Novel fluorinated acridone derivatives. Part 1: Synthesis and evaluation as potential anticancer agents

Article abstract of DOI:10.1016/j.bmcl.2008.05.078

We report on the synthesis of a novel series of fluorinated acridones from 5-trifluoromethyl-1,3-cyclohexanedione. The cytotoxic activities of the compounds were studied in several cancer cells. Compounds 9a, 9c, 9e, 9f, and 9h exhibited significant anticancer activities in selected cell lines. Compound 9c is the most active showing GI₅₀ that ranged in values from 0.13 to 26 μM, covering a wide range of cancer cell lines.

Full text of DOI:10.1016/j.bmcl.2008.05.078

Bioorganic & Medicinal Chemistry Letters 18 (2008) 4172–4176
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Novel fluorinated acridone derivatives. Part 1: Synthesis and evaluation
as potential anticancer agents
Olugbeminiyi O. Fadeyi a, Saudat T. Adamson b, E. Lewis Myles b, Cosmas O. Okoro a,
*
a Department of Chemistry, Tennessee State University, 3500 John A. Merritt Boulevard, Nashville, TN 37209-1561, USA
b Department of Biological Sciences, Tennessee State University, 3500 John A. Merritt Boulevard, Nashville, TN 37209-1561, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
We report on the synthesis of a novel series of fluorinated acridones from 5-trifluoromethyl-1,3-cyclo-
hexanedione. The cytotoxic activities of the compounds were studied in several cancer cells. Compounds
9a, 9c, 9e, 9f, and 9h exhibited significant anticancer activities in selected cell lines. Compound 9c is the
Received 24 April 2008
Revised 19 May 2008
Accepted 19 May 2008
Available online 23 May 2008
most active showing GI50 that ranged in values from 0.13 to 26
lines.
lM, covering a wide range of cancer cell
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Acridone
DNA
Acridine
Anticancer
Fluorinated
Tricyclic
Cancer, the uncontrolled, rapid, and pathological proliferation
of abnormal cells, is the leading cause of human death, after car-
diovascular diseases.1 Over 1 million cases of cancer occur in the
United States annually and cancer-related deaths are estimated
to reach 12 million world-wide, by the year 2015. Despite consid-
erable progress in the understanding of its biology and pharmacol-
ogy, cancer remains a serious health problem. Although there has
been increasing sophistication of conventional therapeutic strate-
gies, such as surgery, radiotherapy, and chemotherapy, such ap-
proaches are capable of remediating approximately half of cancer
patients, while over 40% of patients are still likely to die from the
disease.1
Therefore, the search for potent, safe, and selective anticancer
compounds is a crucial aspect of modern cancer research. Natural
products are a rich source of new medicinal leads and, therefore,
the preparation of natural product-based libraries of compounds
is an important area of research in modern drug discovery.2 As
structural building block in many natural products, the acridine
or acridone ring is one of the most commonly encountered hetero-
cycles in medicinal chemistry. It is present in many biologically
important molecules, such as amsacrine (1) (cytotoxic and antivi-
ral agents),3a,b botiacrine (2) (antiparkinsonian drug),3c,d clomacran
(3) (tranquilizer),3e,f monometacrine (antidepressant),3g,h acridine
carboxamide (DACA) (4) (antitumor),3i–k and in natural products
such as plakinidine A (5a) and B (5b) (anthelmintic),3l dercitin
(6) (anticancer),3m glyfoline (7) (anticancer),3n and acronycine (8)
(antitumor)3o (Fig. 1).
In addition, acridine- and acridone-based derivatives have been
mostly studied as anticancer agents,3p,q which are believed to ex-
press their activity through binding or intercalation of DNA.3r The
planar area of the tricyclic acridine and acridone nuclei aid in tar-
geting DNA by intercalating between nucleotide base pairs in the
helix and the positive charge. Examples that are in clinical trials in-
clude amsacrine,4 anilino acridine derivative asulacrine (or CI-
921),5 and N-[(2-dimethyl amino)-ethyl] acridine-4-carboxamide
4 (DACA).6 DACA (4) entered phase I clinical trial on the basis of
its mixed inhibition of both DNA topoisomerase-I and topoisomer-
ase-II, and excellent activity against solid tumors.3i–k
Other derivatives that have shown interesting antitumor prop-
erties are acridone-4-carboxamide,7 and the bis-functionalized
acridone/acridine-4-carboxamides.8 Although, good correlation
between high affinity for DNA and cytotoxicity was observed, the
intercalating property was found not to be sufficient for antitumor
activities. It was therefore proposed that the antitumor properties
of acridines and acridones were not only due to their mode of bind-
ing to DNA, but also due to their specific interaction with other nu-
clear receptors.9
It has been shown that the introduction of fluorine(s),
difluoromethyl, or trifluoromethyl group to bioactive molecules
often leads to improved pharmacological properties,10–12 due to
increased membrane permeability, enhanced hydrophobic bind-
* Corresponding author. Tel.: +1 615 963 5332; fax: +1 615 963 5326.
E-mail address: cokoro@tnstate.edu (C.O. Okoro).
0960-894X/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2008.05.078

O. O. Fadeyi et al. / Bioorg. Med. Chem. Lett. 18 (2008) 4172–4176
4173
H
N
O
MeO
Me
N
S
O
S
Me
Me
O
N
Me
(CH2)3
N
Me
Cl
N
H
N
2, Botiacrine
1, Amsacrine
3, Clomacran
R1
N
N
R2
O
N
Me
N
NH
N
O
N
H
Me
5a, Plakinidine A,R1=H, R2=Me
5b, Plakinidine B, R1=R2=Me
4 (DACA)
Me
S
N
O
OMe
O
OH
OMe
N
N
N
O
HO
N
OMe
Me
N
OMe Me
OMe
Me
Me
8, Acronycine
6, Dercitin
7, Glyfoline
Figure 1. Chemical structures of biologically important acridone- and acridine-based derivatives.
ing, stability against metabolic oxidation, etc. Fluorine, most
especially trifluoromethyl can have significant effects on the
binding affinity in protein–ligand complexes. This effect can
be direct by interaction of the fluorine with the protein, or it
can be indirect by modulation of the polarity of other groups
of the ligand that interact with the protein. Frequently, it is
found that a fluorine substituent leads to a slight enhancement
of the binding affinity due to an increased lipophilicity of the
molecule that results in an increased affinity for the protein.13
One typical example is the increased cytotoxicity of taxoids
where the phenyl group of the isoserine side chain in docetaxel
preliminary anticancer activity of a series of new fluorinated acri-
done derivatives.
The preparation of fluorinated acridone derivatives (9a–h) is
outlined in Scheme 1.
Recently, we synthesized compound 10, as a useful intermedi-
ate in organic synthesis, as a synthon for the design of biologically
active compounds, heterocyclic compounds, and as an efficient
building block.15 The series were prepared using the Friedlander
reaction16 in the presence of a Bronsted acid and water. Typically,
a mixture of 5-(trifluoromethyl)cyclohexane-1,3-dione (10) and
2-aminoacetophenone or benzophenone (11) in 1 N hydrochloric
acid was stirred at 60 °C for the designated time (Table 1) as re-
quired for the completion of the reaction.17 The progress of the
reaction was monitored by thin layer chromatography (TLC). The
cooled reaction mixture was neutralized with aqueous sodium
hydroxide (10%), wherein precipitates separated and were filtered
to obtain pure crystalline solids.17 Under the above conditions the
reaction proceeded smoothly with almost quantitative yields
is replaced by
resulting in a more than 10-fold increase in antitumor activity.
Studies also demonstrated that fluorine substitution has
a trifluoromethyl group (CF3-Ac-docetaxel)
a
strong effect on the conformational equilibrium of the side
chain in hydrophobic medium.14
In continuation of our search for biologically active fluorine-
containing compounds, we report in this letter the synthesis and
R1
R1
O
O
R2
R2
R3
1N HCl (1equiv.)
H2O, 60 ºC
O
NH2
+
R3
N
CF3
F3C
O
R4
R4
10
11
9a-h
Scheme 1. Synthesis of fluorinated acridone derivatives 9a–h.

4174
O. O. Fadeyi et al. / Bioorg. Med. Chem. Lett. 18 (2008) 4172–4176
Table 1
Table 4
Reaction of 10 with benzophenone derivative 11 affording trifluoromethylated
acridone 9a–h
In vitro anticancer activity of compound 9c on 60 human cancer cell lines
Cell line
GI50 (lM)
Entry
Compounds
R1
R2
R3
R4
Time (h)
Yield (%)a
Leukemia
CCRF-CEM
HL-60 (TB)
K-562
MOLT-4
RPMI-8226
1
2
3
4
5
6
7
8
9a
9b
9c
9d
9e
9f
2-Cl-Ph
Ph
H
Me
Ph
2-F-Ph
Ph
Me
Cl
H
Br
O-CH2-O
Cl
Br
NO2
Cl
H
H
H
H
H
Br
H
H
H
H
H
0.5
0.5
0.5
0.5
0.5
1.0
2.0
0.5
93
98
90
94
96
80
75
98
21.9
2.94
6.23
20.8
4.32
H
H
H
H
Non-small-cell lung cancer
A549/ATCC
EKVX
HOP-62
HOP-92
NCI-H226
NCI-H23
NCI-H322M
NCI-H460
NCI-H522
9g
9h
4.65
3.54
4.52
11.2
10.7
3.14
6.26
3.10
11.1
a
Yields refer to pure products.
Table 2
IC50 M) values on different human cancer cell lines
(l
R1
O
Colon cancer
COLO 205
HCC-2998
HCT-116
HCT-15
HT29
KM12
SW-620
R2
3.23
2.60
4.03
3.35
4.42
2.02
15.7
N
CF3
Compounds
R1
R2
Cell lines (IC50 SEM, lM)
BT-549
BT-20
SW-480
JURKAT
CNS cancer
SF-268
SF-295
SF-539
SNB-19
SNB-75
U251
9a
9e
9f
2-Cl-Ph
Ph
2-F-Ph
Me
Cl
Cl
Br
Cl
39.3 0.5
16.1 0.3
17.4 1.2
12.1 0.4
42.1 1.1
22.1 1.7
23.3 0.6
6.7 2.5
21.3 1.2
28.4 0.8
15.5 1.1
15.3 1.5
87.6 0.7
12.3 1.6
11.6 1.3
5.1 0.6
4.35
2.96
2.85
11.3
1.46
11.9
9h
IC50 (l
M) values obtained from AlamarblueTM assays with tested cancer cell lines;
means SD obtained from three independent experiments performed in
triplicate.18
Melanoma
LOX IMVI
MALME-3M
M14
SK-MEL-28
SK-MEL-5
UACC-257
UACC-62
19.0
7.15
5.47
8.98
5.03
16.1
9.87
Table 3
Percent inhibition of growth at 10
cell lines
lM of compounds 9a–h on different human cancer
Cell line
Compound
9a
9b
9c
9d
9e
9f
9h
Ovarian cancer
IGROV1
1.29
1.79
6.49
1.91
26.0
7.55
Breast cancer
MCF7
T-47D
OVCAR-3
OVCAR-4
OVCAR-5
OVCAR-8
SK-OV-3
<20
<20
<20
<20
41
66
<20
<20
<20
<20
<20
<20
95
43
Lung cancer
HOP-92
A549/ATCC
38
50
70
<20
57
—
<20
67
37
80
48
<20
58
<20
Renal cancer
786-0
A498
Colon cancer
HCT-116
HT-29
8.12
2.69
17.5
5.03
8.82
7.89
3.86
38
<20
70
<20
64
77
<20
<20
25
<20
35
<20
<20
43
ACHN
CAKI-1
SN12C
TK-10
Leukemia
MOLT-4
HL-60 (TB)
CCRF-CEM
46
<20
60
<20
45
<20
31
58
—
<20
<20
<20
—
—
<20
<20
29
28
95
<20
—
UO-31
Prostate cancer
PC-3
DU-145
Renal cancer
CAK1-1
786-0
5.75
4.13
<20
<20
<20
<20
44
54
<20
<20
66
<20
45
62
<20
<20
Breast cancer
MCF7
NCI/ADR-RES
MDA-MB-231/ATCC
HS 578T
MDA-MB-435
BT-549
T-47D
Melanoma
UACC-257
SK-MEL-28
0.13
2.55
5.89
16.3
1.56
4.63
3.55
5.11
<20
<20
77
<20
39
40
<20
<20
40
<20
<20
<20
<20
<20
CNS cancer
SF-295
SNB-75
<20
<20
<20
<20
61
76
32
25
48
<20
<20
<20
<20
<20
MDA-MB-468
(Table 1). It is worth mentioning that under basic conditions
(NaOH or sodium methoxide), the target compounds (9a–h) were
obtained in much lower yields, requiring extensive purification
by column chromatography.
We first examined the antiproliferative activity of 9a, 9e, 9f, and
9h in a preliminary screen comprising a panel of human colon
(SW480), breast (BT-20 and BT-549), and leukemia (JURKAT) can-
cer cell lines in 72 h drug exposure AlamarblueTM assays (Table
2).18 The dose of the compound that inhibited 50% cell proliferation
(IC50) was calculated using the data generated from the assay.

O. O. Fadeyi et al. / Bioorg. Med. Chem. Lett. 18 (2008) 4172–4176
4175
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rangeof5.1–12.3 M;theleastsensitivecelllinewasBT-20(IC50 val-
ues 23.3–42.1 M) except compound 9h with IC50 values of 6.7 M.
l
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l
l
Because 9a, 9e, 9f, and 9h exhibited inhibitory activity on the
panel of human cancer cell lines, the eight fluorinated acridone
derivatives 9a–h were selected as model for further screening.
The synthesized compounds 9a–h were then submitted to the Na-
tional Cancer Institute (NCI, Bethesda, MD) for the standard 60 can-
cer cell line screen. Selected compounds were tested initially at a
single dose in the cell panel.19 Only compounds which satisfy
pre-determined threshold inhibition criteria progressed to evalua-
tion in the same full panel using five different concentrations. The
concentration causing 50% cell growth inhibition (GI50) compared
with the control was calculated.
Results for test compounds are reported as percentage inhibi-
tion of the treated cells at single dose of 10
lM in comparison with
that of the untreated control cells (Table 3).
It was found that among the series of the eight fluorinated acri-
done derivatives only compound 9c exhibited in vitro cytotoxic
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activity at 10 lM in greater than 90% of the 60 cell lines. As a result,
9c was selected for a 5-dose repeat screening. The result for the 5-
dose testing is shown in Table 4.
This compound shows good anticancer potency in a wide spec-
trum of cell lines causing 50% cell growth inhibition (GI50), and the
values range from 0.13 to 26.0 lM as shown in Table 4.
Among the eight fluorinated acridone derivatives 9a–h, those
containing aryl-substituted analogs (R1 = Ph) overall showed
weaker cell growth inhibition compared with the unsubstituted
phenyl (R1 = H) or methyl-substituted phenyl (R1 = Me) (Tables 2
and 3). It appears that the substitution at R1 of the acridone ring
is essential for activity, since less bulky groups gave better activity.
Compound 9c (R1 = H), is the most active, with GI50 value of
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0.13
(R1 = Me) also showed moderate activity, with IC50 value of 5.1
and 6.7 M in leukemia cell line (JURKAT) and breast cancer cell
lM (Table 4), in breast cancer cell line. Compound 9h
l
line (BT-20), respectively (Table 2). The introduction of phenyl
group at R1 led to a decrease in activity (Tables 2 and 3). However,
compound 9e and 9f showed significant growth inhibition of JUR-
KAT with IC50 values of 11.6 and 12.3
9e and 9f also inhibited BT-549 with IC50 values of 16.1 and
17.4 M, respectively (Table 2).
lM, respectively. Compounds
l
A new series of trifluoromethylated acridone derivatives have
been synthesized and characterized.
The preliminary anticancer studies showed that 9a, 9c, 9e, 9f,
and 9h represent novel leads for further development. Compound
9c was the most active among the series and will be subjected to
in-depth structure–activity relationship (SAR). The mechanism of
action of these novel leads will be the subject of future studies,
aimed at identifying highly potent, safe, and selective agents for
the treatment of cancer.
12. (a) Nair, V. A.; Mustafa, S. M.; Mohler, M. L.; Fisher, S. J.; Dalton, J. T.; Miller, D.
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T.; Chang, E.; Lee, Y.; Tsai, M. Y.; Chang, C.; Lee, K. H. J. Med. Chem. 2002, 45,
5037. and references cited therein.
13. Böhm, H. J.; Banner, D.; Bendels, S.; Kansy, M.; Kuhn, B.; Müller, K.; Sander, U.
O.; Stahl, M. ChemBioChem 2004, 5, 637.
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Acknowledgments
15. Fadeyi, O. O.; Okoro, C. O. Tetrahedron Lett. 2008, in press.
16. Friedländer, P.; Gohring, C. F. Ber. 1883, 16, 1833.
17. Experimental and spectral data for title compounds.
We are thankful to the U.S. Department of Education Title III
Grant, Tennessee State University, for financial support. We also
acknowledge the National Cancer Institute (NCI), Maryland, for
providing in vitro cytotoxicity data on our compounds.
Typical procedure for the synthesis of fluorinated acridone 9:To a mixture of
substituted 2-aminoarylketone or 2-aminoarylaldehyde 11 (1.0 mmol) and 5-
trifluoromethyl-cyclohexanedione 10 (1 mmol) (1.2 mmol), 1 mL of 1 N HCl
aqueous solution was added. The reaction mixture was stirred at 60–75 °C for a
designated time. After completion of the reaction (monitored by TLC), the
resulting suspension was neutralized with 1 mL of 1 N NaOH. The solid was
filtrated, washed with water (3Â 6 mL ), air-dried to give the product as white
or slightly yellow powder. The solid product was further purified by
recrystallization with aqueous ethanol when necessary.
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Neuroimmunomodulation 2004, 11, 255; (c) Arve, L.; Voigt, T.; Waldmann, H.
QSAR Comb. Sci. 2006, 25, 449.
2. (a) Koehn, F. E.; Carter, G. T. Nat. Rev. Drug Discov. 2005, 4, 206; (b) Arve, L.;
Voigt, T.; Waldmann, H. QSAR Comb. Sci. 2006, 25, 449; (c) Breinbauer, R.;
Vetter, I. R.; Waldmann, H. Angew. Chem., Int. Ed. 2002, 41, 2879; (d) Tan, D. S.
Comb. Chem. High Throughput Screening 2004, 7, 631; (e) Boldi, A. M. Curr. Opin.
7-Chloro-9-(2-chlorophenyl)-3-(trifluoromethyl)-3,4-dihydroacridin-1(2H)-one
9a:Yellow solid, mp = 182–185 °C. IR (nujol) 2930, 1605, 1495, 1156,
760 cmÀ1 1H NMR (CDCl3) d 2.36–2.47 (dd, 2H), 2.87–2.96 (dd, 2H), 3.06 (m,
;
1H), 7.4–7.77 (m, 4H), 7.83 (s, 1H), 7.99–8.20 (d, 2H). EIMS m/z; 305 (5%), 374
(100%), 376 (50%), 375(25%), 377 (12.6%), 410 (2%) (M+).

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O. O. Fadeyi et al. / Bioorg. Med. Chem. Lett. 18 (2008) 4172–4176
9-Phenyl-3-(trifluoromethyl)-3,4-dihydroacridin-1(2H)-one 9b:Yellow solid,
mp = 203–206 °C. IR (nujol) 2930, 1612, 1491, 1147 cmÀ1 1H NMR (CDCl3) d
(CDCl3) d 2.36–2.48 (dd, 2H), 2.83–2.97 (dd, 2H), 3.01 (m, 1H), 7.21–7.57 (m,
;
5H), 7.71- 8.49 (d, 2H), 9.35 (s, 1H). EIMS m/z; 235 (25%), 331 (15%), 359
2.35–2.48 (dd, 2H), 2.85–2.97 (dd, 2H), 3.02 (m, 1H), 7.21 (d, 2H), 7.41–7.55 (m,
3H), 7.69–7.98 (m, 2H), 8.09–8.15 (d, 2H). EIMS m/z; 51 (12.5%), 217 (15%), 247
(14%), 313 (50%), 340 (100%), 341 (75%) (M+). 5,7-Dibromo-3-(trifluoromethyl)-
3,4-dihydroacridin-1(2H)-one 9c:Yellow solid, mp = 140–143 °C. IR (nujol)
(12.5%), 411(30%), 439 (100%) (M++1).
7-Chloro-9-methyl-3-(trifluoromethyl)-3,4-dihydroacridin-1(2H)-one 9h: Yellow
solid, mp = 122–125 °C. IR (nujol) 1679, 1560 cmÀ1 1H NMR (CDCl3) d 2.39 (s,
;
3H), 2.4–2.49 (dd, 2H), 2.81–2.97 (dd, 2H), 3.19 (m, 1H), 7.93 (d, 1H), 8.03 (d,
1H), 8.33 (s, 1H). EIMS m/z; 51 (12.5%), 154 (20%), 217 (23%), 285 (100%), 313
(95%) (M+).
2925, 1600, 1465, 964, 787 cmÀ1 1H NMR (CDCl3) d 2.4–2.49 (dd, 2H), 2.88–
;
2.93 (dd, 2H), 3.22 (m, 1H), 8.32 (d, 1H), 8.59 (d, 1H), 8.91 (s, 1H). EIMS m/z; 69
(13%), 139 (12%), 220 (12.5%), 2993 (15%), 396 (50%), 397 (25%) 423 (100%)
(M+), 425 (60%).
18. Materials and methods: Human colon (SW480), breast (BT-20 and BT-549), and
leukemia (JURKAT) cancer cell lines were obtained from the American Type
Culture Collection (Manassas, VA). Cell lines were maintained in RPMI 1640
supplemented with 10% fetal bovine serum (FBS), 0.15% sodium bicarbonate,
0.011% sodium pyruvate, 0.24% Hepes and 10 ml/L of antibiotic solution. The
cells were grown in 150 cm2 culture plates in an air/CO2 (95:5) atmosphere at
37 °C and passaged approximately every 3 days. All four cancer cell lines
(1 Â 104 cells per well) were plated using RPMI 1640 medium containing FBS
in 96-well plates and left to attach for 24 h. Cells were then treated with either
vehicle (DMSO) or the indicated concentrations of different compounds. Cells
were exposed for a total of 72 h to test compounds and vehicle controls.
AlamarblueTM reagent dye was added to wells in a 1:10 following exposure
period and incubated at 37 °C overnight. The plates were then analyzed using a
microtiter plate reader at dual wavelengths (560 nm k excitation, 590 nm k
emission). Each experiment was done in triplicate and results are expressed as
means SE for each determination. The IC50 values were calculated using
10-Methyl-7-(trifluoromethyl)-7,8-dihydro-6H-[1,3]dioxolo[4,5-b]acridin-9-one
9d:Yellow solid, mp = 209–212 °C. IR (nujol) 2925, 1600, 1465, 964, 787 cmÀ1
;
1H NMR (CDCl3) d 2.39 (s, 3H), 2.4–2.49 (dd, 2H), 2.81–2.97 (dd, 2H), 3.23 (m,
1H), 5.97 (s, 2H), 7.29 (s, 1H), 7.41 (s, 1H). EIMS m/z; 169 (13%), 227 (25%), 295
(80%), 323 (100%), (M+).
7-Chloro-9-phenyl-3-(trifluoromethyl)-3,4-dihydroacridin-1(2H)-one 9e:Yellow
solid, mp = 151–153 °C. IR (nujol) 2931, 1605, 1491, 1155, 764 cmÀ1 1H
;
NMR (CDCl3) d 2.36 - 2.47 (dd, 2H), 2.87-2.99 (dd, 2H), 3.06 (m, 1H), 7.18-7.55
(m, 5H), 7.83 (s, 1H), 7.99 - 8.21 (d, 2H). EIMS m/z; 305 (5%), 375 (100%) (M+).
7-Bromo-9-(2-fluoro-phenyl)-3-(trifluoromethyl)-3,4-dihydroacridin-1(2H)-one
9f: Yellow solid, mp = 134–136 °C. IR (nujol) 2941, 1609, 1487, 1149,
759 cmÀ1 1H NMR (CDCl3) d 2.36–2.49 (dd, 2H), 2.83–2.97 (dd, 2H), 3.01 (m,
;
1H), 7.31–7.53 (m, 4H), 7.87 (s, 1H), 8.19–8.23 (d, 2H). EIMS m/z; 235 (25%),
331 (15%), 359 (12.5%), 411(30%), 439 (100%) (M+ +1).
7-Nitro-9-phenyl-3-(trifluoromethyl)-3,4-dihydroacridin-1(2H)-one 9g: Yellow
linear regression method and are expressed in micromolar (lM).
19. Boyd, M. R.; Paul, K. D. Drug Dev. Res. 1995, 34, 91.
solid. mp = 194–198 °C. IR (nujol) 2941, 1609, 1487, 1149, 759 cmÀ1
;
1H NMR