Synthesis and biological evaluation of some new 3,4-dihydropyrimidin-4-ones

Article abstract of DOI:10.1016/S0014-827X(01)01118-1

Condensation of 5-cyano-2-hydrazino-3-N-methyl-6-phenyl/p-chlorophenyl-3,4-dihydropyrimidin-4 -one (3a and 3b) with 2,4-bisalkyl/arylamino-6-chloro-s-triazine (4) gave the corresponding 2,4-bisalkyl/arylamino-6-[5′-cyano-3′-N-methyl]-6′-phenyl/p -chlorophenyl-3′,4′-dihydropyrimidin-4′-one-2′-yl-hyd razino-s-triazines (5a-n and 6a-n). The compounds 4 have been prepared by the condensation of cyanuric chloride and different alkyl/aryl amines. The reaction between 5-cyano-3-N-methyl-2-methylthio-6-phenyl/p-chlorophenyl-3,4-dihydropyrimidin- 4-one (2a and 2b) with hydrazine hydrate furnished 3a and 3b, respectively. The condensation of 6-phenyl/p-chlorophenyl/5-cyano-2-mercapto-3,4-dihydropyrimidin-4-one (1a and 1b) with methyl iodide yielded 2a and 2b, respectively. All the products have been evaluated in vitro for their antimicrobial activity against several microbes and antitubercular activity against Mycobacterium tuberculosis H37 Rv. Copyright

Full text of DOI:10.1016/S0014-827X(01)01118-1

www.elsevier.com/locate/farmac
Il Farmaco 56 (2001) 641–646
Synthesis and biological evaluation of some new
3,4-dihydropyrimidin-4-ones
Jayesh Modha, Neela Datta, Hansa Parekh *
Department of Chemistry, Saurashtra Uni6ersity, Rajkot 360 005, Gujarat, India
Received 11 September 2000; accepted 13 March 2001
Abstract
Condensation of 5-cyano-2-hydrazino-3-N-methyl-6-phenyl/p-chlorophenyl-3,4-dihydropyrimidin-4-one (3a and 3b) with 2,4-
bisalkyl/arylamino-6-chloro-s-triazine (4) gave the corresponding 2,4-bisalkyl/arylamino-6-[5%-cyano-3%-N-methyl]-6%-phenyl/p-
chlorophenyl-3%,4%-dihydropyrimidin-4%-one-2%-yl-hydrazino-s-triazines (5a–n and 6a–n). The compounds 4 have been prepared by
the condensation of cyanuric chloride and different alkyl/aryl amines. The reaction between 5-cyano-3-N-methyl-2-methylthio-6-
phenyl/p-chlorophenyl-3,4-dihydropyrimidin-4-one (2a and 2b) with hydrazine hydrate furnished 3a and 3b, respectively. The
condensation of 6-phenyl/p-chlorophenyl/5-cyano-2-mercapto-3,4-dihydropyrimidin-4-one (1a and 1b) with methyl iodide yielded
2a and 2b, respectively. All the products have been evaluated in vitro for their antimicrobial activity against several microbes and
antitubercular activity against Mycobacterium tuberculosis H37 R6. © 2001 Elsevier Science S.A. All rights reserved.
Keywords: Dihydropyrimidine; s-Triazine; Antitubercular activity; Antimicrobial activity
1. Introduction
resistance. On the basis of the above considerations and
in order to contribute to the definition of antimicrobial
properties of compounds and structurally related
analogs, some new 3,4-dihydro pyrimidine derivatives
have been investigated.
The target compounds 5a–n and 6a–n have been
synthesized by the condensation of 5-cyano-2-hydra-
zino-3-N-methyl-6-phenyl/p-chlorophenyl-3,4-dihydro-
pyrimidin-4-one (3) and 2,4-bisalkyl/arylamino-6-
chloro-s-triazine (4) (Scheme 1). The condensation of
cyanuric chloride and different alkyl/arylamines gave 4.
The reaction between 2 and hydrazine hydrate fur-
nished 3.
The 3,4 dihydropyrimidine derivatives have been in-
vestigated for their medicinal interest related to the
traditional antithyroid activity of the 5-fluoro-2-thiou-
racil [1]. The 3,4-dihydropyrimidine derivatives ethiri-
mol and methirimol were some of the earliest
fungicides. Furthermore dihydropyrimidine derivatives
also show the different pharmacological activities like
antitumor [2], analgesic [3], antineoplastic [4], cardio-
vascular [5], antiallergic [6], etc. Substituted s-triazines
have become attractive targets in organic synthesis be-
cause of their reactivity and significance in biological
activities such as antitumor [7], antiviral [8], fungicidal
[9], antimalarial [10], CNS depressant [11], herbicidal
[12], etc.
The constitution of these products have been sup-
1
ported by elemental analyses, IR, H NMR and mass
spectral studies. All the products have been screened for
their in vitro antimicrobial activity against different
strain of bacteria and fungi, and antitubercular activity
against Mycobacterium tuberculosis H37 R6. The com-
pounds demonstrating at least \90% inhibition in the
primary screen have been retested at lower concentra-
tion to determine the actual minimum inhibition con-
centration (MIC) in the BACTEC 460.
Although several potent antibiotics usable in the
therapy are available, research on new substances pos-
sessing an antimicrobial activity is still of considerable
interest owing to the continuous increase in bacterial
* Corresponding author.
E-mail address: hhparekh@yahoo.com (H. Parekh).
0014-827X/01/$ - see front matter © 2001 Elsevier Science S.A. All rights reserved.
PII: S0014-827X(01)01118-1

642
J.J. Modha et al. / Il Farmaco 56 (2001) 641–646
2. Results and discussion
Looking at the structure–activity relationship, it can
be concluded that the presence of halogen at 3 and/or 4
position, i.e. 5f–5h, 6d–6g in 1H aryl ring of the
arylamino substituted s-triazinyl group showed maxi-
mum activity towards B. megaterium and S. typhosa.
Presence of halogen (Cl) at 3, 4 or 5 position in the aryl
ring, i.e. 5f–5h, 6f and also methoxy at 4 position in 5l,
6l has been found to enhance the antibacterial activity
Tables 2 and 3, respectively, describe the in vitro
antimicrobial activity against strains of S. albus, B.
mega, S. typhosa, E. coli, A. niger and antitubercular
activity against Mycobacterium tuberculosis H37 R6
with MIC data of the synthesized compounds 5a–n and
6a–n.
Scheme 1.

J.J. Modha et al. / Il Farmaco 56 (2001) 641–646
643
towards E. coli. The diethyl chain in the triazinyl
nucleus 5a showed the highest activity towards B.
megaterium and S. typhosa but diminished in the pres-
ence of chlorine when present with the pyrimidine
structure 6a.
A perusal of the data in Table 2 indicates that
compounds having halogen at 3 and/or 4 position (5d,
5f, 6e, 6f) showed maximum antitubercular activity up
to 92% inhibition. MIC data of these compounds
showed 5i to be highly potent with a MIC value of 6.25
mg. The rest of the compounds displayed their activity
in the range of 12.5 mg. However, none of the com-
pounds could match the activity of the rifampicin.
added dropwise at 0 °C and followed by increasing
temperature but keeping the pH of the solution just
about 7 by occasional addition of saturated solution of
sodium bicarbonate. After completion of the addition,
the reaction mixture was stirred at room temperature
(r.t.) for 4 h maintaining the pH at 7. The content was
then poured onto ice, filtered and crystallized from
ethanol. Yield 70%.
Other
2,4-bisalkyl/arylamino-6-chloro-s-triazines
were prepared similarly.
3.4. Synthesis of 2,4-bisethylamino-6-(5%-cyano-3%-N-
methyl-6%-phenyl-3%,4%-dihydropyrimidin-4%-one-2%-yl-
hydrazino)-s-triazine: (5a–n)
3. Chemical experimental section
A mixture of 5-cyano-2-hydrazino-3-N-methyl-6-
phenyl-3,4-dihydropyrimidin-4-one (2.41 g, 0.01 mol)
and 2,4-bisethylamino-6-chloro-s-triazine (2.01 g, 0.01
mol) in dioxane (25 ml) was refluxed for 3 h during
which solution of sodium bicarbonate (0.84 g, 0.01 mol)
was added in fractions. The content was then poured
onto crushed ice, product isolated was crystallized from
absolute alcohol. Yield 63%, m.p. 225 °C.
Melting points were determined in open capillaries
and are uncorrected, purity of the compounds was
checked by TLC. IR (KBr) spectra were recorded on a
Nicolet-Magna-IR 550 Series-II spectrophotometer and
1H-NMR spectra were recorded on a BRUKER spec-
trometer 300 MHz using TMS as an internal standard.
Anal. Calc. for C19H22N10O: C, 56.15; H, 5.41; N,
3.1. Synthesis of 5-cyano-3-N-methyl-2-methylthio-6-
phenyl-3,4-dihydropyrimidin-4-one: 2a and 2b
34.48. Found: C, 56.11; H, 5.38; N, 34.32%. IR (cm−1
,
KBr): wmax(NꢀH str.) 3262, wmax(CꢀH str.) 2975, 2930,
wmax(CꢁN str.) 2191, wmax(CꢂO str.) 1635, wmax(CꢂN+
1
To a solution of 5-cyano-2-mercapto-6-phenyl-3,4-di-
hydropyrimidin-4-one (2.63 g, 0.01 mol) in DMF (20
ml), potassium carbonate (2.76 g, 0.02 mol) and methyl
iodide (2.84 g, 0.02 mol) were added and the mixture
was stirred for 3 h. The contents were poured into
water and crystallized from DMF. Yield 60%, m.p.
174 °C.
CꢂC str.) 1564, wmax(NꢀC str.) 1111. H NMR (TFA, l
ppm): 1.17 (t, 6H, 2×CH2ꢀCH3), 3.16 (q, 4H, 2×
CH2ꢀCH3), 3.37 (s, 3H, NꢀCH3), 7.42–7.46 (m, 3H,
Ar-H), 7.85–7.87 (d, 2H, Ar-H).
Other s-triazine derivatives have been prepared simi-
larly. The physical constants are recorded in Table 1.
6-p-Chlorophenyl-5-cyano-3-N-methyl-2-methylthio-
3,4-dihydropyrimidin-4-one (2b) was prepared similarly.
Yield 73%, m.p. 211 °C.
3.5. Synthesis of 2,4-bis (4¦-chlorophenylamino)-6-
(6%-p-chlorophenyl-5%-cyano-3%-N-methyl-3%,4%-dihydro-
pyrimidin-4%-one-2%-yl-hydrazino)-s-triazine: (6a–n)
3.2. Synthesis of 5-cyano-2-hydrazino-3-N-methyl-6-
phenyl-3,4-dihydropyrimidin-4-one: 3a and 3b
A mixture of 5-cyano-2-hydrazino-3-N-methyl-6-p-
chlorophenyl-3,4-dihydropyrimidin-4-one (2.41 g, 0.01
mol) and 2,4-bischlorophenylamino-6-chloro-s-triazine
(2.66 g, 0.01 mol) in dioxane (25 ml) was refluxed for 3
h during which solution of sodium bicarbonate (0.84 g,
0.01 mol) was added in fractions. The content was then
poured onto crushed ice, product isolated was crystal-
lized from absolute alcohol. Yield 42%, m.p. 260 °C.
Anal. Calc. for C27H19N10OCl3: C, 53.50; H, 3.13; N,
A mixture of 5-cyano-3-N-methyl-2-methylthio-6-
phenyl-3,4-dihydropyrimidin-4-one (2.57 g, 0.01 mol)
and hydrazine hydrate (2.5 g, 0.05 mol) in absolute
alcohol was refluxed for 12 h in an oil bath and poured
onto crushed ice, filtered and crystallized from absolute
alcohol. Yield 65%, m.p. 275 °C.
6-p-Chlorophenyl-5-cyano-2-hydrazino-3-N-methyl-
3,4-dihydropyrimidin-4-one (3b) was prepared similarly.
Yield 55%, m.p. 230 °C.
23.12. Found: C, 53.44; H, 3.09; N, 22.92%. IR (cm−1
,
KBr): wmax(NꢀH str.) 3391, wmax(CꢀH str.) 2950,
wmax(CꢁN str.) 2222, wmax(CꢂO str.) 1664, wmax(CꢂN+
CꢂC str.) 1544, wmax(NꢀC str.) 1101, wmax(CꢀCl str.) 764.
1H NMR (TFA, l ppm): 3.88 (s, 3H, NꢀCH3), 6.89–
7.36 (m, 12H, Ar-H), 8.30 (s, 2H, 2×NꢀH), 9.37 (s,
1H, NꢀH), 9.83 (s, 1H, NꢀH).
3.3. Synthesis of 2,4-bisethylamino-6-chloro-s-triazine
(4)
To a solution of cyanuric chloride (3.65 g, 0.02 mol)
in acetone (20 ml), ethylamine (2.56 ml, 0.04 mol) was
Other s-triazine derivatives have been prepared simi-
larly. The physical constants are recorded in Table 1.

644
J.J. Modha et al. / Il Farmaco 56 (2001) 641–646
Table 1
Physical constants of the compounds 5a–n and 6a–n
Comp.
R
Yield (%) Melting point (°C) Molecular formula Analysis
N (%)
Calc.
C (%)
H (%)
Found Calc.
Found Calc. Found
5a
5b
5c
5d
5e
5f
5g
5h
5i
C2H5ꢀ
63
51
47
63
59
48
46
47
225
277
170
\300
290
80
125
160
130
240
85
C
19H22N10
O
O
34.48 34.32
56.15 56.11
65.66 65.62
58.82 58.78
56.74 56.79
56.74 56.69
53.37 53.32
50.62 50.57
50.62 50.57
66.66 66.62
61.92 61.87
61.92 61.86
61.92 61.88
54.72 54.67
48.72 48.66
51.75 51.70
61.64 61.58
55.09 55.04
53.50 53.44
53.50 53.46
50.50 50.45
48.03 48.00
48.03 47.98
62.78 62.73
58.53 58.48
58.53 58.49
58.53 58.47
51.71 51.66
51.06 51.01
5.41
4.90
4.31
3.50
3.50
2.96
2.81
2.81
5.37
4.62
4.62
4.62
3.37
2.58
4.76
4.42
3.85
3.13
3.13
2.65
2.52
2.52
4.89
3.86
3.86
3.86
3.03
3.14
5.38
4.87
4.26
3.44
3.45
2.92
2.76
2.75
5.32
4.57
4.56
4.58
3.32
2.51
4.71
4.37
3.80
3.09
3.08
2.60
2.46
2.47
4.83
3.82
3.81
3.80
3.00
3.09
C6H5ꢀCH2ꢀ
C4H3OꢀCH2ꢀ
3-ClꢀC6H4ꢀ
4-ClꢀC6H4ꢀ
3-Cl-4-FꢀC6H3ꢀ
2,4-Cl2ꢀC6H4ꢀ
3,5-Cl2ꢀC6H3ꢀ
C29H26N10
C25H22N10O3
26.41 26.33
27.45 27.33
24.51 24.40
24.51 24.38
23.06 22.92
21.87 21.69
21.87 21.69
25.08 24.91
24.91 24.82
24.91 24.82
24.91 24.82
28.37 28.30
38.73 38.61
31.78 31.66
24.80 24.67
25.71 25.60
23.12 22.92
23.12 22.98
21.82 21.72
20.75 20.64
20.75 20.67
23.62 23.55
23.47 23.33
23.47 23.42
23.47 23.38
26.81 26.67
36.29 36.21
C27H20N10OCl2
C27H20N10OCl2
C27H18N10OCl2F2
C27H18N10OCl4
C27H18N10OCl4
2,4-(CH3)2ꢀC6H3ꢀ 42
C31H30N10O
5j
5k
5l
2-OCH3ꢀC6H4ꢀ
3-OCH3ꢀC6H4ꢀ
4-OCH3ꢀC6H4ꢀ
3-NO2ꢀC6H4ꢀ
2-C5H4Nꢀ
51
48
54
50
48
65
48
49
48
42
49
51
53
C29H26N10O3
C29H26N10O3
C29H26N10O3
C27H20N12O5
180
80
5m
5n
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
\300
207
192
160
280
260
227
164
126
160
135
185
\300
120
270
C28H18N14O
C2H5ꢀ
C19H21N10OCl
C29H25N10OCl
C25H21N10O3Cl
C27H19N10OCl3
C6H5ꢀCH2ꢀ
C4H3OꢀCH2ꢀ
3-ClꢀC6H4ꢀ
4-ClꢀC6H4ꢀ
C27H19N10OCl3
3-Cl-4-FꢀC6H3ꢀ
2,4-Cl2ꢀC6H4
3,5-Cl2ꢀC6H3ꢀ
C27H17N10OCl3F2
C27H17N10OCl5
C27H17N10OCl5
2,4-(CH3)2ꢀC6H3ꢀ 47
C31H29N10OCl
2-OCH3ꢀC6H4ꢀ
3-OCH3ꢀC6H4ꢀ
4-OCH3ꢀC6H4ꢀ
3-NO2ꢀC6H4ꢀ
2-C5H4Nꢀ
53
41
45
52
50
C29H23N10O3Cl
C29H23N10O3Cl
C29H23N10O3Cl
C27H19N12O5Cl
6m
6n
C
23H17N14OCl
4. Biological experimental section
were incubated at 37 °C for 24 h and the resultant
zones of inhibition of bacterial growth were measured
in mm and are recorded in Table 2.
4.1. Antimicrobial acti6ity
Antimicrobial activity experiments were carried out
by the cup–plate method [13] towards different strains
of bacteria and fungi which are described below.
4.1.2. Antifungal acti6ity
A. niger was employed for testing antifungal activity
using the cup–plate method. The culture was main-
tained on Sabouraud’s agar slants. Fifteen milliliters of
sterilized Sabouraud’s agar medium was spread in a
Petri dish (13 cm in diameter) and allowed to set for 30
min. Five milliliters of sterilized Sabouraud’s agar
medium was inoculated with 72 h old 0.2 ml suspension
of fungal spores in a test-tube and spread over the
previously settled layer of Sabouraud’s agar medium in
the Petri dish. The cups (8 mm in diameter) were
punched in the Petri dish and filled with 0.05 ml (40 mg)
of a solution of the sample in DMF. The plates were
incubated at 30 °C for 48 h. After the completion of
the incubation period, the zones of inhibition of growth
in millimeter were measured. Along with the test solu-
tions in each Petri dish one cup was filled up with
solvent, which acts as the control. The zones of inhibi-
tion are recorded in Table 2.
4.1.1. Antibacterial acti6ity
The purified products were screened for their an-
tibacterial activity towards strains of S. albus, B. mega-
terium, S. typhosa and E. coli. The nutrient agar broth
was prepared by the usual method. Fifteen milliliters of
N-agar were spread in a Petri dish (13 cm in diameter)
and allowed to set for 30 min. About 5 ml of N-agar
was inoculated aseptically in a test-tube with 0.2 ml of
24 h old bacterial subculture at 40–50 °C, mixed well
by gentle shaking and spread over the previously settled
layer of N-agar in the Petri dish. The cups (8 mm in
diameter) were formed with the help of borer and filled
with 0.05 ml (40 mg) solution of sample in DMF. Along
with the test solutions in each Petri dish one cup was
filled with solvent which acts as the control. The plates

J.J. Modha et al. / Il Farmaco 56 (2001) 641–646
645
Table 2
Biological activities of the compounds 5a–n and 6a–n
Comp.
R
Antimicrobial activity (zone of inhibition in
mm)
Antifungal activity
(zone of inhibition in mm)
Antitubercular activity
(% of inhibition)
S. albus
B. mega
S. typhosa
E. coli
A. niger
Mycobacterium tuberculosis
H37 R6
5a
5b
5c
5d
5e
5f
5g
5h
5i
C2H5ꢀ
C6H5ꢀCH2ꢀ
C4H3OꢀCH2ꢀ
3-ClꢀC6H4ꢀ
4-ClꢀC6H4ꢀ
4-Cl-4-FꢀC6H3ꢀ
2,4-(Cl)2ꢀC6H3ꢀ
3,5-(Cl)2ꢀC6H3ꢀ
2,4-(CH3)2ꢀC6H3ꢀ
2-OCH3ꢀC6H4ꢀ
3-OCH3ꢀC6H4ꢀ
4-OCH3ꢀC6H4ꢀ
3-NO2ꢀC6H4ꢀ
2-C5H4Nꢀ
C2H5ꢀ
C6H5ꢀCH2ꢀ
C4H3OꢀCH2ꢀ
3-ClꢀC6H4ꢀ
4-ClꢀC6H4ꢀ
3-Cl-4-FꢀC6H3ꢀ
2,4-Cl2ꢀC6H3ꢀ
3,5-Cl2ꢀC6H3ꢀ
2,4-(CH3)2ꢀC6H3ꢀ
2-OCH3ꢀC6H4ꢀ
3-OCH3ꢀC6H4ꢀ
4-OCH3ꢀC6H4ꢀ
3-NO2ꢀC6H4ꢀ
2-C5H4Nꢀ
11
11
12
10
14
13
12
12
11
12
11
11
10
12
14
13
11
12
13
14
10
11
17
12
12
10
10
12
23
20
14
14
12
14
17
17
19
12
11
12
12
11
13
14
10
10
15
15
18
18
10
11
12
12
11
12
12
17
18
12
15
16
14
14
15
15
13
12
11
12
13
14
12
10
11
11
13
14
11
15
15
11
12
10
11
20
12
12
18
20
18
18
14
16
12
20
15
12
14
14
13
15
17
18
15
14
17
14
14
18
18
11
20
17
08
25
10
10
18
14
14
20
27
20
20
20
20
10
13
22
10
13
21
25
22
13
10
09
15
46
82
47
92
98
14
98
95
63
92
71
58
5j
5k
5l
5m
5n
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
69
84
17
94
98
66
56
12
21
52
98
6m
6n
Benzylpenicillin
Chloramphenicol
Griseofulvin
19
19
20
Rifampicin
98
Table 3
MIC of the compounds which demonstrated \90% inhibition in primary screen against M. tuberculosis H37 R6
Comp. MIC versus
H37 Rv
IC 50 VERO
cely (mg/ml)
SI (IC50/MIC)
Comment
(mg/ml)
5d
5f
12.5
12.5
27
2
MIC RMP=0.25 mg/ml IC50 (INH [ 1000; RMP=61; DMSO=1.08%)
MIC RMP=0.25 mg/ml insoluble, fell out in tissue culture medium at 5
mg/ml unable to test IC50
MIC RMP=0.25 mg/ml IC50 (INH [ 1000; RMP=80; DMSO=1.30%)
MIC RMP=0.25 mg/ml IC50 (INH [ 1000; RMP=80; DMSO=1.30%)
MIC RMP=0.25 mg/ml IC50 (INH [ 1000; RMP=61; DMSO=1.08%)
MIC RMP=0.25 mg/ml insoluble, in DMSI 5 mg/ml unable to test IC50
MIC RMP=0.25 mg/ml IC50 (INH [ 1000; RMP=80; DMSO=1.30%)
MIC RMP=0.25 mg/ml IC50 (INH [ 1000; RMP=80; DMSO=1.30%)
5h
5i
5k
6e
6f
\12.5
13
8
32
B1
1.3
B2.6
6.25
\12.5
12.5
\12.5
\12.5
41
9
B3
B0.7
6m
4.2. Antitubercular acti6ity
mary screening of the compounds for antitubercular
activity have been conducted at 12.5 mg/ml towards
Mycobacterium tuberculosis H37 R6 in BACTEC 12B
medium using the BACTEC 460 radiometric system.
The compounds demonstrating at least \90% inhibi-
The antitubercular evaluation of the compounds was
carried out at the Tuberculosis Antimicrobial Acquisi-
tion and Coordinating Facility (TAACF), USA. Pri-

646
J.J. Modha et al. / Il Farmaco 56 (2001) 641–646
5,6-dihydro-6-oxo-5-pyrimidin-carboxylic acid, Chem. Pharm.
Bull. 37 (1989) 1780–1787.
tion (Table 3) in the primary screen have been retested
at lower concentration towards Mycobacterium tuber-
culosis H37 R6 to determine the actual minimum in-
hibitory concentration (MIC) in the BACTEC 460.
[7] B.A. Ivin, V.A.F. Belogorodskii, V.A. Filov, Dependence of the
antitumor activity and toxicity of some alkylating agents on
structure and physicochemical properties, Tselenapravlennyi
Poisk Nov Protivorak Protivovirusn Prep. (1978) 209–216
(Chem. Abstr. 92 (1980) 157545d).
[8] E.M. Sanders, Diamino (aminoxy)-s-triazines, US Patent US
4,576,945 (Cl 514-245, C 07 D 251/52), 18 March 1986, US
Appl. 436,682, 26 October 1982; 5 pp. cont-in-part of US Ser.
No. 436,682.
[9] N.C. Misra, Studies on the derivatives of 1,3,5-s-triazine: synthe-
sis of some substituted salicylamides for possible use as fungi-
cides, J. Inst. Chem. 51 (1979) 149–150.
[10] W.M. Leslie, E.F. Edward, H. Carolyn, H.P. Marland, Anti-
malarial activity of 2-(substituted amino)-4,6-bis(trichloro-
methyl)-1,3,5-triazines and N-(chlorophenyl)-N%-[4-(substituted
methyl)-1,3,5-triazine-2-yl-guanidines], J. Med. Chem. 30 (1987)
1943–1948.
[11] K. Alfred, S. Irmtraut, Central nervous system depressant. VII:
(Diallylamino)-1,3,5-triazine substituted at the triazine nucleus,
Arch. Pharm. (Weighheim, Germany) 321 (1988) 827–830 (in
German).
[12] R.H. Jochem, (Bayer AG), Preparation of 2-cyanamino-4,6-di-
alkoxy-1,3,5-triazine as intermediate for herbicides and plant
growth regulators, Ger. Offen. DE 3,515,287 (Cl C 07 D 251/46),
6 November 1986, Appl. 27 April 1985, 17 pp.
[13] A.L. Barry, The Antimicrobial Susceptibility Tests: Principle and
Practices, Illus. Lea and Febiger, Philadelphia, PA, 1976, p. 108
(Biol. Abstr. 64 (1977) 25183).
References
[1] E.B. Eastwood, A. Bissel, A.M. Hughes, 5-Cyano-6-aryluracil
and 2-thiouracil derivatives as potential chemotherapeutic
agents, Encriology 38 (1946) 308–314 (in German).
[2] A. Kreutzberger, H. Schimmelpfenning, Tumour inhibitory
agents. Part-12: 2-Ureido-4-(3H)-pyrimidinones, Arch. Pharm.
314 (1981) 34–41 (in German).
[3] T. Veda, J. Sakkakibara, J. Nakagami, Synthesis of 5-amino-
4(3H)-pyrimidinones for their analgesic and antiinflammatory
activity, Chem. Pharm. Bull. 31 (1984) 4263–4269.
[4] R. Kotwa, J. Krepelka, M. Melka, Preparation of 5(2-NH2,
4=0, 6-me, 3,4-dihydro-5-pyrimidinyl) pentamides as neoplasm
inhibitors. Czech CS 254, 620 (Cl C 07 D 239/47) 15 September
1988, Appl. 86/3, 907, 28 Mar. 1986, 3pp.
[5] K. Atwal, Preparation of 2-amino dihydropyrimidin-5-carboxy-
lates as cardiovascular agents. US Patent US 4,769,371 (Cl
514-275, C 07 D 239/42) 6 September 1988, Appl. 45956 01
March 1987, 14pp.
[6] K. Ozeki, T. Ichikawa, T. Hiroyuki, K. Tanimury, M. Sato, H.
Yaginuna, Studies on antiallergic agents: synthesis of 2-anilino-
.