Microwave-assisted synthesis and evaluation of substituted aryl propyl acridone-4-carboxamides as potential chemosensitizing agents for cancer

Article abstract of DOI:10.2174/157018011794578169

A novel class of compounds with structure Aryl propyl acridone-4- carboxamides were synthesized by conventional and microwave (MW) irradiation methods and evaluated for their inhibitory effects on the transport activity of P- glycoprotein (P-gp) by standard Hoechst 33342 assay method. The title compounds with phenoxy substitution exhibited better activity.

Full text of DOI:10.2174/157018011794578169

268
Letters in Drug Design & Discovery, 2011, 8, 268-275
Microwave-Assisted Synthesis and Evaluation of Substituted Aryl Propyl
Acridone-4-Carboxamides as Potential Chemosensitizing Agents for
Cancer
Vinaykumar S. Velingkar* and Vikrant D. Dandekar
Department of Pharmaceutical Chemistry, Prin. K.M.Kundnani College of Pharmacy, Cuffe Parade, Mumbai-4000005,
India
Received July 09, 2010: Revised November 30, 2010: Accepted December 02, 2010
Abstract: A novel class of compounds with structure Aryl propyl acridone-4-carboxamides were synthesized by conven-
tional and microwave (MW) irradiation methods and evaluated for their inhibitory effects on the transport activity of P-
glycoprotein (P-gp) by standard Hoechst 33342 assay method. The title compounds with phenoxy substitution exhibited
better activity.
Keywords: Aryl propyl acridone-4-carboxamides, Microwave, Chemosensitizing agents.
INTRODUCTION
changes in pharmacokinetics of the anticancer drugs [15,
16].
Every year, more than 6 million cancer deaths were
reported in the world. Of the 10 million new cases each year,
more than half occur in developing countries. WHO
predictions show that, out of 15 million cases, 66% will
occur in developing countries, by 2015.
The continued development of these agents may establish
the true therapeutic potential of P-gp-mediated MDR rever-
sal. Moreover, given tumor diversity, it is rational to assume
that more than one MDR reversal agent will be needed in
clinic.
Drug resistance is the major cause of death in cancer. 30
to 80% of cancers can become resistant to cytotoxic drugs,
leaving patients and doctors with few options when
treatment fails [1].
Microwave (MW) dielectric heating, as an emerging
processing technology is attracting more and more attention.
Due to the reduced reaction time significantly, increasing
yield of products, high selectivity and safety as compared to
conventional heating methods, it has been widely employed
in the fields of organic synthesis, for example, drug interme-
diates and fine chemicals [17].
Multidrug Resistance (MDR) operated by extrusion
pumps such as P-glycoprotein and multidrug-resistance-
associated-proteins, is a major reason for poor responses and
failures in cancer chemotherapy [2-4].
The use of MW irradiation has introduced several new
concepts in chemistry, since the absorption and transmission
of the energy is completely different from the conventional
mode of heating. The MW technology has been applied to a
number of useful research and development processes such
as polymer technology, organic synthesis, and application to
waste treatment; drug targeting; ceramic and alkane decom-
position [18].
Many compounds have been investigated for their ability
to inhibit the P-gp function, thus leading to development of
several generations of MDR reversal agents.
The search for effective MDR reversal agents is now into
the third generation. First generation candidates were drugs
already approved for other non-cancerous indications, such
as verapamil, cyclosporin A and progesterone [5,6]. Unfor-
tunately, although successful in vitro, patients could not
benefit from these MDR reversal agents, because their clini-
cally relevant doses exceed safety limits resulting in unac-
ceptable adverse effects, frequent poor solubility and toxicity
[7-9]. Chemical modifications of first generation molecules
and combinatorial chemistry lead to second and third genera-
tion MDR reversal agents, such as VX-710, PSC 833,
XR9051, XR9576, MS-209, GF120918, LY335979 and
ONT- 093, some of which are in clinical trials [10-14].
Several of the latter, whereas more potent and less toxic
than first generation compounds, may still be prone
to adverse effects, poor solubility and unfavorable
Very recently, we reported the MW irradiation method
for the synthesis of substituted Acridone analogues [19].
In the present work, potent novel analogs of Aryl Propyl
Acridone carboxamide were developed by Pharmacophore
drug designing, MW-assisted technique and Standard
Hoechst 33342 assay method.
A five point pharmacophore generation was developed
by using fourteen active ligands belonging to acridone-4-
carboxamide class [20]. All the ligands were first processed
with the LigPrep software program to assign protonation
states, generate stereoisomers and convert 2D to 3D struc-
tures. Conformer generation was carried out with the Mac-
roModel ligand torsion search with OPLS_2005 force field.
*Address correspondence to this author at the Prin K.M. Kundnani College
of Pharmacy, Department of Pharmaceutical Chemistry, Plot. No.23, Jote
Joy Building, Rambhau Salgaonkar Marg, Cuffe Parade, Mumbai-4000005,
India; Tel: +91-022-22164387; Fax: +91-022-22165282;
Pharmacophore with five features common to all active
ligands were identified then scored according to superposi-
tion of pharmacophore site, alignment of vector characteris-
E-mail: vsvelingkar@gmail.com
1570-1808/11 $58.00+.00
© 2011 Bentham Science Publishers Ltd.

Microwave-Assisted Synthesis and Evaluation of Substituted
Letters in Drug Design & Discovery, 2011, Vol. 8, No. 3 269
Fig. (1). The top scoring Pharmacophore hypothesis ADHRR (A4 is acceptor point, D6 is donor point, H8 is hydrophobic point, R12 and
R13 are aromatic points).
tics, and penalization of matches to inactive training set
molecules.
for 9min at 350W to get compounds 13-16 (Scheme 2).
Compound 6 was reacted with sodium iodide in acetone by
The basic nucleus, Aryl propyl acridone-4-carboxamides
was build using the top scoring hypothesis ADHRR (Fig. 1).
The designing study was performed using phase drug design-
ing software (SCHRODINGER,INC) on INTEL CORE 2
Duo 2 GHz computer.
COOH
NH2
Br
+
COOH
2
1
RESULTS AND DISCUSSION
Chemistry
reflux, 6h
Ethanol
anhydrous K2CO3
Copper powder
MW,15min,400W
Synthesis of substituted Aryl-propyl-acridone-4-carbo-
xamide analogs involved N-arylation of o-bromobenzoic
acid 1 with anthranilic acid 2 in presence of copper powder
and anhydrous potassium carbonate in ethanol by MW heat-
ing at 400W MW intensity for 15min to get N-(2-carboxy
phenyl) anthranilic acid 3 which on cyclization with concen-
trated sulfuric acid by MW irradiation at 400W MW inten-
sity for 7min produced Acridone-4-carboxylic acid 4. Acri-
done-4-carboxylic acid was converted to Acridone carbonyl
chloride 5 using thionyl chloride (Scheme 1).
COOH
COOH
H
N
H
N
MW,7min,400W
100 ˚C,4h
Conc.H2SO4
COOH
3
4
O
Reduction of 3-chloro-propiophenone 6 using sodium
borohydride in methanol gave 3-chloro-1-phenyl-1-propanol
7. This was further reacted with sodium iodide in acetone by
MW heating at 350W for 25min yielded 3-iodo-1-phenyl-1-
propanol 8.This iodo alcohol on reaction with methylamine
in tetrahydrofuran gave N-methyl-3-phenyl-3-hydroxy pro-
pylamine 9 and on reaction with ammonia yielded 3-phenyl-
3-hydroxy propylamine 10.
ꢀ
2h
SOCl2
COCl
H
N
Compounds 9 and 10 were respectively treated by thionyl
chloride to afford the corresponding derivatives 11 and 12.
Both the chloro propylamines (compounds 11 and 12) were
individually treated with substituted phenol by MW heating
O
5
Scheme 1. Synthesis of compounds 4-5.

270 Letters in Drug Design & Discovery, 2011, Vol. 8, No. 3
Velingkar and Dandekar
Table 1. Comparative Reaction Time and Percentage Yield of Intermediates and Title Compounds by Conventional and MW
Method
Reaction Time
Conventional (h)
Yield
Compound No.
MW (min)
Conventional (%)
MW (%)
3
6
4
15
7
64
55
63
83
75
46
48
48
53
53
54
63
46
45
42
40
40
79
71
4
5
2
-----
-----
25
-----
-----
9
-----
-----
86
7
1
8
12
4
11
12
13
14
15
16
17
22
23
24
25
26
-----
-----
58
4.5
4.5
4.5
4.5
4.5
10
6
9
62
9
60
9
67
22
15
16
12
14
14
75
64
6.5
5
62
58
5.5
5.5
54
52
O
C
NaBH4,
Methanol
OH
CH CH2 CH2 Cl
CH2 CH2 Cl
R.T. ,1h
7
6
Reflux,12h
MW,25min.,350W
Acetone,NaI
OH
OH
CH CH2 CH2
THF,R.T.
CH CH2 CH2 NHR
9-10
I
NH3 or
CH3NH2
8
SOCl2,dry CHCl3
reflux,4h
9
R = CH3
Cl
10 R = H
11 R = CH3
12 R = H
CH CH2 CH2 NHR
11-12
OH
NaOH, ethanol
reflux, 4.5h
R1
MW,9min., 350W
13 R1 = H
14 R1 = CH3
15 R1 = H
16 R1 = CH3
CH CH2 CH2 NHR
O
R1
13-16
Scheme 2. Synthesis of compounds 13-16.

Microwave-Assisted Synthesis and Evaluation of Substituted
Letters in Drug Design & Discovery, 2011, Vol. 8, No. 3 271
MW irradiation for 22min at 350W MW intensity produced
3-iodopropiophenone 17 which on reaction with methy-
lamine in tetrahydrofuran yielded 3-(N-methylamino)
propiophenone 18 and on reaction with ammonia gave 3-
amino propiophenone 19 (Scheme 3).
CH CH2 CH2 NHCH3
O
R1
15 R1 = H
O
16 R1 = CH3
15-16
C
CH2 CH2 Cl
MW,22min.,350W
COCl
K2CO3,DMF
70 ˚C, 6.5h
H
N
6
reflux,10h
NaI,Acetone
O
5
MW ,15min.,350W
O
O
C
CH2 CH2
I
17
N
H
O
N
CH2 CH2 CH
THF,R.T.
NH3 or CH3NH2
O
CH3
R1
O
C
22 R1 = H
CH2 CH2 NHR
23 R1 = CH3
22-23
18-19
Scheme 5. Synthesis of compounds 22-23.
18 R = CH3
19 R = H
Z
CH2 CH2 NHCH3
Scheme 3. Synthesis of compounds 18-19.
9,Z = CH(OH), 18,Z = C=O, 11,Z = CH(Cl)
CH CH2 CH2
NH2
COCl
H
O
DMF , K2CO3
N
R1
70 ˚C,5h
O
13-14
5
COOH
MW , 14min.,350W
H
N
DCC
R.T.
O
O
4
O
N
H
O
N
CH2 CH2
Z
N
H
CH3
24-26
O
N
CH2 CH2 CH
O
24, Z = CH(OH)
25, Z = C=O
H
R1
20 R1 = H
21 R1 = CH3
26, Z = CH(Cl)
20-21
Scheme 6. Synthesis of compounds 24-26.
Scheme 4. Synthesis of compounds 20-21.
5 was condensed with compounds 15 and 16 in presence of
anhydrous potassium carbonate in dimethylformamide by
MW irradiation for 17min at 350W and 6.5h by conventional
Further, compound 4 was condensed with compounds 13
and 14 respectively using N,N'-dicyclohexylcarbodiimide
(DCC) to get compounds 20 and 21 (Scheme 4). Compound

272 Letters in Drug Design & Discovery, 2011, Vol. 8, No. 3
Velingkar and Dandekar
method offered compounds 22 and 23, respectively (Scheme
5). Condensation of compound 5 with compounds 9, 18 and
11 individually using potassium carbonate in dimethylfor-
mamide by MW technique for 14min at 350W and conven-
tional method for 5h gave compound 24, 25 and 26 (Scheme
6). Compound 4 was condensed with compounds 10, 19 and
12 respectively using DCC gave compounds 27, 28 and 29
respectively (Scheme 7).
grown in T75 or T175-flasks. At a confluence of approxi-
mately 80% cells were harvested by trypsination. Pelleted
cells were resuspended in fresh culture medium and counted
with a Casy I Modell TT cell counter. After three washing
steps with Krebs–Hepes buffer, cells were seeded into black
96 well plates at a density of approximately 30,000 cells in a
volume of 90 ꢀl per well. Then, 10 ꢀl of various title com-
pounds in different concentrations were added, resulting in a
final volume of 100 ꢀl per well. The prepared 96-well plates
were kept under 5% CO2 at 370C for 30 min After this prein-
cubation period, 20 ꢀl of a 30 ꢀM Hoechst 33342 solution
were added to each well. Subsequently, fluorescence was
measured immediately at constant time intervals (120 s) up
to 46 min at an excitation wavelength of 365 nm and an
emission wavelength of 450 nm using a 370C tempered
BMG POLARstar microplate reader.
Z
CH2 CH2 NH2
10,Z = CH(OH),19,Z = C=O,12,Z = CH(Cl)
COOH
H
N
DCC
The fluorescence-data points were measured in 46 min.
The slopes were calculated by linear regression and used as
dependent parameters.
R.T.
O
4
From these data concentration–response curves were
generated by nonlinear regression using the 4-parameter lo-
gistic equation with variable Hill slope. The inhibitory ef-
fects are reported as logarithm of the reciprocal IC50 values
(pIC50).
O
N
H
The inhibitory effect of P-gp is expressed in terms of
PIC50 value (Table 2). It was observed that the test com-
pounds 20, 21 and 22 exhibited better activity as compared
to the standard Verapamil.
O
N
H
CH2 CH2
Z
27-29
Table 2. pIC50 Values of Title Compounds by Standard
Hoechst 33342 Assay Method
27,Z = CH(OH)
28,Z = C=O
Compound No.
pIC50 ± SD
29,Z = CH(Cl)
20
5.70 ± 0.16
5.48 ± 0.14
5.28 ± 0.16
5.12 ± 0.09
4.22 ± 0.18
4.34 ± 0.16
4.32 ± 0.07
4.28 ± 0.06
4.66 ± 0.18
4.35 ± 0.23
5.18 ± 0.25
21
Scheme 7. Synthesis of compounds 27-29.
22
A new MW-assisted method for the rapid and efficient
synthesis of substituted Aryl propyl acridone-4-
carboxamides has been developed. The MW irradiation ef-
fectively reduced reaction time with considerable increase in
the yields as compared to the conventional method.
23
24
25
26
27
28
Pharmacological Evaluation
The title compounds 20-29 were screened to evaluate
their inhibitory effects on the transport activity of P-
glycoprotein (P-gp) by standard Hoechst 33342 assay
method [21].
29
Verapamil
Human ovarian carcinoma cell lines A2780 were culti-
vated in RPMI-1640 medium supplemented with 10% fetal
bovine serum, 50 ꢀg/mL streptomycin, 50U/mL penicillin G,
and 365 ꢀg/mL L-glutamine. Cells were grown to 80–90%
confluence and treated with trypsin–EDTA before subcultur-
ing. Every 5th passage doxorubicin (0.1 ꢀM final concentra-
tion) was added to the cell culture medium of A2780adr cells
to maintain a resistance pressure and to conserve P-gp over-
expression.
EXPERIMENTAL
All the chemicals and solvents were obtained from com-
mercial source and purified by the established methods.
Melting points of the synthesized molecules were deter-
mined by open capillary tube and were uncorrected. The
purity of the compounds was ascertained by thin layer chro-
matography (TLC) on pre-coated silica gel G plate.
All intermediates were characterized by recording their
physical constant and I.R. spectroscopy. The title compounds
Human ovarian carcinoma cell lines A2780 and the cor-
responding adriamycin-resistant A2780adr cell line were

Microwave-Assisted Synthesis and Evaluation of Substituted
Letters in Drug Design & Discovery, 2011, Vol. 8, No. 3 273
were characterized by I.R., 1H NMR, mass spectroscopy and
Elemental analysis.
ESMSm/z=448.1521[M]+.Anal Calcd for C29H24N2O3: C,
77.66; H, 5.39; N, 6.25; Found: C, 77.52; H, 5.35; N, 6.20.
I.R. spectra were recorded on Jasco FT/IR-5300 spec-
trometer using KBr pellet method. Nuclear magnetic reso-
nance spectra were recorded using Joel FT/NMR 300 MHz
spectrometer using TMS as internal standard. Mass spectros-
copy was carried out on Q-Tof micro (YA-105), Micromass
(Water’s) Mass spectrometer. Elemental analysis was per-
formed using EA-112, Thermoquest CHN analyzer. MW
heating was done in a QPro-M, Questron Tech. MW oven.
(21): Yield 45%. mp 1420C. 1H-NMR (300 MHz, CDCl3)
ꢀ: 2.31 (s, 3H, CH3), 2.26 (q, 2H, CH2), 3.36 (t, J=5.8 Hz,2H,
CH2), 4.48 (t, J=8.2 Hz,1H, CH), 7.30 (s,1H,NH),6.32-8.39
(m, 16H, Ar). IR (KBr) cm-1: 3474 (NH), 3394 (CH), 1626
(C=O), 1554 (C =O), 1462 (NH), 1310, 1202 (C-O). ESMS
m/z = 461.9865[M]+.Anal Calcd for C30H26N2O3: C, 77.90;
H, 5.67; N, 6.06; Found: C, 77.86; H, 5.54; N, 6.01.
General Procedure for Synthesis of 4-[N-methyl-3-
phenyl-3-(substituted phenoxy) propyl]acridone carbox-
amide (22-23)
Synthesis of Acridone-4-Carboxylic Acid (4)
Conventional Synthesis
Conventional Synthesis
A mixture of N-(2-carboxy phenyl) anthranilic acid, 15 g
(0.066 mole) and conc. sulfuric acid,48 ml was heated at
1000C for 4 h, cooled at room temperature and then poured
into ice water. The precipitate formed was collected and
washed with water. The crude product was purified by re-
crystallization using ethanol.
A mixture of acridone carbonyl chloride 5 (0.038 mole),
(0.038 mole) suitable N-methyl-3-phenyl-3-(substituted phe-
noxy) propylamine 15-16, 2.8g of anhydrous potassium car-
bonate in 100 ml of DMF was heated at 700C with stirring
for 6.5 h To the mixture, 100 ml ice cold water was added
and extracted with dichloromethane. The organic layer was
washed with water and evaporated to give a residue that was
purified by column chromatography.
MW-Assisted Synthesis
A mixture of N-(2-carboxy phenyl) anthranilic acid, 15 g
(0.066 mole) and conc. sulfuric acid, 48 ml was irradiated
with MW at 400W MW intensity for 7 min, cooled at room
temperature and then poured into ice water. The precipitate
formed was collected and washed with water. The crude
product was purified by recrystallization using ethanol.
(4): Yield 71%. mp 3250C 1H-NMR (300 MHz, DMSO-
d6) ꢀ: 7.41-7.89 (m,7H,Ar), 7.54 (s,1H,NH), 10.80
(s,1H,COOH). IR (KBr) cm-1: 3331 (NH), 2964 (CH),
2883(OH), 1666 (C=O),1618(C=O),1579(NH). ESMS m/z =
240.1171 [MH+].Anal Calcd for C29H24N2O3: C, 70.29; H,
3.79; N, 5.85; Found: C, 70.18; H, 3.58; N, 5.64.
MW-Assisted Synthesis
A mixture of acridone carbonyl chloride 5 (0.038 mole),
(0.038 mole) suitable N-methyl-3-phenyl-3-(substituted phe-
noxy) propylamine 15-16, 2.8g of anhydrous potassium car-
bonate in 100 ml of DMF was irradiated with MW at 350W
MW intensity for 15min After completion of reaction, the
work-up was done in a manner similar to the conventional
method.
(22): Yield 64%. mp 1720C. 1H-NMR (300 MHz, CDCl3)
ꢀ: 2.32 (q, 2H, CH2), 2.67 (s, 3H, CH3), 3.28 (t, J=6.0 Hz,2H,
CH2), 4.74 (t, J=8.4 Hz, 1H, CH), 7.38 (s,1H,NH), 6.70-8.38
(m, 17H, Ar). IR (KBr) cm-1: 3382 (C-H), 1638 (C=O), 1594
(C=O), 1532 (NH), 1204,1016 (C-O), 1016 (C-N). ESMS
m/z = 461.7684 [M]+. Anal Calcd for C30H26N2O3: C, 77.90;
H, 5.67; N, 6.06. Found: C, 77.82; H, 5.63; N, 6.02.
General Procedure for Synthesis of 4-[3-phenyl-3-
(substituted phenoxy) propyl]acridone carboxamide (20-
21)
Acridone carboxylic acid 4 (0.035 mole) was dissolved in
35 ml DMF in RBF with guard tube attached at the neck and
stirred at 200 r.p.m. for 30 min at 0-40C. DCC (0.035 mole)
was dissolved separately in 35ml DMF in a beaker and was
then added drop-wise to a solution of acridone carboxylic
acid and stirred at 200 r.p.m. for 2 h at 0-40C. Appropriate 3-
phenyl-3-(substituted phenoxy) propylamine 13-14 (0.035
mole) was dissolved in 50 ml DMF in a beaker and stirred at
200 r.p.m. for 1 h at 0-40C. This solution was then added to
above mixture and stirred at 200 r.p.m. for 4 h at 0-40C and
then overnight at room temp. The reaction mixture was fil-
tered; the filtrate was then concentrated under vacuum at
800C and extracted with dichloromethane. The organic layer
was washed with water and evaporated to give a residue that
was finally purified by column chromatography.
(23): Yield 62%. mp 1580C. 1H-NMR (300 MHz,
CDCl3) ꢀ: 2.22 (q, 2H, CH2), 2.44 (s, 3H, CH3), 2.85 (s, 3H,
CH3), 3.21 (t, J=5.4 Hz,2H, CH2), 5.08 (t, J=7.8 Hz,1H, CH),
7.36 (s,1H,NH), 6.67-8.42 (m, 16H, Ar). IR (KBr) cm-1
:
3292 (C-H), 1652 (C=O),1594 (C=O), 1504 (NH), 1088,
1208 (C-O), 1088 (C-N). ESMS m/z = 475.9981[M]+.Anal
Calcd for C31H28N2O3: C, 78.13; H, 5.92; N, 5.88; Found: C,
78.08; H, 5.88; N, 5.78.
General Procedure for Synthesis of 4-(N-methyl-3-
phenyl-3-substituted propyl)acridone-carboxamide (24-
26)
Conventional Synthesis
A mixture of acridone carbonyl chloride 5 (0.030 mole),
(0.030 mole) appropriate N-methyl–3-phenyl–3-substituted
propylamine 9, 18, 11 and 1.4g of anhydrous potassium car-
bonate in 50 ml of DMF was heated at 700C with stirring for
5h. To the mixture, 50 ml ice-cold water was added and ex-
tracted with ethylacetate. The organic layer was washed and
(20): Yield 40%. mp 1680C. 1H-NMR (300 MHz,
CDCl3) ꢀ: 2.34 (q, 2H, CH2), 3.38 (t, J=6.2 Hz, 2H, CH2),
4.68 (t, J=8.0 Hz, 1H, CH), 7.40 (s,1H,NH), 6.24-8.40
(m,17H,Ar). IR (KBr) cm-1: 3334 (NH), 2998 (CH), 1688
(C=O), 1596 (C=O), 1448 (NH), 1268, 1106(C-O).

274 Letters in Drug Design & Discovery, 2011, Vol. 8, No. 3
Velingkar and Dandekar
evaporated to give a residue that was purified by column
chromatography.
5.49 (s, 1H, NH), 7.52 (s,1H,NH), 6.51-8.15 (m,12H,Ar). IR
(KBr) cm-1: 3356 (NH), 2921 (CH), 1694 (C=O), 1682
(C=O), 1628 (NH). ESMS m/z = 370.1648[M]+.Anal Calcd
for C23H18N2O3: C, 74.58; H, 4.90; N, 7.56; Found: C, 74.52;
H, 4.78; N, 7.53.
(29): Yield 40%. mp 1460C. 1H NMR (300 MHz, CDCl3)
ꢀ: 2.11 (q, 2H, -CH2), 3.42 (t, J=5.4 Hz, 2H, -CH2), 3.67 (t,
J=7.4 Hz, 1H, -CH), 5.12 (s, 1H, NH), 7.35 (s, 1H, NH),
6.69-8.03 (m, 12H, Ar). IR (KBr) cm-1: 3412 (NH), 3324
(CH), 1686 (C=O), 1672 (C=O), 1624 (NH), 754 (C-Cl).
ESMS m/z = 390.2144[M] +. Anal Calcd for C23H19 ClN2O2:
C, 70.68; H, 4.90; N, 7.17; Found: C, 70.67; H, 4.78; N,
7.14.
MW-Assisted Synthesis
A mixture of acridone carbonyl chloride 5 (0.030 mole),
(0.030 mole) appropriate N-methyl–3-phenyl–3-substituted
propylamine 9, 18, 11 and 1.4g of anhydrous potassium car-
bonate in 50 ml of DMF was irradiated with MW at 350W
MW intensity for 14 min. After completion of reaction, the
work-up was done in a manner similar to the conventional
method.
(24): Yield 58%. mp 1760C. 1H-NMR (300 MHz, CDCl3)
ꢀ: 2.01 (q, 3H, CH2 and OH), 2.84 (s, 3H, CH3), 3.41 (t,
J=6.4 Hz, 2H, CH2), 3.82 (q, 1H, CH), 7.21 (s,1H,NH),
6.64–8.22(m, 12H, Ar); IR (KBr) cm-1: 3406 (OH), 2906 (C-
H), 1684 (NH), 1685 (C=O ),1618 (C=O), 1094 (C-N).
ESMS m/z = 386.1143 [M]+.Anal Calcd for C24H22N2O3: C,
74.59; H, 5.74; N, 7.25; Found: C, 74.48; H, 5.68; N, 7.18.
ACKNOWLEDGEMENTS
The authors are also thankful to All India Council for
Technical Education (AICTE) for the financial support.
(25): Yield 54%. mp 1860C. 1H-NMR (300 MHz,
CDCl3) ꢀ: 2.61 (t, J=6.8 Hz,2H, CH2), 2.88 (s, 3H, CH3),
3.51 (t, J=6.4 Hz, 2H, CH2), 7.49 (s,1H,NH) 7.16-8.31
(m,12H,Ar). IR (KBr) cm-1: 2934 (CH), 1696 (C=O), 1682
(NH), 1588 (C=O), 1526 (C=O), 1056 (C-N).ESMS m/z
=385.0602 [MH+].Anal Calcd for C24H20N2O3: C, 74.98; H,
5.24; N, 7.29; Found: C, 74.72; H, 5.22; N, 7.21.
(26): Yield 52%. mp 1580C. 1H-NMR (300 MHz, CDCl3)
ꢀ: 2.14 (q, 2H, CH2), 2.91 (s, 3H, CH3), 3.52 (t, J=5.4 Hz,2H,
CH2), 3.84 (t, J=6.4 Hz, 1H, CH), 7.33 (s,1H,NH), 6.62 –
8.42 (m, 12 H, Ar). IR (KBr) cm-1: 2962(CH), 1672 (C=O),
1656 (C=O), 1518 (NH), 1032 (C –N), 704 (C-Cl).ESMS
m/z = 403.0422[M]+. Anal Calcd for C24H21Cl N2O2: C,
71.19; H, 5.23; N, 6.92; Found: C, 71.11; H, 5.19; N, 6.84.
The authors are grateful to Institute of Pharmacy, Univer-
sity of Bonn,Germany for Biological evaluation.
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