Synthesis and structural characterization of the C-6 fluoroalkylated pyrimidine derivatives

Article abstract of DOI:10.1016/j.molstruc.2008.12.037

C-6 substituted fluoroalkenyl 2,4-dimethoxypyrimidine derivative (4) was synthesized by lithiation of 2,4-dimethoxy-6-methylpyrimidine (3) and subsequent reaction of thus obtained organolithium intermediate with ethyl pentafluoropropionate. The novel 2,4-pyrimidinedione containing 3,3,4,4,4-pentafluoro-1-butenyl side chain (5) was prepared by demethoxylation of 4 using sodium iodide and chlorotrimethylsilane. The structures of 4 and 5 were confirmed by ¹H, ¹³C and ¹⁹F NMR spectra, as well as IR spectra. The structure of 4 was also unambiguously confirmed by X-ray crystal structure analysis. The molecules of 4 are weakly linked by aromatic π···π stacking interactions into infinite chains parallel to the a axis.

Full text of DOI:10.1016/j.molstruc.2008.12.037

Journal of Molecular Structure 923 (2009) 19–23
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Synthesis and structural characterization of the C-6 fluoroalkylated
pyrimidine derivatives
a
a
b
c
Svjetlana Krištafor , Tatjana Gazivoda , Mario Cetina , Damjan Makuc ,
c
a,
*
Janez Plavec , Silvana Rai c´ -Mali c´
Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Maruli ´c ev trg 20, P.O. Box 177, HR-10000 Zagreb, Croatia
Department of Applied Chemistry, Faculty of Textile Technology, University of Zagreb, Prilaz baruna Filipovi ´c a 28a, HR-10000 Zagreb, Croatia
Slovenian NMR Centre, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia
a
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 20 October 2008
Received in revised form 8 December 2008
Accepted 12 December 2008
Available online 25 December 2008
C-6 substituted fluoroalkenyl 2,4-dimethoxypyrimidine derivative (4) was synthesized by lithiation of
2,4-dimethoxy-6-methylpyrimidine (3) and subsequent reaction of thus obtained organolithium inter-
mediate with ethyl pentafluoropropionate. The novel 2,4-pyrimidinedione containing 3,3,4,4,4-pentaflu-
oro-1-butenyl side chain (5) was prepared by demethoxylation of
4 using sodium iodide and
chlorotrimethylsilane. The structures of 4 and 5 were confirmed by 1H, C and F NMR spectra, as well
13
19
as IR spectra. The structure of 4 was also unambiguously confirmed by X-ray crystal structure analysis.
Keywords:
C-6 fluoroalkylated pyrimidines
X-ray crystal structure analysis
pꢀꢀꢀp interactions
The molecules of 4 are weakly linked by aromatic
to the a axis.
p
ꢀꢀꢀp
stacking interactions into infinite chains parallel
Ó 2009 Elsevier B.V. All rights reserved.
1
. Introduction
Fluorine containing compounds are widely used in the synthe-
In this paper, we report the synthesis and structural study of
C-6 3,3,4,4,4-pentafluoro-2-hydroxy-1-butenyl substituted 2,4-
dimethoxypyrimidine (4) and 2,4-pyrimidinedione (5).
sis of pharmaceuticals due to their favourable chemical and biolog-
ical properties such as solubility and bioavailability, they enhance
the lipophilicity and thus increase the rate of cell penetration and
transport of drug to an active site [1]. The excellent biological
activities exhibited by 6-substituted uracil derivatives provide a
new emphasis to explore the chemistry and biological activities
of these pyrimidine derivatives [2–7]. A large number of acyclic
nucleoside analogues showed antiviral activities against herpes
viruses due to their selective and efficient activation through
monophosphorylation by the viral enzyme in the intact cells
2
. Experimental
Melting points were determined on a Kofler micro hot-stage
apparatus (Reichert, Wien) and are uncorrected. The electron im-
pact mass spectra were recorded with an EXTREL FT MS 2002
instrument with ionizing energy of 70 eV. H and C NMR 1D
and 2D spectra were recorded on a Bruker Avance 600 MHz NMR
spectrometer, operating at 150.92 MHz for the C resonance,
and Varian Unity Inova 300 MHz NMR spectrometer. The samples
3 6
of 4 and 5 were dissolved in CD OD and DMSO-d , respectively,
and measured in 5 mm NMR tubes. The H, C and F NMR chem-
ical shift values (d) are expressed in ppm and coupling constants (J)
in Hz. Proton and carbon chemical shifts are referred to TMS,
3
whereas fluorine chemical shifts are given with respect to CCl F.
The sample temperature was set at 298 K and controlled to
1
13
1
3
[
8,9]. Therefore, radiolabeling of these antiviral agents with the
18
1
13
19
positron-emitting isotope F allows in non-invasive imaging of
the viral thymidine kinase (TK) enzyme activity by means of posi-
tron-emission tomography (PET) [10,11]. Besides, the PET tech-
nique has proven to be vital in early detection of cancer and
monitoring the efficacy of chemo- or radiotherapy response
12,13]. Furthermore, we have reported that 18F-radiolabeled C-6
1
[
approximately ±0.5 K. H NMR measurements were performed un-
acyclic pyrimidine nucleosides can be suitable candidates for the
development of non-toxic PET-tracer molecules that are specifi-
cally and efficiently phosphorylated by the herpes simplex virus
type 1 TK [10,11].
der the following spectral and processing conditions: 4.0 kHz
sweep width, 90° pulse (11
main, zero filling to 64 K and line broadening of 0.5 Hz. 2D NMR
spectra: NOESY: 4096 ( 1) data points, 16 scans per
2) ꢁ 256 (
FID, 32 dummy scans, a pulse delay of 2 s, with mixing time of
50 ms, 4.0 kHz ( 1) spectral width, transformed
2) ꢁ 4.0 kHz (
after multiplication with a sine-bell squared filter shifted by /2
ls), 2 s relaxation delay, 32 K time do-
x
x
1
x
x
*
Corresponding author. Tel.: +385 1 45 97 213; fax: +385 1 45 97 224.
E-mail address: sraic@fkit.hr (S. Rai c´ -Mali c´ ).
p
0
022-2860/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2008.12.037

2
0
S. Krištafor et al. / Journal of Molecular Structure 923 (2009) 19–23
in both
x
2 and
x
1 to give 4 K ꢁ 1 K matrix. The infrared spectra
ual oily product was extracted with CH
2 2
Cl and water. The organic
were recorded by a Fourier transform infrared (FTIR) spectrometer
Bruker Vertex 70 equipped with an attenuated total reflection
layer was dried over Na SO and purified by silica gel column chro-
2
4
matography using petroleum ether:EtOAc = 5:1 as eluent to give
(
ATR) accessory with a diamond crystal. Sixteen scans were
compound 4 as yellow solid (424 mg, 72.5%, m.p. = 58–60 °C).
collected for each measurement over the spectral range of
ꢂ1
ꢂ1
4
00–4000 cm with resolution of 4 cm . Precoated Merck Silica
Gel 60F-254 plates were used for thin layer chromatography
TLC) and the spots were detected under UV light (254 nm). Col-
umn chromatography (CLC) was performed using silica gel
0.063–0.2 mm) Fluka; glass column was slurry-packed under
2.1.2. 6-(3,3,4,4,4-Pentafluoro-2-hydroxy-1-butenyl)-2,4-pyrimi-
dinedione (5)
(
A
mixture of
4
3
(0.1 g, 0.33 mmol), Me SiCl (0.15 mL,
1.16 mmol), and NaI (0.17 g, 1.16 mmol) in dry MeCN (7 mL) was
stirred at room temperature for 18 h and then at 60 °C for 3 h,
under argon atmosphere. The solvent was evaporated under re-
duced pressure, and the residue was chromatographed using
(
gravity. Compounds purity was analyzed by HPLC with DAD
detector.
2 2
CH Cl :MeOH = 15:1 as eluent to give crystalline compound 5
2.1. Synthesis
(60 mg, 66.6%, m.p. = 278–281 °C).
+
MS m/z 273.02 [MH] . Anal. Found: C, 35.23; H, 1.85; N, 10.26;
2
,4-Dichloro-6-methylpyrimidine (2) and 2,4-dimethoxy-6-
8 5 5 2 3
Calcd for [C H F N O ]: C, 35.31; H, 1.85; N, 10.29.
methylpyrimidine (3) were synthesized using an analogous proce-
dures given in the literature [10].
2.2. Crystal structure determination
The novel fluoroalkenyl substituted pyrimidine derivative con-
taining free 2,4-diketo functionalities (5) was prepared by treat-
ment of 4 with sodium iodide and chlorotrimethylsilane. In
comparison with other synthetic methods used for hydrolysis of
Single crystal of 4 suitable for X-ray single crystal analysis was
obtained at room temperature by partial evaporation from the
CH
295 K on a Oxford Diffraction Xcalibur2 diffractometer with a Sap-
phire 3 CCD detector using graphite-monochromated Mo K radia-
2 2
Cl /n-hexane solution (1:1). The intensities were collected at
2
,4-dimethoxy groups, such as acetyl chloride and water or 35%
aqueous hydrochloric acid, applied method gave compound 5 in
a
higher yield [7] (Scheme 1).
tion (k = 0.71073 Å). The data collection and reduction were
carried out with the CrysAlis programs [14]. The SHELXS97 and SHEL-
XL97 [15] programs were used for structure solution and refinement.
ThePLATON [16]program was usedfor structureanalysis and molec-
ular and crystal structure drawings preparation.
2.1.1. 6-(3,3,4,4,4-Pentafluoro-2-hydroxy-1-butenyl)-2,4-dimethoxy-
pyrimidine (4) [7]
The solution of 2,4-dimethoxy-6-methylpyrimidine (3)
(
300 mg, 1.95 mmol) in THF (5 mL) was cooled at ꢂ70 °C and lith-
The crystal structure was solved by direct methods. All non-
hydrogen atoms were refined anisotropically by full-matrix least-
squares calculations based on F . The hydroxyl hydrogen atom
H3 was found in a difference Fourier map and its coordinates
and isotropic thermal parameter have been refined freely. The
O3ꢂH3 bond amounts 1.17(6) Å, as a result of an involvement of
ium diisopropylamide (2.1 mL, 2 M in THF/heptane/ethyl benzene)
was added. After the reaction mixture was stirred for 30 min at
ꢂ55 °C ethyl pentafluoropropionate (0.35 mL, 2.34 mmol) was
added. Mixture was additionally stirred for 3 h and neutralized
with glacial acetic acid. The solvent was evaporated and the resid-
2
O
Cl
OCH3
HN
i
ii
N
N
O
N
H
CH3
Cl
N
CH3
H3CO
N
CH3
1
2
3
iii
OCH3
N
OH
H3CO
N
O
CF2CF3
4
iv
HN
OH
O
N
H
CF2CF3
5
3
; (ii) Na/MeOH; (iii) LDA, THF, ethyl pentafluoropropionate; (iv) NaI, Me SiCl, MeCN.
Scheme 1. Reagents and conditions: (i) POCl
3

S. Krištafor et al. / Journal of Molecular Structure 923 (2009) 19–23
21
hydroxyl hydrogen atom in intramolecular hydrogen bond (see
Section 3). All other hydrogen atoms were included in calculated
positions as riding atoms, with SHELXL97 [15] defaults. Details of
crystal data, data collection and refinement parameters are given
in Table 1. CCDC 685948 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free
of charge via www.ccdc.cam.ac.uk/data_request/cif, by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cambridge
Crystallographic Data Centre, 12, Union Road, Cambridge CB2
1
EZ, UK; fax: +44 1223 336033.
3
. Results and discussion
3.1. Antitumoral activity
Fluoroalkylated pyrimidine derivatives 4 [7] and 5 were evalu-
ated for their activity against human carcinoma cell lines. Compar-
ison of cytostatic activities of 4 and 5 against acute lymphoblastic
leukemia (Molt-4), colon carcinoma (HCT 116 and SW 620), breast
carcinoma (MCF-7) and lung carcinoma (H 460) cell lines showed
that demethoxylation caused the absence of inhibitory effect of no-
vel 2,4-pyrimidinedione derivative 5. While compound 4 showed
moderate activity against cell lines (IC50 = 43–76
oxylated structural congener showed no activity (IC50 > 100
l
M), its demeth-
M).
l
3.2. NMR and IR spectra of 4 and 5
The structures of 4 [7] and 5 have been confirmed by 1H, 13
C
and 19F NMR spectra (Table 2). The analysis of the spectra was
performed on the basis of the chemical shift, signal multiplicity
19
and magnitude of C–F coupling. F NMR resonances were well
1
13
resolved (Table 2). H decoupled C NMR showed C–F coupling
constants that enables straightforward identification of fluori-
nated carbon atoms and their neighbours. Namely, CF
2
group
displayed triplet of quartets due to the coupling with three
neighbouring fluorine atoms, while CF group displayed quartet
3
Table 1
Crystal data and summary of data collection and refinement for 4.
Formula
10 9 5 2 3
C H F N O
Formula weight
Crystal size [mm]
Crystal colour
Crystal system
Space group
Unit cell dimensions
a [Å]
300.19
0.10 ꢁ 0.16 ꢁ 0.71
Colourless
Monoclinic
P2 /c
1
6.9062 (4)
23.5039 (11)
9.6244 (5)
126.763 (6)
1251.55 (11)
4
b [Å]
c [Å]
b [°]
3
V [Å ]
Z
D
l
ꢂ3
calc. [g cm
]
1.593
0.165
ꢂ1
[mm
]
F(000)
608
Scan-mode
h range [°]
Index ranges
x
4.07–26.99
ꢂ7 6 h 6 8
ꢂ25 6 k 6 30
ꢂ12 6 l 6 9
8914/2707
1321/0.0684
187
Collected/independent reflections No.
Reflections No. [I P 2
Parameters refined
Goodness-of-fit on F2
r(I)]/Rint.
0.922
R[I P 2
wR[I P 2
Max./min. electron density [e
r
(I)]/R [all data]
0.0489/0.1083
0.1274/0.1601
0.253/ꢂ0.242
r(I)]/wR [all data]
ꢂ3
]

2
2
S. Krištafor et al. / Journal of Molecular Structure 923 (2009) 19–23
of triplets due to the long-range coupling constants with two
fluorine atoms. One-bond and two-bond C–F coupling values
are in agreement with those found for related fluorinated com-
pounds [17].
Although fluoroalkenyl substituted pyrimidine derivatives 4
and 5 are structurally alike, the demethoxylation of 4 caused sig-
Table 3
Selected bond lengths (Å), bond and torsion angles (°) for 4.
Bond lengths
Bond and torsion angles
N1–C2
C2–N3
C2–O1
O1–C7
N3–C4
C4–O2
O2–C8
C4–C5
C5–C6
C6–N1
C6–C9
C9–C10
O3–C10
F1–C11
F2–C11
F3–C12
F4–C12
F5–C12
1.330(3)
1.319(3)
1.326(3)
1.441(3)
1.323(3)
1.341(3)
1.437(3)
1.381(3)
1.381(3)
1.363(3)
1.439(3)
1.343(4)
1.319(3)
1.353(3)
1.342(3)
1.300(5)
1.313(4)
1.315(4)
N1–C2–N3
N1–C2–O1
C2–O1–C7
O1–C2–N3
C2–N3–C4
N3–C4–O2
C4–O2–C8
O2–C4–C5
N3–C4–C5
C4–C5–C6
C5–C6–C9
C9–C6–N1
C5–C6–N1
C6–N1–C2
C7–O1–C2–N1
C8–O2–C4–N3
O3–C10–C11–F1
O3–C10–C11–F2
F1–C11–C12–F3
F1–C11–C12–F4
F1–C11–C12–F5
126.4(2)
113.30(19)
117.65(19)
120.3(2)
115.6(2)
118.7(2)
118.1(2)
117.4(2)
123.9(2)
116.7(2)
123.7(2)
116.3(2)
120.0(2)
117.4(2)
178.40(19)
1.4(3)
nificant shielding of pyrimidine ring carbon atoms (Dd values were
between 9 and 11 ppm). The most pronounced shielding was ob-
0
served for C1 , where
D
d exceeds 20 ppm (Table 2). Related upfield
0
chemical shift changes were observed for H5 and H1 protons.
The configuration along C1 @C2 double bond in 5 was evalu-
H1
ated through JC3 coupling constant. Its small value of 1.4 Hz is
0 0
in agreement with Z-configuration along C1 @C2 double bond.
The conformational properties of 5 were assessed also by 1D differ-
ence NOE experiments. Unfortunately proton signals were over-
lapped and therefore enhancements could not be quantified
unequivocally.
0
0
3
0
0
178.1(2)
61.2(3)
71.5(3)
Besides characteristic bands that can be ascribed to pyrimi-
dine moiety [18], the IR spectrum of 4 showed bands at 1191
ꢂ1
ꢂ50.2(4)
and 1096 cm
arising from asymmetric C–O–C stretching and
ꢂ168.1(3)
symmetric C–O–C stretching vibrations, respectively. On the
ꢂ1
contrary to this, strong band at 1668 cm
in the spectrum of
5
is caused by C@O stretching vibration. Besides, the frequencies
ꢂ1
at 1155–1050 and 680–750 cm
can be associated with C–F
stretching vibrations, which are typical for the fluorinated
pyrimidines [17].
conformation with respect to the N1 and N3 atoms of the pyrimi-
dine ring, whereas in 4, the C7 atom with respect to the N1 atom
adopts an antiperiplanar conformation (Table 3). Furthermore, the
F1 atom is antiperiplanar with respect to the hydroxyl oxygen atom
O3, and F3 and F4 atoms are synclinal with respect to the fluorine
atom F1. The bond lengths in 3,3,4,4,4-pentafluoro-1-butenyl moi-
ety are within the expected values [20–22]. The hydroxyl hydrogen
atom is directed towards the N1 atom of pyrimidine ring (Fig. 1),
thus forming intramolecular hydrogen bond [O3ꢀꢀꢀN1 = 2.567(2) Å;
O3-HꢀꢀꢀN1 = 152(5)°] and six-membered ring which can be de-
scribed by graph-set notation as S(6) [23]. Besides, the hydrogen
H9 atom participates in intramolecular C–HꢀꢀꢀF interaction, so
forming S(5) ring [C9ꢀꢀꢀF1 = 2.713(3) Å; C9–HꢀꢀꢀF1 = 102°].
3.3. X-ray crystal structure of 4
The compound 4 (Fig. 1) crystallized in monoclinic space group
P2 /c. In 4, two methoxy groups are bonded to pyrimidine ring
1
atoms C-2 and C-4, and a 2-hydroxy-3,3,4,4,4-pentafluoro-1-bute-
nyl moiety is bonded to the pyrimidine ring atom C-6. The bond
lengths and angles of 2,4-dimethoxypyrimidine (Table 3) agree
well with the equivalent ones in similar structures [19]. The mole-
cule is essentially planar, with the exception of the F1 and F2
atoms, and terminal trifluoromethyl group. The dihedral angle be-
tween the mean plane defined by the C9/C10/O3/C11 atoms and
the mean plane of the pyrimidine ring is 0.8(2)°. Both methoxy
groups in three closely related structures [19] adopt a synperiplanar
The molecules of 4 are aligned along the b axis and are mutually
parallel (Fig. 2). The 3,3,4,4,4-pentafluoro-1-butenyl moieties of
neighbouring molecules are oriented in such manner that they
generate hydrophobic layers. Such orientation of the molecules
prevents hydrogen bonds formation and C–Hꢀꢀꢀ
p interactions, but
enables a weak aromatic stacking interactions [24] between
the pyrimidine rings of the neighbouring molecules. An interplanar
pꢀꢀꢀp
angle between the pyrimidine rings is 0.00°, interplanar spacings
i
ii
i
are ca 3.43 and 3.46 Å, a centroid separations 3.6452(17) and
ii
3
1
1
.6136(17) Å, and
a
corresponding centroid–centroid offsets
.225 and 1.039 Å, respectively [symmetry codes: (i) 1 ꢂ x, ꢂy,
interactions link the molecules
i
ii
ꢂ z; (ii) 2 ꢂ x, ꢂy, 1 ꢂ z]. The
pꢀꢀꢀp
of 4 into infinite chains parallel to the a axis. One short intermolec-
ular FꢀꢀꢀF contact is also present in this structure
iii
[
F1ꢀꢀꢀF2 = 2.886(3) Å; (iii): x, ꢂ1/2 ꢂ y, ꢂ1/2 + z]. This FꢀꢀꢀF interac-
iii
tion can be classified as type-I interaction [25], as C11–F1ꢀꢀꢀF2 and
iii
iii
F1ꢀꢀꢀF2 –C11 angles are 141.3(2)° and 159.0(2)°, respectively. The
recent charge density study of intermolecular interactions involv-
ing organic fluorine has classified FꢀꢀꢀF contacts as a well-defined
weak intermolecular interactions [26]. In the absence of any other
significant intermolecular interactions, these interactions can also
provide stability of molecular assembly.
4
. Conclusion
Pyrimidine derivatives (4 and 5) with C-6 3,3,4,4,4-pentafluoro-
1
-butenyl side chain were synthesized, and their structures were
Fig. 1. A molecular structure of 4, with the atom-numbering scheme. Displacement
ellipsoids for non-hydrogen atoms are drawn at the 20% probability level.
1
13
19
elucidated by H, C and F NMR spectra, and IR spectra. The Z-

S. Krištafor et al. / Journal of Molecular Structure 923 (2009) 19–23
23
Fig. 2. Crystal packing diagram of 4, showing the
pꢀꢀꢀp interactions that link the molecules of 4 into infinite chains. pꢀꢀꢀp interactions are indicated by dotted lines.
0
0
configuration of C1 @C2 double bond in 5 was determined through
J
[7] S. Prekupec, D. Makuc, J. Plavec, L. Šuman, M. Kralj, K. Paveli c´ , J. Balzarini, E. De
Clercq, M. Mintas, S. Rai c´ -Mali c´ , J. Med. Chem. 50 (2007) 3037.
3
CH coupling constant. X-ray crystal structure analysis of 4 showed
that the molecule is essentially planar, and that the mutually par-
allel molecules are aligned along the b axis. Aromatic stacking
[
8] P. Pospisil, D.B. Pilger, S. Marveggio, P. Schelling, C. Wurth, L. Scapozza, G. Folkers,
M. Pongra cˇ i c´ , M. Mintas, S. Rai c´ -Mali c´ , Helv. Chim. Acta 85 (2002) 3237.
p
ꢀꢀꢀ
p
[9] T. Kulikowski, Pharm. World Sci. 16 (1994) 127.
[
[
[
[
[
[
10] S. Rai c´ -Mali c´ , A. Johayem, S. Ametamey, S. Batinac, E. De Clercq, G. Folkers, L.
Scapozza, Nucleosides Nucleotides Nucleic Acids 23 (2004) 1707.
11] A. Johayem, S. Rai c´ -Mali c´ , K. Lazzati, P.A. Schubiger, L. Scapozza, S.M.
Ametamey, Chem. Biodiversity 3 (2006) 274.
12] J. Eary, D.A. Mankoff, A.M. Spence, M.S. Berger, A. Olshen, J. Link, F. O’Sullivan,
K.A. Krohn, Cancer Res. 59 (1999) 615.
13] D.A. Mankoff, A.F. Shields, J.M. Link, M.M. Graham, M. Muzi, L.M. Peterson, J.F.
Eary, K.A. Krohn, J. Nucl. Med. 40 (1999) 614.
14] Oxford Diffraction, Xcalibur CCD System. CrysAlis CCD and CrysAlis RED,
Versions 171.32.4, Oxford Diffraction, Oxford, United Kingdom, 2007.
15] G.M. Sheldrick, Acta Crystallogr. A64 (2008) 112.
interactions link the molecules of 4 into infinite chains parallel to
the a axis.
Acknowledgements
Support for this study was provided by the Ministry of Science
of the Republic of Croatia (Projects #125-0982464-2925 and #119-
193079-3069). The authors wish to thank Dr. Marijeta Kralj for
cytostatic evaluation of 6-(3,3,4,4,4-pentafluoro-2-hydroxy-1-
butenyl)-2,4-pyrimidinedione (5).
1
[16] A.L. Spek, J. Appl. Crystallogr. 36 (2003) 7.
17] L.M. Popova, A.U. Trishina, S.V. Vershilov, A.I. Ginak, B.N. Maksimov, J. Fluorine
Chem. 96 (1999) 51.
[
[
[
18] M. Futamata, D. Diesing, Vibr. Spectrosc. 19 (1999) 187.
19] T. Gazivoda, S. Krištafor, M. Cetina, A. Nagl, S. Rai c´ -Mali c´ , Struct. Chem. 19
References
(
2008) 441.
20] V.F. Snegirev, M.Y. Antipin, V.N. Khrustalev, Y.T. Struchkov, Russ. Chem. Bull.
3 (1994) 1009.
[
[
[
1] D. Chopra, T.N.G. Row, CrystEngComm. 10 (2008) 54.
2] P. Das, C.P. Spears, A.H. Shahinian, S.K. Dasgupta, N.G. Kundu, Bioorg. Med.
Chem. Lett. 6 (1996) 2477.
4
[
[
21] G.F. Jiang, J. Sun, Y. Shen, J. Fluorine Chem. 108 (2001) 207.
22] V.I. Filyakova, D.S. Yufit, Y.T. Struchkov, K.I. Pashkevich, Russ. Chem. Bull. 39
[
3] M. Baba, E. De Clercq, H. Tanaka, M. Ubasawa, H. Takashima, K. Sekiya, I. Nitta,
K. Umezu, R.T. Walter, S. Mori, Mol. Pharmacol. 39 (1991) 805.
4] J. Balzarini, A. Karlsson, E. De Clercq, Mol. Pharmacol. 44 (1993) 694.
5] A. Mai, M. Artico, G. Sbardella, S. Quartarone, S. Massa, A.G. Loi, A. De Montis, F.
Scintu, M. Putzolu, P. LaColla, J. Med. Chem. 40 (1997) 1447.
6] S. Prekupec, D. Makuc, J. Plavec, S. Kraljevi c´ , M. Kralj, K. Paveli c´ , G. Andrei, R.
Snoeck, J. Balzarini, E. De Clercq, S. Rai c´ -Mali c´ , M. Mintas, Antiviral Chem.
Chemother. 16 (2005) 327.
(
1990) 936.
23] J. Bernstein, R.E. Davis, L. Shimoni, N.L. Chang, Angew. Chem. Int. Ed. Engl. 34
1995) 1555.
[
[
[
(
[
[
[
24] C.A. Hunter, J.K.M. Sanders, J. Am. Chem. Soc. 112 (1990) 5525.
25] G.R. Desiraju, R. Parthasarathy, J. Am. Chem. Soc. 111 (1989) 8725.
26] D. Chopra, T.S. Cameron, J.D. Ferrara, T.N. Guru Row, J. Phys. Chem. A 110
[
(
2006) 10465.