A facile synthesis and chemical properties of 3,4-dihydro-2H-1,5,2-benzo[f]dithiazepin-3-ones with potential anticancer activity

Article abstract of DOI:10.3987/COM-00-9104

The syntheses of 3,4-dihydro-2H-1,5,2-benzo[f]dithiazepin-3-one 1,1-dioxides (8-11, 14, 17-20) and corresponding 1,1,5,5-tetraoxides (12, 13) are described. Reactivity of these compounds in their alcoholysis, alkaline hydrolysis and alkylation is also rep

Full text of DOI:10.3987/COM-00-9104

HETEROCYCLES，Vol. 55, No. 4, 2001, pp. 753 - 761, Received, 13th November, 2000
A FACILE SYNTHESIS AND CHEMICAL PROPERTIES
OF 3,4-DIHYDRO-2H-1,5,2-BENZO[f]DITHIAZEPIN-3-ONES
WITH POTENTIAL ANTICANCER ACTIVITY
Elżbieta Pomarnacka*, Anita Kornicka, and Franciszek Sączewski
Department of Chemical Technology of Drugs, Medical University
of Gdańsk, 107 Gen. J. Hallera Str., 80-416 Gdańsk, Poland
e-mail: zopom@farmacja.amg.gda.pl
Abstract –The syntheses of 3,4-dihydro-2H-1,5,2-benzo[f]dithiazepin-3-one 1,1-
dioxides (8-11, 14, 17-20) and corresponding 1,1,5,5-tetraoxides (12, 13) are
described. Reactivity of these compounds in their alcoholysis, alkaline hydrolysis
and alkylation is also reported. Evaluation performed at the US National Cancer
Institute (Bethesda) revealed the in vitro antitumor activity of 7-chloro-3,4-
dihydro-8-methyl-4-phenyl-2H-1,5,2-benzo[f]dithiazepin-3-one 1,1-dioxide (11).
Arylsulfonamides represent a class of drugs with a well-established safety profile.1 Currently there is
intense interest in the discovery and development of novel arylsulfonamides for the treatment of cancer2
and HIV infections.3 As part of a broad investigation of structures containing 2-mercaptoarylsulfonamide
moiety, a series of anticancer compounds4 and potent inhibitors of HIV-1 integrase was discovered in our
laboratories (MBSAs, Figure 1).5 We also found that cyclic sulfonamides of type (A) possess interesting
biological properties, particularly as anticancer agents.6 This prompted us to investigate further
the chemistry and biological activity of the related heterocyclic system (B) which may be considered
“bridged” version of MBSAs (Figure 1).
R1
Cl
R1
SH
Cl
S
S(O)n
CH
CO
NH
Cl
N
R2
R2
R2
S
1
S
O2
SO NHR
2
O2
A
B
MBSAs
2-mercaptobenzenesulfonamides
Figure 1

As outlined in Scheme 1, the 3,4-dihydro-2H-1,5,2-benzo[f]dithiazepin-3-one 1,1-dioxides (8-14) were
obtained in 42-74% yield starting from suitable 2-sulfamoylphenyl(thio or sulfonyl)alkanoates (1-7),7-9
based on the cyclocondensation carried out in methanol in the presence of sodium methoxide. It should be
mentioned, that the compound (8) has been previously isolated from the reaction of 1 with biguanide in
17% yield.7
Compounds (8-14) containing a lactam group proved to be susceptible to base-catalysed hydrolysis. Thus,
o
heating of 8 in 1% aqueous NaOH at 90 C for 3 h, followed by treatment with 5% hydrochloric acid,
furnished the carboxylic acid derivative (15). Moreover, the compounds (8-14) were found to undergo
methanolysis upon prolonged heating in boiling methanol. The reaction is reversible and, depending on
the nature of substituents R1 and R2, reaches a state of equilibrium within 10-20 h. For example, the
alcoholysis of 8 reaches the ring-chain equilibrium after 10 h, and the proportion of product (1) to the
starting material was about 53%.
1
R1
R2
R
Compd
n
S(O) CHCOOCH
Cl
3
n
1, 8
2, 9
CH3
CH3
0
0
H
CH3
2
3, 10
4, 11
CH3
CH3
0
0
2
2
0
(CH2)2CH3
C6H5
H
H
H
R
SO NH
2
2
1 - 7
5, 12
6, 13
7, 14
CH3
CH3
COOH
(iii)
(i)
1
1
R
R
S(O)
CH
(ii)
S(O)
CH
CO
NH
Cl
Cl
n
n
Na
C O
2
2
R
S
N
R
S
O
O
2
2
8 - 14
8a - 14a
(vi)
(iv, v)
Cl
S
CH
SCH COOH
Cl
2
2
CO
CH
S
O
N
CH
3
SO NH
3
2
2
2
CH
2
16
15
COOCH
3
Scheme 1. (i) CH3ONa / CH3OH / reflux; (ii) HCl / H2O; (iii) CH3OH / reflux; (iv) 1% NaOH / H2O / 90 oC; (v) 5% HCl; (vi)
ClCH2COOCH3 / toluene / DMF / reflux.

Although the IR spectra run in KBr of the secondary lactams (8-14) exhibited characteristic C=O
vibrations in the range of 1690-1730 cm-1 and no keto-enol tautomerism was observed in solution (S-CH2
1
signals in H NMR spectra), the probable lactam-lactim tautomerism shown in Scheme 2 was studied by
means of ab initio MO calculations.10 Comparison of the calculated energies of the lactam (8) and lactim
(8A) confirmed that in vapor phase 8 is more stable by 8.36 kcal/mol, and therefore, the equilibrium lies
well to the side of the lactam form.
Cl
S
CH
Cl
S
CH
2
2
CO
C OH
CH
S
N
3
CH
S
O
N
3
O
H
2
2
8
8A
E = _1878.9507225 hartree
∆E = _0.0133347 hartree = _8.36 kcal/mol
E = _1878.9373878 hartree
Scheme 2
Deprotonation of the lactam (8) with sodium methoxide in methanol and successive alkylation of the
resulting ambident nucleophile (8a) with methyl chloroacetate in the toluene-DMF medium gave the
tertiary lactam (16) (Scheme 1). The reaction was regioselective since no O-alkylation side reaction was
observed. In order to confirm the preferential susceptibility of the nitrogen atom to the electrophilic attack,
the distribution of electron density in 8a was computed at ab initio level by direct Hartree-Fock method.10
The formal charges and values of the electrostatic potential on the electron density isosurface
corresponding to the van der Waals surface are shown in Figure 2. For the two nucleophilic sites in 8a the
following charges were calculated: _1.121 e (the nitrogen atom) and _0.733 e (the oxygen atom), while the
_
_
values of electrostatic potential were 138.93 kcal/mol and 119.53 kcal/mol respectively. In this
viewpoint, the electrophile can easily approach the former site, giving rise to the formation of the product
(16).
S
CH
Cl
2
-0.733 e
C O
(-119.53 kcal/mol)
CH
3
S
N
O
2
-1.121 e
8a
(-138.93 kcal/mol)
Figure 2
As depicted in Scheme 3, the obtained acid (14) was converted into the acid chloride (17), which in turn
underwent aminolysis to the corresponding amides (18-20). The structures of the compounds (8-14) and

1
(16-20) were confirmed by IR, H NMR, and 13C NMR spectra as well as elemental analyses (see
experimental section).
Cl
S
CH
2
Cl
S
CH
Cl
S
CH
2
2
(i)
(ii)
CO
CO
CO
1
ClOC
HOOC
N C
S
N
H
R
S
O
N
S
N
H
O
H
O
2
2
2
O
H
18 - 20
14
17
1
Compd
R
18
19
20
H
Cl
CH
3
Scheme 3. (i) SOCl2 / THF / reflux; (ii) 4-R1C6H4NH2 / THF / rt.
The compounds obtained were tested at the US National Cancer Institute (Bethesda) for their in vitro
anticancer activity. The antitumor activity was evaluated using a total of 60 human cell lines derived from
nine different cancer types (lung, colon, melanoma, prostate, breast, renal, ovarian, CNS, and leukemia).
The compounds were tested in a broad concentration range (10-4 M – 10-8 M). The response parameters
GI50, TGI, and LC50 are interpolated values representing the concentration at which the Percentage
Growth is +50, 0, and _50 respectively and were calculated from dose-response curves.11 It was found that
compound (11) was the only cyclic analogue of MBSAs which showed a moderate activity in some tumor
cell lines. The data presented in Table 1 display the highest activity of 11 against the melanoma cell lines
SK-MEL-2 with the mean graph midpoints values of log10 GI50, log10 TGI, and log10 LC50 equal to
_4.76, _4.48, _4.20, respectively.
Table 1. In vitro anticancer data for compound (11)
Panel
Cell Line
GI50
µM
TGI
µM
LC50
µM
Panel
Cell Line
GI50
µM
TGI
µM
LC50
µM
Leukemia
HL-60 (TB)
MOLT-4
SR
Non-Small Cell
Lung Cancer
NCI-H23
NCI-H522
Colon Cancer
HCC-2998
HCT-116
CNS Cancer
U251
29.3
26.0
27.6
58.9
60.7
73.8
*
*
*
23.0
60.5
*
Melanoma Cancer
SK-MEL-2
SK-MEL-5
Ovarian Cancer
OVCAR-3
Renal Cancer
A498
UO-31
Prostate Cancer
PC-3
17.3
21.6
32.9
48.8
62.8
*
24.4
25.9
56.2
59.7
*
*
21.6
53.4
*
26.9
28.1
75.5
75.1
*
*
30.3
20.5
25.0
70.8
45.6
64.0
*
*
*
HCT-15
26.4
27.5
70.8
59.4
*
*
CNS Cancer
SF-539
Breast Cancer
HS 578T
26.7
73.3
*
The response parameters GI50, TGI, and LC50 are interpolated values of the concentrations at which the Percentage Growth is
+50, 0, and _50, respectively. *The values of LC50 > 100 µM.

In conclusion, we have presented facile syntheses of 3,4-dihydro-2H-1,5,2-benzo[f]dithiazepin-3-ones,
which, as exemplified by 8, exist predominantly in the lactam form. The in vitro evaluation showed
anticancer activity of the compound (11).
EXPERIMENTAL
Melting points were determined on a Bűchi 535 apparatus and are uncorrected. IR (KBr pellets) spectra
were recorded on a Perkin Elmer 1600 FTIR spectrophotometer, ν values in cm-1. 1H NMR and 13C NMR
spectra were recorded on a Varian Gemini spectrometer (200 MHz). Chemical shifts were reported in
ppm (δ) downfield from Me4Si. The starting methyl 5-chloro-4-R2-2-sulfamoylphenyl(thio or sulfon-
yl)alkanoates (1-7) were obtained by the methods described previously.7-9
General procedure for the preparation of 4-R1-7-chloro-3,4-dihydro-8-methyl-2H-1,5,2-benzo[f]di-
thiazepin-3-one 1,1-di(or 1,1,5,5-tetra)oxides (8-13). A mixture of the appropriate ester (1-6) (16
mmol) and sodium methoxide (0.86 g, 16 mmol) in anhydrous methanol (60 mL) was refluxed for 20 h.
Then, solvent was partly removed under reduced pressure. The precipitate thus obtained was collected by
filtration, washed with methanol (6 mL) and dried. The sodium salt (8a-13a) was dissolved in water (300-
700 mL), filtered off with charcoal added and the pH of filtrate was adjusted to 3 with 1% hydrochloric
acid. After stirring at rt for 2 h, the crude product (8-13) was separated by suction, washed with water (15
mL), dried and purified by recrystallization from suitable solvent.
7-Chloro-3,4-dihydro-8-methyl-2H-1,5,2-benzo[f]dithiazepin-3-one 1,1-dioxide (8): mp 223-225 oC (ace-
tic acid) (lit.,7 mp 223-225 oC); yield 74%. IR: 3125, 3025 (NH), 1700 (CO), 1350, 1170 (SO2). 1H NMR
13
(DMSO-d6): 2.35 (s, 3H, 8-CH3); 4.31 (s, 2H, SCH2); 7.69 (s, 1H, 6-H); 7.92 (s, 1H, 9-H). C NMR
(DMSO-d6): 18.88 (8-CH3); 32.82 (SCH2); 128.69, 129.24, 132.58, 133.78, 134.23, 138.27 (6 C arom.);
166.48 (CO). Anal. Calcd for C9H8NO3ClS2: C, 38.92; H, 2.90; N, 5.04. Found: C, 38.69; H, 2.61; N,
5.10.
o
7-Chloro-3,4-dihydro-4,8-dimethyl-2H-1,5,2-benzo[f]dithiazepin-3-one 1,1-dioxide (9): mp 281-282 C
1
(methanol); yield 70%. IR: 3120, 3035 (NH), 1690 (CO), 1345, 1165 (SO2). H NMR (DMSO-d6): 1.40
(d, J = 6.8 Hz, 3H, CHCH3); 2.36 (s, 3H, 8-CH3); 5.23 (q, J = 6.8 Hz, 1H, SCHCH3); 7.68 (s, 1H, 6-H);
7.95 (s, 1H, 9-H). 13C NMR (DMSO-d6): 13.97 (CH3); 18.87 (8-CH3); 38.05 (SCH); 128.19, 129.03,
132.63, 133.86, 133.96, 138.29 (6 C arom.); 168.73 (CO). Anal. Calcd for C10H10NO3ClS2: C, 41.16; H,
3.45; N, 4.80. Found: C, 40.97; H, 3.16; N, 4.96.
7-Chloro-3,4-dihydro-8-methyl-4-propyl-2H-1,5,2-benzo[f]dithiazepin-3-one 1,1-dioxide (10): mp 158-
o
1
160 C (methanol); yield 42%. IR: 3135, 3065 (NH), 1695 (CO), 1350, 1165 (SO2). H NMR (DMSO-
d6): 0.91 (t, J = 7.0 Hz, 3H, CH2CH3); 1.32-2.11 (m, 4H, CH2CH2); 2.36 (s, 3H, CH3); 5.10 (t, J = 6.7 Hz,

1H, SCHCH2); 7.69 (s, 1H, 6-H); 7.96 (s, 1H, 9-H). Anal. Calcd for C12H14NO3ClS2: C, 45.06; H, 4.41; N,
4.38. Found: C, 45.35; H, 4.36; N, 4.26.
7-Chloro-3,4-dihydro-8-methyl-4-phenyl-2H-1,5,2-benzo[f]dithiazepin-3-one 1,1-dioxide (11): mp 187-
o
1
190 C (methanol); yield 67%. IR: 3130, 3050 (NH), 1695 (CO), 1360, 1170 (SO2). H NMR (DMSO-
d6): 2.39 (s, 3H, CH3); 6.31 (s, 1H, SCH); 7.38-7.51 (m, 5H, ArH); 7.73 (s, 1H, 6-H); 8.01 (s, 1H, 9-H).
Anal. Calcd for C15H12NO3ClS2: C, 50.92; H, 3.42; N, 3.98. Found: C, 50.54; H, 3.13; N, 3.77.
7-Chloro-3,4-dihydro-8-methyl-2H-1,5,2-benzo[f]dithiazepin-3-one 1,1,5,5-tetraoxide (12): mp 195-197
1
oC (toluene); yield 45%. IR: 3260 (NH), 1730 (CO), 1350, 1315, 1175, 1140 (SO2). H NMR (DMSO-
d6): 2.50 (s, 3H, CH3); 5.26 (s, 2H, SO2CH2); 8.07 (s, 1H, 6-H); 8.09 (s, 1H, 9-H). Anal. Calcd for
C9H8NO5ClS2: C, 34.93; H, 2.60; N, 4.52. Found: C, 34.64; H, 2.31; N, 4.49.
7-Chloro-3,4-dihydro-4,8-dimethyl-2H-1,5,2-benzo[f]dithiazepin-3-one 1,1,5,5-tetraoxide (13): mp 237-
o
1
240 C (toluene); yield 60%. IR: 3135, 3065 (NH), 1710 (CO), 1350, 1315, 1170, 1140 (SO2). H NMR
(DMSO-d6): 1.55 (d, J = 6.8 Hz, 3H, SO2CHCH3); 2.50 (s, 3H, CH3); 5.91 (q, J = 6.8 Hz, 1H,
SO2CHCH3); 8.09 (s, 1H, 6-H); 8.13 (s, 1H, 9-H). Anal. Calcd for C10H10NO5ClS2: C, 37.10; H, 3.11; N,
4.33. Found: C, 36.84; H, 2.92; N, 4.59.
7-Chloro-1,1,3-trioxo-3,4-dihydro-2H-1,5,2-benzo[f]dithiazepin-8-carboxylic acid (14). A solution of
ester (6) (5.44 g, 16 mmol) and solution of sodium methoxide (1.73 g, 32 mmol) in anhydrous methanol
(70 mL) was refluxed for 20 h. Then the solvent was distilled off with rotary evaporator. The dry residue
was dissolved in water (150 mL), filtered off with charcoal added and the pH of the filtrate was adjusted
to 2 with 1% hydrochloric acid. After stirring for 2 h, the precipitate was collected by filtration, washed
with water (15 mL), dried and purified by recrystallization from methanol to give 14 (3.6 g, 73%), mp
295-297 oC. IR: 3200-2490 (3120, 3090, 3020, 3010, 2850, 2785, 2640 NH, CH2, OH), 1710 (CO lactam),
1695 (CO acid), 1360, 1170 (SO2). 1H NMR (DMSO-d6): 4.40 (s, 2H, SCH2); 7.87 (s, 1H, 6-H); 8.34 (s,
1H, 9-H). Anal. Calcd for C9H6NO5ClS2: C, 35.13; H, 1.97; N, 4.55. Found: C, 34.97; H, 1.69; N, 4.40.
7-Chloro-3,4-dihydro-8-methyl-N-(methoxycarbonyl)methyl-2H-1,5,2-benzo[f]dithiazepin-3-one
1,1-dioxide (15). A mixture of 8 (2 g, 7 mmol) and sodium methoxide (0.38 g, 7 mmol) in anhydrous
methanol (30 mL) was refluxed for 2 h, then allowed to cool. The precipitate was filtered off, washed
with methanol and dried to give 1.7 g (81%) of the sodium salt (8a).
To a stirred suspension of 8a (1.7 g, 5.7 mmol) in dry toluene (65 mL) and dry DMF (40 mL), methyl
chloroacetate (0.68 g, 6.3 mmol) was added. The suspension was refluxed for 20 h, then solvent was
distilled off under reduced pressure. The dry residue was treated with water (200 mL) and the resulting
mixture was neutralized to pH 7.5 with 5% aqueous Na2CO3 and stirred at rt for 30 min. The product that
precipitated was collected by filtration, washed with water, dried and purified by recrystallization from

methanol to give 15 (1.1 g, 55%), mp 96-99 oC. IR: 2965, 2920, 2850 (CH2, CH3), 1755 (CO), 1710 (CO
lactam), 1360, 1170 (SO2). 1H NMR (Acetone-d6): 2.42 (s, 3H, 8-CH3); 3.60 (s, 3H, OCH3); 4.59 (s, 4H,
13
SCH2 and NCH2); 7.58 (s, 1H, 6-H); 7.91 (s, 1H, 9-H). C NMR (Acetone-d6): 19.79 (8-CH3); 34.87
(SCH2); 47.61 (OCH3); 53.07 (NCH2); 129.55, 129.87, 131.42, 134.91, 135.04, 140.25 (6 C arom.);
167.01 (CO); 168.81 (CO lactam). Anal. Calcd for C12H12NO5ClS2: C, 41.20; H, 3.46; N, 4.00. Found: C,
41.06; H, 3.24; N, 3.92.
Hydrolysis of 1,5,2-benzo[f]dithiazepin-3-one 1,1-dioxide (8). A suspension of 8 (0.5 g, 2 mmol) in 1%
aqueous NaOH (30 mL) was stirred at 90 oC for 3 h. The resulting solution was acidified with 5% hydro-
chloric acid to pH 2. The precipitate was filtered off, washed with water and dried to give (5-chloro-4-
methyl-2-sulfamoylphenylthio)acetic acid (16) (0.4 g, 75%) (lit.,9 mp 179-181 oC).
Alcoholysis of 1,5,2-benzo[f]dithiazepin-3-one 1,1-dioxide (8). A suspension of 8 (0.5 g, 2 mmol) in
anhydrous methanol (15 mL) was refluxed for 10 h. Then, the solvent was distilled off under reduced
pressure and the dry residue was treated with water (60 mL). The mixture thus obtained was neutralized
to pH 7.5 with 5% aqueous Na2CO3 and filtered off (filtrate A’’ was stored for further workup) to give
methyl (5-chloro-4-methyl-2-sulfamoylphenylthio)acetate (1) (0.3 g, 53%) (lit.,9 mp 138-139 oC).
After separation of 1, the filtrate A’’ was acidified with 1% hydrochloric acid to pH 3 to afford the
starting material (8).
7-Chloro-1,1,3-trioxo-3,4-dihydro-2H-1,5,2-benzo[f]dithiazepin-8-carbonyl chloride (17). A solution
of the acid derivative (14) (30.77 g, 100 mmol) and thionyl chloride (11 mL, 150 mmol) in THF (300
mL) was refluxed for 4 h. The solvent and excess of thionyl chloride were evaporated under vacum and
coevaporated with toluene (3 x 50 mL) and benzene (3 x 50 mL). The dry residue was treated with
benzene (150 mL) to give 17 which was collected by filtration and dried. Yield: 25.5 g, (78%), mp 170-
1
173 oC. IR: 3140-3000 (3135, 3080, 3010 NH), 1780 (CO), 1720 (CO lactam), 1350, 1170 (SO2). H
NMR (Acetone-d6): 4.53 (s, 2H, SCH2); 7.87 (s, 1H, 6-H); 8.78 (s, 1H, 9-H). Anal. Calcd for
C9H5NO4Cl2S2: C, 33.14; H, 1.54; N, 4.29. Found: C, 33.27; H, 1.31; N, 4.39.
General procedure for the preparation of 7-chloro-3,4-dihydro-8-(4-R1-phenylcarbamoyl)-2H-
1,5,2-benzo[f]dithiazepin-3-one 1,1-dioxides (18-20). To a solution of the chloride (17) (3.26 g, 10
mmol) in THF (20 mL) a solution of the appropriate amine (20 mmol) in THF (20 mL) was added
o
dropwise with stirring while the temperature was maintained below 15 C with external cooling. Stirring
was continued at rt for 24 h, and then, the solvent was distilled off and a dry residue was suspended in
0.05% aqueous HCl (200 mL). The resulting mixture was stirred for 2 h and the crude product was
filtered off and purified by crystallization from acetic acid.
According to the above procedure the following compounds were obtained:

7-Chloro-3,4-dihydro-8-(phenylcarbamoyl)-2H-1,5,2-benzo[f]dithiazepin-3-one 1,1-dioxide (18): mp
279-281 oC; yield 80%. IR: 3275, 3255 (NH), 1710 (CO lactam), 1650 (CO), 1345, 1170 (SO2). 1H NMR
(DMSO-d6): 4.40 (s, 2H, SCH2); 7.09-7.92 (m, 5H, ArH); 7.98 (s, 1H, 6-H); 8.06 (s, 1H, 9-H); 10.65 (s,
1H, CONH). Anal. Calcd for C15H11N2O4ClS2: C, 47.06; H, 2.90; N, 7.32. Found: C, 46.83; H, 2.64; N,
7.07.
7-Chloro-3,4-dihydro-8-(4-chlorophenylcarbamoyl)-2H-1,5,2-benzo[f]dithiazepin-3-one 1,1-dioxide (19):
o
1
mp 296-298 C; yield 69%. IR: 3280, 3250 (NH), 1710 (CO lactam), 1650 (CO), 1345, 1170 (SO2). H
NMR (DMSO-d6): 4.40 (s, 2H, SCH2); 7.41-7.73 (m, 4H, ArH); 7.93 (s, 1H, 6-H); 8.09 (s, 1H, 9-H);
10.78 (s, 1H, CONH). 13C NMR (DMSO-d6): 33.31 (SCH2); 121.61, 127.90, 128.09, 129.06, 129.97,
133.45, 134.39, 135.11, 137.72, 137.99 (12 C arom.); 163.0 (CO); 166.43 (CO lactam). Anal. Calcd for
C15H10N2O4Cl2S2: C, 43.17; H, 2.41; N, 6.71. Found: C, 42.91; H, 2.31; N, 6.66.
7-Chloro-3,4-dihydro-8-(4-methylphenylcarbamoyl)-2H-1,5,2-benzo[f]dithiazepin-3-one 1,1-dioxide (20)
o
1
mp 291-293 C; yield 60%. IR: 3280, 3240 (NH), 1710 (CO lactam), 1650 (CO), 1340, 1170 (SO2). H
NMR (DMSO-d6): 2.28 (s, 3H, 4-CH3); 4.40 (s, 2H, SCH2); 7.15-7.58 (m, 4H, ArH); 7.91 (s, 1H, 6-H);
8.04 (s, 1H, 9-H); 10.78 (s, 1H, CONH). Anal. Calcd for C16H13N2O4ClS2: C, 48.42; H, 3.30; N, 7.06.
Found: C, 48.14; H, 3.16; N, 6.84.
ACKNOWLEDGEMENT
We express our thanks to Dr V.L. Narayanan, Chief of Drug Synthesis Chemistry Branch US NCI
(Bethesda), for carrying the in vitro anticancer tests.
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of atomic charges and obtaining a graph that shows the values of the electrostatic potentials
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