Synthesis and biological evaluation of some pyrrolo[2,3-d]pyrimidines

Article abstract of DOI:10.1002/ardp.200600055

Pyrrolo[2,3-d]pyrimidine and tetrazolopyrimidine derivatives 2a, b-5a, b were prepared. Also, acyclic and cyclic C-nucleosides 7a, b-12a, b were prepared by treating compound 6 with some aldoses. All prepared products were tested for antiviral activity ag

Full text of DOI:10.1002/ardp.200600055

664
Arch. Pharm. Chem. Life Sci. 2006, 339, 664–669
Full Paper
Synthesis and Biological Evaluation of Some
Pyrrolo[2,3-d]pyrimidines
Aymn E. Rashad1, Mosaad S. Mohamed2, Magdy E. A. Zaki1, and Samar S. Fatahala2
1 Photochemistry Department, National Research Centre, Dokki, Cairo, Egypt
2 Organic Chemistry Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt
Pyrrolo[2,3-d]pyrimidine and tetrazolopyrimidine derivatives 2a,b–5a,b were prepared. Also,
acyclic and cyclic C-nucleosides 7a,b–12a,b were prepared by treating compound 6 with some
aldoses. All prepared products were tested for antiviral activity against hepatitis-A virus (HAV,
MBB-cell culture adapted strain) and herpes simplex virus type-1 (HSV-1). Plaque reduction infec-
tivity assay was used to determine virus count reduction as a result of treatment with tested
compounds. Compound 2a showed the highest effect on HAV, while compound 11b showed the
highest effect on the HSV-1 virus.
Keywords: Acyclic and Cyclic C-nucleosides / Antiviral activity / Pyrrolo[2,3-d]pyrimidine /
Received: May 22, 2006; accepted: July 28, 2006
DOI 10.1002/ardp.200600055
as potential antimicrobial [5] and antiviral agents [15].
Introduction
During the last time, many reports [16–23] have
appeared dealing with this class of nucleosides. However,
to the best of our knowledge, C-nucleosides of pyr-
rolo[2,3-d]pyrimidine derivatives are not known.
In continuation of our previous work on the synthesis
of biologically active fused pyrimidines [24–27] and
different nucleoside derivatives [28, 29], we aimed to pre-
pare new compounds which are expected to possess nota-
ble chemical and biological activities.
Toyocamycin, tubercidin, sangivamycin, and sugar-modi-
fied analogues have been known for a long time as
nucleoside analogues effective against a large variety of
viruses [1, 2]. When the sugar moiety of these compounds
was replaced by a benzyl moiety, pyrrolo[2,3-d]pyrimi-
dine derivatives were turned into specific inhibitors of
human cytomegalovirus (HCMV) replication [3, 4]. On the
other hand, pyrimidines and fused heterocyclic pyrimi-
dines have received a great biological interest [5], in parti-
cular 4-hydrazinopyrimidine derivatives, which were
tested for their bactericidal and fungicidal activity [6, 7].
Condensation of the appropriate heterocyclic hydrazino
pyrimidine derivatives with monosaccharides give the
corresponding sugar hydrazones, which upon cycliza-
tion give the corresponding acyclo C-nucleosides [8–12].
Actually, some C-nucleosides were shown to exhibit pro-
minent and versatile biological activities [13, 14] and
many of their derivatives have recently been synthesized
Chemistry
In this investigation, when compounds 1a,b [24] were
stirred with sodium azide or thiourea, derivatives 2a,b or
3a,b were obtained (Scheme 1, Table 1). The IR spectra of
compounds 2a,b revealed the absence of an azido group,
which indicates that they were in the tetrazolo structure;
1
while the IR and H-NMR spectra of compounds 3a,b
revealed the presence of a NH group (Table 2).
On heating compounds 3a,b with dimethylsulfate or 2-
chloroethyl methyl ether, derivatives 4a,b or 5a,b were
obtained (Scheme 1). The structure of the latter com-
pounds was confirmed on the basis of their spectral data
(Table 2).
Correspondence: Dr. Aymn E. Rashad, Photochemistry Department,
National Research Centre, Dokki, Ciro 1258943, Cairo, Egypt.
E-mail: aymnelzeny@yahoo.com
The hydrazone derivatives 7a,b and 8a,b were prepared
by reacting compounds 6a,b [24] with some monosachar-
Fax: +20 23 370-931
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Arch. Pharm. Chem. Life Sci. 2006, 339, 664–669
Pyrrolo[2,3-d]pyrimidines
665
Table 1. Physical data of the new compounds.
Compound
No.
M. p. (8C)
From ethanol
Yield
(%)
2a
2b
3a
3b
4a
4b
5a
5b
7a
7b
8a
8b
9a
182–184
188–190
185–187
253–255
155–157
133–135
135–137
132–134
125–127
122–124
132–134
135–137
130–132
188–190
136–138
180–184
132–134
185–187
140–144
188–192
80
75
80
76
80
75
60
66
75
80
60
65
70
85
80
75
65
70
70
75
9b
10a
10b
11a
11b
12a
12b
Scheme 1. Synthesis route of compounds 1–5.
ides: namely D-ribose or D-glucose in the presence of a cat-
alytic amount of glacial acetic acid. The products
revealed absorption bands for (OH, NH) and (C=N) in the
IR spectra and their 1H-NMR spectra showed the presence
of the sugar protons, NH and azo-methine (CH=N)
(Scheme 2, Table 2).
Acetylation of the hydrazone derivatives 7a,b and 8a,b
with acetic anhydride in dry pyridine at room tempera-
ture, gave the O-acetylated sugar derivatives 9a,b and
10a,b, respectively. The IR spectra of the latter com-
pounds revealed the absence of hydroxyl groups and
showed absorption bands due to (NH) and (C=O), while
their 1H-NMR spectra showed the presence of OAc groups
and one exchangeable NH (Table 2).
On the other hand, heating of derivatives 7a,b and
8a,b in acetic anhydride gave products to which the
structures of compounds 11a,b and 12a,b, respectively,
could be assigned. This can be explained via acetylation
of the hydrazone derivatives 7a,b and 8a,b to give their
corresponding O-acetylated sugar hydrazone derivatives
9a,b and 10a,b, followed by oxidative cyclization [18–20]
to give the O-acetylated cyclic C-nucleosides 11a,b and
12a,b, respectively (Scheme 2). The IR spectra of the latter
Scheme 2. Synthesis route of compounds 6–12.
compounds revealed the absence of NH and hydroxyl
groups and showed absorption bands due to (C=O). The
absence of NH, the azo-methine (CH=N) and the presence
1
of OAc groups in H-NMR spectra of compounds 11a,b
and 12a,b confirmed their structures (Table 2).
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Arch. Pharm. Chem. Life Sci. 2006, 339, 664–669
Table 2. Spectral data of the newly prepared compounds.
Compd.
No.
Mass (m/z)
IR (m, cm– 1
)
1H-NMRa, b) (d, ppm)
2a
2b
402 [M+] (100%)
1520 (C=N),
1630 (C=C)
1560 (C=N),
1610 (C=C)
b) 5.5 (s, 2H, CH2), 6.9-7.5 (m, 15H, Ar-H), 9.05 (s, 1H, C5-H)
b) 6.8-7.5 (m, 8H, Ar-H), 7.8 (s, 1H, C8-H), 9.3 (s, 1H, C5-H)
381 [M+] (100%),
383 [M+2] (62%),
385 [M+4] (11%)
393 [M+] (100%)
3a
b
3330 (NH),
1682 (CS)
3330 (NH),
1682 (CS)
b) 5.5 (s, 2H, CH2), 6.9-7.5 (m, 15H, Ar-H), 9.05 (s, 1H, C2-H), 12.2 (s,
1H, NH, D2O exch.)
371 [M+] (100%),
373 [M+2] (60%),
375 [M+4] (12%)
407 [M+] (100%)
b) 7.2-7.9 (m, 8H, Ar-H), 8.1 (s, 1H, C6-H), 8.3 (s, 1H, C2-H), 12.2 (s, 1H,
NH, D2O exch.)
4a
4b
1590 (C=N)
1560 (C=N)
b) 2.5 (s, 3H, SCH3), 5.5 (s, 2H, CH2), 7.2-7.9 (m, 15H, Ar-H), 8.3 (s, 1H,
C2-H)
385 [M+] (100),
387 [M+2] (60),
389 [M+4] (12)
451 [M+] (100)
b) 2-6 (s, 3H, SCH3), 6.9-7.5 (m, 8H, Ar-H), 7.80 (s, 1H, C6-H), 9.05 (s,
1H, C2-H)
5a
5b
1560 (C=N),
1280 (C-O)
1580 (C=N),
1260 (C-O)
b) 2.6 (s, 3H, OCH3), 3.5 (t, 2H, SCH2), 3.6 (t, 2H, CH2O), 5.7 (s, 2H,
CH2), 7.2-7.9 (m, 15H, Ar-H), 8.3 (s, 1H, C2-H)
429 [M+] (90),
431 [M+2] (60),
433 [M+4] (12)
b) 2.7 (s, 3H, OCH3), 3.5 (t, 2H, SCH2), 3.70 (s, 2H, CH2O), 6.9-7.5 (m,
8H, Ar-H), 7.8 (s, 1H, C6-H), 9.05 (s, 1H, C2-H)
7a
7b
3350–3220
(broad, OH and
NH), 1595 (C=N)
b) 3.2-3.6 (protons of the alditol congregated with the water absorp-
tion), 4.3-4.5 (m, 1H, CH2OH, D2O exch.), 4.96 (m, 2H, 2OH, D2O
exch.), 5.35 (m, 2H, CH2), 5.96 (m, 1H, OH, D2O exch.), 6.70 (s, 1H,
N=CH), 7.0-7.5 (m, 16H, Ar-H and NH, D2O exch.), 8.20 (s, 1H, C2-H)
b) 3.22-3.65 (protons of the alditol congregated with the water ab-
sorption), 4.39-4.54 (m, 1H, CH2OH, D2O exch.), 4.90 (m, 1H, OH,
D2O exch.), 5.9 (m, 1H, OH, D2O exch.), 6.55 (m, 1H, OH, D2O exch.),
7.0-7.4 (m, 9H, Ar-H and NH, D2O exch.), 7.5 (s, 1H, N=CH), 7.6 (s, 1H,
C6-H), 8.30 (s, 1H, C2-H)
3350–3220
(broad, OH+NH),
1595 (C=N)
8a
8b
553 [M+] (90),
555 [M+2] (60),
557 [M+4] (12)
3333–3398
(broad, OH+NH),
1594 (C=N)
b) 3.2-3.6 (protons of the alditol congregated with the water absorp-
tion), 3.75-3.8 (m, 2H, CH2OH), 4.2-4.3 (m, 1H, OH, D2O exch.), 4.42-
4.59 (m, 2H, 2OH, D2O exch.), 5.2 (d, J = 6.4 Hz, 1H, OH, D2O exch.),
5.35 (m, 2H, CH2), 6.3 (s, 1H, CH=N), 7.1-7.6 (m, 16H, Ar-H, NH, D2O
exch.), 8.1 (s, 1H, C2-H)
3390–3238 (broad,
OH and NH),
1598 (C=N)
b) 3.25-3.5 (protons of the alditol congregated with the water ab-
sorption), 3.55-3.6 (m, 2H, CH2OH), 4.4-4.5 (m, 1H, OH, D2O exch.),
4.8-4.9 (m, 2H, 2OH, D2O exch.), 6.10 (d, J = 6.80 Hz, 1H, OH, D2O
exch.), 6.2 (s, 1H, CH=N), 7.3-7.6 (m, 9H, Ar-H, NH, D2O exch.), 7.8 (s,
1H, C6-H), 8.1 (s, 1H, C2-H)
9a
3228 (NH),
1728 (CO),
1608 (C=N )
a) 2.0-2.2 (4s, 12H, 4OAc), 2.89 (m, 2H, CH2OAc), 3.85-4.2 (m, 1H,
CHOAc), 4.9 (m, 1H, CHOAc), 5.1 (m, 1H, CHOAc), 5.4 (s, 2H, CH2 ),
7.0 (s, 1H, CH=N), 7.1-7.8 (m, 16H, Ar-H, NH, D2O exch.), 8.5 (s, 1H,
C2-H)
9b
3330 (NH),
1710 (CO),
1598 (C=N)
a) 2.0-2.2 (4s, 12H, 4OAc), 2.9 (m, 2H, CH2OAc), 3.9-4.1 (m, 1H,
CHOAc), 4.96 (m, 1H, CHOAc), 5.10-5.25 (m, 1H, CHOAc), 7.1 (s, 1H,
CH=N), 7.3-7.6 (m, 9H, Ar-H, NH, D2O exch.), 7.8 (s, 1H, C6-H), 8.1 (s,
1H, C2-H)
10a
3325 (NH),
1728 (CO),
1608 (C=N)
b) 2.0-2.2 (5s, 15H, 5OAc), 2.8-2.9 (m, 2H, CH2OAc), 4.3-4.4 (m, 1H,
CHOAc), 5.2-5.3 (m, 2H, 2CHOAc), 5.4-5.5 (m, 1H, CHOAc), 5.6 (s, 2H,
CH2 ), 7.0 (s, 1H, CH=N), 7.1-7.6 (m, 16H, Ar-H, NH, D2O exch.), 8.2 (s,
1H, C2-H)
10b
11a
3420 (NH),
1726 (CO),
1608 (C=N)
1728 (CO),
1608 (C=N)
b) 2.1-2.2 (5s, 15H, 5OAc), 2.84-2.95 (m, 2H, CH2OAc), 4.3-4.45 (m, 1H,
CHOAc), 5.22-5.35 (m, 2H, 2CHOAc), 5.4-5.65 (m, 1H, CHOAc),7.4-
7.6 (m, 9H, Ar-H, NH, D2O exch.), 7.8 (s, 1H, C6-H), 8.1 (s, 1H, C2-H)
a) 2.1-2.2 (4s, 12H, 4OAc), 2.82-2.8 (m, 2H, CH2OAc), 4.2-4.4 (m, 1H,
CHOAc), 5.0 (s, 2H, CH2), 5.2-5.3 (m, 1H, CHOAc), 5.21-5.45 (m, 1H,
CHOAc), 7.1-7.4 (m, 15H, Ar-H), 8.2 (s, 1H, C2-H)
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Arch. Pharm. Chem. Life Sci. 2006, 339, 664–669
Table 2. Continued ...
Pyrrolo[2,3-d]pyrimidines
667
Compd.
No.
Mass (m/z)
IR (m, cm– 1
)
1H-NMRa, b) (d, ppm)
11b
12a
12b
1710 (CO),
1608 (C=N)
a) 2.1-2.24 (4s, 12H, 4OAc), 2.84-2.9 (m, 2H, CH2OAc), 4.3-4.45 (m, 1H,
CHOAc), 5.22-5.35 (m, 1H, CHOAc), 5.4-5.45 (m, 1H, CHOAc), 7.3-7.6
(m, 8H, Ar-H), 7.8 (s, 1H, C8-H), 8.2 (s, 1H, C5-H)
1724 (CO),
1608 (C=N)
b) 2.0-2.2 (5s, 15H, 5OAc), 2.7-2.82 (m, 2H, CH2OAc), 4.3-4.4 (m, 1H,
CHOAc), 5.2-5.3 (m, 2H, 2CHOAc), 5.4-5.5 (m, 1H, CHOAc), 5.6 (s, 2H,
CH2), 7.1-7.6 (m, 15H, Ar-H), 8.2 (s, 1H, C5-H)
1720 (CO),
1608 (C=N)
b) 2.0-2.2 (5s, 15H, 5OAc), 2.8-2.9 (m, 2H, CH2OAc), 4.3-4.4 (m, 2H,
2CHOAc), 5.25-5.39 (m, 1H, CHOAc), 5.4-5.5 (m, 1H, CHOAc), 7.4-7.6
(m, 8H, Ar-H), 7.85 (s, 1H, C8-H), 8.2 (s, 1H, C5-H)
a)
CDCl3:
b)
DMSO-d6; exch. = exchangeable.
Antiviral Screening
Plaque infectivity assay was carried out to test com-
pounds 2a; 3a, b; 6a,b; 7a, b; 8a, b; 9a; 10a; 11a, b; and 12a
for antiviral activity. The test was performed to include
the three possibilities for antiviral activity, virucidal
effect, virus adsorption, and effect on virus replication
for HAV and HSV-1. It was noticed that compounds 2a, 8a,
and 11b revealed the highest anti-HAV activity in compar-
ison with amantadine (C#) as a control. In general, com-
pound 2a showed the highest effect on HAV compared to
the other tested compounds and the control (amanta-
dine), where its antiviral activity increased from 89% at
concentration of 10 lg/105 cells to 97% at concentration
of 20 lg/105 cells. On the other hand, compounds 3a, 8b,
and 11b revealed the highest anti-HSV-1 activity in com-
parison with acyclovir (A#) as a control. At both concen-
trations, all tested compounds revealed no higher anti-
viral activity than acyclovir (A#). In general, compound
11b showed the highest effect on HSV-1 compared to the
other tested compounds, where its antiviral activity
increased from 64% at concentration of 20 lg/105 cells to
88% at concentration of 40 lg/105 cells. Compound 6a did
not show any activity against HSV-1.
Figure 1. Effect of some novel pyrrolopyrimidines on HAV
(MBB cell culture strain) in comparison with amantadine (C#) as
control.
Figure 2. Effect of some novel pyrrolopyrimidines on HSV-1
(MBB cell culture strain) in comparison with acyclovir (A#) as
control.
Results and discussion
zole ring) or addition of sugar moieties to the pyrrolopyr-
imidines increases the antiviral activity (% of HAV reduc-
tion or% of HSV-1 reduction; Figs. 1 and 2).
Some pyrrolopyrimidine, tetrazolopyrimidine, and acyc-
lic and cyclic C-nucleoside derivatives were prepared.
Some of the prepared products were tested for antiviral
activity against hepatitis-A virus (HAV, MBB-cell culture
adapted strain) and herpes simplex virus type-1 (HSV-1).
Compound 2a showed the highest effect on HAV virus
while compound 11b showed the highest effect on the
HSV-1 virus.
Experimental
Chemistry
All melting points are uncorrected and measured using Electro-
thermal IA 9100 apparatus (Shimadzu, Japan). IR spectra were
recorded as potassium bromide pellets on a Perkin-Elmer 1650
spectrophotometer (Perkin-Elmer, Norwalk, CT, USA), National
Structure activity correlation of the obtained results
revealed that the addition of another fused ring (tetra-
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A. E. Rashad et al.
Arch. Pharm. Chem. Life Sci. 2006, 339, 664–669
Research Centre, Cairo, Egypt. 1H-NMR spectra were determined
on a Varian Mercury (300 MHz) spectrometer (Varian, UK) and
chemical shifts were expressed as ppm against TMS as internal
reference (Faculty of Science, Cairo University, Cairo, Egypt).
Mass spectra were recorded on 70 eV EI Ms-QP 1000 EX (Shi-
madzu, Japan), National Research Centre, Cairo, Egypt. Microa-
nalyses were operated using Vario, Elementar apparatus (Shi-
madzu, Japan), Organic Microanalysis Unit, National Research
Centre, Cairo, Egypt and the results were within the accepted
range (l0.40) of the calculated values. Column chromatography
was performed on Silica gel 60 (particle size 0.06–0.20 mm)
(Merck, Darmstadt, Germany). Physicochemical and spectral
data for the synthesized compounds are given in Tables 1 and 2.
For synthesis of compounds 1a,b and 6a,b see reference [24].
Per-O-acetyl-aldehydo-D-aldose N-(6,7-disubstituted-
5-phenyl-7H-pyrrolo [2,3-d]pyrimidin-4-yl)hydrazones,
9, 10
General procedure: Compounds 7a or 7b and 8a or 8b (0.01 mol)
were stirred in a water bath in a mixture of pyridine/acetic anhy-
dride (20 mL) for 3 h. The reaction mixtures were poured onto
ice-water with stirring and the solids that precipitated were col-
lected by filtration, washed with water, dried, and recrystallized
from ethanol to give 2,3,4,5-tetra-O-acetyl-D-ribose N-(6,7-disubsti-
tuted-5-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)hydrazones 9a,b
or 2,3,4,5,6-penta-O-acetyl-D-glucose N-(6,7-disubstituted-5-phe-
nyl-7H-pyrrolo[2,3-d] pyrimidin-4-yl)hydrazones 10a,b.
(1S)-Per-O-acetyl-1-C-(7,8-disubstituted-9-phenyl-7H-
pyrrolo[3,2-e] [1,2,4]triazolo[1,5-c]pyrimidin-2-yl)polyols,
11, 12
7,8-Disubstituted-9-phenyl-7H-pyrrolo[3,2-
e][1,2,4]tetrazolo[1,5-c] pyrimidines, 2a,b
A mixture of 1a or 1b (0.01 mol) and sodium azide (0.23 g,
0.02 mol) was stirred in glacial acetic acid (20 mL) at 708C for
4 h, cooled, poured onto ice-water to give precipitates which
were filtered off, dried, and recrystallized from ethanol to give
2a or 2b.
General procedure: Compounds 7a or 7b and 8a or 8b (0.01 mol)
in acetic anhydride (20 mL) were stirred in a water bath for 3 h.
The reaction mixtures were poured onto ice-water with stirring
and the solids that precipitated were collected by filtration,
washed with water, dried, and recrystallized from ethanol to
give (1S)-1,2,3,4-tetra-O-acetyl-1-C-(7,8-disubstituted-9-phenyl-7H-
pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine-2-yl)-D-erithritoles
11a,b or (1S)-1,2,3,4,5-penta-O-acetyl-1-C-(7,8-disubstituted-9-phe-
nyl-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-2-yl)-D-arabini-
toles 12a,b.
6,7-Disubstituted-5-phenyl-7H-pyrrolo[2,3-d]pyrimidine-
4-thiones, 3a,b
A mixture of 1a or 1b (0.01 mol) and thiourea (0.02 mol) was
refluxed in absolute ethanol (20 mL) for 4 h. The solvent was
removed under reduced pressure and the residues were recrys-
tallized from methanol to give 3a or 3b.
Antiviral screening
Preparation of synthetic compounds for bioassay: Tested com-
pounds, 100 mg each, were dissolved in 1 mL of 10% DMSO in
water. The final concentration was 100 lg/lL (stock solution).
The dissolved stock solutions were sterilized by addition of
50 lg/lL antibiotic-antimycotic mixture (10000 U penicillin G
sodium, 10000 lg streptomycin sulfates and 250 lg amphoteri-
cin B, PAA Laboratories GmbH, Austria).
6,7-Disubstituted-4-methylsulfanyl-5-phenyl-7H-
pyrrolo[2,3-d]pyrimidines, 4a,b
To a solution of 3a or 3b (0.01 mol) in cold H2O (2 mL) containing
(0.005 mol) KOH, dimethylsulfate (15 mL) was added and the
reaction mixture was stirred overnight, poured onto ice-water
to give precipitates which were filtered off, dried, and recrystal-
lized from ethanol to give 4a or 4b.
Cell culture: African green monkey kidney-derived cells (Vero)
and human hepatoma cell line (HepG2) were used. The cells
were propagated in Dulbeccos' minimal essential medium;
DMEM supplemented with 10% fetal bovine serum, 1% antibio-
tic-antimycotic mixture. The pH was adjusted to 7.20–7.40 by
7.50% sodium bicarbonate solution. The mixture was sterilized
by filtration through 0.2 mm pore size nitrocellulose mem-
brane.
Viruses: Herpes simplex virus type-1 and hepatitis A virus
(MBB strain) were obtained from Environmental Virology Lab.,
Department of Water Pollution Research, National Research
Centre.
Cytotoxicity assay: Cytotoxicity was assayed for both
dimethylsulfoxide (DMSO) and the tested compounds. Serial
dilutions were prepared and inoculated on Vero cells grown in
96-well tissue culture plates. The maximum tolerated concentra-
tion (MTC) for each compound was determined by both cell mor-
phology and cell viability by staining with trypan blue dye.
Plaque reduction assay: A 6-well plate was cultivated with cell
culture (105 cell/mL) and incubated for two days at 378C. HAV
was diluted to give 104 PFU/mL final concentrations for each
virus and mixed with the tested compound at the previous con-
centration and incubated overnight at 48C. Growth medium was
removed from the multiwell plate and virus-compound mixture
was inoculated (100 lL/well). After 1 h contact time, the inocu-
lum was aspirated and 3 mL of MEM with 1% agarose was laid
6,7-Disubstituted-4-(2-methoxyethyllsulfanyl)-5-phenyl-
7H-pyrrolo[2,3-d]pyrimidines, 5a,b
To a solution of 3a or 3b (0.01 mol) in alcoholic potassium hydro-
xide solution (30 mL), 2-chloroethyl methyl ether (2 mL) was
added and left to stir overnight. Then, the solvent was removed
under reduced pressure and the residues were recrystallized
from methanol to give 5a or 5b.
Aldose N-(6,7-disubstituted-5-phenyl-7H-pyrrolo[2,3-
d]pyrimidin-4-yl)hydrazones, 7, 8
General procedure: A mixture of compound 6a or 6b (0.01 mol),
D-ribose (1.4 g, 0.01 mol), or D-glucose (1.8 g, 0.01 mol) in ethanol
(30 mL), and a catalytic amount of acetic acid (3 drops) was
heated at 808C for 2 h. The formed precipitates were filtered off,
washed with water several times, and dried to give D-ribose N-
(6,7-disubstituted-5-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)hydr-
azones 7a,b or D-glucose N-(6,7-disubstituted-5-phenyl-7H-pyr-
rolo[2,3-d]pyrimidin-4-yl)hydrazones 8a,b.
i 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.archpharm.com

Arch. Pharm. Chem. Life Sci. 2006, 339, 664–669
Pyrrolo[2,3-d]pyrimidines
669
over the cell sheets. The plates were left to solidify and incubated
at 378C until the development of virus plaques. Cell sheets were
fixed in 10% formalin solution for 2 h and stained with crystal
violet stain. Control virus and cells were treated identically with-
out chemical compound. Virus plaques were counted and the
percentage of reduction was calculated [30].
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