Novel 1-[5-(4-bromophenoxy)pentyl]-3-(2-arylamino- 2-oxoethyl)uracils and their antiviral properties

Article abstract of DOI:10.1016/j.mencom.2017.01.027

The title compounds were prepared from 1-[5-(4-bromophenoxy) pentyl]uracil by the introduction of N-arylacetamide moiety at the 3-position, the better approach involving the use of N-aryl-2-chloroacetamides as the reactants. Antiviral activity of the obtained compounds was estimated.

Full text of DOI:10.1016/j.mencom.2017.01.027

Mendeleev
Communications
Mendeleev Commun., 2017, 27, 85–87
Novel 1-[5-(4-bromophenoxy)pentyl]-3-(2-arylamino-
-oxoethyl)uracils and their antiviral properties
2
a
b
Maria P. Paramonova, Anastasia L. Khandazhinskaya,*
c
a
Katherine L. Seley-Radtke and Mikhail S. Novikov
a
b
c
Department of Pharmaceutical and Toxicological Chemistry, Volgograd State Medical University,
00131 Volgograd, Russian Federation
V. A. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russian
Federation. Fax: +7 499 135 1405; e-mail: khandazhinskaya@bk.ru
Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, Baltimore,
MD 21250, USA
4
DOI: 10.1016/j.mencom.2017.01.027
The title compounds were prepared from 1-[5-(4-bromo-
phenoxy)pentyl]uracil by the introduction of N-arylacet-
amide moiety at the 3-position, the better approach involving
the use of N-aryl-2-chloroacetamides as the reactants. Anti-
viral activity of the obtained compounds was estimated.
O
N
H
N
N
Br
O
O
O
Human cytomegalovirus (HCMV) is a member of the subfamily
O
H
Betaherpesvirinae; it is prevalent in nearly 90% of the adult
N
N
1
population worldwide. HCMV infection is associated with viral
Br
O
persistence in a latent form similar to other herpesviruses and
reactivation of HCMV is a serious issue for patients with impaired
immune systems. For example, there is a high probability of serious
coinfections such as pneumonia and gastrointestinal diseases,
among others, in recipients of donor organs and bone marrow
N
O
O
O
1
2
transplants or HIV-infected patients. Because of the high pre-
phenoxy)pentyl]-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl}-
N-arylacetamides (1-[5-(4-bromophenoxy)pentyl]-3-(2-aryl-
amino-2-oxoethyl)uracils) 2–5 (Scheme 1).
Initially target N-arylamides 2–5 were prepared by conversion
of 1-[5-(4-bromophenoxy)pentyl]uracil 6 to uracil-3-acetic acid
derivative 7 (Scheme 1, Method A), whose synthesis was described
valence of the virus throughout the human population, HCMV is
the most common cause of congenital viral infections in new-
3
borns. HCMV is able to penetrate the placenta and subsequently
4
5
infect the fetus, leading to stillbirths and innate deformities.
The current treatment for HCMV infections is focused on five
6
14
FDA-approved drugs: ganciclovir, its oral prodrug form valgan-
previously. Subsequent treatment of acid 7 with thionyl chloride
7
8
9
ciclovir, foscarnet, cidofovir and its prodrug brincidofovir.
and condensation of the resulting acyl chloride with the appro-
priate arylamines (aniline, 4-phenylaniline, 2-amino-9H-fluorene
or 1-aminopyrene) in the presence of pyridine in 1,2-dichloro-
ethane led to the desired N-arylamides 2–5 in 56–74% yields.
The second route (Scheme 1, Method B) was proposed to
potentially increase the yields of the target compounds. This
approach employed substituted N-aryl-2-chloroacetamides as
alkylating agents. We have previously described the synthesis of
several related compounds by this method. Conversion of the
Unfortunately, these drugs also cause some serious side effects,
which significantly limit their clinical utility.10 Aside from low
bioavailability these drugs also exhibit significant toxicity. In
1
1
particular, foscarnet and cidofovir lead to nephrotoxicity, while
ganciclovir inhibits the functions of bone marrow, thereby leading
to thrombocytopenia and granulocytopenia.12 Further, it has been
found that long-term treatment of HCMV infections leads to the
generation of resistant HCMV variants.13 As a result, there is an
urgent need to find safer compounds that exhibit potent anti-
HCMV activity, which is not accompanied by such serious side
effects.
†
15
corresponding anilines into their N-trimethylsilyl derivatives was
†
All reagents of the highest grade were available from Sigma and Acros
Previously we have synthesized a series of 1-[w-(aryloxy)alkyl]
uracil derivatives containing an N-(4-phenoxyphenyl)acetamide
fragment at the N atom of the pyrimidine ring. These compounds
Organics and used as purchased unless otherwise noted. Anhydrous solvents
were purified according to the standard procedures. TLC was performed on
Merck TLC silica gel 60 F254 plates eluting with the specified solvents
and the plates visualized with a UV lamp, VL-6.LC. Acros Organics
silica gel (Kieselgur 60–200 µm, 60 Å) was used for column chromato-
graphy. Yields refer to spectroscopically ( H and C NMR) homo-
geneous materials. Melting points were determined in glass capillaries on a
Mel-Temp 3.0 (Laboratory Devices Inc.).
3
exhibited potent inhibitory activity against HCMV in HEL cell
1
4
cultures. The most active was uracil derivative 1 bearing five
1
13
1
4
methylene groups. We have now designed and synthesized
a new series of analogues for the purpose of gaining a better
understanding of their structure–activity relationships. The targets
proposed herein are based on a series of 2-{3-[5-(4-bromo-
2-Chloro-N-phenylacetamide 8 was obtained according to published
procedures.14
©
2017 Mendeleev Communications. Published by ELSEVIER B.V.
–
85 –
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.

Mendeleev Commun., 2017, 27, 85–87
presence of a 1.5-fold excess of potassium carbonate led to the
target compounds 2–5 in 78–90% yields.
Compounds 2–5 were then evaluated as potential inhibitors
against a broad set of DNA and RNA viruses, including HIV-1,
O
N
NH
Br
O
O
2-{3-[5-(4-Bromophenoxy)pentyl]-2,6-dioxo-3,6-dihydropyrimidin-
1
(2H)-yl}-N-arylacetamides 2–5 (general procedure). Method A. A mix-
6
Method A
Method B
ArNH2
ture of carboxylic acid derivative 7 (0.7 g, 1.70 mmol) and thionyl
chloride (0.15 ml, 2.06 mmol) in anhydrous 1,2-dichloroethane (10 ml)
was refluxed with the exclusion of moisture for 6 h. The volatiles were
evaporated under reduced pressure and the residue was dissolved in
anhydrous 1,2-dichloroethane (10 ml). The resulting solution was added
dropwise to a stirred and cooled (0°C) solution of arylamine (1.72 mmol)
and pyridine (2 ml) in anhydrous 1,2-dichloroethane (40 ml), and this was
stirred for an additional 3 h at 0°C and then kept overnight at room tem-
perature. The mixture was then washed with 4% aqueous HCl (2×30 ml)
and water (2×30 ml), the solvents were evaporated under reduced pres-
sure, and the crude product purified by flash chromatography eluting
with 1,2-dichloroethane–EtOAc (1:2). The product was recrystallized
from a mixture of hexane–EtOAc (1:1).
i, BrCH2COOEt,
K2CO3, DMF
ii, LiOH, EtOH/H2O
O
i, HDMS
ii, ClC(O)CH Cl,
DCE, 0 °C
OH
2
N
Br
O
O
N
O
Cl
Ar
N
H
O
K2CO3, DMF
7
8
–11
i, SOCl2, DCE,
ii, ArNH2, DCE, 0 °C
O
N
H
N
Ar
Br
O
N
O
Method B. A mixture of 1-[5-(4-bromophenoxy)pentyl]uracil 6 (0.5 g,
1
.42 mmol) and K CO (0.3 g, 2.17 mmol) in DMF (10 ml) was stirred
2 3
O
at 80°C for 1 h. After cooling to room temperature, the corresponding
-chloroacetamide 8–11 (1.46 mmol) was added and stirring was con-
2
–5
2
Yield (%)
Method A Method B
tinued for 24 h. The reaction mixture was filtered, concentrated under
reduced pressure, purified by flash chromatography eluting with 1,2-di-
chloroethane–EtOAc (1:2) and then recrystallized from a mixture of
hexane–EtOAc (1:1).
Product
Ar
Ph
2
3
4
5
74
72
66
56
90
87
88
78
4-PhC6H4
9H-fluoren-2-yl
pyren-1-yl
2-{3-[5-(4-Bromophenoxy)pentyl]-2,6-dioxo-3,6-dihydropyrimidin-
1(2H)-yl}-N-phenylacetamide 2: mp 157–158.5°C, R 0.58 (1,2-dichloro-
f
1
ethane–EtOAc, 1:1). H NMR (400 MHz, DMSO-d ) d: 1.39 (quin., 2H,
6
Scheme 1
CH , J 7.1 Hz), 1.66 (quin., 2H, CH , J 7.1 Hz), 1.72 (quin., 2H, CH ,
2
2
2
J 7.1 Hz), 3.75 (t, 2H, NCH , J 7.4 Hz), 3.93 (t, 2H, OCH , J 6.3 Hz),
2
2
4
.61 (s, 2H, COCH ), 5.76 (d, 1H, Ura-H-5, J 7.8 Hz), 6.88 (d, 2H, H-2',
accomplished by boiling the reaction components in excess
HMDS, followed by treatment (without further purification)
with chloroacetyl chloride in anhydrous 1,2-dichloroethane to
give the new N -substituted chloroacetamides. Thus, chloroacet-
amides 8–11 were obtained in 78–89% yields.
2
H-6', J 8.8 Hz), 7.04 (t, 1H, H-4'', J 7.2 Hz), 7.30 (t, 2H, H-3'', H-5'',
J 8.3 Hz), 7.40 (d, 2H, H-3', H-5', J 9.0 Hz), 7.55 (dd, 2H, H-2'', H-6'',
13
J 8.3, 1.0 Hz), 7.77 (d, 1H, Ura-H-6, J 7.9 Hz), 10.25 (s, 1H, NH). C NMR
100 MHz, DMSO-d ) d: 22.6, 28.4, 43.5, 48.8, 67.8, 100.3, 112.1, 117.0,
3
(
1
6
19.3, 123.6, 129.1, 132.4, 139.1, 144.9, 151.4, 158.2, 162.6, 165.6.
Similarly, alkylation of 1-[5-(4-bromophenoxy)pentyl]uracil
with the corresponding chloroacetamides 8–11 in DMF in the
2-{3-[5-(4-Bromophenoxy)pentyl]-2,6-dioxo-3,6-dihydropyrimidin-
1(2H)-yl}-N-(4-phenylphenyl)acetamide 3: mp 178–179°C, Rf 0.45.
616
1
H NMR (400 MHz, DMSO-d ) d: 1.40 (quin., 2H, CH , J 7.1 Hz), 1.66
6
2
(
quin., 2H, CH , J 7.1 Hz), 1.73 (quin., 2H, CH , J 7.6 Hz), 3.76 (t, 2H,
N-Arylacetamides 9–11 (general procedure). A mixture of 8.14 mmol
2
2
NCH , J 7.3 Hz), 3.93 (t, 2H, OCH , J 6.4 Hz), 4.64 (s, 2H, COCH ),
of arylamine, HMDS (15 ml) and NH Cl (0.1 g) was refluxed for 12 h until
2
2
2
4
5
(
.77 (d, 1H, Ura-H-5, J 7.9 Hz), 6.88 (d, 2H, H-2'', H-6'', J 9.1 Hz), 7.32
t, 1H, H-4''', J 7.3 Hz), 7.40 (d, 2H, H-3', H-5', J 9.0 Hz), 7.43 (t, 2H,
H-3''', H-5''', J 7.6 Hz), 7.60–7.66 (m, 6H, H-2', H-6', H-3'', H-5'', H-2''',
a homogeneous solution was obtained. Excess HMDS was removed under
reduced pressure, and the residual clear oil was dissolved in anhydrous
,2-dichloroethane (40 ml). A solution of chloroacetyl chloride (0.7 ml,
.80 mmol) in anhydrous 1,2-dichloroethane (10 ml) was added dropwise
with stirring at 0°C. The mixture was stirred overnight at room tempera-
ture and then evaporated under reduced pressure to 1/3 volume. Hexane
20 ml) was added and the mixture was kept overnight in a refrigerator.
1
8
1
3
H-6'''), 7.78 (d, 1H, Ura-H-6, J 7.8 Hz), 10.36 (s, 1H, NH). C NMR
100 MHz, DMSO-d ) d: 22.6, 28.4, 43.5, 48.7, 67.9, 100.3, 112.1, 117.0,
(
1
1
6
19.7, 126.6, 127.3, 127.4, 129.2, 132.4, 135.3, 138.6, 139.9, 144.9, 151.4,
58.2, 162.6, 165.6.
(
2
-[3-[5-(4-Bromophenoxy)pentyl]-2,6-dioxo-3,6-dihydropyrimidin-
The resulting precipitate was filtered and recrystallized from a mixture of
EtOAc–hexane (1:1 or 1:2).
1
(2H)-yl]-N-(9H-fluoren-2-yl)acetamide 4: mp 119–121°C, Rf 0.68.
1
H NMR (400 MHz, DMSO-d ) d: 1.40 (quin., 2H, CH , J 7.9 Hz), 1.66
6
2
2
-Chloro-N-(4-phenylphenyl)acetamide 9.Yield 89%, mp 180–182°C,
(
quin., 2H, CH , J 7.9 Hz), 1.72 (quin., 2H, CH , J 7.3 Hz), 3.76 (t, 2H,
1
2
2
R 0.59 (hexane–EtOAc, 1:1). H NMR (400 MHz, DMSO-d ) d: 4.28 (s,
f
6
NCH , J 7.1 Hz), 3.87 (s, 2H, CH ), 3.93 (t, 2H, OCH , J 6.3 Hz), 4.64 (s,
2
2
2
2
2
H, COCH ), 7.33 (tt, 1H, H-4', J 9.1, 1.8 Hz), 7.44 (t, 2H, H-3', H-5',
2
H, COCH ), 5.77 (d, 1H, Ura-H-5, J 7.9 Hz), 6.88 (d, 2H, H-2'', H-6'',
2
J 8.1 Hz), 7.64 (d, 2H, H-3, H-5 J 7.1 Hz), 7.65 (d, 2H, H-2', H-6',
J 9.1 Hz), 7.67 (d, 2H, H-2, H-6, J 9.3 Hz), 10.41 (s, 1H, NH). 13C NMR
J 9.0 Hz), 7.27 (t, 1H, H-7'', J 7.6 Hz), 7.35 (t, 1H, H-6', J 7.6 Hz), 7.40
d, 2H, H-3', H-5', J 8.8 Hz), 7.51–7.54 (m, 2H, H-5', H-8'), 7.77–7.81 (m,
(
3
(
1
100 MHz, DMSO-d ) d: 43.9, 120.1, 126.6, 127.4, 127.5, 129.6, 135.8,
13
6
H, Ura-H-6, H-3', H-4'), 7.87 (s, 1H, H-1'), 10.34 (s, 1H, NH). C NMR
38.3, 139.9, 165.0.
-Chloro-N-(9H-fluoren-2-yl)acetamide 10.Yield 80%, mp 194.5–196°C,
(100 MHz, DMSO-d ): 22.6, 28.4, 36.8, 43.6, 48.7, 67.9, 100.3, 112.1,
6
2
1
16.2, 117.0, 118.1, 119.8, 120.5, 125.3, 126.5, 127.1, 132.4, 136.8, 138.1,
1
R 0.63 (hexane–EtOAc, 1:1). H NMR (400 MHz, DMSO-d ) d: 3.91 (s,
f
6
141.3, 143.1, 144.1, 144.8, 151.4, 158.2, 162.6, 165.5.
2
1
H, CH ), 4.28 (s, 2H, COCH ), 7.27 (dt, 1H, H-7, J 7.6, 1.0 Hz), 7.35 (t,
2
2
2-{3-[5-(4-Bromophenoxy)pentyl]-2,6-dioxo-3,6-dihydropyrimidin-
H, H-6, J 7.3 Hz), 7.55 (d, 2H, H-5, H-8, J 7.8 Hz), 7.82 (d, 1H, H-3,
1
1
(
(2H)-yl}-N-(pyren-1-yl)acetamide 5: mp 176.5–178°C, R 0.60. H NMR
f
J 7.1 Hz), 7.83 (d, 1H, H-4, J 8.1 Hz), 7.92 (s, 1H, H-1), 10.39 (s, 1H,
400 MHz, DMSO-d ) d: 1.40 (quin., 2H, CH , J 7.6 Hz), 1.65–1.75 (m,
6
2
NH). 13C NMR (100 MHz, DMSO-d ) d: 36.9, 44.0, 116.5, 118.5, 119.9,
6
4H, 2×CH ), 3.80 (t, 2H, NCH , J 7.1 Hz), 3.90 (t, 2H, OCH , J 6.4 Hz),
4
H-6'', J 9.1 Hz), 7.35 (d, 2H, H-2'', H-6'', J 9.0 Hz), 7.80 (d, 1H, Ura-H-6,
J 7.8 Hz), 8.07 (t, 1H, H-7, J 7.6 Hz), 8.15 (m, 2H, H ), 8.18–8.25 (m, 2H,
H ), 8.28–8.36 (m, 4H, H ), 10.62 (s, 1H, NH). C NMR (100 MHz,
DMSO-d ) d: 22.6, 28.4, 43.6, 48.8, 67.8, 100.4, 112.0, 117.0, 122.7,
123.5, 124.2, 124.7, 125.3, 125.6, 126.8, 127.0, 127.6, 128.7, 130.8, 131.2,
131.7, 132.4, 144.9, 151.5, 158.2, 162.7, 166.8, 170.0.
2
2
2
1
20.6, 125.4, 126.6, 127.1, 137.3, 137.8, 141.2, 143.2, 144.2, 164.9.
.88 (s, 2H, COCH2), 5.81 (d, 1H, Ura-H-5, J 7.8 Hz), 6.83 (d, 2H, H-2'',
2
-Chloro-N-(pyren-1-yl)acetamide 11. Yield 78%, mp 240–241°C,
1
R 0.60 (hexane–EtOAc, 1:1). H NMR (400 MHz, DMSO-d ) d: 4.55
f
6
Ar
13
(
(
(
s, 2H, COCH ), 8.07 (t, 1H, H-7, J 7.5 Hz), 8.15 (m, 2H, H ), 8.22–8.25
2
Ar
Ar Ar
13
m, 2H, H ), 8.28–8.31 (m, 4H, H ), 10.68 (s, 1H, NH). C NMR
Ar
Ar
6
100 MHz, DMSO-d ) d: 43.8, 122.4, 123.7, 124.1, 124.5, 124.7, 125.3,
6
1
25.5, 125.8, 126.8, 127.2, 127.5, 127.7, 129.0, 130.7, 131.1, 131.2, 166.2.
–
86 –

Mendeleev Commun., 2017, 27, 85–87
HIV-2, HSV-1, HSV-2, HCMV, VZV, Vaccinia virus, Para-
Online Supplementary Materials
influenza-3 virus, Reovirus-1, Sindbis virus, Vesicular stomatitis
virus, Respiratory syncytial virus, Coxsackie virus B4 or Feline
Corona Virus, etc., using standard methods.16 Disappointingly,
none of the compounds in this series showed any meaningful
antiviral activity. However, in further analyzing the screening
results it appears that the oxygen atom of the acetanilide frag-
ment of 1 likely makes a critical contribution to the anti-HCMV
activity. Thus, the new uracil acetamide derivatives seem to be a
promising class of viral replication inhibitors and warrant further
structure–activity investigations.
Supplementary data associated with this article can be found
in the online version at doi: 10.1016/j.mencom.2017.01.027.
References
1
S. A. S. Staras, S. C. Dollard, K. W. Radford, W. D. Flanders, R. F. Pass
and M. J. Cannon, Clin. Infect. Dis., 2006, 43, 1143.
2 P. D. Griffiths and S. Walter, Curr. Opin. Infect. Dis., 2005, 18, 241.
3
4
5
K. M. Bialas, G. K. Swamy and S. R. Permar, Clin. Perinatol., 2015,
2, 61.
W. D. Rawlinson, B. Hall, C. A. Jones, H. E. Jeffery, S. M. Arbuckle,
N. Graf, J. Howard and J. M. Morris, Pathology, 2008, 40, 149.
E. C. Swanson and M. R. Schleiss, Pediatr. Clin. North. Am., 2013, 60,
335.
4
This work was supported by the Russian Foundation for Basic
Research (grant no. 15-44-02299). The authors are grateful to
Professors C. Pannecouque, G. Andrei and R. Snoeck of the
Rega Institute for antiviral evaluation of synthesized compounds.
6 D. Faulds and R. C. Heel, Drugs, 1990, 39, 597.
7
J. S. Chawla, A. Ghobadi, J. Mosley, 3rd., L. Verkruyse, K. Trinkaus,
C. N. Abboud, A. F. Cashen, K. E. Stockerl-Goldstein, G. L. Uy,
P. Westervelt, J. F. DiPersio and R. Vij, Transpl. Infect. Dis., 2012, 14,
2
59.
2
-{3-[5-(4-Bromophenoxy)pentyl]-2,6-dioxo-3,6-dihydropyrimidin-
(2H)-yl}acetic acid 7. A mixture of 1-[5-(4-bromophenoxy)pentyl]-
uracil 6 (0.5 g, 1.42 mmol) and K CO (0.3 g, 2.17 mmol) in anhydrous
8
9
P. Chrisp and S. P. Clissold, Drugs, 1991, 41, 104.
P. Griffiths and S. Lumley, Curr. Opin. Infect. Dis., 2014, 27, 554.
1
2
3
10 E. C. Villarreal, Prog. Drug Res., 2003, 60, 263.
1 J. B. Kendle and P. Fan-Havard, Ann. Pharmacother., 1998, 32, 1181.
12 B. C. Marshall and W. C. Koch, Pediatr. Drugs, 2009, 11, 309.
13 C. Deback, S. Burrel, S. Varnous, G. Carcelain, F. Conan, Z. Aït-Arkoub,
B. Autran, I. Gandjbakhch, H. Agut and D. Boutolleau, Antivir. Ther.,
2015, 20, 249.
DMF (10 ml) was stirred at 80°C for 40 min. After cooling to room
temperature, ethyl bromoacetate (0.17 ml, 1.56 mmol) was added and
stirring was continued for 24 h. The reaction mixture was filtered, con-
centrated under reduced pressure and purified by flash chromatography
eluting with 1,2-dichloroethane. The crude product was then dissolved
in EtOH (20 ml), LiOH (0.2 g, 8.35 mmol) and water (10 ml) were
added, and the resulting mixture was stirred at room temperature for 12 h.
After adjusting the pH to 2 with the addition of 1 m HCl, the resulting
precipitate was filtered and recrystallized from a mixture of hexane–
1
14 D.A. Babkov,A. L. Khandazhinskaya,A. O. Chizhov, G.Andrei, R. Snoeck,
K. L. Seley-Radtke and M. S. Novikov, Bioorg. Med. Chem., 2015, 23,
7
035.
1
5 M. S. Novikov, D. A. Babkov, M. P. Paramonova, A. O. Chizhov, A. L.
Khandazhinskaya and K. L. Seley-Radtke, Tetrahedron Lett., 2013,
54, 576.
16 M. S. Novikov, D. A. Babkov, M. P. Paramonova, A. L. Khandazhinskaya,
A. A. Ozerov, A. O. Chizhov, G. Andrei, R. Snoeck, J. Balzarini and
K. L. Seley-Radtke, Bioorg. Med. Chem., 2013, 21, 4151.
i
Pr OH (1:2) to give the desired product as a white powder (2.68 g,
i
1
00%), R 0.54 (Pr OH–EtOAc–NH OH, 9:6:5), mp 142.5–145°C.
H NMR (400 MHz, DMSO-d ) d: 1.39 (quin., 2H, CH , J 7.4 Hz), 1.65
quin., 2H, CH2, 7.4 Hz), 1.72 (quin., 2H, CH J 7.3 Hz), 3.75 (t, 2H,
NCH , J 7.1 Hz), 3.93 (t, 2H, OCH , J 6.4 Hz), 4.44 (s, 2H, COCH ),
f
4
1
6
2
(
2
2
2
2
5.74 (d, 1H, Ura-H-5, J 7.8 Hz), 6.89 (d, 2H, H-2', H-6', J 8.8 Hz), 7.42
(
1
4
d, 2H, H-3', H-5', J 8.8 Hz), 7.77 (d, 1H, Ura-H-6, J 7.8 Hz), 12.90 (br.s,
H, COOH). 13C NMR (100 MHz, DMSO-d ) d: 22.6, 28.37, 28.41, 41.9,
6
8.8, 67.8, 100.2, 112.1, 117.1, 132.4, 145.0, 151.2, 158.2, 162.3, 169.5.
Received: 27th April 2016; Com. 16/4921
–
87 –