Synthesis of new 4(3H)-quinazolinone derivatives by reaction of 3-amino-2(1H)-thioxo-4(3H)-quinazolinone with selected substituted cinnamic acids and halogenoketones

Article abstract of DOI:10.1080/10426500701648044

Two series of N-acylated (2-6) and S-alkylated (7-13) 4(3H)-quinazolinone derivatives have been synthesized by reaction of 3-amino-2(1H)-thioxo-4(3H)- quinazolinone (1) with selected substituted cinnamic acids and halogenoketones, respectively. The struct

Full text of DOI:10.1080/10426500701648044

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Phosphorus, Sulfur, and Silicon
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Synthesis of New 4(3H)-
Quinazolinone Derivatives by
Reaction of 3-Amino-2(1H)-
thioxo-4(3H)-quinazolinone
with Selected Substituted
Cinnamic Acids and
Halogenoketones
Wanda P. Nawrocka a , Jan J. Staśko a & Hanna
Liszkiewicz a
a Wroclaw Medical University , Wroclaw, Poland
Published online: 04 Jun 2008.
To cite this article: Wanda P. Nawrocka , Jan J. Staśko & Hanna Liszkiewicz (2008)
Synthesis of New 4(3H)-Quinazolinone Derivatives by Reaction of 3-Amino-2(1H)-
thioxo-4(3H)-quinazolinone with Selected Substituted Cinnamic Acids and
Halogenoketones, Phosphorus, Sulfur, and Silicon and the Related Elements, 183:6,
1379-1387, DOI: 10.1080/10426500701648044
To link to this article: http://dx.doi.org/10.1080/10426500701648044
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Phosphorus, Sulfur, and Silicon, 183:1379–1387, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701648044
Synthesis of New 4(3H)-Quinazolinone Derivatives by
Reaction of 3-Amino-2(1H)-thioxo-4(3H)-quinazolinone
with Selected Substituted Cinnamic Acids and
Halogenoketones
´
Wanda P. Nawrocka, Jan J. Stasko, and
Hanna Liszkiewicz
Wroclaw Medical University, Wroclaw, Poland
Two series of N-acylated (2–6) and S-alkylated (7–13) 4(3H)-quinazolinone
derivatives have been synthesized by reaction of 3-amino-2(1H)-thioxo-4(3H)-
quinazolinone (1) with selected substituted cinnamic acids and halogenoketones,
1
respectively. The structures of the compounds obtained result from the IR, H NMR,
and mass spectra.
Keywords 1H NMR; 2-phenacylthio-; 3-amino-2(1H)-thioxo-4(3H)-quinazolinone
derivatives; 3-cinnamoylamino-; IR; mass spectra; synthesis
INTRODUCTION
4(3H)-Quinazolinone derivatives show different biological and phar-
macological activities. Approximately 30 medicines based on 4(3H)-
quinazolinone derivatives are used worldwide. Methaqualone, ke-
tanserin, and quinetazone are used on a large scale1 and recently,
raltitrexyd and nolatrexed have been introduced as cytostatic drugs.2
Alkaloids of antibiotics and toxins isolated from plants and fungi in-
corporating the 4(3H)-quinazolinone moiety were also described. Some
of them like asperlicine and ruteacarpine3 became objects of detailed
pharmacological research.
In recent years the synthesis and biological studies of 4(3H)-
quinazolinone derivatives were described. 4−8
We have described the synthesis of 3-amino-2(1H)-thioxo-4(3H)-
quinazolinone (1)9. It is a universal starting material for the prepara-
tion of substituted and annulated compounds based on the reactivity of
the 3-amino and 2-thiocarbonyl group. We have reported the reaction
Received 9 July 2007; accepted 22 August 2007.
Address correspondence to Wanda P. Nawrocka, Department of Drugs Technology,
Wroclaw Medical University, Nankiera 1 Sq, 50-140 Wroclaw, Poland. E-mail:
1379

1380
W. P. Nawrocka et al.
of 1 with chloroacetic acid and its derivatives,9 cyanogen bromide,10
halocarbonyl compounds, and α,β-unsaturated carbonyl compounds, as
well as the immunotropic properties of the resulting products.11.
Here, we describe the synthesis of new derivatives by reaction of
4(3H)-quinazolinone 1 with selected substituted cinnamic acids and
with haloketones (Scheme 1), which are intended to be used for biolog-
ical research.
Polyphenolic acids including cinnamic acid and its substituted
derivatives have been the subject of synthesis and biological re-
search for several years. Curcumin and cinarine exhibit chola-
gogic activity, and some amides are inhibitors of 5-lipoxygenase (5-
LO)12. Cinnamic acid derivatives with antibacterial,13 anticancerous,14
and anti-UV radiation activity15 were also described. Cinnamoyl
derivatives of 1,5-benzodiazepine synthesized in our group show
psychotropic,16 high anticancerous,17 and immunotropic18 activity.
Very high immunotropic activity with no toxicity is exhibited by
3-cinnamoylamino-2(1H)-thioxo- and 3-amino-2-cinnamoylthio-4(3H)-
quinazolinone.11 Anticancerous activity is shown by S-alkylated haloke-
tone derivatives of imidazo[4,5-b]pyridine.19
RESULTS AND DISCUSSION
Reaction of 4(3H)-quinazolinone 1 with p-nitrocinnamoyl chloride was
carried out in anhydrous tetrahydrofurane at room temperature.11 Acy-
lation using substituted cinnamic acids was performed also in THF
solution at room temperature in the presence of thionyl chloride and
catalytic amounts of DMF.
The results of the elemental analysis of compounds 2–6, and the
mass spectrum of derivative 2 confirmed the addition of one cinnamoyl
moiety to the 4(3H)-quinazolinone 1 molecule. There are no bands for
a NH2 group in the IR spectra of derivatives 2–6, while they appear
in the IR spectrum of 4(3H)-quinazolinone 19 at 3400, and 3320 cm−1
.
Characteristic bands for an amide moiety are observed at 3340–3320
cm−1 (NH) and at 1680 cm−1(CO). The (CH CH) group shows bands at
1660 and 1290 cm−1
.
The formation of the amides 2–6 is also confirmed by the1H NMR
spectra. Two signals are observed at 10.75–10.80 ppm and at 12.23–
12.70 ppm, which are attributed to the protons of the NHCO and NHCS
groups, respectively. The signals of the vinyl protons appear as doublets
at 6.66–7.10 ppm (COCH=), and at δ ∼ 7.15 ppm ( CHAr). The cou-
3
pling constants J = 15.7–16.0 Hz indicate the trans configuration at
the −CH CH moiety.

Synthesis of New 4(3H)-Quinazolinone Derivatives
1381
SCHEME 1
In a previous study we have shown, that heating of 4(3H)-
quinazolinone 1 in glacial acetic acid with chloroacetone or ω-
bromoacetophenone results in the formation of tricyclic derivatives of
1,4,5-thiadiazin[2,3-b]quinazolin-6-one.11

1382
W. P. Nawrocka et al.
In continuation of these studies, reactions of 4(3H)-quinazolinone
1 with substituted haloketones in glacial acetic acid were carried out
at room temperature for 7–14 days. Reaction of 4(3H)-quinazolinone
1 with ω-bromo-4ꢀ-nitroacetophenone was the fastest, that with ω-
bromoacetophenone was the slowest reaction observed. All reactions
led to the formation of homogenous products.
The structures of the compounds formed were confirmed unambi-
1
giously by the results of elemental analysis and by the IR, H NMR,
and mass spectra.
The IR spectra showed, that acylation of the amino group at posi-
tion three did not occur: in the region of 3500–3300 cm−1 characteristic
bands for a primary amino group were observed. The bands of the C O
group appeared in the region of ∼1690 cm−1
.
Similar conclusions can be drawn from analysis of the 1H NMR spec-
tra. No signal was observed at δ ∼ 14.5 ppm, a region characteristic for
the NH proton of the NH C S group. However, a singlet corresponding
to two amino protons was observed at ∼ 6.70 ppm. In the case of 10 and
12, the signal for the NH2 group overlaps with the signals of the aro-
1
matic protons. In the H NMR spectra of compounds 7–13, the signal
for the methylene group is observed at 5.15–5.23 ppm at low field.
The mass spectra of compounds 7–13 display the respective molecu-
lar ion peaks. In the mass spectra of compounds 11 and 12 the expected
isotopic pattern is observed, indicating the presence of chlorine and
bromine in the molecules. Cleavage of the bond between the α carbon
atom and the C O group is the main fragmentation pathway. It leads
to the formation of acyl ions, which yield the basic peaks for deriva-
tives 7–11. In the case of compound 12, the o-iminobenzoyl ion m/e =
118 (100%), is preferably formed as the result of the fragmentation of
4(3H)-quinazolinone 1. In the case of compound 13, an ion with m/e =
120 (100%) yields the basic peak. It is formed as the result of the rear-
rangement of the p-nitrobenzoyl ion, m/e = 150, to the corresponding
nitrite followed by NO. radical elimination.
The synthesized compounds are intended for biological research and
may act as suitable starting materials for further syntheses.
EXPERIMENTAL
Melting points (uncorrected) were measured with a Boethius melting
point apparatus. Analyses were performed with a Perkin Elmer 2400
analyser and satisfactory results within 0.4% of the calculated values
were obtained for all new compounds. IR spectra (in KBr) were recorded
with an IR 75 spectrophotometer. 1H NMR spectra were obtained with
a Bruker AVANCE DRX 300 instrument using DMSO-d6 as solvent

Synthesis of New 4(3H)-Quinazolinone Derivatives
1383
at room temperature and chemical shifts are referred to the residual
solvent signal at δ = 2.50 ppm. Mass spectra were obtained with a
GCMS -LK 82091 spectrometer at ionization energy of 15 or 70 eV. The
course of the reactions and the purity of the products were checked by
TLC (Kieselgel G, Merck) in diethyl ether : ethanol = 5:1 as eluent.
3-Amino-2(1H)-thioxo-4(3H)-quinazolinone (1)
Compound 1 was prepared exactly as described previously.9
3-(4-Nitrocinnamoylamino)-2(1H)-thioxo-4(3H)-quinazolinone
(2)
Compound 2 was prepared exactly as described previously.11
General Procedure for the Synthesis of Compounds 3–6
To a mixture of compound 1 (1.93 g, 0.01 mol) and the respective cin-
namic acid (0.01 mol) was added dropwise with mechanical stirring at
room temperature 3 drops of DMF, anhydrous THF (50 mL), and SOCl2
(10 mL). Stirring was continued for 25–48 h. The product was filtered
off, washed with Et2O (20 mL), 5% aq NaHCO3 (20 mL) solution and
water (50 mL), dried, and recrystallized from ethanol (3, 5) or n-butanol
(4, 6).
3-(2-Nitrocinnamoylamino)-2(1H)-thioxo-4(3H)-quinazolinone
(3)
Yield: 51%; yellow solid from ethanol; m.p. 238–240◦C. IR (KBr): ν
[cm−1] = 3320 (NHCO), 3080 (CH ), 3010 (CH), 1680 (NHCO), 1660
(CH CH), 1620 (C CHAr), 1530, 1330 (NO2), 1290 (CH CH), 740 (C-
H arom.), 705 (CS). 1H NMR (DMSO-d6): δ 6.68 (m, 2H), 6.90 (m, 1H),
7.10 (d, J = 15.8 Hz, 1H), 7.30 (m, 2H) 7.65 (m, 2H), 7.95 (d, J = 7.7
Hz, 1H), 8.10 (d, J = 8.0 Hz, 1H), 10.80 (s, 1H), 12.25 (s, 1H).
3-(4-Chlorocinnamoylamino)-2(1H)-thioxo-4(3H)-
quinazolinone (4)
Yield: 57%; white solid from n-butanol; m.p. 265–268◦C. IR (KBr): ν
[cm−1] = 3330 (NHCO), 3010 (CH CH), 1680 (NHCO), 1660 (CH CH),
1220, 760 (CH-arom.), 705 (CS). 1H NMR (DMSO-d6): δ = 6.79 (d, J =
16.0 Hz, 1H), 6.92 (m, 2H), 7.01 (d, J = 7.7 Hz, 1H), 7.28 (m, 3H), 7.60
(m, 2H), 8.09 (m, 1H), 10.80 (s, 1H), 12.23 (s, 1H).

1384
W. P. Nawrocka et al.
3-(4-Methoxycinnamoylamino)-2(1H)-thioxo-4(3H)-
quinazolinone (5)
Yield: 34%; white solid form ethanol; m.p. 256 – 257◦C. IR (KBr): ν
[cm−1
]
3330 (NHCO), 3010 (CH), 2840 (OCH3), 1680 (NHCO), 1660
(CH CH), 1290 (CH CH), 1270 (N-H, C-N), 1225, 740 (C-H arom.), 705
(CS). 1H NMR (DMSO-d6): δ = 3.70 (s, 3H), 6.66 (d, J = 15.7, 1H), 6.82
(m, 2H), 7.01 (m, 2H), 7.15 (d, J = 15.7 Hz, 1H), 7.30 (m, 2H), 7.70 (m,
1H), 8.10 (m, 1H), 10.75 (s, 1H), 12.30 (s, 1H).
3-(2,4-Dimethoxycinnamoylamino)-2(1H)-thioxo-4(3H)-
quinazolinone (6)
Yield: 60%; white solid from n-butanol; m.p. 260–262◦C. IR (KBr): ν
[cm−1] = 3330 (NHCO), 3010 (CH), 2840 (OCH3), 1675 (NHCO), 1660
(CH CH), 1220, 1000, 760 (C-H arom.), 705 (CS). 1H NMR (DMSO-d6):
δ = 3.69 (s, 3H), 3.78 (s, 3H), 6.72 (d, J = 15.7 Hz, 1H), 6.95 (m, 2H),
7.18 (m, 3H), 7.40 (m, 2H), 8.12 (m, 1H), 10.80 (s, 1H), 12.30 (s, 1H).
General Procedure for the Synthesis of Compounds 7–13
To a suspension of compound 1 (1.93 g, 0.01 mol) in 50 mL of glacial
acetic acid was added at room temperature with stirring the appropriate
phenacyl bromide (0.01 mol). After stirring for 7–14 days (TLC) the
precipitate was collected by filtration and washed 5% solution (20 mL)
of NaHCO3 and water (100 mL), dried, and recrystallized from ethanol
(7–12) or n-butanol (13).
3-Amino-2-phenacylthio-4(3H)-quinazolinone (7)
Yield: 50%; white solid; m.p. 158–160◦C. IR (KBr): ν [cm−1] = 3465,
3340 (NH), 3060 (CH), 2870 (CH2), 1695, 1670 (C O), 1620 (NH), 1480
(C N), 1450 (CH2), 760, 745 (CH arom.), 700 (CS). 1H NMR (DMSO-d6):
δ = 5.17 (s, 2H), 6.62 (m, 2H), 6.63 (s, 2H), 7.21 (m, 3H), 7.62 (m, 2H),
8.09 (m, 2H). MS (70 eV): m/e [%] − 313 (4), 312 (13), 311 (73), 206 (3),
120 (50), 119 (4), 118 (77), 105 (100), 77 (26), 65 (10), 44 (20), 39 (9).
3-Amino-2-(4 ꢀ-methylphenacylthio)-4(3H)-quinazolinone (8)
Yield: 60%; white solid; m.p. 171–172◦C. IR (KBr): ν [cm−1] = 3465,
3340 (NH), 2950 (CH3), 2915 (CH2), 1680 (C O), 1625 (NH), 1490 (CH2),
1475 (C N), 1445 (CH2), 760, 745 (CH arom.), 700 (CS). 1H NMR
(DMSO-d6): δ = 2.20 (s, 3H), 5.17 (s, 2H), 6.62 (m, 2H), 6.73 (s, 2H),
6.92 (m, 3H), 7.92 (m, 1H), 8.10 (m, 2H). MS (70 eV): m/e [%] = 326 (4),
325 (12), 324 (65), 160 (2), 120 (58), 119 (100), 118 (23), 92 (16), 91 (29),
65 (12).

Synthesis of New 4(3H)-Quinazolinone Derivatives
1385
3-Amino-2-(4 ꢀ-methoxyphenacylthio)-4(3H)-quinazolinone (9)
Yield: 61%; white solid; m.p. 182–184◦C. IR (KBr): ν [cm−1] = 3435,
3360 (NH), 2930 (CH3), 2860 (Ar-O-CH3), 1695 (C O), 1625 (NH), 1490
(C N), 1430 (CH2), 1190, 770, 760 (CH arom.), 705 (CS). 1H NMR
(DMSO-d6): δ = 3.87 (s, 3H), 5.16 (s, 2H), 6.43 (s, 2H), 7.10 (d, J =
8.0 Hz, 2H), 7.71 (m, 4H), 8.17 (m, 2H). MS (70 eV): m/e [%] = 342 (5),
341 (26), 136 (10), 135 (100), 120 (16), 119 (3), 118 (9), 92 (16), 77 (8),
65 (5).
3-Amino-2-(4’-fluorophenacylthio)-4(3H)-quinazolinone (10)
Yield: 52%; white solid; m.p. 182–184◦C. IR (KBr): ν [cm−1] = 3460,
3330 (NH), 3060 (CH), 2940 (CH2), 1690, 1670 (C O), 1620 (NH), 1480
(C N), 1440 (CH2), 1180, 760, 745 (CH arom.), 700 (CS). 1H NMR
(DMSO-d6): δ = 5.16 (s, 2H), 6.62 (m, 3H), 6.87 (d, J = 7.7 Hz, 1H),
7.24 (m, 1H), 7.43 (m, 2H), 7.55 (m, 1H), 8.16 (m, 2H). MS (70e V): m/e
[%] = 331 (6), 330 (89), 206 (8), 160 (9), 124 (13), 123 (100), 121 (9), 120
(80), 108 (66), 95 (36), 92 (16), 92 (32), 91 (9), 77 (6), 75 (12), 65 (22), 39
(11).
3-Amino-2-(4’-chlorophenacylthio)-4(3H)-quinazolinone (11)
Yield: 62%; white solid; m.p. 180–182◦C. IR (KBr): ν [cm−1] = 3460,
3340 (NH), 3080 (CH), 2940 (CH2), 1690 (C O), 1620 (NH), 1490 (C N),
1480 (CH2), 1190, 760, 740 (CH arom.), 690 (CS). 1H NMR (DMSO-d6):
δ = 5.15 (s, 2H), 6.61 (d, J = 7.2 Hz, 1H), 6.64 (s, 2H), 6.85 (d, J = 8.2
Hz, 1H), 7.25 (m, 3H), 7.54 (m, 1H), 7.67 (d, J = 8.9 Hz, 1H), 8.09 (d,
J = 8.6 Hz, 1H). MS (70 eV): m/e [%] = 348 (4), 347 (25), 346 (12), 345
(71), 206 (7), 160 (9), 142 (3), 141 (38), 140 (9), 139 (100), 120 (98), 118
(58), 111 (22), 65 (21), 51 (9), 39 (9).
3-Amino-2-(4’-bromophenacylthio)-4(3H)-quinazolinone (12)
Yield: 53%; white solid; m.p. 191 – 193◦C. IR (KBr): ν [cm−1
]
3460,
3340 (NH), 3070 (CH), 2900 (CH2), 1690, 1660 (C O), 1610 (NH), 1490
(C N), 1440 (CH2), 1210, 760, 740 (CH arom.), 690 (CS). 1H NMR
(DMSO-d6): δ = 5.15 (s, 2H), 6.62 (m, 3H), 6.87 (d, J = 8.4 Hz, 1H),
7.25 (m, 1H), 7.54 (d, J = 7.9 Hz, 1H), 7.80 (d, J = 7.8 Hz, 2H), 8.00 (d,
J = 7.8 Hz, 1H). MS (70 eV): m/e [%] = 393 (5), 392 (16), 391 (81), 390
(15), 238 (86), 206 (12), 186 (8), 185 (80), 184 (9), 183 (97), 160 (15), 142
(3), 121 (13), 120 (81), 119 (10), 118 (100), 104 (8), 92 (49), 91 (14), 90
(13), 77 (10), 76 (23), 65 (34), 39 (13).

1386
W. P. Nawrocka et al.
3-Amino-2-(4 ꢀ-nitrophenacylthio)-4(3H)-quinazolinone (13)
Yield: 72%; white solid; m.p. 207–209◦C. IR (KBr): ν [cm−1] = 3460,
3360 (NH), 3080 (CH), 2900 (CH2), 1685, 1660 (C O), 1620 (NH), 1490
1
(C N), 1440 (CH2), 1545, 1340, 840 (NO2), 760, 740 (CH arom.). H
NMR (DMSO-d6): δ = 5.23 (s, 2H), 6.63 (s, 2H), 6.64 (m, 1H), 6.87 (d,
J = 8.4 Hz, 1H), 7.25 (m, 1H), 7.56 (d, J = 7.8 Hz, 1H), 8.34 (m, 4H).
MS (70 eV): m/e [%] = 358 (5), 357 (13), 356 (76), 206 (5), 160 (13), 150
(21), 121 (11), 120 (100), 118 (73), 104 (16), 92 (33), 91 (4), 65 (17), 39
(3).
REFERENCES
[1] The Merck Index. An Encyclopedia of Chemical Drugs and Biologicals., (Merck and
Co. Inc., Rathway, NY, 1989), 11th ed.
[2] (a) P. R. Marsham, L. R. Hughes, A. L. Jackman, and D. L. Alison, J. Med. Chem., 34,
1594 (1991); (b) H. H. Backus, H. M. Pinedo, D. Wouters, C. M. Kuiper, G. Jansen,
C. J. Groeningen, and G. J. Peters, Oncology Research, 12, 231 (2000); (c) T. S. Mok,
T. W. Leung, S. D. Lee, Y. Chao, A. T. Chan, A. Huang, M. Lui, K. Chak, A. Johnston,
and P. Johnson, Cancer Chemotheraphy and Pharmacology, 44, 307 (1999); (d) S. E.
Weber, T. M. Bleckman, J. Attard, J. G. Deal, V. Kathardekar, and K. M. Welsh, J.
Med. Chem., 36, 733 (1993).
[3] (a) G. J. Wang, J. Shan, P. K. Pang, M. C. Yang, C. J. Chou, and C. F. Chen, J.
Pharmacol. Exp. Ther., 276, 1016 (1996); (b) J. R. Sheu, W. C. Hung, Y. M. Lee, and
M. H. Yen, Eur. J. Pharmacol., 318, 469 (1996); (c) H. Matsuda, J. X. Wu, M. Linuma,
and M. Kobo, Biol. Pharm. Bull., 20, 243 (1997); (d) S. B. Mhaske and N. P. Argade,
Tetrahedron, 62, 9787 (2006).
[4] H. Amin, D. R. Mehta and S. S. Samarth, Arzneim. Forsch., 14, 218 (1970).
[5] W. Nawrocka and J. J. Stas´ko, Bull. Chim. Farm., 137, 35 (1998).
[6] W. Nawrocka and J. J. Stas´ko, Bull. Chim. Farm., 140, 195 (2001).
[7] W. Nawrocka and J. J. Stas´ko, Bull. Chim. Farm., 141, 84, (2002).
[8] W. Nawrocka and J. J. Stas´ko, Farm. Pol., 60, 603 (2004).
[9] W. Nawrocka and B. Sztuba, Polish J. Chem., 70, 197 (1996).
[10] W. Nawrocka and J. J. Stas´ko, Polish J. Chem., 71, 792 (1997).
[11] W. Nawrocka and M. Zimecki, Arch. Pharm. Pharm. Med. Chem., 330, 339 (1997).
[12] (a) A. Yesilada, E. Zorlu, F. Aksu, and E. Yesilada, Farmaco, 51, 595 (1996); (b) M.
Sugiura, Y. Naito, Y. Yamaura, C. Fukaya, and K. Yokoyama, Chem. Pharm. Bull.,
37, 1039 (1989); (c) S. Iwakami, M. Shibuya, C. Tseng, F. Hanaoka, and U. Sankawa,
Chem. Pharm. Bull., 34, 3960 (1986).
[13] E. M. Schneidewind, A. Buge, H. Kala, J. Metzner, and A. Zschunke, Pharmazie, 34,
103 (1979).
[14] (a) A. Varnavas, C. Nisi, L. Lassiani, G. Sava, L. Perissin, and E. Boccu, Arzneim.
Forsch. Drug. Res., 41, 1168 (1991); (b) L. Liu, W. R. Hudgins, S. Shack, M. Q. Yin,
and D. Samid, Int. J. Cancer, 62, 345 (1995).
[15] G. Blazso, M. Hilbert, P. Hegyes, A. Megyeri, and M. Gabor, Pharmazie, 53, 425
(1998).
[16] W. Nawrocka, H. Liszkiewicz, A. Nawojski, M. Wilimowski, L. KÍdzierska-Goüdzik,
J. BarczyÒska, W. Wojewo´dzki, E. Duú, A. Szelg, and M. Rutkowska, Pol. J. Phar-
macol. Pharm., 43, 495 (1991).

Synthesis of New 4(3H)-Quinazolinone Derivatives
1387
[17] W. Nawrocka, B. Sztuba, A. Opolski, J. Wietrzyk, M. W. Kowalska, and T. Glꢀowiak,
Arch. Pharm. Pharm. Med. Chem., 334, 11 (2001).
[18] W. Nawrocka, B. Sztuba, and M. Zimecki, Arch. Pharm. Pharm. Med. Chem., 334,
3 (2001).
[19] H. Liszkiewicz, M. W. Kowalska, W. Nawrocka, A. Wo´jcicka, J. Wietrzyk, A. Na-
sulewicz, M. Pelꢀczyn´ska, and A. Opolski, Phosphorus, Sulfur, and Silicon, 178,
2725 (2003).