 15.6 Hz, –CH]CH–), 7.57–
7.54 (m, 2H, Ar-Qn, furan), 7.47 (d, 1H, J ¼ 15.3 Hz, –CH]CH–), 7.28
(d, 2H, J ¼ 8.4 Hz, Ar), 6.76 (d, 1H, J ¼ 3.3 Hz, furan), 6.67 (d, 1H,
J ¼ 5.13 Hz, Ar-Qn), 6.57–6.54 (m, 1H, furan); 13C NMR (75 MHz,
2918, 2362, 1658, 1597, 1492, 1376, 1216, 1092, 982, 809, 770 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
8.71 (d,1H, J ¼ 5.46 Hz, Ar-Qn), 8.31 (d,
1H, J ¼ 9.0 Hz, Ar-Qn), 8.26 (d, 2H, J ¼ 8.7 Hz, Ar), 8.17 (d, 2H,
J ¼ 8.6 Hz, Ar), 7.81 (d, 1H, J ¼ 15.6 Hz, –CH]CH–), 7.73 (d, 1H,
J ¼ 2.1 Hz, Ar-Qn), 7.51–7.46 (m, 3H, Ar, –CH]CH–), 7.39 (d, 1H,
J ¼ 9.0 Hz, Ar-Qn), 6.79(d, 2H, J ¼ 8.7 Hz, Ar), 6.91 (d, 1H, J ¼ 5.6 Hz,
CDCl3 þ CD3OD):
d 182.23, 154.77, 151.32, 145.41, 144.89, 143.19,
138.81, 130.31, 129.02, 124.80, 124.51, 121.16, 120.80, 116.83, 114.14,
113.40, 112.01, 110.47, 106.30, 98.87; Anal. Calcd. for C22H14ClNO3: C
70.31, H 3.75, N 3.73; Found: C 70.29, H 3.66, N 3.78%.
Ar-Qn), 2.19 (s, 3H, –CH3); 13C NMR (75 MHz, CDCl3):
d 189.38,
161.72, 158.92, 153.08, 146.68, 137.82, 136.81, 133.62, 129.06, 127.68,
126.48, 125.38, 123.16, 122.38, 121.64, 120.69, 119.49, 119.32, 105.38,
98.13, 21.56; Anal. Calcd. for C25H18ClNO2: C 75.09, H 4.54, N 3.50;
Found: C 75.28, H 4.78, N 3.70%.
6.3.7. 1-(4-(7-Chloroquinolin-4-yloxy)phenyl)-3-(2,3-
dimethoxyphenyl)prop-2-en-1-one (10)
Yield: 70%; m.p 158–160 ꢀC; MS: 446 (M þ 1); IR (KBr): 3067,
6.3.3. 1-(4-(7-chloroquinolin-4-yloxy)phenyl)-3-(4-
methoxyphenyl)prop-2-en-1-one (6)
2953, 2361, 1666, 1604, 1481, 1383, 1266, 1171, 1080, 776, 696 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
8.73 (d, 1H, J ¼ 5.4 Hz, Ar-Qn), 8.47 (d,
Yield: 65%; m.p 158–160 ꢀC; MS: 416 (M þ 1); IR (KBr): 3045,
1H, J ¼ 9.0 Hz, Ar-Qn), 8.17 (d, 2H, J ¼ 8.6 Hz, Ar), 7.88–7.83 (m, 2H,
Ar-Qn, –CH]CH–), 7.55–7.46 (m, 4H, –CH]CH–, Ar), 7.43 (d, 1H,
J ¼ 9.0 Hz, Ar-Qn), 7.17–7.13 (m, 2H, Ar), 6.97 (d, 1H, J ¼ 5.3 Hz, Ar-
Qn), 4.01 (s, 3H, OCH3), 3.91 (s, 3H, OCH3); 13C (75 MHz
2918, 2362, 1658, 1597, 1480, 1367, 1206, 1198, 980, 823, 770 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
8.73 (d, 1H, J ¼ 5.4 Hz, Ar-Qn), 8.30 (d,
1H, J ¼ 9.0 Hz, Ar-Qn), 8.16 (d, 2H, J ¼ 8.6 Hz, Ar), 8.07 (d, 1H,
J ¼ 1.8 Hz, Ar-Qn), 7.93 (d, 2H, J ¼ 8.7 Hz, Ar), 7.63 (d, 1H, J ¼ 15.6 Hz,
–CH]CH–), 7.59–7.55 (q, 1H, J ¼ 2.1 Hz), 7.41 (d, 1H, J ¼ 15.6 Hz,
–CH]CH–), 6.97 (d, 2H, J ¼ 8.7 Hz, Ar), 6.94 (d, 2H, J ¼ 9.0 Hz, Ar),
6.37 (d, 1H, J ¼ 5.3 Hz, Ar-Qn), 3.93 (s, 3H, OCH3); 13C NMR (75 MHz,
CDCl3 þ CD3OD):
d 187.67, 160.72, 158.67, 155.37, 151.63, 148.31,
142.67, 141.37, 140.78, 138.23, 136.83, 135.31, 132.81, 131.62, 128.81,
127.56, 124.49, 121.26, 119.68, 119.12, 105.71, 105.31, 64.58, 62.63;
Anal. Calcd. for C26H20ClNO4: C 70.03, H 4.52, N 3.14; Found: C
70.22, H: 4.76, N 3.31%.
CDCl3 þ CD3OD):
d 190.32, 160.38, 158.91, 157.26, 152.37, 151.78,
147.28, 136.76, 134.98, 134.23, 131.67, 128.32, 126.27, 125.91, 125.48,
124.02, 122.38, 121.36, 119.05, 98.31, 23.38; Anal. Calcd. for
C25H18ClNO3: C 72.20, H 4.36, N 3.37; Found: C 72.36, H 4.17, N 3.08%.
6.3.8. 1-(4-(7-Chloroquinolin-4-yloxy)phenyl)-3-(2,5-
dimethoxyphenyl)prop-2-en-1-one (11)
Yield: 75%; m.p 160–162 ꢀC; MS: 444 (M þ 1); IR (KBr): 3071,
6.3.4. 1-(4-(7-Chloroquinolin-4-yloxy)phenyl)-3-(3,4,5-
trimethoxyphenyl)prop-2-en-1-one (7)
Yield: 78%; m.p 168–170 ꢀC; MS: 476 (M þ 1); IR (KBr): 3063,
2999, 2832, 2362, 1658, 1590, 1452, 1377, 1211, 1130, 1032, 826, 768,
2998, 2367, 1655, 1610, 1521, 1479, 1377, 1280, 1078, 786, 776,
696 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d
8.74 (d, 1H, J ¼ 5.13 Hz, Ar-
Qn), 8.43 (d, 1H, J ¼ 8.7 Hz, Ar-Qn), 8.37 (d, 2H, J ¼ 8.3 Hz, Ar),
7.97 (d, 1H, J ¼ 1.8 Hz, Ar-Qn), 7.83 (d, 1H, J ¼ 15.6 Hz, –CH]CH–),

2086
M. Sharma et al. / European Journal of Medicinal Chemistry 44 (2009) 2081–2091
7.67–7.63 (m, 3H, Ar), 7.61 (d, 1H, J ¼ 9.0 Hz, Ar-Qn), 7.53–7.47 (m,
2H, –CH]CH–, Ar), 7.27 (d, 1H, J ¼ 8.7 Hz, Ar), 6.91 (d, 1H,
J ¼ 5.34 Hz, Ar-Qn), 3.97 (s, 3H, OCH3), 3.89 (s, 3H, OCH3); 13C NMR
(75 MHz, CDCl3 þ CD3OD): 188.23, 160.32, 157.36, 154.72, 151.67,
147.23, 142.87, 141.39, 141.03, 137.71, 137.31, 135.82, 133.06, 131.32,
128.83, 127.58, 123.48, 120.71, 118.93, 118.17, 104.61, 103.93, 63.37,
61.81; Anal. Calcd. for C26H20ClNO4: C 70.03, H 4.52, N 3.14; Found:
C 70.12, H 4.76, N 3.35%.
6.3.13. 1-(4-(7-Chloroquinolin-4-ylamino)phenyl)-3-phenylprop-
2-en-1-one (16)
Yield: 68%; m.p 190–192 ꢀC; MS: 385 (M þ 1); IR (KBr): 3331,
2998, 2967, 2364, 1655, 1610, 1570, 1521, 1479, 1428, 1377, 1210,
756 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
8.61 (d, 1H, J ¼ 5.1 Hz, Ar-
Qn), 8.13–8.07 (m, 3H, Ar-Qn, Ar), 7.87–7.83 (m, 2H, Ar-Qn,
–CH]CH), 7.73 (d, 1H, J ¼ 15.3 Hz, –CH]CH), 7.56 (d, 2H, J ¼ 9.0 Hz,
Ar), 7.39–7.33 (m, 3H, Ar-Qn, Ar), 7.29–7.23 (m, 2H, Ar), 7.19–7.13
(m, 2H, Ar-Qn, Ar), 6.67 (s, 1H, NH); 13C NMR (75 MHz, CDCl3,
6.3.9. 3-(4-Chlorophenyl)-1-(4-(7-chloroquinolin-4-
yloxy)phenyl)prop-2-en-1-one (12)
DMSO-d6): d 190.63, 152.22, 151.44, 149.10, 148.64, 141.23, 139.41,
134.66, 131.03, 129.14, 128.52, 127.57, 124.23, 122.16, 121.92, 119.64,
114.26, 112.87, 61.30, 55.82; Anal. Calcd. for C24H17ClN2O: C 74.90, H
4.45, N 7.28; Found: C 74.89, H 4.26, N 7.48%.
Yield: 72%; m.p 172–174 ꢀC; MS: 420 (M þ 1); IR (KBr): 3063,
2918, 2362, 1666, 1606, 1496, 1379, 1266, 1218, 1030, 976, 831,
752 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
8.74 (d, 1H, J ¼ 5.6 Hz, Ar-
Qn), 8.26–8.21 (m, 3H, Ar-Qn, Ar), 8.17 (d,1H, J ¼ 1.8 Hz, Ar-Qn), 8.10
(d, 2H, J ¼ 8.7 Hz, Ar), 7.79 (d, 1H, J ¼ 15.6 Hz, –CH]CH–), 7.52–7.43
(m, 4H, Ar, Ar-Qn, –CH]CH–), 7.13 (d, 2H, J ¼ 9.0 Hz, Ar), 6.87 (d,1H,
6.3.14. 1-(4-(7-Chloroquinolin-4-ylamino)phenyl)-3-p-tolylprop-2-
en-1-one (17)
Yield: 65%; m.p 170–172 ꢀC; MS: 399 (M þ 1); IR (KBr): 3349,
3020, 2360, 1729, 1640, 1578, 1522, 1480, 1324, 1216, 1031, 851, 771,
J ¼ 5.1 Hz, Ar-Qn); 13C (75 MHz, CDCl3 þ CD3OD):
d 187.38, 161.41,
152.38, 151.67, 151.06, 150.23, 147.68, 137.71, 135.08, 134.76, 132.61,
129.11, 125.21, 124.81, 124.08, 123.71, 122.39, 121.68, 118.73, 96.38;
Anal. Calcd. for C24H15Cl2NO2: C 68.59 H 3.60, N 3.33; Found: C
68.52, H 3.76, N 3.25%.
669 cmꢂ1 1H NMR (300 MHz, CDCl3, DMSO-d6):
; d (ppm) 8.47 (d,
1H, J ¼ 5.7 Hz, Ar-Qn), 8.13 (d, 1H, J ¼ 9.0 Hz, Ar-Qn), 8.01 (d, 2H,
J ¼ 8.7 Hz, Ar), 7.87 (d, 1H, J ¼ 2.1 Hz, Ar-Qn), 7.70 (d, 1H, J ¼ 15.0 Hz,
–CH]CH), 7.53 (d, 2H, J ¼ 9.0 Hz, Ar), 7.43–7.37 (m, 4H, Ar-Qn, Ar,
–CH]CH), 7.29–7.23 (m, 3H, Ar-Qn, Ar), 6.91 (s, 1H, NH), 2.98 (s, 3H,
6.3.10. 3-(2-Chlorophenyl)-1-(4-(7-chloroquinolin-4-
yloxy)phenyl)prop-2-en-1-one (13)
–CH3); 13C NMR (75 MHz, CDCl3, DMSO-d6):
d 192.02, 157.38,
148.07, 145.46, 145.03, 138.93, 136.71, 135.67, 135.12, 134.71, 134.21,
133.07, 132.81, 132.0, 131.06, 130.93, 130.78, 128.69, 125.04, 123.76,
23.38; Anal. Calcd. for C25H19ClN2O: C 75.28, H 4.80, N 7.02; Found:
C 75.30, H 4.54, N 7.15%.
Yield: 70%; m.p 178–180 ꢀC; MS: 420 (M þ 1); IR (KBr): 3061,
2909, 2367, 1655, 1610, 1570, 1479, 1428, 1377, 1268, 1210, 1023, 831,
756 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
8.76 (d, 1H, J ¼ 5.6 Hz, Ar-
Qn), 8.21 (d,1H, J ¼ 8.7 Hz, Ar-Qn), 8.11–8.06 (m, 2H, Ar-Qn, Ar), 7.97
(d, 2H, J ¼ 8.6 Hz, Ar), 7.81 (d, 1H, J ¼ 15.3 Hz, –CH]CH–), 7.67 (d,
1H, J ¼ 8.7 Hz, Ar), 7.59–7.51 (m, 6H, Ar, Ar-Qn, –CH]CH–), 6.89 (d,
6.3.15. 1-(4-(7-Chloroquinolin-4-ylamino)phenyl)-3-(4-
methoxyphenyl)prop-2-en-1-one (18)
1H, J ¼ 5.4 Hz, Ar-Qn); 13C NMR (75 MHz, CDCl3 þ CD3OD):
d
187.61,
Yield: 60%; m.p 172–174 ꢀC; MS: 415 (M þ 1); IR (KBr): 3343,
3023, 2921, 2372, 1651, 1610, 1573, 1526, 1476, 1428, 1374, 1267,
159.91, 158.31, 156.12, 151.63, 144.23, 141.32, 140.68, 138.27, 137.57,
136.81, 135.13, 132.67, 131.17, 129.06, 127.67, 124.51, 121.13, 119.13,
118.78, 105.56, 104.93; Anal. Calcd. for C24H15Cl2NO2: C 68.59, H
3.60, N 3.33; Found: C 68.22, H 3.46, N 3.25%.
1229, 1178, 1072, 1002, 827, 776 cmꢂ1
;
1H NMR (300 MHz,
CDCl3 þ DMSO-d6):
d
8.67 (d, 1H, J ¼ 5.1 Hz, Ar-Qn), 8.13 (d, 1H,
J ¼ 9.0 Ar-Qn Hz), 8.08 (d, 2H, J ¼ 8.3 Hz, Ar), 7.95 (d, 1H, J ¼ 2.1 Hz,
Ar-Qn), 7.94 (d, 2H, J ¼ 9.0 Hz, Ar), 7.83 (d, 1H, J ¼ 15.3 Hz,
–CH]CH), 7.53 (d, 1H, J ¼ 8.4 Hz, Ar-Qn), 7.31–7.23 (m, 3H, Ar,
–CH]CH), 7.06 (d, 2H, J ¼ 8.6 Hz, Ar-Qn), 6.71 (d, 1H, J ¼ 5.1 Hz, Ar-
Qn), 6.37 (s, 1H, NH), 3.87 (s, 3H, –OCH3); 13C NMR (75 MHz, CDCl3):
188.87, 160.71, 158.07, 152.23, 150.38, 146.41, 139.91, 137.13, 136.06,
132.17, 131.09, 128.68, 127.43, 126.31, 124.11, 120.68, 120.31, 118.91,
106.08, 105.32, 56.79; Anal. Calcd. for C25H19Cl–N2O2: C 72.37, H
4.62, N 6.75; Found: C 72.35, H 4.72, N 6.58%.
6.3.11. 1-(4-(7-Chloroquinolin-4-yloxy)phenyl)-3-(4-
(methylthio)phenyl)prop-2-en-1-one (14)
Yield: 68%; m.p 180–182 ꢀC; MS: 432 (M þ 1); IR (KBr): 3042,
2928, 2367, 1655, 1592, 1490, 1377, 1218, 1096, 980, 801, 756 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
8.67 (d, 1H, J ¼ 5.4 Hz, Ar-Qn), 8.27 (d,
1H, J ¼ 9.0 Hz, Ar-Qn), 8.19 (d, 2H, J ¼ 8.7 Hz, Ar), 8.03 (d, 2H,
J ¼ 8.6 Hz, Ar), 7.73 (d, 1H, J ¼ 15.6 Hz, –CH]CH–), 7.53 (d, 1H,
J ¼ 15.6 Hz, –CH]CH–), 7.47–7.43 (m, 3H, Ar, Ar-Qn), 7.31 (d, 1H,
J ¼ 9.0 Hz, Ar-Qn), 7.02 (d, 2H, J ¼ 8.6 Hz, Ar), 6.47 (d, 1H, J ¼ 5.1 Hz,
Ar-Qn), 3.81 (s, 3H, –S–CH3); 13C NMR (75 MHz, CDCl3 þ CD3OD):
6.3.16. 1-(4-(7-Chloroquinolin-4-ylamino)phenyl)-3-(3,4,5-
trimethoxyphenyl)prop-2-en-1-one (19)
d
181.27, 161.75, 159.03, 152.38, 151.68, 146.38, 137.67, 135.91, 134.81,
Yield: 72%; m.p 187–189 ꢀC; MS: 475 (M þ 1); IR (KBr): 3382,
3025, 2973, 2361, 1653, 1611, 1573,1528, 1429, 1335, 1216,1182,1031,
132.08, 126.71, 126.27, 126.01, 125.61, 123.17, 122.67, 121.08, 118.68,
103.56, 97.91, 32.08; Anal. Calcd. for C25H18ClNO2S: C 69.52, H 4.20,
N 3.24; Found: C 69.43, H 4.36, N 3.35%.
847, 759, 669 cmꢂ1 1H NMR (300 MHz, CDCl3):
; d 8.59 (d, 1H,
J ¼ 5.1 Hz, Ar-Qn), 8.33–8.27 (m, 3H, Ar-Qn, Ar), 7.97 (d,1H, J ¼ 2.1 Hz,
Ar-Qn), 7.89 (d, 1H, J ¼ 15.3 Hz, –CH]CH), 7.71 (d, 1H, J ¼ 15.1 Hz,
–CH]CH), 7.59–7.53 (m, 5H, Ar-Qn, Ar), 7.19 (d, 1H, J ¼ 5.3 Hz, Ar-
Qn), 6.93 (s, 1H, NH), 3.93 (s, 6H, –OCH3), 3.87 (s, 3H, –OCH3); 13C
6.3.12. 1-(4-(7-Chloroquinolin-4-yloxy)phenyl)-3-(pyridin-3-
yl)prop-2-en-1-one (15)
Yield: 68%; m.p 168–170 ꢀC; MS: 387 (M þ 1); IR (KBr): 3031,
NMR (75 MHz, CDCl3, DMSO-d6): d 188.81, 160.78, 158.08, 153.53,
2938, 2357, 1645, 1580, 1479, 1387, 1210, 1013, 836, 779 cmꢂ1
;
1H
152.24, 150.41, 145.45, 140.68, 136.44, 135.57, 131.06, 130.19, 128.29,
127.49, 123.24, 120.79, 120.53, 119.98, 105.80, 105.62, 61.02, 56.26;
Anal. Calcd. for. C27H23ClN2O4 C 68.28, H 4.88, N 5.90; Found: C 68.37,
H 4.89, N 5.89%.
NMR (300 MHz, CDCl3):
d
9.13 (s, 1H, Ar-Py), 8.68 (d, 1H, J ¼ 5.1 Hz,
Ar-Qn), 8.61 (d, 1H, J ¼ 6.38 Hz, Ar-Py), 8.33–8.27 (m, 2H, Ar-Qn, Ar-
Py), 8.16 (d, 2H, J ¼ 8.6 Hz, Ar), 7.87 (d, 1H, J ¼ 2.1 Hz, Ar-Qn), 7.83 (d,
1H, J ¼ 15.6 Hz, –CH]CH–), 7.61 (d, 1H, J ¼ 15.6 Hz, –CH]CH–),
7.43 (d, 1H, J ¼ 9.0 Hz, Ar-Qn), 7.37–7.31 (m, 3H, Ar-Py), 6.87 (d, 1H,
6.3.17. 1-(4-(7-Chloroquinolin-4-ylamino)phenyl)-3-(2,3,4-
trimethoxyphenyl)prop-2-en-1-one (20)
J ¼ 5.6 Hz, Ar-Qn); 13C NMR (75 MHz, CDCl3 þ DMSO-d6):
d 197.79,
157.03, 154.67, 153.83, 154.03, 152.38, 144.38, 141.23, 140.38, 139.67,
136.37, 136.07, 135.81, 135.23, 133.09, 130.61, 128.23, 124.91, 124.67,
124.19, 110.08; Anal. Calcd. for C23H15ClNO2: C 71.41, H 3.91, N 7.24;
Found: C 71.53, H 3.76, N 7.45%.
Yield: 78%; m.p 175–177 ꢀC; MS: 475 (M þ 1); IR (KBr): 3392,
3020, 2973, 2361, 1653, 1611, 1573, 1528, 1491, 1429, 1335, 1258,
1216, 1182, 1031, 850, 775, 759, 669 cmꢂ1 1H NMR (300 MHz,
;
CDCl3):
d
8.53 (d, 1H, J ¼ 5.34 Hz, Ar-Qn), 8.27–8.22 (m, 3H, Ar-Qn,

M. Sharma et al. / European Journal of Medicinal Chemistry 44 (2009) 2081–2091
2087
Ar), 7.87–7.83 (m, 2H, Ar-Qn, –CH]CH), 7.71 (d, 1H, J ¼ 15.3 Hz,
–CH]CH), 7.65 (d, 1H, J ¼ 8.4 Hz, Ar), 7.53 (d, 2H J ¼ 8.7 Hz, Ar), 7.19
(d, 1H, J ¼ 8.4 Hz, Ar), 7.03 (d, 1H, J ¼ 5.1 Hz, Ar-Qn), 6.93 (s, 1H, NH),
3.97 (s, 3H, –OCH3), 3.95 (s, 3H, –OCH3), 3.87 (s, 3H, –OCH3); 13C
Ar), 7.26–7.30 (m, 2H, Ar-Qn), 6.88 (s, 1H, NH); 13C NMR (75 MHz,
192.11, 154.9, 151.2, 151.0, 146.78, 140.26,
135.46, 135.24, 133.96, 132.99, 130.51, 129.76, 127.73, 124.55, 124.18,
118.2, 113.2, 110.14, 100.76; Anal. Calcd. for. C24H16Cl2N2O: C 68.75,
H 3.85, N 6.68, Found: C 68.56, H 3.98, N 6.42%.
CDCl3 þ DMSO-d6):
d
NMR (300 MHz, CDCl3 þ DMSO-d6):
d 189.69, 157.59, 155.26, 151.84,
148.37, 144.03, 140.45, 136.64, 134.24,132.34, 132.04, 131.85, 129.96,
127.43, 126.38, 125.40, 123.49, 122.45, 121.29, 121.12, 109.93, 106.77,
63.30, 62.53, 57.93; Anal. Calcd. for C27H23ClN2O4: C 68.28, H 4.88, N
5.90; Found: C 68.36, H 4.98, N 5.92%.
6.3.22. 3-(2-Chlorophenyl)-1-(4-(7-chloroquinolin-4-
ylamino)phenyl)prop-2-en-1-one (25)
Yield: 70%; m.p 172–175 ꢀC; MS: 419 (M þ 1); IR (KBr): 3390,
3022, 2973, 2361, 1653, 1619, 1573, 1528, 1493, 1429, 1376, 1335,
6.3.18. 1-(4-(7-Chloroquinolin-4-ylamino)phenyl)-3-(furan-2-
yl)prop-2-en-1-one (21)
1216, 1182, 1031, 867, 770, 759 cmꢂ1 1H NMR (300 MHz, CDCl3):
;
d
8.57 (d, 1H, J ¼ 5.13 Hz, Ar-Qn), 8.19–8.13 (m, 4H, Ar-Qn, Ar), 7.93
Yield: 78%; m.p 188–190 ꢀC; MS: 375 (M þ 1); IR (KBr): 3386,
3065, 3021, 2932, 2361, 1656, 1520, 1427, 1312, 1215, 1033, 760,
(d, 1H, J ¼ 2.1 Hz, Ar-Qn), 7.86 (d, 1H, J ¼ 15.3 Hz, –CH]CH), 7.59–
7.53 (m, 4H, Ar-Qn, Ar, –CH]CH), 7.41 (d, 1H, J ¼ 8.3 Hz, Ar), 7.38–
7.31 (m, 2H, Ar), 7.10 (d, 1H, J ¼ 5.13 Hz, Ar-Qn), 6.76 (s, 1H, NH); 13C
690 cmꢂ1 1H NMR (300 MHz, CDCl3, DMSO-d6):
; d 8.61 (d, 1H,
J ¼ 5.34 Hz, Ar-Qn), 8.23–8.17 (m, 3H, Ar-Qn, Ar), 7.93 (d,
1H, J ¼ 2.1 Hz, Ar-Qn), 7.81 (d, 1H, J ¼ 15.3 Hz, –CH]CH–), 7.73 (d,
1H, J ¼ 8.4 Hz, Ar-Qn), 7.55–7.49 (m, 4H, Ar, furan, –CH]CH), 7.21–
7.17 (m, 2H, Ar-Qn, furan), 6.67–6.63 (m, 2H, NH, furan); 13C NMR
NMR (75 MHz, CDCl3 þ DMSO-d6):
d 187.88, 156.32, 152.18, 148.31,
148.12, 143.67, 139.38, 138.21, 135.12, 134.16, 133.06, 133.41, 128.62,
127.91, 125.34, 124.69, 122.68, 121.98, 121.67, 111.03, 108.71; Anal.
Calcd. for C24H16Cl2N2O: C 68.75, H 3.85, N 6.68; Found: C 68.76, H
3.84, N 6.79%.
(75 MHz, CDCl3 þ DMSO-d6):
d 192.93, 155.50, 155.02, 153.08,
151.30, 149.19, 148.71, 139.85, 136.45, 134.63, 134.31, 131.07, 130.25,
127.36,123.76,123.35,122.65,120.51,116.63,108.56; Anal. Calcd. for
C22H15ClN2O2: C 70.50, H 4.03, N 7.47; Found: C 70.32, H 4.34, N
7.59%.
6.3.23. 1-(4-(7-Chloroquinolin-4-ylamino)phenyl)-3-(4-
(methylthio)phenyl)prop-2-en-1-one (26)
Yield: 68%; m.p 176–179 ꢀC; MS: 431 (M þ 1); IR (KBr): 3315,
3025, 2922, 2369, 1580, 1531, 1428, 1375, 1344, 1239, 813, 775,
6.3.19. 1-(4-(7-Chloroquinolin-4-ylamino)phenyl)-3-(2,3-
dimethoxyphenyl)prop-2-en-1-one (22)
669 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
8.53 (d, 1H, J ¼ 5.1 Hz, Ar-
Qn), 8.07 (d, 1H, J ¼ 9.0 Hz, Ar-Qn), 7.98–7.91 (m, 3H, Ar-Qn, Ar),
7.69 (d,1H, J ¼ 15.6 Hz, –CH]CH), 7.37 (d, 2H, J ¼ 8.1 Hz, Ar), 7.29 (d,
1H, J ¼ 15.3 Hz, –CH]CH), 7.06–6.97 (m, 6H, Ar-Qn, Ar, NH), 6.29 (d,
1H, J ¼ 5.1 Hz, Ar-Qn), 3.81 (s, 3H, SCH3); 13C NMR (75 MHz,
Yield: 78%; m.p 160–162 ꢀC; MS: 445 (M þ 1); IR (KBr): 3333,
3073, 2931, 2362, 1651, 1610, 1573, 1526, 1476, 1428, 1374, 1267,
1229, 1178, 1072, 817, 776, 710, 683 cmꢂ1 1H NMR (300 MHz,
;
CDCl3 þ DMSO-d6):
d
8.69 (d, 1H, J ¼ 5.1 Hz, Ar-Qn), 8.09–8.16 (m,
CDCl3 þ DMSO-d6):
d 188.27, 160.75, 157.99, 152.09, 150.44, 144.72,
3H, –CH]CH–, Ar), 7.90–7.97 (m, 2H, Ar-Qn, Ar), 7.64 (d, 1H,
J ¼ 15.6 Hz, –CH]CH–), 7.51 (d, 1H, J ¼ 8.7 Hz, Ar-Qn), 7.37 (d, 1H,
J ¼ 8.7 Hz, Ar), 7.25–7.31 (m, 3H, Ar, Ar-Qn), 7.11 (d, 1H, J ¼ 5.1 Hz,
Ar-Qn), 6.99 (d, 1H, J ¼ 7.8 Hz, Ar), 6.90 (s, 1H, NH), 3.92 (s, 3H,
OMe), 3.86 (s, 3H, OMe); 13C NMR (75 MHz, CDCl3 þ DMSO-d6):
142.77, 136.45, 135.67, 131.16, 130.98, 128.84, 128.33, 127.47, 125.93,
123.16, 120.49, 120.36, 120.18, 105.49, 23.71; Anal. Calcd. for
C25H19ClN2OS: C 69.68, H 4.44, N 6.50; Found: C 69.65, H 4.26, N
6.32%.
d
190.61, 152.22, 151.40, 149.15, 148.60, 141.28, 139.46, 134.64,
6.3.24. 1-(4-(7-Chloroquinolin-4-ylamino)phenyl)-3-(pyridin-3-
yl)prop-2-en-1-one (27)
131.04, 129.15, 128.58, 127.52, 124.23, 122.14, 121.92, 119.64, 114.22,
112.84, 61.30, 55.81; Anal. Calcd. for C26H21ClN2O3: C 70.19, H 4.76,
N 6.30; Found: C 70.23, H 4.90, N 6.68%.
Yield: 65%; m.p 174–176 ꢀC; MS: 386 (M þ 1); IR (KBr): 3450,
3360, 3025, 2945, 2362, 1637, 1570, 1522, 1489, 1377, 1244, 773,
669 cmꢂ1 1H NMR (300 MHz, CDCl3, DMSO-d6):
; d 9.23 (s, 1H, Py),
6.3.20. 1-(4-(7-Chloroquinolin-4-ylamino)phenyl)-3-(2,5-
dimethoxyphenyl)prop-2-en-1-one (23)
8.65 (d, 1H, J ¼ 7.7 Hz, Py), 8.51 (d, 1H, J ¼ 5.38 Hz, Ar-Qn), 8.41–8.33
(m, 2H, Ar-Qn, Py), 8.17 (d, 2H, J ¼ 8.3 Hz, Ar), 7.93 (d, 1H, J ¼ 1.8 Hz,
Ar-Qn), 7.89 (d, 1H, J ¼ 15.3 Hz, –CH]CH), 7.76 (d, 1H, J ¼ 15.1 Hz,
–CH]CH), 7.49–7.43 (m, 4H, Ar-Qn, Ar, Py), 7.13 (d, 1H, J ¼ 5.2 Hz,
Yield: 78%; m.p 172–174 ꢀC; MS: 445 (M þ 1); IR (KBr): 3366,
2939, 2834, 2362, 1652, 1610, 1570, 1528, 1458, 1429, 1375, 1322,
1258,1220, 1178, 1029, 984, 836, 775, 670 cmꢂ1; 1H NMR (300 MHz,
Ar-Qn), 6.91 (s, 1H, NH); 13C (75 MHz, CDCl3 þ DMSO-d6):
d 197.79,
CDCl3):
d
8.70 (d, 1H, J ¼ 5.1 Hz, Ar-Qn), 8.09–8.15 (m, 4H, Ar,
153.64, 151.72, 151.66, 151.26, 149.27, 141.72, 137.41, 136.83, 136.22,
132.62, 132.62, 132.31, 131.72, 131.42, 129.90, 125.73, 125.08, 121.42,
121.12, 120.91, 106.99; Anal. Calcd. for C23H16ClN3O: C: 71.59, H 4.18,
N 10.89; Found: C 71.82, H 4.39, N 10.99%.
–CH]CH–), 7.94 (d, 1H, J ¼ 9 Hz, Ar-Qn), 7.63 (d, 1H, J ¼ 15.6 Hz,
–CH]CH–), 7.51 (d, 1H, J ¼ 8.7 Hz), 7.36 (d, 1H, J ¼ 8.4 Hz, Ar), 7.28
(d, 2H, Ar, J ¼ 8.7), 7.19 (d, 1H, J ¼ 2.7 Hz, Ar-Qn), 6.95 (d, 1H,
J ¼ 2.7 Hz, Ar), 6.91 (s, 1H, NH), 6.90 (d, 1H, J ¼ 5.1 Hz, Ar-Qn), 3.90
(s, 3H, OMe), 3.84 (s, 3H, OMe); 13C NMR (75 MHz, CDCl3, DMSO-
6.3.25. 1-(4-(7-Chloroquinolin-4-ylamino)phenyl)-3-(4-
isopropylphenyl)prop-2-en-1-one (28)
d6):
d 191.70, 156.77, 152.38, 151.12, 150.84, 143.33, 135.34, 135.16,
132.92, 129.33, 127.12, 124.54, 120.11, 122.56, 118.01, 117.55, 116.59,
115.72, 113.42, 109.81, 61.12, 60.69; Anal. Calcd. for C26H21ClN2O3: C
70.19, H 4.76, N 6.30; Found: C 70.56, H 4.55, N 6.12%.
Yield: 60%; m.p 190–192 ꢀC; MS: 427 (M þ 1); IR (KBr) 3362,
3010, 2953, 2334, 1650, 1609, 1545, 1500, 1429, 1376, 1324, 1210,
1082, 867, 759 cmꢂ1 1H NMR (300 MHz, CDCl3, DMSO-d6):
; d 8.67
(d, 1H, J ¼ 5.1 Hz, Ar-Qn), 8.23–8.17 (m, 3H, Ar-Qn, Ar), 8.14 (d, 2H,
J ¼ 8.7 Hz, Ar), 7.93 (d, 1H, J ¼ 2.1 Hz, Ar-Qn), 7.71 (d, 1H, J ¼ 15.1 Hz,
–CH]CH), 7.63–7.55 (m, 4H, Ar-Qn, Ar, –CH]CH), 7.39 (d, 2H
J ¼ 8.6 Hz, Ar), 7.13 (d, 1H, J ¼ 5.3 Hz, Ar-Qn), 6.93 (s, 1H, NH), 2.96–
2.94 (m, 1H, –CH), 1.27 (d, 6H, J ¼ 6.0 Hz, –CH(CH3)2); 13C NMR
6.3.21. 3-(4-Chlorophenyl)-1-(4-(7-chloroquinolin-4-
ylamino)phenyl)prop-2-en-1-one (24)
Yield: 78%; m.p 175–177 ꢀC; MS: 419 (M þ 1); IR (KBr): 3392,
3020, 2973, 2361, 1653, 1611, 1573, 1528, 1491, 1429, 1376, 1335,
1216, 1182, 1031, 867, 759, 669 cmꢂ1
;
1H NMR (300 MHz, CDCl3,
(75 MHz CDCl3 þ DMSO-d6):
d 190.37, 166.23, 165.71, 165.12, 156.45,
DMSO-d6):
d
8.71 (d, 1H, J ¼ 5.1 Hz, Ar-Qn), 8.10–8.13 (m, 2H,
155.23, 152.67, 149.08, 140.73, 139.81, 137.70, 133.72, 133.32, 132.57,
130.75, 130.14, 126.51, 124.43, 106.64, 36.01, 26.34; Anal. Calcd. for.
C27H23ClN2O: C 75.96, H 5.43, N 6.56; Found: C 75.66, H 5.18, N
6.22%.
J ¼ 9 Hz, Ar), 7.94 (d, 1H, J ¼ 8.7 Hz, Ar-Qn), 7.81 (d, 1H, J ¼ 15.6 Hz,
–CH]CH–), 7.57–7.62 (m, 3H, Ar, –CH]CH–), 7.46 (d, 1H,
J ¼ 9 Hz, Ar-Qn), 7.42 (d, 2H, J ¼ 8.4 Hz, Ar), 7.37 (d, 2H, J ¼ 8.7 Hz,

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M. Sharma et al. / European Journal of Medicinal Chemistry 44 (2009) 2081–2091
6.3.26. 3-(3-Bromophenyl)-1-(4-(7-chloroquinolin-4-
ylamino)phenyl)prop-2-en-1-one (29)
6.4.2. 4-(4-(7-Chloroquinolin-4-yloxy)phenyl)-6-p-tolylpyrimidin-
2-amine (33)
Yield: 68%; m.p 180–182 ꢀC; MS: 476 (M þ 1); IR (KBr): 3392,
3020, 2963, 2354, 1655, 1621, 1575, 1526, 1489, 1427, 1370, 1325,
Yield: 50%; m.p 178–180 ꢀC; MS: 439 (M þ 1); IR (KBr): 3420,
3020, 2361, 1725, 1598, 1492, 1422, 1301, 1216, 1017, 761, 670 cmꢂ1
;
1206, 1172, 1031, 867, 759, 555 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
1H NMR (300 MHz, CDCl3):
d
8.73 (d, 1H, J ¼ 5.3 Hz, Ar-Qn), 8.39 (d,
d
8.71 (d, 1H, J ¼ 5.3 Hz, Ar-Qn), 8.13–8.09 (m, 3H, Ar-Qn, Ar), 7.95
1H, J ¼ 9 Hz, Ar-Qn), 8.27 (d, 2H, J ¼ 8.4 Hz, Ar), 8.12 (d, 2H,
J ¼ 8.4 Hz, Ar), 7.86 (s, 1H, Ar-Pym), 7.51 (d, 1H, J ¼ 1.8 Hz, Ar-Qn),
7.46 (d, 2H, J ¼ 8.6 Hz, Ar), 7.36 (d,1H, J ¼ 9.0 Hz, Ar-Qn), 6.97 (d, 2H,
J ¼ 8.4 Hz, Ar), 6.83 (d, 1H, J ¼ 5.4 Hz, Ar-Qn), 5.86 (s, 2H, NH2), 2.63
(d, 1H, J ¼ 2.1 Hz, Ar-Qn), 7.81 (d, 1H, J ¼ 15.3 Hz, –CH]CH), 7.59–
7.50 (m, 3H, Ar-Qn), 7.38–6.93 (m, 6H, Ar-Qn, Ar, –CH]CH), 6.89 (s,
1H, NH); 13C NMR (75 MHz, CDCl3, DMSO-d6):
d 189.12, 153.73,
151.86, 148.12, 148.07, 143.49, 139.27, 136.63, 134.77, 133.53, 132.60,
132.45, 127.50, 127.46, 126.50, 125.34, 124.62, 121.50, 121.32, 121.09,
110.05, 109.87; Anal. Calcd. for C24H16BrClN2O: C 62.16, H 3.48, N
6.04; Found: C 62.35, H 3.54, N 6.39%.
(s, 3H, –CH3); 13C NMR (75 MHz, CDCl3):
d 162.34, 160.0, 154.32,
149.37, 147.32, 145.87, 143.62, 134.37, 130.08, 129.62, 128.67, 126.13,
123.57, 121.62, 120.08, 116.92, 114.78, 113.09, 98.23, 97.25, 97.02,
51.63; Anal. Calcd. for C26H19ClN4O: C 71.15, H 4.36, N 12.77; Found:
C 71.34, H 4.34, N 12.49%.
6.3.27. 3-(2-Bromophenyl)-1-(4-(7-chloroquinolin-4-
ylamino)phenyl)prop-2-en-1-one (30)
6.4.3. 4-(4-(7-Chloroquinolin-4-yloxy)phenyl)-6-(4-
methoxyphenyl)pyrimidin-2-amine (34)
Yield: 65%; m.p 175–177 ꢀC; MS: 463 (M þ 1); IR (KBr): 3392,
3020, 2973, 2361,1653, 1611,1573,1528,1491,1429,1376,1335,1216,
Yield: 50%; m.p 162–164 ꢀC; MS: 454 (M þ 1); IR (KBr): 3421,
1182, 1031, 759, 569 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d 8.61 (d, 1H,
3029, 2830, 2346, 1722, 1568, 1430, 1345, 1225, 1127, 1420, 776, 669,
J ¼ 5.3 Hz, Ar-Qn), 8.17–8.10 (m, 4H, Ar-Qn, Ar), 7.89 (d,1H, J ¼ 2.1 Hz,
Ar-Qn), 7.81 (d, 1H, J ¼ 15.3 Hz, –CH]CH), 7.55–7.49 (m, 4H, Ar-Qn,
Ar, –CH]CH), 7.43–7.35 (m, 3H, Ar), 7.08 (d, 1H, J ¼ 5.3 Hz, Ar-Qn),
486 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d
8.72 (d, 1H, J ¼ 5.34 Hz, Ar-
Qn), 8.33 (d, 1H, J ¼ 9.0 Hz, Ar-Qn), 8.19 (d, 2H, J ¼ 8.7 Hz, Ar), 8.13
(d, 1H, J ¼ 2.13 Hz, Ar-Q), 8.07 (d, 2H, J ¼ 8.4 Hz, Ar), 7.59–7.55 (dd,
1H, J ¼ 8.4 Hz, J ¼ 1.8 Hz, Ar-Qn), 7.45 (s, 1H, Ar-Pym), 7.31 (d, 2H,
J ¼ 8.71 Hz, Ar), 7.04 (d, 2H, J ¼ 9.0 Hz, Ar), 6.65 (d, 1H, J ¼ 5.34 Hz,
Ar-Qn), 5.21 (s, 2H, NH2), 3.90 (s, 3H, OCH3); 13C NMR (75 MHz,
6.65 (s, 1H, NH); 13C NMR (75 MHz, CDCl3 þ DMSO-d6):
d 181.23,
158.13, 155.03, 144.84, 142.64, 136.60, 131.93, 131.64, 131.21, 130.87,
130.68, 130.13, 129.02, 126.87, 120.61, 120.14, 116.24, 115.87, 115.21,
113.57, 112.85, 98.43; Anal. Calcd. for C24H16BrClN2O: C 62.16, H 3.48,
N 6.04; Found: C 62.18, H 3.67, N 6.20%.
CDCl3): d 162.34, 160.0, 154.32, 149.37, 147.32, 145.87, 143.62, 134.37,
130.08, 129.62, 128.67, 126.13, 123.57, 121.62, 120.08, 116.92, 114.78,
113.09, 98.23, 97.25, 97.02, 51.63; Anal. Calcd. for C26H19ClN4O2: C
68.65, H 4.21, N 12.32; Found: C 68.72, H 4.66, N 12.58%.
6.3.28. 1-(4-(7-Chloroquinolin-4-ylamino)phenyl)-3-(3-
nitrophenyl)prop-2-en-1-one (31)
Yield: 60%; m.p 178–180 ꢀC; MS: 430 (M þ 1); IR (KBr): 3389,
3022, 2963, 2351, 1655, 1621, 1563, 1530, 1491, 1429, 1376, 1355,
1219, 1082, 776, 759 cmꢂ1; 1H NMR (300 MHz, CDCl3 þ DMSO-d6):
6.4.4. 4-(4-(7-Chloroquinolin-4-yloxy)phenyl)-6-(3,4,5-
trimethoxyphenyl)pyrimidin-2-amine (35)
Yield: 58%; m.p 195–197 ꢀC; MS: 515 (M þ 1); IR (KBr): 3423,
d
8.97 (d, 1H, J ¼ 2.3 Hz, Ar), 8.84 (d, 1H, J ¼ 8.7 Hz, Ar), 8.69 (d, 1H,
3020, 2930, 2361, 1726, 1572, 1421, 1369, 1215, 1128, 1428, 760, 669,
J ¼ 5.3 Hz, Ar-Qn), 8.12 (d, 1H, J ¼ 9 Hz, Ar), 8.02–8.09 (m, 3H, Ar-Qn,
Ar), 7.62–7.71 (m, 3H, Ar-Qn, Ar, –CH]CH–), 7.65 (d, 1H, J ¼ 15.6 Hz,
–CH]CH–), 7.43 (d, 1H, J ¼ 8.6 Hz, Ar-Qn), 7.23 (d, 2H, J ¼ 8.6 Hz,
Ar), 6.83 (d, 1H, J ¼ 5.4 Hz, Ar-Qn), 6.31 (s, 1H, NH); 13C NMR
480 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d
8.73 (d, 1H, J ¼ 5.13 Hz, Ar-
Qn), 8.46 (d, 1H, J ¼ 8.7 Hz, Ar-Qn), 8.13 (d, 2H, J ¼ 8.7 Hz, Ar), 8.01
(d, 1H, J ¼ 1.8 Hz, Ar-Qn), 7.90 (s, 1H, Ar-Pym), 7.63 (d, 2H, J ¼ 8.4 Hz,
Ar), 7.56 (s, 2H, Ar), 7.51 (d, 1H, J ¼ 9.0 Hz, Ar-Qn), 7.01 (d, 1H,
J ¼ 5.34 Hz, Ar-Qn), 5.67 (s, 2H, NH2), 4.07 (s, 6H, OCH3), 3.93 (s, 3H,
(75 MHz, CDCl3 þ DMSO-d6):
d 189.03, 153.51, 150.68, 148.67,
142.61, 139.13, 138.32, 137.03, 136.89, 134.32, 133.33, 132.89, 130.31,
129.21, 128.67, 127.89, 127.23, 125.37, 124.31, 122.03, 121.93, 108.11;
Anal. Calcd. for C24H16ClN3O3: C 67.06, H 3.75, N 9.78; Found: C
67.15, H 3.79, N 9.89%.
OCH3); 13C NMR (75 MHz, CDCl3 þ CD3OD):
d 161.87, 159.01, 158.12,
155.07, 148.85, 146.37, 144.81, 142.36, 133.23, 129.90, 128.73, 128.26,
125.79, 122.51, 120.60, 119.88, 116.49, 114.20, 112.85, 97.76, 97.52,
96.80, 53.79, 49.14; Anal. Calcd. for C28H23ClN4O4: C 65.31, H 4.50, N
10.88; Found: C 65.43, H 4.46, N 10.78%.
6.4. General procedure for the synthesis of compounds 32–59
6.4.5. 4-(4-(7-Chloroquinolin-4-yloxy)phenyl)-6-(2,3,4-
trimethoxyphenyl)pyrimidin-2-amine (36)
To a solution of guanidine hydrochloride (1.5 equiv) in DMF, NaH
(3.0 equiv), and chalcones (1.0 equiv) were added. The reaction
mixture was refluxed for 8 h. Water was added to the reaction
mixture, a solid started to separating out. The solid was filtered out
and purified by column chromatography to afford the pure
compounds 32–59.
Yield: 65%; m.p 185–187 ꢀC; MS: 515 (M þ 1); IR (KBr): 3422,
3025, 2930, 2356, 1726, 1562, 1428, 1367, 1205, 1028, 1430, 760, 669,
486 cmꢂ1; 1H NMR (300 MHz, CDCl3) :
d
8.53 (d, 1H, J ¼ 5.34 Hz, Ar-
Qn), 8.27–8.21 (m, 3H, Ar-Qn, Ar), 7.87 (d, 1H, J ¼ 2.1 Hz, Ar-Qn),
7.81 (s, 1H, Ar-Pym), 7.73 (d, 1H, J ¼ 9.0 Hz, Ar-Qn), 7.61 (d, 1H,
J ¼ 8.7 Hz, Ar), 7.53 (d, 2H, J ¼ 8.3 Hz, Ar), 7.21 (d, 1H, J ¼ 8.71 Hz,
Ar), 6.97 (d, 1H, J ¼ 5.13 Hz, Ar-Qn), 6.12 (s, 2H, J ¼ 5.34 Hz, NH2),
4.01 (s, 3H, OCH3), 3.99 (s, 3H, OCH3), 3.87 (s, 3H, OCH3); 13C NMR
6.4.1. 4-(4-(7-Chloroquinolin-4-yloxy)phenyl)-6-phenylpyrimidin-
2-amine (32)
Yield: 55%; m.p 189–190 ꢀC; MS: 425 (M þ 1); IR (KBr): 3419, 3021,
(75 MHz, CDCl3 þ CD3OD):
d 161.68, 159.23, 158.67, 154.98, 149.03,
2361, 1725, 1593, 1484, 1424, 1216, 1084, 767, 670 cmꢂ1
;
1H NMR
148.03, 148.31, 146.71, 144.45, 142.39, 133.37, 129.87, 129.07, 125.23,
122.81, 119.93, 119.08, 116.78, 115.20, 113.87, 111.92, 101.72, 100.98,
98.20, 54.71, 54.23, 48.78; Anal. Calcd. for C28H23ClN4O4: C 65.31, H
4.50, N 10.88; Found: C 65.23, H 4.46, N 10.58%.
(300 MHz, CDCl3):
d
8.74 (d, 1H, J ¼ 5.13 Hz, Ar-Qn), 8.27 (d, 1H,
J ¼ 9.0 Hz, Ar-Qn), 8.16 (d, 2H, J ¼ 8.7 Hz, Ar), 8.14 (d, 1H, J ¼ 1.8 Hz,
Ar-Qn), 7.84 (s, 1H, Ar-Pym), 7.69–7.66 (m, 2H, Ar), 7.55 (d, 1H,
J ¼ 8.7 Hz, Ar-Qn), 7.28 (d, 2H, J ¼ 8.34 Hz, Ar), 7.16 (d, 1H, J ¼ 8.7 Hz,
Ar), .6.96(d,1H, J ¼ 5.1 Hz,Ar-Qn), 5.37 (s,2H, NH2); 13C NMR(75 MHz,
6.4.6. 4-(4-(7-Chloroquinolin-4-yloxy)phenyl)-6-(furan-2-
yl)pyrimidin-2-amine (37)
CDCl3 þ DMSO-d6):
d 162.41, 160.37, 147.72, 145.38, 143.67, 143.67,
143.08, 134.91, 130.26, 127.64, 127.13, 125.23, 124.53, 122.67, 119.92,
119.33, 116.72, 114.26, 111.67, 98.23, 97.56; Anal. Calcd. for
C25H17ClN4O:C70.67, H4.03,N13.19;Found:C70.89,H4.26,N13.28%.
Yield: 65%; m.p 180–182 ꢀC; MS: 414 (M þ 1); IR (KBr): 3420,
3020, 2361, 1725, 1598, 1492, 1422, 1301, 1216, 1017, 761, 670 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
8.72 (d, 1H, Ar-Qn, J ¼ 5.1 Hz), 8.33 (d,

M. Sharma et al. / European Journal of Medicinal Chemistry 44 (2009) 2081–2091
2089
1H, Ar-Qn, J ¼ 9 Hz), 8.21 (d, 2H, Ar, J ¼ 8.7 Hz), 8.14 (d, 1H, Ar-Qn,
J ¼ 2.1 Hz), 7.61 (d, 1H, furan, J ¼ 3.0 Hz), 7.57 (dd, 1H, Ar-Qn, J ¼ 8.7,
2.13 Hz), 7.45 (s, 1H, Ar-Pym), 7.31(d, 2H, Ar, J ¼ 8.4 Hz), 7.24 (d, 1H,
furan, J ¼ 3.3 Hz), 6.65 (d, 1H, J ¼ 5.4 Hz), 6.59–6.61 (m, 1H, furan),
C25H16Cl2N4O: C 65.37, H 3.51, N 12.20, Found: C 65.59, H 3.78,
N 12.47%.
6.4.11. 4-(4-(7-Chloroquinolin-4-yloxy)phenyl)-6-(4-
(methylthio)phenyl)pyrimidin-2-amine (42)
5.19 (s, 2H, NH2); 13C NMR (75 MHz, CDCl3):
d 166.02, 165.57,
158.28, 157.23, 156.98, 153.38, 152.0, 149.48, 144.68, 136.91, 133.82,
131.23, 129.84, 129.68, 127.08, 123.0, 126.87, 121.0, 115.92, 113.82,
111.0, 101.38, 99.65; Anal. Calcd. for C23H15ClN4O2: C 66.59, H 3.64,
N 13.51; Found: C 66.79, H 3.86, N 13.68%.
Yield: 60%; m.p 180–182 ꢀC; MS: 471 (M þ 1); IR (KBr): 3420,
3020, 2361, 1725, 1598, 1492, 1422, 1301, 1216, 1017, 761, 670 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
8.71 (d, 1H, J ¼ 5.1 Hz, Ar-Qn), 8.37 (d,
1H, J ¼ 9 Hz, Ar-Qn), 8.21 (d, 2H, J ¼ 8.7 Hz, Ar), 8.09 (d, 2H, J ¼ 8.4 Hz,
Ar), 7.83 (s, 1H, Ar-Pym), 7.51–7.47 (m, 3H, Ar-Qn, Ar), 7.23 (d, 1H,
J ¼ 9.0 Hz, Ar-Qn), 6.89 (d, 2H, J ¼ 8.7 Hz, Ar), 6.37 (d, 1H, J ¼ 5.3 Hz,
Ar-Qn), 5.72 (s, 2H, NH2), 3.83 (s, 3H, –S–CH3); 13C NMR (75 MHz,
6.4.7. 4-(4-(7-Chloroquinolin-4-yloxy)phenyl)-6-(2,3-
dimethoxyphenyl)pyrimidin-2-amine (38)
Yield: 60%; m.p 162–164 ꢀC; MS: 485 (M þ 1); IR (KBr):3419,
CDCl3): d 167.39,167.10,165.71,162.98,161.34,159.75,154.64,145.46,
3020, 2361, 1725, 1576, 1492, 1367, 1261, 1216, 1084, 762, 670 cmꢂ1
;
136.83, 134.27, 131..69, 130.16, 129.75, 129.57, 127.90, 126.29, 123.65,
125.68, 115.57, 111.83, 100.13, 57.18; Anal. Calcd. for C26H19ClN4OS: C
66.30, H 4.07, N 11.90; Found: C 66.49, H 4.26, N 11.89%.
1H NMR (300 MHz, CDCl3):
d
8.69 (d, 1H, J ¼ 5.13 Hz, Ar-Qn), 8.41 (d,
1H, J ¼ 9.0 Hz, Ar-Qn), 8.11 (d, 2H, J ¼ 8.7 Hz, Ar), 7.86 (d, 1H,
J ¼ 2.1 Hz, Ar-Q), 7.47–7.41 (m, 3H, Ar), 7.51 (s, 1H, Ar-Qn), 7.36 (d,
1H, J ¼ 9.0 Hz, Ar-Qn), 7.16–7.10 (m, 2H, Ar), 6.97 (d, 1H, J ¼ 5.1 Hz,
6.4.12. 4-(4-(7-Chloroquinolin-4-yloxy)phenyl)-6-(pyridin-3-
yl)pyrimidin-2-amine (43)
Ar-Qn), 5.37 (s, 2H, NH2), 3.89 (s, 2H, OCH3), 3.94 (s, 3H, OCH3); 13
C
NMR (75 MHz, CDCl3 þ CD3OD):
d
163.34, 161.10, 159.81, 149.75,
Yield: 62%; m.p 178–180 ꢀC; MS: 426 (M þ 1); IR (KBr): 3486,
3156, 2931, 2364, 1720, 1568, 1456, 1355, 1214, 1164, 1098, 762,
147.32, 146.89, 144.02, 142.37, 135.38, 134.27, 131.19, 130.27, 127.28,
124.58, 122.68, 121.37, 117.42, 115.23, 113.28, 111.87, 108.29, 107.93,
102.89, 53.28, 50.37; Anal. Calcd. for C27H21ClN4O3: C 66.87, H 4.36,
N 11.55; Found: C 66.72, H 4.46, N 11.68%.
681 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d 9.21 (s, 1H, Ar-Py), 8.73 (d,
1H, J ¼ 5.3 Hz, Ar-Qn), 8.64 (d, 1H, J ¼ 6.0 Hz, Ar-Py), 8.43–8.37 (m,
2H, Ar-Qn, Ar-Py), 8.17 (d, 2H, J ¼ 8.6 Hz, Ar), 7.87 (d, 1H, J ¼ 2.1 Hz,
Ar-Qn), 7.57 (s, 1H, Ar-Py), 7.43–7.38 (m, 4H, Ar-Qn, Ar, Ar-Py), 6.93
(d, 1H, J ¼ 5.28 Hz, Ar-Qn), 5.73 (s, 2H, NH2); 13C NMR (75 MHz,
6.4.8. 4-(4-(7-Chloroquinolin-4-yloxy)phenyl)-6-(2,5-
dimethoxyphenyl)pyrimidin-2-amine (39)
CDCl3): d 159.46,157.53,157.33,155.71,150.05,145.90,144.61,144.12,
Yield: 60%; m.p 160–162 ꢀC; MS: 485 (M þ 1); IR (KBr): 3419,
143.62, 141.88, 130.66, 129.08, 128.89, 123.38, 121.46, 121.31, 121.21,
117.33, 115.12, 113.82, 98.81, 97.69; Anal. Calcd. for C24H16ClN5O: C
67.69, H 3.79, N 16.44; Found: C 67.53, H 3.86, N 16.65%.
3023, 2361, 1730, 1572, 1482, 1365, 1263, 1206, 1089, 762, 670 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
8.73 (d,1H, J ¼ 5.34 Hz, Ar-Qn), 8.47 (d,
1H, J ¼ 8.7 Hz, Ar-Qn), 8.27 (d, 2H, J ¼ 8.3 Hz, Ar), 8.03 (d, 1H,
J ¼ 1.8 Hz, Ar-Qn), 7.77–7.69 (m, 4H, Ar, Ar-Pym), 7.59 (d, 1H,
J ¼ 9.0 Hz, Ar-Qn), 7.41 (d,1H, J ¼ 9.0 Hz, Ar), 7.37 (d,1H, J ¼ 8.34, Ar),
6.93 (d, 1H, J ¼ 5.13 Hz, Ar-Qn), 5.18 (s, 2H, NH2), 4.01 (s, 3H, OCH3),
6.4.13. N-(4-(2-Amino-6-phenylpyrimidin-4-yl)phenyl)-7-
chloroquinolin-4-amine (44)
Yield: 52%; m.p 198–200 ꢀC; MS: 424 (M þ 1); IR (KBr): 3421,
3.93 (s, 3H, OCH3); 13C NMR (75 MHz, CDCl3 þ CD3OD) :
d
165.36,
3329, 2936, 2362, 1621, 1572, 1530, 1438, 1335, 1216, 1161, 774 cmꢂ1
;
163.13, 161.87, 151.25, 149.38, 148.71, 146.0, 144.38, 136.29, 136.21,
133.18, 132.81, 129.25, 126.57, 124.69, 123.32, 119.67, 117.62, 115.23,
113.89, 110.26, 109.34, 105.67, 58.36; Anal. Calcd. for C27H21ClN4O3:
C 66.87, H 4.36, N 11.55; Found: C 66.92, H 4.56, N 11.58%.
IR (KBr); 1H NMR (300 MHz, CDCl3):
d 9.26 (s, 1H, NH), 8.51 (d, 1H,
J ¼ 5.7 Hz, Ar-Qn), 8.11 (d, 1H, J ¼ 9.0 Hz, Ar-Qn), 8.03 (d, 2H,
J ¼ 8.6 Hz, Ar), 7.87 (d,1H, J ¼ 2.1 Hz, Ar), 7.77 (s,1H, Ar-Pym), 7.58 (d,
2H, J ¼ 9.0 Hz, Ar), 7.37–7.42 (m, 3H, Ar-Qn, Ar), 7.28–7.33 (m, 2H, Ar),
7.21–7.26 (m, 2H, Ar-Qn, Ar), 6.65 (s, 2H, NH2); 13C NMR
6.4.9. 4-(4-Chlorophenyl)-6-(4-(7-chloroquinolin-4-
yloxy)phenyl)pyrimidin-2-amine (40)
(CDCl3 þ DMSO-d6, 75 MHz):
d 160.13, 157.87, 143.93, 141.89, 135.88,
132.40, 128.74, 126.33, 123.57, 123.43, 121.69, 121.49, 121.40, 120.53,
120.02, 119.04, 116.06, 114.58, 114.02, 100.70; Anal. Calcd. for
C25H18ClN5: C 70.84, H 4.28, N 16.52; Found: C 70.51, H 4.46, N 16.35%.
Yield: 52%; m.p 174–176 ꢀC; MS: 459 (M þ 1); IR (KBr): 3420,
3020, 2361, 1725, 1598, 1492, 1422, 1301, 1216, 1017, 761, 670 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
8.73 (d, 1H, J ¼ 5.1 Hz, Ar-Qn), 8.27 (d,
1H, J ¼ 9 Hz, Ar-Qn), 8.22 (d, 2H, J ¼ 8.7 Hz, Ar), 8.12 (d,1H, J ¼ 2.1 Hz,
Ar-Qn), 8.03 (d, 2H, J ¼ 8.7 Hz, Ar), 7.83 (s, 1H, Ar-Pym), 7.57 (d, 1H,
J ¼ 8.7, Ar-Qn), 7.48 (d, 2H, J ¼ 8.4 Hz, Ar), 7.07(d, 2H, J ¼ 9.0 Hz, Ar),
6.83 (d, 1H, J ¼ 5.4 Hz, Ar-Qn), 5.39 (s, 2H, NH2); 13C NMR (75 MHz,
6.4.14. N-(4-(2-Amino-6-p-tolylpyrimidin-4-yl)phenyl)-7-
chloroquinolin-4-amine (45)
Yield: 48%; m.p 170–172 ꢀC; MS: 438 (M þ 1); IR (KBr): 3433,
3382, 2973, 2362, 1653, 1618, 1573, 1530, 1494, 1429, 1367, 1335,
1231, 1182, 835, 759, cmꢂ1; 1H NMR (300 MHz, CDCl3 þ DMSO-d6):
CDCl3): d 161.91,159.28,152.37,148.39,146.42,144.83,142.91,133.21,
131.67, 130.09, 127.71, 125.67, 122.71, 120.78, 119.09, 115.71, 113.23,
112.21, 97.21, 96.38, 95.98; Anal. Calcd. for C25H16Cl2N4O: C 65.37, H
3.51, N 12.20.; Found: C 65.49, H 3.26, N 12.39%.
d
9.27 (s, 1H, NH), 8.42 (d, 1H, J ¼ 6.0 Hz, Ar-Qn), 8.10 (d, 1H,
J ¼ 9.0 Hz, Ar), 7.98 (d, 2H, J ¼ 8.7 Hz, Ar), 7.85 (d, 1H, J ¼ 2.1 Hz, Ar-
Qn), 7.71 (s, 1H, Ar-Pym), 7.51 (d, 2H, J ¼ 9.0 Hz, Ar), 7.33–7.38 (m,
3H, Ar-Q, Ar), 7.20–7.25 (m, 3H, Ar-Q, Ar), 6.65 (s, 2H, NH2), 3.23 (s,
6.4.10. 4-(2-Chlorophenyl)-6-(4-(7-chloroquinolin-4-
yloxy)phenyl)pyrimidin-2-amine (41)
3H, CH3); 13C NMR (75 MHz, CDCl3 þ DMSO-d6):
d 160.11, 156.93,
143.91, 140.98, 135.88, 132.40, 128.75, 127.03, 123.73, 123.56, 121.63,
121.53, 121.33, 120.33, 120.06, 119.12, 117.03, 114.75, 114.06, 100.70,
95.15; Anal. Calcd. for C26H20ClN5: C 71.31, H 4.60, N 15.99; Found: C
71.21, H 4.46, N 15.65%.
Yield: 55%; m.p 172–174 ꢀC; MS: 459 (M þ 1); IR (KBr): 3420,
3020, 2361, 1725, 1598, 1492, 1422, 1301, 1216, 1017, 761, 670 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
8.72 (d, 1H, J ¼ 5.3 Hz, Ar-Qn), 8.26 (d,
1H, J ¼ 9.0 Hz, Ar-Qn), 8.19 (d, 1H, J ¼ 8.7 Hz, Ar), 8.16 (d, 1H,
J ¼ 1.8 Hz, Ar-Qn), 7.98 (d, 2H, J ¼ 8.7 Hz, Ar), 7.87 (s, 1H, Ar-Pym),
7.63 (d, 1H, J ¼ 8.4, Ar), 7.55–7.45 (m, 5H, Ar, Ar-Qn), 6.87 (d, 1H,
J ¼ 5.4 Hz, Ar-Qn), 5.71 (s, 2H, NH2); 13C NMR (75 MHz, CDCl3):
6.4.15. N-(4-(2-Amino-6-(4-methoxyphenyl)pyrimidin-4-
yl)phenyl)-7-chloroquinolin-4-amine (46)
Yield: 50%; m.p 162–164 ꢀC; MS: 455 (M þ 1); IR (KBr): 3544,
3421, 3020, 2936, 2361, 1572, 1516, 1438, 1325, 1216, 1113, 838,
d
162.12, 159.83, 145.64, 141.23, 132.32, 131.32, 128.68, 125.34,
125.03, 123.67, 122.07, 121.67, 121.08, 120.73, 119.23, 118.93, 118.78,
117.32, 117.13, 116.82, 115.06, 110.32, 100.29; Anal. Calcd. for
760 cmꢂ1
;
1H NMR (300 MHz, CDCl3 þ DMSO-d6):
d 9.23 (s, 1H,
NH), 8.71(d, 1H, J ¼ 5.3 Hz, Ar-Q), 8.33 (d, 1H, J ¼ 9 Hz, Ar-Q), 8.19 (d,

2090
M. Sharma et al. / European Journal of Medicinal Chemistry 44 (2009) 2081–2091
2H, J ¼ 8.7 Hz, Ar), 8.13 (d, 1H, J ¼ 1.8 Hz, Ar-Q), 8.08 (d, 2H,
J ¼ 9.0 Hz, Ar), 7.57 (dd, 1H, J ¼ 8.4 Hz, J ¼ 2.1 Hz, Ar-Q), 7.45 (s, 1H,
Ar-Pym), 7.32 (d, 2H, J ¼ 8.4 Hz, Ar), 7.08 (d, 2H, J ¼ 8.7 Hz, Ar), 6.65
(d, 1H, J ¼ 5.3 Hz, Ar-Q), 5.18 (s, 2H, NH2), 3.91 (s, 3H, OCH3); 13C
6.4.20. N-(4-(2-Amino-6-(2,5-dimethoxyphenyl)pyrimidin-4-
yl)phenyl)-7-chloroquinolin-4-amine (51)
Yield: 55%; m.p 178–180 ꢀC; MS: 484 (M þ 1); IR (KBr): 3344,
3207, 2932, 2362,1568,1526,1446,1351,1332,1226,1126,1025, 870,
NMR (75 MHz, CDCl3 þ DMSO-d6):
d
169.91, 166.72, 157.13, 155.15,
776, 667, cmꢂ1; 1H NMR (300 MHz, CDCl3 þ DMSO-d6):
d 9.23 (s,1H,
152.85, 148.12, 139.83, 137.85, 135.32, 133.90, 130.63, 129.90, 126.53,
124.32,119.33,108.60,106.31, 60.77; Anal. Calcd. for C26H20ClN5O: C
68.80, H 4.44, N 15.43; Found: C 68.65, H 4.29, N 15.39%.
NH), 8.73 (d, 1H, J ¼ 5.1 Hz, Ar-Q), 8.43 (d, 1H, J ¼ 9.0 Hz, Ar-Q), 8.12
(d, 2H, J ¼ 8.1 Hz, Ar), 7.96 (s, 1H, Ar-Q), 7.63–7.52 (m, 4H, Ar, Ar-Py),
7.49 (d, 1H, J ¼ 9.0 Hz, Ar-Q), 7.37 (d, 1H, J ¼ 8.4 Hz, Ar), 7.32 (d, 1H,
J ¼ 8.4 Hz, Ar-Q), 7.13 (d, 1H, J ¼ 5.1 Hz, Ar-Q), 6.37 (s, 2H, NH2), 3.90
(s, 3H, OCH3), 3.84 (s, 3H, OCH3); 13C NMR (75 MHz, CDCl3 þ DMSO-
6.4.16. N-(4-(2-Amino-6-(3,4,5-trimethoxyphenyl)pyrimidin-4-
yl)phenyl)-7-chloroquinolin-4-amine (47)
Yield: 65%; m.p 170–172 ꢀC; MS: 524 (M þ 1); IR (KBr): 3544, 3207,
2932, 2362, 1566, 1526, 1446, 1371, 1312, 1226, 1126, 997, 817, 776,
d6):
d 167.89, 166.93, 166.37, 162.13, 158.17, 153.53, 152.37, 151.31,
148.87, 135.39, 133.20, 132.17, 129.67, 128.31, 128.06, 127.57, 125.68,
124.06,123.13,121.26,120.69,104.86,100.67, 58.97; Anal. Calcd. for.:
C 67.01, H 4.58, N 14.47; Found: C 67.36, H 4.38; N 14.14%.
713 cmꢂ1, 1H NMR (300 MHz, CDCl3 þ DMSO-d6):
d 9.27 (s, 1H, NH),
8.51 (d, 1H, J ¼ 5.4 Hz, Ar-Q), 8.36 (d, 1H, J ¼ 9 Hz), 8.23 (d, 2H,
J ¼ 8.6 Hz, Ar), 7.93 (d,1H, J ¼ 2.1 Hz, Ar-Q), 7.89(s,1H, Ar-Py), 7.54–7.50
(m, 5H, Ar-Q, Ar), 7.43(s, 2H, NH2), 7.16 (d,1H, J ¼ 5.34 Hz, Ar-Q), 3.98 (s,
6H, OCH3), 3.86 (s, 3H, OCH3); 13C NMR (75 MHz, CDCl3 þ DMSO-d6):
6.4.21. N-(4-(2-Amino-6-(4-chlorophenyl)pyrimidin-4-yl)phenyl)-
7-chloroquinolin-4-amine (52)
Yield: 62%; m.p 182–184 ꢀC; MS: 458 (M þ 1); IR (KBr): 3329,
3207, 2925, 2362, 1618, 1573, 1530, 1432, 1367, 1332, 1231, 1089,
d
165.5, 164.35, 157.77, 155.30, 148, 137.69, 132.8, 131.04, 130.31, 129.8
128.33, 126.25, 115.4, 108.9, Anal. Calcd. for C28H24ClN5O3: C 65.43, H
4.71, N 13.63. Found: C 65.56, H 4.68, N 13.76%.
865, 774, 713 cmꢂ1
;
1H NMR (300 MHz, CDCl3 þ DMSO-d6):
d 9.39
(s, 1H, NH), 8.55 (d, 1H, J ¼ 5.34 Hz, Ar-Qn), 8.45 (d, 1H, J ¼ 9.0 Hz,
Ar-Qn), 8.28 (d, 2H, J ¼ 8.70 Hz, Ar-Qn), 8.25 (d, 2H, J ¼ 8.64 Hz, Ar),
7.94 (d, 1H, J ¼ 2.13 Hz, Ar-Qn), 7.74 (s, 1H, Ar-Pym), 7.62–7.56 (m,
3H, Ar, Ar-Qn), 7.50 (d, 2H, J ¼ 8.64 Hz, Ar), 7.17 (d, 1H, J ¼ 5.34 Hz,
Ar-Qn), 6.79 (s, 2H, NH2); 13C NMR (75 MHz, CDCl3 þ DMSO-d6):
6.4.17. N-(4-(2-Amino-6-(2,3,4-trimethoxyphenyl)pyrimidin-4-
yl)phenyl)-7-chloroquinolin-4-amine (48)
Yield: 58%; m.p 164–166 ꢀC; MS: 524 (M þ 1); IR (KBr): 3344,
3207, 2932, 2362, 1566, 1526, 1446, 1371, 1312, 1226, 1126, 817, 776,
d
163.37, 157.89, 147.53, 143.71, 132.87, 131.37, 126.91, 126.69, 125.67,
713, cmꢂ1; 1H NMR (300 MHz, CDCl3 þ DMSO-d6):
d
9.24 (s,1H), 8.47
122.57, 122.12, 121.71, 121.13, 120.89, 120.12, 119.83, 119.34, 118.97,
118..10, 114.67, 114.03, 103.21, 100.67; Anal. Calcd. for C25H17Cl2N5: C
65.51, H 3.74, N 15.28; Found: C 65.76, H 3.82, N 15.37%.
(d,1H, J ¼ 5.34 Hz, Ar-Qn), 8.47 (d,1H, J ¼ 5.34 Hz, Ar-Qn), 8.31 (d,1H,
J ¼ 8.7 Hz, Ar-Qn), 8.19 (d, 2H, J ¼ 8.34 Hz, Ar), 7.87 (d,1H, J ¼ 2.13, Ar-
Qn), 7.76 (s, 1H, Ar-Pym), 7.65 (d, 1H, J ¼ 8.4 Hz, Ar), 7.51 (d, 2H,
J ¼ 8.3 Hz, Ar), 7.39 (s, 2H, NH2), 7.23 (d,1H, J ¼ 8.4 Hz, Ar), 7.11 (d,1H,
J ¼ 5.34 Hz, Ar-Qn), 3.94 (s, 3H, OCH3), 3.91 (s, 3H, OCH3); 13C NMR
6.4.22. N-(4-(2-Amino-6-(2-chlorophenyl)pyrimidin-4-yl)phenyl)-
7-chloroquinolin-4-amine (53)
Yield: 68%; m.p 178–180 ꢀC; MS: 458 (M þ 1); IR (KBr): 3475,
3327, 2923, 2363,1618,1571,1525,1454,1367,1236,1195,1080, 866,
(75 MHz, CDCl3 þ DMSO-d6):
d
167.19, 166.93, 166.63, 162.87, 162.53,
157.37, 153.38, 153.06, 151.37, 148.87, 135.89, 133.32, 131.93, 129.62,
128.97, 128.63, 127.72, 125.37, 123.32, 122.21, 120.49, 104.83, 102.19,
59.34, 59.27, 53.71; Anal. Calcd. for C28H24ClN5O3: C 65.43, H 4.71, N
13.63. Found: C 65.66, H 4.59, N 13.74%.
776, 702 cmꢂ1; 1H NMR (300 MHz, CDCl3 þ DMSO-d6):
d 9.32 (s, 1H,
NH), 8.49 (d, 1H, J ¼ 5.27 Hz, Ar-Q), 8.47 (d, 1H, J ¼ 9.0 Hz, Ar-Q),
8.25 (d, 2H, J ¼ 8.70 Hz, Ar-Qn), 8.19 (dd, 2H, J ¼ 8.64 Hz, J ¼ 2.1 Hz,
Ar), 7.91 (d, 1H, J ¼ 2.13 Hz, Ar-Qn), 7.67 (s, 1H, Ar-Pym), 7.52–7.43
(m, 3H, Ar, Ar-Qn), 7.39 (dd, 1H, J ¼ 8.37 Hz, 2.1 Hz), 7.36–7.26 (m,
2H, Ar), 7.11 (d, 1H, J ¼ 5.27 Hz), 6.68 (s, 2H, NH2); 13C NMR
6.4.18. N-(4-(2-Amino-6-(furan-2-yl)pyrimidin-4-yl)phenyl)-7-
chloroquinolin-4-amine (49)
Yield: 60%; m.p 176–178 ꢀC; MS: 414 (M þ 1); IR (KBr): 3586, 3322,
(75 MHz, CDCl3 þ DMSO-d6):
d 161.12, 158.87, 144.58, 141.97, 133.86,
2989, 2361,1556,1520,1427,1312,1215,1033, 929, 760 cmꢂ1; 1H NMR
131.38, 127.67, 126.87, 125.37, 122.53, 121.98, 121.34, 121.03, 120.93,
120.87, 120.31, 119.98, 119.06, 117.41, 114.53, 114.07, 102.67, 98.13;
Anal. Calcd. for C25H17Cl2N5: C 65.51, H 3.74, N 15.28. Found: C
65.36, H 3.52, N 15.47%.
(300 MHz, CDCl3 þ DMSO-d6): 9.27 (s,1H, NH), 8.49 (d,1H, J ¼ 5.1 Hz,
d
Ar-Q), 8.38 (d,1H, J ¼ 9 Hz, Ar-Q), 8.11 (d, 2H, J ¼ 8.4 Hz, Ar), 7.86(d,1H,
J ¼ 1.2 Hz, Ar-Q), 7.75 (dd, 1H, J ¼ 8.4 Hz, 2.1 Hz, Ar-Q), 7.43–7.45 (m,
3H, Ar, furan), 7.37 (s,1H, Ar-Pym), 7.17–7.11 (m, 2H, Ar-Qn, furan), 6.58
(m, 1H, furan), 6.39 (s, 2H, NH2); 13C NMR (300 MHz, CDCl3 þ DMSO-
6.4.23. N-(4-(2-Amino-6-(4-(methylthio)phenyl)pyrimidin-4-
yl)phenyl)-7-chloroquinolin-4-amine (54)
d6):
d 166.02, 165.50, 158.22, 154.10, 153.32, 151.23, 149.12, 146.40,
144.61, 136.12, 133.72, 129.70, 129.41, 126.90, 126.22, 122.72, 120.63,
113.90, 112.81,104.90, 101.31; Anal. Calcd. for C23H16ClN5O: C 66.75, H
3.90, N 16.92; Found: C 66.56, H 3.78, N 16.72%.
Yield:55%;m.p 190–192 ꢀC;MS:470(M þ 1);IR(KBr):3315, 3195,
2922, 2361,1570,1521,1427,1365,1324,1234, 813, 775, 669 cmꢂ1; 1H
NMR (300 MHz, CDCl3 þ DMSO-d6):
d 9.10 (s, 1H, NH), 8.46 (d, 1H,
J ¼ 5.1 Hz, Ar-Qn), 8.34 (d,1H, J ¼ 9 Hz, Ar-Qn), 8.11 (d, 2H, J ¼ 8.4 Hz,
Ar), 8.05 (d, 2H, J ¼ 8.7 Hz, Ar), 7.85 (s, 1H, Ar-Qn), 7.40–7.45 (m, 4H,
Ar, Ar-Qn), 7.08 (d, 1H, J ¼ 5.4 Hz, Ar-Qn), 6.93 (d, 2H, J ¼ 8.7 Hz, Ar),
6.09 (s, 2H, NH2), 3.79 (s, 3H, –SCH3); 13C NMR (75 MHz,
6.4.19. N-(4-(2-amino-6-(2,3-dimethoxyphenyl)pyrimidin-4-
yl)phenyl)-7-chloroquinolin-4-amine (50)
Yield: 55%; m.p 160–162 ꢀC; MS: 484 (M þ 1); IR (KBr): 3327,
3205, 2932, 2362, 1649, 1571, 1528, 1438, 1356, 1331, 1234, 1190,
1121, 1028, 869, 774, 670, cmꢂ1; 1H NMR (300 MHz, CDCl3 þ DMSO-
CDCl3 þ DMSO-d6):
d 165.56, 163.01, 153.31, 151.30, 149.28, 144.40,
136.21, 134.12, 131.65, 130.12, 129.71, 129.54, 126.01, 124.70, 122.92,
120.61, 115.52, 104.82, 102.80, 32.56; Anal Calcd. for C26H20ClN5S: C
66.44, H 4.29, N: 14.90; Found: C 66.20, H 4.56, N 14.66%.
d6):
d
9.22 (s, 1H, NH), 8.45 (d, 1H, J ¼ 5.1 Hz, Ar-Qn), 8.39 (d, 1H,
J ¼ 9.0 Hz, Ar-Q), 8.10 (d, 2H, J ¼ 8.4 Hz, Ar), 7.88 (s,1H, Ar-Qn), 7.53–
7.38 (m, 4H, Ar, Pym), 7.32 (d, 1H, J ¼ 9.0 Hz, Ar-Qn), 7.13–7.07 (m,
3H, Ar-Qn, Ar), 6.34 (s, 2H, NH2), 3.85 (s, OCH3), 3.76 (s, OCH3); 13
C
6.4.24. N-(4-(2-Amino-6-(pyridin-3-yl)pyrimidin-4-yl)phenyl)-7-
chloroquinolin-4-amine (55)
NMR (75 MHz, CDCl3 þ DMSO-d6):
d 168.03, 167.71, 167.13, 162.87,
158.31, 154.09, 152.87, 151.13, 148.73, 135.95, 133.38, 132.03, 129.87,
128.67, 128.17, 127.75, 125.21, 123.37, 122.71, 121.13, 120.79, 105.03,
101.98, 59.37, 53.79; Anal. Calcd. for C27H22ClN5O2: C 67.01, H 4.58,
N 14.47; Found: C 67.26, H 4.78, N 14.67%.
Yield: 55%; m.p 170–172 ꢀC; MS: 450 (M þ 1); IR (KBr): 3460,
3308, 3194, 2362, 1637, 1570, 1522, 1426, 1327, 1244, 773, 669 cmꢂ1
;
1H NMR (300 MHz, CDCl3 þ DMSO-d6):
d 9.27 (s, 1H, Py), 9.10 (s,
1H, NH), 8.62 (d, 1H, J ¼ 5.7 Hz, Py), 8.47 (d, 1H, J ¼ 5.4 Hz, Ar-Qn),

M. Sharma et al. / European Journal of Medicinal Chemistry 44 (2009) 2081–2091
2091
8.33–8.41 (m, 2H, Py, Ar-Qn), 8.15 (d, 2H, J ¼ 8.1 Hz, Ar), 7.84 (d, 1H,
J ¼ 1.8 Hz, Ar-Qn), 7.54 (s, 1H, Pym), 7.39–7.43 (m, 4H, Ar, Py, Ar-Qn),
7.11 (d, 1H, J ¼ 5.28 Hz, Ar-Qn), 6.24 (s, 2H, NH2); 9.27 (s, 1H), 9.10 (s,
1H, NH), 8.62 (d,1H, J ¼ 1.2 Hz), 8.47 (d,1H, J ¼ 5.4 Hz), 8.41–8.33 (m,
2H), 8.15 (d, 2H, J ¼ 8.1 Hz), 7.84 (d, 1H, J ¼ 1.8 Hz), 7.54 (s, 1H), 7.43–
7.39 (m, 4H), 7.11 (d, 1H, J ¼ 5.28 Hz), 6.24 (s, 2H, NH2); 13C NMR
J ¼ 5.3 Hz, Ar-Qn), 8.13–8.20 (m, 4H, Ar-Qn, Ar), 7.77–7.83 (m, 2H,
Ar-Qn, Ar), 7.51 (s,1H, Pym), 7.43 (d,1H, J ¼ 9 Hz, Ar-Qn), 7.32 (d, 2H,
J ¼ 8.7 Hz, Ar), 6.91 (d, 1H, J ¼ 5.4 Hz, Ar-Qn), 6.52 (s, 2H, NH2); 13
C
NMR (300 MHz, CDCl3 þ DMSO-d6):
d 163.23, 161.67, 159.54, 153.32,
149.78, 148.13, 139.55, 138.65, 137.67, 137.09, 134.23, 133.13, 132.32,
129.87, 129.34, 128.35, 127.67, 127.43, 125.07, 124.45, 121.04, 107.89,
103.91; Anal. Calcd. for C25H17ClN6O2: C 64.04, H 3.65, N 17.92;
Found: C 64.26, H 3.78, N 17.81%.
(75 MHz, CDCl3 þ DMSO-d6):
d 166.50, 164.52,153.21, 152.40, 151.36,
149.91, 146.52, 147.21, 136.29, 134.81, 133.62, 129.82, 128.30, 126.82,
124.51, 122.63, 120.60, 115.72, 112.60, 103.67; Anal Calcd. for
C24H17ClN6: C 67.84, H 4.03, N 19.78; Found: C 67.61, H 4.24, N 19.63%.
Acknowledgments
6.4.25. N-(4-(2-Amino-6-(4-isopropylphenyl)pyrimidin-4-
yl)phenyl)-7-chloroquinolin-4-amine (56)
M. S. thanks to Indian Council of Medical Research (ICMR) for
providing financial support. We are also thankful to S.A.I.F. Division,
CDRI, Lucknow for providing spectroscopic data. CDRI communi-
cation No 7510.
Yield: 50%; m.p 200–205 ꢀC; MS: 466 (M þ 1); IR (KBr): 3455,
3323, 3020, 2967, 2360, 1572, 1518, 1430, 1386, 838, 761 cmꢂ1; 1H
NMR (300 MHz, CDCl3 þ DMSO-d6):
d 9.34 (s, 1H, NH), 8.56 (d, 1H,
J ¼ 5.1 Hz, Ar-Qn), 8.45 (d, 1H, J ¼ 9 Hz, Ar-Qn), 8.27 (d, 2H, J ¼ 9 Hz,
Ar), 8.14 (d, 2H, J ¼ 6.6 Hz, Ar), 7.94 (d, 1H, J ¼ 2.1 Hz, Ar-Qn), 7.68 (s,
1H, Pym), 7.61 (d, 1H, J ¼ 9 Hz, Ar-Qn), 7.50 (d, 2H, J ¼ 8.4 Hz, Ar),
7.37 (d, 2H, J ¼ 6.0 Hz, Ar), 7.18 (d, 1H, J ¼ 5.4 Hz, Ar-Qn), 6.69 (s, 2H,
NH2), 2.98–2.93 (m, 1H, CH(CH3)2), 1.24 (d, 6H, J ¼ 6 Hz, CH(CH3)2);
References
[1] E. Bogatcheva, C. Hanrahan, B. Nikonenko, R. Samala, P. Chen, J. Gearhart,
F. Barbosa, L. Einck, C.A. Nacy, M. Protopopova, J. Med. Chem. 49 (2006) 3045–
3048.
[2] Y.L. Janin, Bioorg. Med. Chem. 15 (2007) 2479–2513.
[3] M. Schlitzer, ChemMedChem 2 (2007) 944–986.
[4] J. Wiesner, R. Ortmann, H. Jomaa, M. Schlitzer, Angew. Chem. Int. Ed. 42 (2003)
5274–5293.
[5] E.L. Corbett, C.J. Watt, N. Walker, D. Maher, B.G. Williams, M.C. Raviglione,
C. Dye, Arch. Intern. Med. 163 (2003) 1009–1021.
[6] L. Ballell, R.A. Field, K. Duncan, R.J. Young, Antimicrob. Agents Chemother. 49
(2005) 2153–2163.
13C NMR (75 MHz, CDCl3 þ DMSO-d6):
d 169.40, 165.82, 156.42,
155.24, 154.95, 152.60, 149.42, 147.84, 137.45, 133.72, 132.31, 131.73,
130.42, 129.82, 123.43, 123.03, 116.86, 112.40, 108.56, 104.12, 39.01,
29.30; Anal. Calcd. for C28H24ClN5: C 72.17, H 5.19, N 15.03; Found: C
72.34, H 5.46, N 15.26%.
[7] World Health Organisation on fact sheet no. 104, WHO information, Geneva,
Switzerland.
[8] S. Jana, J. Paliwal, Int. J. Antimicrob. Agents 30 (2007) 4–10.
[9] P.M. Sivakumar, S.K.G. Babu, D. Mukesh, Chem. Pharm. Bull. 55 (2007)
44–49.
[10] P.B. Jones, N.M. Parrish, T.A. Houston, A. Stapon, N.P. Bansal, J.D. Dick,
D.D. James, C.A. Townsend, J. Med. Chem. 43 (2000) 3304–3314.
[11] K. Zhang, P.K. Rathod, Science 296 (2002) 545–547.
[12] S.F. Nielsen, S.B. Christensen, G. Cruciani, A. Kharazmi, T. Liljefors, J. Med.
Chem. 41 (1998) 4819–4832.
[13] M. Liu, P. Wilairat, M.L. Go, J. Med. Chem. 44 (2001) 4443–4452.
[14] H.K. Hsieh, T.H. Lee, J.P. Wang, J.J. Wang, C.N. Lin, Pharm. Res. 15 (1998) 39–46.
[15] L. Barford, K. Kemp, M. Hansen, A. Kharazmi, Int. Immunopharmacol. 2 (2002)
545–555.
6.4.26. N-(4-(2-Amino-6-(3-bromophenyl)pyrimidin-4-yl)phenyl)-
7-chloroquinolin-4-amine (57)
Yield: 50%; m.p 186–188 ꢀC; MS: 502 (M þ 1); IR (KBr): 3434,
3187, 2932, 2362, 1566, 1446, 1371, 1322, 1246, 1176, 760, 776,
636 cmꢂ1
;
1H NMR (300 MHz, CDCl3 þ DMSO-d6):
d 9.23 (s, 1H,
NH), 8.51 (d, 1H, J ¼ 5.4 Hz, Ar-Qn), 8.29 (d, 1H, J ¼ 9.0, Ar-Qn), 8.02
(d, 1H, J ¼ 2.13 Hz, Ar-Qn), 8.16 (d, 2H, J ¼ 8.34 Hz, Ar), 8.02 (d, 1H,
J ¼ 2.1 Hz, Ar-Qn), 7.85 (d, 1H, J ¼ 9.0 Hz), 7.62–7.54 (m, 5H, Ar), 7.44
(m, 1H, Ar-Qn), 7.36 (s, 1H, Ar-Pym), 7.27 (d, 1H, J ¼ 5.4 Hz, Ar-Qn),
6.87 (s, 2H, NH2); 13C NMR (75 MHz, CDCl3 þ DMSO-d6):
d 163.12,
160.87, 145.29, 144.34, 138.87, 135.39, 131.62, 129.34, 128.62, 126.51,
126.37, 123.87, 123.71, 123.65, 122.57, 122.07, 121.13, 119.08, 117.68,
117.58,117.17,103.12, 97.69; Anal. Calcd. for C25H17BrClN5: C 59.72, H
3.41, N 13.93; Found: C 59.86, H 3.58, N 13.75%.
[16] A. Agarwal, K. Srivastava, S.K. Puri, P.M.S. Chauhan, Bioorg. Med. Chem. Lett. 15
(2005) 531–533.
[17] S. Hawser, S. Lociuro, K. Islam, Biochem. Pharmacol. 71 (2006) 941–948.
[18] N.P. Agarwal, A. Srivastava, S.K. Raghuwanshi, D.N. Upadhyay, S. Sinha,
P.K. Shukla, V.J. Ram, Bioorg. Med. Chem. 10 (2002) 869–874.
[19] A. Agarwal, K. Srivastava, S.K. Puri, P.M.S. Chauhan, Bioorg. Med. Chem. Lett. 15
(2005) 3133–3136.
[20] S. Srivastava, S. Tewari, P.M.S. Chauhan, S.K. Puri, A.P. Bhaduri, V.C. Pandey,
Bioorg. Med. Chem. Lett. 9 (1999) 653–658.
[21] A. Agarwal, K. Srivastava, S.K. Puri, P.M.S. Chauhan, Bioorg. Med. Chem. Lett. 15
(2005) 1881–1883.
[22] A. Agarwal, K. Srivastava, S.K. Puri, S. Sinha, P.M.S. Chauhan, Bioorg. Med.
Chem. Lett. 15 (2005) 5218–5221.
[23] A. Agarwal, N. RameshAshutoshGoyal, S. Gupta, P.M.S. Chauhan, Bioorg. Med.
Chem. 13 (2005) 6678–6684.
[24] A. Agarwal, K. Srivastava, S.K. Puri, P.M.S. Chauhan, Bioorg. Med. Chem. 13
(2005) 6226–6232.
[25] A. Agarwal, K. Srivastava, S.K. Puri, S. Sinha, P.M.S. Chauhan, Bioorg. Med.
Chem. Lett. 15 (2005) 4923–4926.
6.4.27. N-(4-(2-Amino-6-(2-bromophenyl)pyrimidin-4-yl)phenyl)-
7-chloroquinolin-4-amine (58)
Yield: 52%; m.p 179–181 ꢀC; MS: 502 (M þ 1); IR (KBr): 3413,
3197, 2926, 2362, 1572, 1439, 1368, 1328, 1257, 1187, 776, 768,
636 cmꢂ1; 1H NMR (300 MHz, CDCl3 þ DMSO-d6):
d
9.17 (s, 1H, NH),
8.46 (d, 1H, J ¼ 5.4 Hz, Ar-Qn), 8.21 (d, 1H, J ¼ 9.0, Ar-Qn), 8.07 (d,
2H, J ¼ 8.58 Hz, Ar), 7.93 (d, 1H, J ¼ 2.1 Hz, Ar-Qn), 7.72 (d, 1H,
J ¼ 7.92 Hz, Ar-Qn), 7.54–7.44 (m, 5H, Ar), 7.34 (m, 1H, Ar), 7.28(s,
1H, Ar-Pym), 7.17 (d, 1H, J ¼ 5.4 Hz, Ar-Qn), 6.79 (s, 2H, NH2); 13C
NMR (75 MHz, CDCl3 þ DMSO-d6):
d 160.11, 157.85, 143.91, 141.87,
135.86, 132.38, 128.72, 126.31, 125.20 123.55, 123.41, 121.67, 121.47,
121.38, 120.51, 120.51, 120.0, 119.02, 116.04, 114.56, 114.0, 100.68,
96.12; Anal. Calcd. for C25H17BrClN5: C 59.72, H 3.41, N 13.93;
Found: C 59.86, H 3.58, N 13.67%.
[26] A. Agarwal, K. Srivastava, S.K. Puri, P.M.S. Chauhan, Bioorg. Med. Chem. 13
(2005) 4645–4650.
[27] A. Agarwal, K. Srivastava, S.K. Puri, P.M.S. Chauhan, Bioorg. Med. Chem. Lett. 15
(2005) 3130–3132.
[28] N. Sunduru, A. Agarwal, S.B. Katiyar, N. NishiGoyal, S. Gupta, P.M.S. Chauhan,
Bioorg. Med. Chem. 14 (2006) 7706–7715.
[29] L. Gupta, K. Srivastava, S. Singh, S.K. Puri, P.M.S. Chauhan, Bioorg. Med. Chem.
Lett. 18 (2008) 3306–3309.
[30] J.K. McClachy, Susceptibility testing of mycobacteria, Lab. Med. 9 (1978) 47.
[31] A.H. Cory, T.C. Owen, J.A. Barltrop, J.G. Cory, Use of an aqueous soluble tetra-
zolium/formazen assay for cell growth assay in culture, Cancer Commun. 3
(1991) 207–212.
6.4.28. N-(4-(2-Amino-6-(3-nitrophenyl)pyrimidin-4-yl)phenyl)-
7-chloroquinolin-4-amine (59)
Yield: 48%; m.p 175–178 ꢀC; MS: 469 (M þ 1); IR (KBr): 3434,
3207, 2932, 2363, 1651, 1572, 1531, 1442, 1353, 1242, 1126, 776, 670,
cmꢂ1
;
1H NMR (300 MHz, CDCl3 þ DMSO-d6):
d 9.27 (s, 1H, NH),
[32] K.H. Rieckmann, L.J. Sax, G.H. Campbell, J.E. Ema, Lancet 311 (1978) 22–23.
[33] C. Trager, J.P. Vanderberg, J. Parasitol. 193 (1979) 673–675.
8.92 (d, 1H, J ¼ 2.3 Hz, Ar), 8.79 (d, 1H, J ¼ 8.7 Hz, Ar), 8.72 (d, 1H,