Synthetic utility of enaminonitrile moiety in heterocyclic synthesis: Synthesis of some new thienopyrimidines

Article abstract of DOI:10.1080/10426500802266407

The hitherto unknown 3-amino-5-bromo-4, 6-dimethylthieno [2, 3-b] pyridine-2-carbonitrile (4) was condensed with p-anisaldehyde affording the Schiff base (5). Acylation of the thienopyridine derivative (4) using freshly distilled acetic anhydride gave a m

Full text of DOI:10.1080/10426500802266407

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Phosphorus, Sulfur, and Silicon
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Synthetic Utility of
Enaminonitrile Moiety in
Heterocyclic Synthesis:
Synthesis of Some New
Thienopyrimidines
H. M. F. Madkour a , A. A. E. Afify a , A. A. Abdalha a
, G. A. Elsayed a & M. S. Salem a
a Synthetic Organic Chemistry Laboratory, Chemistry
Department, Faculty of Science , Ain Shams
University , Abbasiya, Cairo, Egypt
Published online: 18 Feb 2009.
To cite this article: H. M. F. Madkour , A. A. E. Afify , A. A. Abdalha , G. A. Elsayed
& M. S. Salem (2009) Synthetic Utility of Enaminonitrile Moiety in Heterocyclic
Synthesis: Synthesis of Some New Thienopyrimidines, Phosphorus, Sulfur, and Silicon
and the Related Elements, 184:3, 719-732, DOI: 10.1080/10426500802266407
To link to this article: http://dx.doi.org/10.1080/10426500802266407
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Phosphorus, Sulfur, and Silicon, 184:719–732, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802266407
Synthetic Utility of Enaminonitrile Moiety in Heterocyclic
Synthesis: Synthesis of Some New Thienopyrimidines
H. M. F. Madkour, A. A. E. Afify, A. A. Abdalha,
G. A. Elsayed, and M. S. Salem
Synthetic Organic Chemistry Laboratory, Chemistry Department,
Faculty of Science, Ain Shams University, Abbasiya, Cairo, Egypt
The hitherto unknown 3-amino-5-bromo-4, 6-dimethylthieno [2, 3-b] pyridine-2-
carbonitrile (4) was condensed with p-anisaldehyde affording the Schiff base (5).
Acylation of the thienopyridine derivative (4) using freshly distilled acetic anhy-
dride gave a mixture of mono and diacetyl derivatives (6) and (7). Condensation
of (4) with triethylorthoformate yielded the ethoxymethyleneamino derivative (8),
which was treated with hydrazine hydrate to give the hydrazide derivative (9),
which in turn was converted to a triazolopyrimidine derivative (10) upon treat-
ment with freshly distilled acetic anhydride. Thiation of (4) with carbon disulfide
afforded the pyrimidine dithione derivative (11), which was alkylated with ethyl io-
dide to give the di-s-ethylpyrimidine derivative (12).On the other hand, treatment of
(4) with formamide yielded the aminopyrimidine derivative (13), whereas its treat-
ment by formic acid produced the thienopyrimidinone derivative (14). Chlorination
of (14) with a mixture of phosphorus pentachloride and phosphorus oxychloride
gave the chloropyrimidine derivative (15), which in turn afforded the hydrazide
derivative (9) upon treatment with hydrazine hydrate. Hydrazinolysis of ethyl-
3-amino-5-bromo-4,6-dimethylthieno[2,3-b]pyridine-2-carboxylate (17) gave the
hydrazino derivative (18), which in turn was converted to 8-bromo-7,9-dimethyl-3-
formylaminopyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidin-4(3H)-one (19) and 8-bromo-
3-diacetylamino-2,7,9-trimethylpyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidin-4(3H)-one
(20) upon treatment with formic acid and freshly distilled acetic anhydride,
respectively.
Keywords Antimicrobial activity; enaminonitrile; thienopyridine; thienopyrimidine
INTRODUCTION
In continuation of our present program in the utility of enam-
inonitrile and enaminoester moieties in the synthesis of different
Received 25 February 2008; accepted 11 June 2008.
Address correspondence to M. S. Salem, Synthetic Organic Chemistry Laboratory,
Chemistry Department, Faculty of Science, Ain Shams University, Abbasiya, Cairo
11566, Egypt. E-mail: s s marwa@yahoo.com
719

720
H. M. F. Madkour et al.
heterocyclic systems,1–4 and due to the pronounced biological and
pharmacological activities of thienopyrimidine derivatives,5–7 such
as anticancer,8 antiviral,9 antitumor,10 anti-inflammatory,11 antimic-
robial,12 antifungal,13 antihistaminic,14 analgesic,15 antibiotic,16,17
antidepressant,18,19 antihypertensive,19,20 antiulcer,21 bactericidal,22,23
blood platelet aggregation inhibitory,24–26 fungicidal,27–29 herbicidal,30
hypersensitivity inhibitory,31 insecticidal,30,32 immunomodulatory, and
oncostatic.33 The therapeutic importance of thienopyrimidines
prompted us to construct several analogs by exotic combinations of
groups and active moieties. The present work aimed to synthesize some
new derivatives of this class of compounds utilizing 3-amino-5-bromo-4,
6-dimethylthieno[2, 3-b]pyridine-2-carbonitrile.
RESULTS AND DISCUSSION
The key starting material, 3-amino-5-bromo-4,6-dimethylthieno[2,3-
b]pyridine-2-carbonitrile (4), has been obtained in fair yield via the cy-
clization of 5-bromo-2-[(cyanomethyl)thio]-4,6-dimethylnicotinonitrile
(3) with sodium ethoxide in ethanolic solution.34 Pyridine deriva-
tive (3) was obtained by treatment the thione derivative (2) with
chloroacetonitrile.34 It was found that (2) was obtained upon thiation
of (1)by phosphorous pentasulfide (Scheme 1). 3-Cyano-4,6-dimethyl-2-
(1H)-pyridone was obtained according to Bardhan’s method.35 Bromi-
nation of the latter compound using N-bromo succinimide in carbon
tetrachloride containing a few drops of hydrogen peroxide (30%) af-
forded 5-bromo-4,6-dimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile
(1).
The structure of compound (1) was confirmed by its mp and mixed
mp and by comparison of these with the literature value,36 although it
was prepared by an alternative method (Br2/glacial AcOH).
The structure of (4) was established by elemental analysis as well as
spectral data (IR,1H-NMR, MS) and chemically via condensation with
p-anisaldehyde to give the corresponding Schiff base (5) (Scheme 2) .
The effect of acetic anhydride on enaminonitrile has been investi-
gated in many publications,37,38 and it has been found that the nature
of the product depends mainly upon the time of the reaction. In our
present work, acylation of the starting material (4) with acetic anhy-
dride afforded a mixture of both mono and diacetyl derivatives (6) and
(7), respectively (Scheme 2).
Alternatively, treatment of the thienopyridine derivative (4) with
triethyl orthoformate39 afforded 5-bromo-2-cyano-4, 6-dimethyl-3-
ethoxy-methyleneaminothieno[2,3-b]pyridine
(8),
which
upon

Synthesis of Some New Thienopyrimidines
721
SCHEME 1
hydrazinolysis40,41 gave 8-bromo-4-hydrazino-7,9-dimethylpyrido[3ꢀ,
2ꢀ:4,5]thieno[3,2-d]pyrimidine (9), whose structure was confirmed by
elemental analysis as well as spectral data. Furthermore, chemical
proof is achieved via acetylation with acetic anhydride to yield the
triazolopyrimidine derivative (10) in fair yield (Scheme 2).
Thiation of the thienopyridine derivative (4) using carbon
disulfide
yielded
8-bromo-7,9-dimethylpyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-
d]pyrimidine-2,4-(1H,3H)-dithione (11), which was alkylated by
ethyl iodide in dry acetone to afford 8-bromo-2,4-di(ethylthio)-7,9-
dimethylpyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidine (12) (Scheme 2).
Treatment of the thienopyridine derivative (4) with formamide7,42
gave the expected aminopyrimidine derivative (13) in quantita-
tive yield (Scheme 2). Furthermore, the reaction of (4) with
formic acid7,43 gave 8-bromo-7,9-dimethylpyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-
d]pyrimidin-4-(3H)-one (14), which underwent chlorination44 using a
mixture of phosphorus pentachloride and phosphorus oxychloride as a
chlorinating reagent to give the chloropyrimidine derivative (15). The
structure of (15) was elucidated via elemental analysis and also spec-
tral data, and chemically through the reaction with hydrazine hydrate
to afford 8-bromo-4-hydrazino-7,9-dimethylpyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-
d]pyrimidine (9) (Scheme 2).

722
H. M. F. Madkour et al.
SCHEME 2
On the other hand, alkylation of the thione derivative (2) using
ethyl chloroacetate34 afforded pyridine derivative (16), which in turn
was cyclized34 to give ethyl-3-amino-5-bromo-4,6-dimethylthieno[2,3-
b]pyridine-2-carboxylate (17) whose structure was confirmed by ele-
mental analysis as well as spectral data (Scheme 3).

Synthesis of Some New Thienopyrimidines
723
SCHEME 3
Furthermore, reaction of (17) with hydrazine hydrate45–47 yielded
3-amino-5-bromo-4,6-dimethylthieno[2,3-b]pyridine-2-carbohydrazide
(18), which in turn was subjected to react with formic acid and
freshly distilled acetic anhydride to give 8-bromo7,9-dimethyl-3-
formylaminopyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidin-4(3H)-one (19) and
8-bromo-3-diacetylamino-2,7,9-trimethylpyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]
pyrimidin-4-(3H)-one (20), respectively (Scheme 3).
EXPERIMENTAL (Tables I and II)
All melting points were measured on a Gallenkamp melting point ap-
paratus and are uncorrected. The infrared spectra were recorded using
potassium bromide disks on a Pye Unicam SP-3-300 infrared spec-
trophotometer. 1H-NMR experiments were run at 300 MHz on a Varian

724
H. M. F. Madkour et al.
TABLE I Characterization Data of Prepared Compounds
Analysis (Required/Found)
Compound
No.
MP ◦
(color)
C
Yield %
(solvent)
Mol. Formula
(M. wt)
C
H
N
(2)
279–280
(yellow)
146–148
(yellow)
258–260
(yellow)
190–192
(yellow)
274–276
(white)
130–132
(yellow)
118–120
(yellow)
260–262
(white)
238–240
(white)
302–305
(orange)
120–122
(white)
> 360
(white)
> 360
(white)
71
T
89
Pa
80
E
56
Pa
50
B
45
Pb
51
Pa
84
A
45
Pa
50
Py
60
Pa
46
D
C8H7BrN2S
(243.12)
39.52
39.20
42.57
42.43
42.57
42.36
54.01
53.89
44.46
44.19
45.91
45.59
46.16
45.89
40.75
40.47
44.84
44.57
36.87
36.55
43.47
43.15
42.73
42.46
42.60
42.28
40.20
39.96
43.78
43.50
43.78
43.50
38.11
37.89
40.81
40.49
45.40
45.16
2.90
2.62
2.86
2.61
2.86
2.54
3.53
3.30
3.11
2.92
3.30
2.99
3.58
3.27
3.11
2.87
2.89
2.62
2.25
1.97
3.89
3.57
2.93
2.65
2.60
2.27
2.15
1.98
3.98
3.70
3.98
3.72
3.52
3.25
2.57
2.30
3.57
3.28
11.52
11.21
14.89
14.58
14.89
14.60
10.50
10.28
12.96
12.65
11.47
11.25
12.42
12.13
21.60
21.25
20.11
19.99
11.73
11.45
10.14
9.89
18.12
17.87
13.55
13.28
12.79
12.50
8.51
8.22
8.51
8.26
(3)
C
10H8BrN3S
(282.16)
(4)
C
10H8BrN3S
(282.16)
(5)
C
C
18H14BrN3OS
(400.29)
12H10BrN3OS
(324.20)
14H12BrN3O2S
(366.23)
13H12BrN3OS
(338.22)
(6)
(7)
C
(8)
C
(9)
C
11H10BrN5S
(324.20)
(10)
(11)
(12)
(13)
(14)
(15)
(16)
(17)
(18)
(19)
(20)
C
13H10BrN5S
(348.22)
C
11H8BrN3S3
(358.30)
C15H16BrN3S3
(414.41)
C
11H9BrN4S
(309.18)
64
A
C
11H8BrN3OS
(310.17)
176–178
(white)
78–80
54
Pb
58
Pa
66
Pb
63
D
63
E
55
E
C
11H7BrClN3S
(328.62)
12H13BrN2O2S
(329.21)
12H13BrN2O2S
(329.21)
10H11BrN4OS
(315.18)
12H9BrN4O2S
(353.19)
16H15BrN4O3S
(423.28)
C
(yellow)
202–204
(yellow)
240–242
(yellow)
258–260
(pale yellow)
218–220
(white)
C
C
17.78
17.53
15.86
15.62
13.24
12.98
C
C
A: Acetic acid,B: Benzene, D: Dioxane, E: Ethanol, Pa: Petroleum ether (60–80◦C),
Pb: Petroleum ether (80–100◦C), Py: Pyridine

725

726

Synthesis of Some New Thienopyrimidines
727
Mercury VX-300 NMR spectrometer using TMS as internal standard
in deuterated chloroform or deuterated dimethylsulphoxide. Chemical
shifts are quoted δ. The mass spectra were recorded on a Shimadzu
GCMS-QP-1000EX mass spectrometers at 70 eV. Elemental analy-
ses were carried out at the Microanalytical Center of Cairo Univer-
sity. All the newly synthesized compounds gave satisfactory elemental
analyses.
5-Bromo-4,6-dimethyl-2-thioxo-1,
2-dihydropyridine-3-carbonitrile (2)
A mixture of (1) (10 mmol, 2.26 g) and phosphorus pentasulfide (5
mmol, 1.11 g) in dry toluene (25 mL) was heated at reflux for 4 h. The
solid product that was separated out while hot was collected, dried, and
recrystallized to give (2).
5-Bromo-2-[(cyanomethyl)thio]-4,6-dimethylnicotinonitrile (3)
A mixture of (2) (10 mmol, 2.42 g) and chloroacetonitrile (11 mmol,
0.75 mL) in ethanol (20 mL) in the presence of fused sodium acetate
(15 mmol, 1.23 g) was heated at reflux for 1.5 h and left to cool. The
solid product that formed was filtered and washed with water, dried,
and recrystallized to afford (3).
3-Amino-5-bromo-4,6-dimethylthieno[2, 3-b]
pyridine-2-carbonitrile (4)
To a hot solution of (3) in ethanol (20 mL), a few drops of sodium
ethoxide solution (prepared by dissolving 0.5 g sodium metal in 20 mL
ethanol) was added dropwise. The solution was heated at reflux for 15
min and allowed to cool. The solid that formed was collected, dried, and
recrystallized to give (4).
5-Bromo-3-{[(4-methoxyphenyl)methylene]amino}-4,
6-dimethylthieno[2,3-b]pyridine-2-carbonitrile (5)
To a hot solution of (4) (1.7 mmol, 0.5 g) in ethanol (20 mL) containing
a few drops of piperidine, p-anisaldehyde (1.7 mmol, 0.24 mL) was
added, and the reaction mixture was heated under reflux for 2 h. The
precipitated solid that separated on cooling was collected by filtration,
dried, and recrystallized to furnish (5).

728
H. M. F. Madkour et al.
N-(5-Bromo-2-cyano-4,6-dimethylthieno[2,3-b]pyridin-3-
yl)acetamide (6) and N-Acetyl-N-(5-bromo-2-cyano-4,
6-dimethylthieno[2,3-b]pyridin-3-yl)acetamide (7)
A mixture of (4) (1.7 mmol, 0.5 g) and freshly distilled acetic anhydride
(10 mL) was heated at reflux for 3 h. The solid that deposited after
distilling the excess solvent was collected and recrystallized to afford
(6) and (7).
N.B.: The diacetylamino derivative (7) was authentically prepared
by acetylating the monoacetylamino derivative (6) using freshly dis-
tilled acetic anhydride.
5-Bromo-2-cyano-4,6-dimethyl-3-
ethoxymethyleneaminothieno[2,3-b]pyridine(8)
A mixture of (4) (1.7 mmol, 0.5 g) and triethyl orthoformate (10 mL) was
heated at reflux for 2 h. An excess of triethyl orthoformate was removed
by distillation under reduced pressure. The solid obtained was filtered,
dried, and recrystallized to afford (8).
8-Bromo-4-hydrazino-7,9-dimethylpyrido[3’,2’:4,5]
thieno[3,2-d]pyrimidine (9)
Method A
To a hot solution of (8) (1.48 mmol, 0.5 g) in ethanol (20 mL), hy-
drazine hydrate (0.5 mL) was added, and the reaction mixture was
heated at reflux for 2 h. The solid product that was separated out while
hot was collected, dried, and recrystallized to afford (9).
Method B
To a hot solution of (15) (1.5 mmol, 0.5 g) in ethanol (20 mL), hy-
drazine hydrate (0.5 mL) was added dropwise while the solution was
heated at reflux for 2 h. The solid product that separated out while hot
was collected, washed with ethanol, dried, and recrystallized to afford
(9).
4-Bromo-3,5,9-trimethylpyrido[3’,2’:4,5]thieno[3,2-d]
1,3,4-triazolo[1,2-f]pyrimidine (10)
A mixture of (9) (0.92 mmol, 0.3 g) and freshly distilled acetic anhydride
(10 mL) was heated at reflux for 5 h. The solid that deposited after
distilling off the excess solvent was collected and recrystallized to afford
(10).

Synthesis of Some New Thienopyrimidines
729
8-Bromo-7,9-dimethylpyrido[3’,2’:4,5]thieno
[3,2-d]pyrimidine-2,4(1H,3H)-dithione (11)
A mixture of (4) (1.7mmol, 0.5 g) and carbon disulfide (10 mL) in
dry pyridine (20 mL) was heated at reflux for 6 h. Upon cooling,
the precipitated solid was collected, dried, and recrystallized to afford
(11).
8-Bromo-2,4-di(ethylthio)-7,9-dimethylpyrido[3’,2’:4,5]
thieno[3,2-d]pyrimidine (12)
A hot solution of (11) (1.54 mmol, 0.55 g) in dry acetone (20 mL) and
ethyl iodide (1.54 mmol, 0.47 mL) was heated at reflux for 10 h. The
solid product that separated out while hot was collected, dried, and
recrystallized to afford (12).
4-Amino-8-bromo-7,9-dimethylpyrido[3’,2’:4,5]thieno[3,2-
d]pyrimidine(13)
A mixture of (4) (1.7 mmol, 0.5 g) and formamide (10 mL) was heated
at reflux for 4 h. The precipitated solid while hot was filtered, washed
with water, dried, and recrystallized to give (13).
8-Bromo-7,9-dimethylpyrido[3’,2’:4,5]thieno[3,2-d]
pyrimidin-4(3H)-one (14)
A mixture of (4) (1.7 mmol, 0.5 g) and formic acid (10 mL) was heated at
reflux for 1.5 h. The solid product that was separated out while hot was
collected, washed with water, dried, and recrystallized to afford (14).
8-Bromo-4-chloro-7,9-dimethylpyrido[3’,2’:4,5]
thieno[3,2-d]pyrimidine (15)
A mixture of (14) (0.16 mmol, 0.5 g) and phosphorus pentachloride (0.16
mmol, 0.5 g) in phosphorus oxychloride (10 mL) was heated in a water
bath at 100◦C for 10 h. The reaction mixture was poured into water,
and the precipitated solid was filtered, washed with water, dried, and
recrystallized to afford (15).

730
H. M. F. Madkour et al.
Ethyl[(5-bromo-3-cyano-4,6-dimethylpyridin-2-yl)thio] acetate
(16)
A mixture of (2) (10 mmol, 2.42 g) and ethyl chloroacetate (11 mmol,
0.75 mL) in ethanol (20 mL) in the presence of fused sodium acetate
(15 mmol, 1.23 g) was heated at reflux for 1.5 h and left to cool. The
solid product that deposited was filtered, washed with water, dried, and
recrystallized to afford (16).
Ethyl 3-amino-5-bromo-4,6-dimethylthieno[2,3-b]
pyridine-2-carboxylate (17)
To a hot solution of (16) in ethanol (20 mL), a few drops of sodium
ethoxide solution (prepared by dissolving 0.5 g sodium metal in 20 mL
ethanol) was added .The solution was heated at reflux for 15 min and
allowed to cool. The solid product that formed was collected, dried, and
recrystallized to give (17).
3-Amino-5-bromo-4,6-dimethylthieno[2,3-b]
pyridine-2-carbohydrazide (18)
Method A
A mixture of (17) (15 mmol, 4.92 g) and hydrazine hydrate (15 mL)
was heated at reflux for 2 h. The separated solid was filtered, triturated
with ethanol, dried, and recrystallized to afford (18).
Method B
A mixture of (16) (15 mmol, 4.92 g) and hydrazine hydrate (15 mL)
was heated at reflux in a water bath at 100◦C for 2 h. The precipitated
solid product was washed several times with ethanol and recrystallized
to afford (18).
8-Bromo-7,9-dimethyl-3-formylaminopyrido[3’,2’:4,5]
thieno[3,2-d]pyrimidin-4(3H)-one (19)
A mixture of (18) (1.59 mmol, 0.5 g) and formic acid (20 mL) was heated
at reflux for 4 h. The cooled reaction mixture was diluted with water,
and the precipitated solid was recrystallized to afford (19).

Synthesis of Some New Thienopyrimidines
731
8-Bromo-3-diacetylamino2,7,9-trimethylpyrido[3’,2’:4,5]
thieno[3,2-d]pyrimidin-4(3H)-one (20)
A mixture of (18) (1.59 mmol, 0.5 g) and freshly distilled acetic anhy-
dride (20 mL) was heated at reflux for 3 h. The solid that precipitated
upon cooling was recrystallized to afford (20).
REFERENCES
[1] H. M. F. Madkour, A. A. E. Afify, G. A. El-Sayed, and M. S. Salem, Bull. Chem.
Commun., 40(2), 147 (2008).
[2] H. M. F. Madkour, M. R. Mahmoud, A. M. Sakr, and M. M. Habashy, Sci. Pharm.,
69, 33 (2001).
[3] M. A. I. Salem, H. M. F. Madkour, E. A. Soliman, and N. F. H. Mahmoud, Heterocy-
cles, 53(5), 1124 (2000).
[4] M. E. Azab, M. A. E. Ibraheem, and H. M. F. Madkour, Phosphorus, Sulfur, and
Silicon, 181, 1299 (2006).
[5] M. H. Bhuiyan, M. Rahman, K. Hossain, A. Rahim, M. I. Hossain, and M. Abu
Naser, Acta Pharm., 56, 441 (2006).
[6] A. H. Bedair, N. A. El-Hady, M. S. AbdEl-Latif, A. H. Fakery, and A. M. El-Agrody,
Il Farmaco, 55, 708 (2000) .
[7] M. M. Ghorab, S. M. Abdel-Gawad, and M. S. A. El-Gaby, Il Farmaco, 55, 249 (2000).
[8] M. S. A. E.-A. El-Gaby, S. G. Abdel-Hamide, M. M. Ghorab, and S. M. El-Sayed, Acta
Pharm., 49, 149 (1999).
[9] M. N. Nasr and M. M. Gineinah, Arch. Pharm., 335, 289 (2002).
[10] P. G. Baraldi, M. G. Pavani, M. Nunez, P. Brigidi, B. Vitali, R. Gambari, and R.
Romagnoli, Bioorg. Med. Chem., 10, 449 (2002).
[11] S. M. Sondhi, M. Johar, S. Rajvanshi, S. G. Dastidar, R. Shukla, R. Raghubir, and J.
W. Lown, Australian J. Chem., 54, 69 (2001).
[12] A. Z. M. S. Chowdhury, M. M. Matin, and M. N. Anwar, Chittagong Univ. Stud. Part
II: Sci., 21, 79 (1997); Chem. Abstr., 130, 237530p (1999).
[13] G. Mangalagiu, M. Ungureanu, G. Grosu, I. Mangalagiu, and M. Petrovanu, Ann.
Pharm. Fr., 59, 139 (2001).
[14] C. J. Shishoo, V. S. Shirsath, I. S. Rathod, M. J. Patil, and S. S. Bhargava, Arzneim.
Forsch, 51, 221 (2001).
[15] O. Bruno, C. Brullo, S. Schenone, A. Ranise, F. Bondavalli, E. Barocelli, M. Tognolini,
F. Magnanini, and V. Bollabeni, Il Farmaco, 57, 753 (2002).
[16] G. E. Robinson and C. J. Squire, Eur. Pat., 253, 507 (1988); Chem. Abstr., 109, 6318
(1988).
[17] V. I. Shvedov, V. M. Aryuzina, M. D. Mashkovskii, A. J. Polezhaeva, and L. F.
Roshchina, USSR Pat. 745, 160 (1983); Chem. Abstr., 99, 82509 (1983).
[18] K. Ninomiya, K. Nitsuta, A. Tobe, M. Egawa, and R. Kikumoto, Jpn. Kokai, 16, 557
(1994); Chem. Abstr., 120, 290120 (1994).
[19] J. B. Press and R. K. Russell, U.S. Pat., 835, 157 (1989); Chem. Abstr., 111, 174121
(1989).
[20] S. E. Delaszlo, A. A. Patchett, E. E. Allen, and W. J. Greenle, Eur. Pat., 502, 725
(1992); Chem. Abstr., 118, 22249 (1993).
[21] F. E. Janssens, I. G. Torremans, J. F. Hens, and T. T. J. M. Offenwert, Eur. Pat., 144,
101 (1985); Chem. Abstr., 104, 68856 (1986).

732
H. M. F. Madkour et al.
[22] R. Bradbury, F. H. Jung, J. J. Lohmann, P. R. Marsham, and G. Pasquet, Aust. Pat.,
584, 898 (1989); Chem. Abstr., 112, 20851 (1990).
[23] K. Fujii, T. Tanaka, and Y. Fukuda, Eur. Pat., 370, 704 (1990); Chem. Abstr., 113,
212005 (1990).
[24] R. Boehm, G. Hanbold, R. Pech, and G. Laban, Ger. Pat., 226, 893 (1985); Chem.
Abstr., 104, 186437 (1986).
[25] Daiichi Seiyaku Co. Ltd., Jpn. Kokai, 77687 (1982); Chem. Abstr., 97, 163007 (1982).
[26] H. Fukumi, F. Saitoh, H. Hovikoshi, and S. Kobayashi, Eur. Pat., 82, 023 (1983);
Chem. Abstr., 99, 158453 (1983).
[27] S. El-Bahaie, A. El-Deeb, and M. G. Assy, Pharmazie, 46, 26 (1991).
[28] D. K. K. Showa, Jpn. Kokai, 53, 681 (1981); Chem. Abstr., 95, 115522 (1981).
[29] D. K. K. Showa, Jpn. Kokai, 56, 8389 (1981); Chem. Abstr., 95, 81010 (1981).
[30] M. Wiesenfeldt, K. Etzbach, P. Hofmeister, C. Kueyast, and K. O. Westpalen, Eur.
Pat., 447, 891 (1991); Chem. Abstr., 115, 256224 (1991).
[31] A. A. Larsen and D. A. Owens, Ger. Pat., 231, 103 (1983); Chem. Abstr., 98, 204410
(1983).
[32] T. Obata, K. Fujii, and I. Narita, Eur. Pat., 356, 158 (1990); Chem. Abstr., 113, 59210
(1990).
[33] M. Arita, Y. Hukumasu, M. Sano, Y. Hoshino, and H. Komatsu, PCT Int. 08, 113
(1989); Chem. Abstr., 112, 98533 (1990).
[34] A. Krauze, Z. Bomika, A. M. Shestopalov, L. A. Rodinovskaya, J. Pelcers, G. Duburs,
Yu, A. Sharanin, and V. K. Promonenkov, Khim. Geterotsikl. Soedin., 3, 377 (1981);
Chem. Abstr., 95, 80662 (1981).
[35] J. C. Bardhan, J. Chem. Soc., 2223 (1929).
[36] W. J. Thompson and J. Gaudino, J. Org. Chem., 49(26), 5237 (1984).
[37] T. I. El-Emary, J. Chin. Chem. Soc., 46, 585 (1999).
[38] M. M. Khafagy, A. H. F. Abd-Elwahab, F. A. Eid, and A. M. El-Agrody, Il Farmaco,
57, 715 (2002).
[39] C. G. Dave and R. D. Shah, J. Heterocycl. Chem., 37, 757 (2000).
[40] A. Sh. Oganisyan, A. S. Noravyan, and M. Zh. Grigoryan, Chem. Heterocycl. Compd.,
40(1), 75 (2004).
[41] S. G. Pilosyan, Authors Abstract, Dissertations of candidates in chemical sciences
(in Russian), Yerevan (1986).
[42] A. M. M. El-Saghier, Molecules, 7, 756 (2002).
[43] A.M. Abdel-fattah, S.M. Sherif, A.M. El-Reedy, and S.A. Gad-Alla, Phosphorus,
Sulfur, and Silicon, 70, 67 (1992).
[44] C.G. Dave and R.D. Shah, J. Heterocycl. Chem., 35, 1295 (1998).
[45] P. K. Bridson, R. A. Davis and l. S. Renner, J. Heterocycl. Chem., 22, 753 (1985).
[46] N. P. Peet and S. Sunder, J. Heterocycl.Chem., 21, 1807 (1984).
[47] I. Lalerzari and C. A. Stein, J. Heterocycl. Chem., 21, 5 (1984).