Please cite this article in press as: Reckzeh et al., Inhibition of Glucose Transporters and Glutaminase Synergistically Impairs Tumor Cell Growth, Cell
0
.08 mmol, 1.0 equiv.). The product was obtained as light yellow solid (11.5 mg, 0.02 mmol, 27%). R
1
:1). H NMR (500 MHz, CDCl
f
= 0.42 (cyclohexane / EtOAc =
1
3
) d 7.80 (d, J = 7.4 Hz, 2H), 7.41 (t, J = 7.4 Hz, 2H), 7.34 (t, J = 7.4 Hz, 1H), 7.28 (s, 1H), 7.13 – 7.02
(
m, 4H), 6.70 (d, J = 7.0 Hz, 2H), 6.55 – 6.56 (m, 2H), 6.20 – 6.13 (m, 1H), 5.10 (d, J = 12.8 Hz, 1H), 4.95 (d, J = 15.0 Hz, 1H), 4.70
d, J = 15.0 Hz, 1H), 4.32 (dd, J = 15.0, 7.0 Hz, 1H), 4.17 (d, J = 12.8 Hz, 1H), 3.80 (dd, J = 15.0 Hz, 1H), 3.31 (q, J = 7.0 Hz, 4H),
(
1
3
.80 (s, 3H), 1.13 ppm (t, J = 7.0 Hz, 6H). C NMR (126 MHz, CDCl
1
3
) d 171.2, 159.1, 152.1, 147.5, 137.2, 134.5, 132.5, 129.8,
1
28.9, 128.6, 128.4, 127.4, 127.0, 125.8, 123.8, 112.1, 105.2, 65.9, 55.9, 45.4, 44.4, 44.0, 21.8, 12.6 ppm. HR-MS: calc. for
+
+
[
36 5 2 35 5 2
M+H] C32H N O 522.2864 found 522.2873, calc. for [M+Na] C32H N O Na 544.2694 found 544.2694.
N-Benzyl-5-(4-(dimethylamino)benzyl)-6-methyl-4-oxo-2-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-6-carboxamide
(2c).
Prepared according to the general procedure 2 using 1-(2-oxopropyl)-3-phenyl-1H-pyrazole-5-carboxylic acid 6a (36.7 mg,
0
.15 mmol, 1.0 equiv.), (4-aminomethyl)-N,N-dimethylaniline 9b (22.2 mL, 0.15 mmol, 1.0 equiv.) and benzyl isocyanide
k (18.3 mL, 0.15 mmol, 1.0 equiv.). The product was obtained as light-yellow solid (44.4 mg, 0.09 mmol, 60%). R = 0.38 (cyclo-
) d 7.81 – 7.79 (m, 2H), 7.42 (t, J = 7.5 Hz, 2H), 7.35 (t, J = 7.5 Hz, 1H), 7.29
d, J = 8.6 Hz, 2H), 7.14 – 7.03 (m, 5H), 6.72 (d, J = 7.1 Hz, 2H), 6.61 (bs, 1H), 6.14 (t, J = 5.4 Hz, 1H), 5.10 (d, J = 12.8 Hz, 1H),
8
f
1
hexane / EtOAc = 1:1). H NMR (500 MHz, CDCl
3
(
4
4
1
.91 (d, J = 14.7 Hz, 1H), 4.77 (d, J = 14.7 Hz, 1H), 4.28 (dd, J = 14.9, 7.0 Hz, 1H), 4.17 (d, J = 12.8 Hz, 1H), 3.88 (dd, J = 14.9,
1
.6 Hz, 1H), 2.92 (s, 6H), 1.78 ppm (s, 3H). C NMR (126 MHz, CDCl
3
3
) d 171.1, 159.1, 152.2, 137.2, 134.4, 132.4, 129.4, 128.9,
+
28.6, 128.4, 127.4, 127.1, 125.8, 112.9, 105.2, 77.4, 65.9, 60.6, 55.9, 45.4, 44.1, 40.6, 21.8 ppm. HR-MS: calc. for [M+H]
+
30 32 5 2 31 5 2
C H N O 494.2551 found 494.2561, calc. for [M+Na] C30H N O Na 516.2370 found 516.2382.
N-Benzyl-5-(4-isopropoxybenzyl)-6-methyl-4-oxo-2-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-6-carboxamide (2e). Pre-
pared according to general procedure 2 using 1-(2-oxopropyl)-3-phenyl-1H-pyrazole-5-carboxylic acid 6a (20.0 mg, 0.08 mmol,
1
.0 equiv.), (4-isopropoxyphenyl)-methanamine 9d (13.7 mL, 0.08 mmol, 1.0 equiv.) and benzyl isocyanide 8k (10.0 mL, 0.08 mmol,
1
1
.0 equiv.). The product was obtained as brown solid (24.9 mg, 0.05 mmol, 60%). R
) d 7.99 (d, J = 7.2 Hz, 2H), 7.71 – 7.45 (m, 5H), 7.31 (d, J = 7.2 Hz, 3H), 6.98 – 7.03 (m, 4H), 6.65 – 6.77 (m, 1H),
.55 – 5.23 (m, 2H), 4.88 (d, J = 15.0 Hz, 1H), 4.73 (hept, J = 6.0 Hz, 1H), 4.59 (d, J = 15.0 Hz, 1H), 4.39 – 4.44 (m, 1H), 4.22
f
= 0.55 (cyclohexane / EtOAc = 1:1). H NMR
(
500 MHz, CDCl
3
5
13
(
3
d, J = 15.0 Hz, 1H), 1.94 (s, 3H), 1.55 ppm (d, J = 6.0 Hz, 6H). C NMR (126 MHz, CDCl ) d 170.9, 159.1, 157.6, 152.2, 137.2,
e13 Cell Chemical Biology 26, 1–15.e1–e25, September 19, 2019