}ˇ ´
L. Szucova et al. / Bioorg. Med. Chem. 14 (2006) 479–491
488
latter cell lines is significantly higher as compared to
those determined for Oxaliplatin and Cisplatin.
1H, (O1)H), 8.59 (t, 1H, (N6)H, J = 6.2 Hz), 8.28 (s,
1H, (C8)H),7.14 (t, 1H, (C14)H, J = 7.9 Hz), 6.94 (t,
1H, (C11)H, J = 1.8 Hz), 6.87 (d, 1H, (C15)H,
J = 7.5 Hz), 6.73 (dd, 1H, (C13)H, Ja = 7.9 Hz,
Jb = 2.3 Hz), 4.76 (sep, 1H, (C16)H, J = 6.8 Hz), 4.75
(d, 2H, (C9)H, J = 6.2 Hz), 1.58 (d, 6H, (C17,18)H,
J = 6.8 Hz). 13C NMR (DMF-d7, ppm): 158.71 (C2),
156.13 (C12), 153.97 (C6), 150.56 (C4), 141.87 (C10),
140.02 (C8), 129.91 (C11), 119.67 (C5), 118.76 (C15),
115.04 (C14), 114.53 (C13), 47.89 (C16), 44.08 (C9),
22.41 (C17,18). L4: found: C, 55.2; H, 5.2; N, 19.8%.
C16H18N5O2C1 requires C, 55.2; H 5.2; N, 20.1%,
mp: 161 - 162 ꢁC; TLC: single spot. 1H NMR
(DMF-d7, ppm): 9.07 (s, 1H, (O1)H), 8.33 (t, 1H,
(N6)H, J = 6.2 Hz), 8.29 (s, 1H, (C8)H), 6.89 (dd,
2H, (C13,15)H, Ja = 7.7 Hz, Jb = 1.8 Hz), 6.74 (t,
1H(C14)H, J = 7.9 Hz), 4.80 (d, 2H, (C9)H,
J = 6.2 Hz), 4.78 (sep, 1H, (C16)H, J = 6.8 Hz), 3.84
(s, 3H, (C19)H), 1.58 (d, 6H, (C17,18)H, J = 6.8 Hz).
13C NMR (DMF-d7, ppm): 156.20 (C2), 153.86 (C6),
150.43 (C4), 148.54 (C12), 145.22 (C11), 140.12 (C8),
126.34 (C10), 121.02 (C15), 119.71 (C5), 119.41
(C14), 111.41 (C13), 56.36 (C19), 47.95 (C16), 39.88
(C9), 22.42 (C17,18).
3. Experimental
3.1. Materials
K2PdCl4 was used as purchased (Sigma-Aldrich Co.),
cis-[Pt(DMSO)2Cl2] and trans-[Pd(DMSO)2Cl2] were
prepared according to the published methods.44,45 The
organic ligands 2-{[l-(hydroxymethyl)propyl]amino}-6-
[(3-hydroxybenzyl)amino]-9-isopropylpurine (L1), 2-{[l-
(hydroxymethyl)-2-(methyl)propyl]amino}-6-[(3-hydro-
xybenzyl)amino]-9-isopropylpurine (L2), 2-chloro-6-[(3-
hydroxybenzyl)amino]-9-isopropylpurine (L3) and 2-
chloro-6-[(2-hydroxy-3-methoxybenzyl)amino]-9-isopro-
pylpurine (L4) were prepared by the slightly modified
methods described in the literature.22
The yellowish crystals of L1 suitable for single crystal
X-ray analysis were obtained by recrystallization from
iso-propanol. L1: found: C, 61.3; H, 7.4; N, 22.6%.
C19H26N6O2 requires C, 61.6;H, 7.1; N, 22.7%, mp:
151–152 ꢁC; TLC: single spot. 1H NMR (DMF-d7,
ppm):9.38 (s, 1H, (O1)H), 7.77 (s, 1H, (C8)H), 7.60
(s, 1H, (N6)H), 7.12 (t, 1H, (C14)H, J = 7.7 Hz), 6.94
(s, 1H, (C11)H), 6.87 (d, 1H, (C15)H, J = 7.5 Hz),
6.71 (dd, 1H, (C13)H, Ja = 7.9 Hz, Jb = 2.2 Hz), 5.82
(d, 1H, (N2)H, J = 7.7 Hz), 4.91 (s, 1H, (02)H), 4.74
(s, 2H, (C9)H), 4.62 (sep, 1H, (C19)H, J = 6.8 Hz),
3.98 (m, 1H, (C16)H), 3.66 (m, 1Ha, (C20)H), 3.58
(m, 1Hb, (C20)H), 1.74 (sep, 1Ha, (C21)H,
J = 7.0 Hz), 1.59 (sep, 1Hb(C21)H, J = 7.0 Hz), 1.53
(d, 6H, (C17,18)H, J = 6.6 Hz), 0.94 (t, 3H, (C22)H,
J = 7.5 Hz). 13C NMR (DMF-d7, ppm): 160.27 (C2),
158.55 (C12), 155.68 (C6), 151.77 (C4), 143.15 (C10),
135.68 (C8), 129.69 (C11), 118.77 (C15), 115.05
(C14), 114.90 (C5), 114.18 (C13), 64.52 (C20), 55.29
(C19), 46.81 (C16), 43.77 (C9), 24.91 (C21), 22.34
(C17,18), 10.99 (C22). L2: found: C, 62.3; H, 7.3; N,
21.9%. C20H28N6O2 requires C, 62.5; H, 7.3; N,
21.9%, mp: 179–180 ꢁC; TLC: single spot. 1H NMR
(DMF-d7, ppm): 9.43 (s, 1H, (O1)H), 7.77 (s, 1H,
(C8)H), 7.58 (s, 1H, (N6)H), 7.12 (t, 1H,(C14)H,
J = 7.7 Hz), 6.94 (t, 1H,(C11)H, J = 1.8 Hz), 6.87 (d,
1H,(C15)H, J = 7.5 Hz), 6.71 (dd, 1H, (C13)H,
Ja = 7.9 Hz, Jb = 2.2 Hz), 5.82 (d, 1H, (N2)H,
J = 7.8 Hz), 4.89 (s, 1H, (O2)H), 4.74 (s, 2H, (C9)H),
4.62 (sep, 1H, (C19)H, J = 6.8 Hz), 3.98 (m, 1H,
(C16)H), 3.66 (qui, 2H, (C20)H, J = 4.5 Hz), 2.07
(sxt, 1H, (C21)H, J = 6.8 Hz), 1.53 (dd, 6H,
(C17,18)H, Ja = 6.8 Hz, Jb = 1.9 Hz), 0.97 (d, 3H,
(C22)H, J = 6.8 Hz), 0.95 (d, 3H, (C23)H,
J = 6.8 Hz). 13C NMR (DMF-d7, ppm): 160.54 (C2),
158.55 (C12), 155.63 (C6), 151.77 (C4), 143.13 (C10),
135.65 (C8), 129.67 (C11), 118.75 (C15), 115.03
(C14), 114.88 (C5), 114.77 (C13), 62.93 (C20), 58.71
(C19), 46.79 (C16), 43.79 (C9), 29.02 (C21), 22.38
(C17), 22.29 (C18), 19.93 (C22), 18.92 (C23). L3:
found: C, 56.5; H, 5.0; N, 21.6%. C15H16N5OC1 re-
quires C, 56.7; H 5.1; N, 22.0%, mp: 217–218 ꢁC;
3.2. Methods
3.2.1. General techniques. Elemental analyses (C, H, and
N) were determined on an EA1112 Flash analyzer
(ThermoFinnigan). Thin layer chromatography (TLC)
was
performed
using
CHC13/CH3OH/NH4OH
(8:2:0.1) mobile phase and carried out using silica gel
60 WF254 plates (Merck Co.). Melting points (mp)
¨
were determined with a BUCHI Melting Point B-540.
Conductivity measurements were performed on a Con-
d340i/SET conductometer (WTW, Germany) in
dimethylformamide (DMF) and acetone solutions
(10À3 M) at 25 ꢁC. FT-IR spectra in the range 150–
600 cmÀ1 were measured using polyethylene (PE) discs
or nujo1 technique, while FT-IR spectra in the region
400–4000 cmÀ1 were obtained by the KBr disc tech-
nique, both using a NEXUS 670 FT-IR spectrometer
(Thermo Nicolet). Thermogravimetric analysis and
differential scanning calorimetry (DSC) measurements
were performed on a TGA XP-10 Thermogravimetric
Analyser (THASS, GmbH). TGA was performed in
the range 20–600 ꢁC with the gradient 5 ꢁC per minute,
while DSC recorded in the range 20–400 ꢁC with the
gradient 5 ꢁC per minute. The measurements were tak-
en in the air atmosphere. ES+ MS spectra were record-
ed using an electrospray probe on a Waters ZMD 2000
mass spectrometer. The mass monitoring interval was
10–1500 m/z. All interpretations of m/z were related
to 35C1, 194Pt and 104Pd. The spectra were collected
using 3.0 s cyclical scans and applying the sample cone
voltage: 20, 40 and 60 V at the source block tempera-
ture of 80 ꢁC. Desolvation temperature was 150 ꢁC
and desolvation gas flowrate 200 L/h. The mass spec-
trometer was directly coupled to a Mass Lynx data
system.
1H, 13C and 195Pt NMR spectra were recorded on a
Bruker Avance 300 spectrometer at 300 K. The sam-
1
TLC: single spot. H NMR (DMF-d7, ppm): 9.48 (s,