RAPID SYNTHESIS AND LIPASE INHIBITION ACTIVITY
339
Table 2. Inhibitory effects of selected synthesized comꢀ
pounds (at final concentration of 1 g/mL). Orlistat was used
as a positive control at the final concentration of 10 ng/mL
2ꢀ(3,4ꢀDichlorobenzyl)ꢀ1
2.35 g (72%); mp: 194–195
3.77 (2 H, s, CH2), 6.58 (2 H, d,
7.11–7.19 (4 H, m, ArꢀH), 7.50 (1 H d,
ArꢀH), 7.62 (1 H, d, = 8.0 Hz, ArꢀH), 7.78 (1 H, s,
ArꢀH); 13C NMR (DMSOꢀd6
(ppm): 38.68 (CH2),
108.27, 120.20, 127.89, 121.44, 128.78, 129.90, 130.41,
131.14, 131.50, 131.61, 135.21, 136.96, 138.88, 157.28.
Anal. calculated for C18H12Cl2N2: C, 66.07; H, 3.70 and
N, 8.56; found: C, 66.15; H, 3.76 and N, 8.57.
Hꢀperimidine (2a). Yield:
1
μ
°
C; H NMR
= 7.2 Hz, ArꢀH),
= 8.0 Hz,
δ
(ppm):
J
J
% Inhibition
(1 μg/mL)
Compound
IC50
(μg/mL)
J
)
δ
(5)
47.4
65.2
65.2
64.1
26.2
29.8
92.7
1.24
0.26
0.20
0.68
1.46
1.81
(2b)
(2f)
(2g)
(6a)
(6g)
2ꢀ(2,4ꢀDichlorobenzyl)ꢀ1
2.48 g (76%); mp: 178–179
3.74 (2 H, s, CH2), 6.80 (2 H, d,
7.00 (2 H, d, = 8.0 Hz, ArꢀH), 7.11 (2 H, t,
ArꢀH), 7.43 (1 H, d, = 8.0 Hz, ArꢀH), 7.51 (1 H, d,
= 8.2 Hz, ArꢀH), 7.62 (1 H, s, ArꢀH), 10.68 (1 H, br,
NH); 13C NMR (DMSOꢀd6
(ppm): 38.04 (CH2),
Hꢀperimidine (2b). Yield:
1
°
C; H NMR
= 7.2 Hz, ArꢀH),
= 8.2 Hz,
δ
(ppm):
J
Orlistat (10 ng/mL)
0.85
×
10–3
J
J
J
J
ArꢀH), 6.42 (2 H, s, ArꢀH), 6.83 (2 H, t, J = 7.4 Hz,
ArꢀH), 7.13 (2 H, d, J = 7.0 Hz, ArꢀH), 7.35 (1 H, s,
ArꢀH), 7.53 (1 H, m, ArꢀH), 12.56 (1 H, s, NH);
)
δ
121.86, 127.89, 128.80, 129.01, 132.65, 133.16,
134.07, 134.97, 135.54, 155.11. Anal. calculated for
C18H12Cl2N2: C, 66.07; H, 3.70 and N, 8.56; found:
C, 66.12; H, 3.74 and N, 8.59.
13C NMR (DMSOꢀd6
) δ (ppm): 39.05 (CH2), 105.01,
114.63, 118.01, 127.49, 130.76, 132.80, 135.37, 140.56,
143.56, 146.12, 156.24. Anal. calculated for C18H13BrN2:
C, 64.11; H, 3.89 and N, 8.31; found: C, 64.14; H, 3.84
and N, 8.31.
2ꢀ(2,6ꢀDichlorobenzyl)ꢀ1
2.52 g (77%); mp: 194–195
Hꢀperimidine (2c). Yield:
1
°
C; H NMR
δ
(ppm):
3.95 (2 H, s, CH2), 6.30 (2 H, dd, J = 1.2, ArꢀH),
6.93–7.10 (4 H, m, ArꢀH), 7.30–7.35 (1 H, m, ArꢀH),
7.48 (1 H, d, J = 1.6, ArꢀH), 10.78 (1 H, s, NH);
2ꢀ[4ꢀ(Bromomethyl)phenyl]ꢀ1
Yield: 2.42 g (72%); mp: 148
C (decomp.); 1H NMR
(ppm): 4.67 (2 H, s, CH2), 6.43 (2 H, d, = 7.1 Hz,
Hꢀperimidine (2g).
°
δ
J
13C NMR (DMSOꢀd6)
δ
(ppm): 38.45 (CH2), 119.18,
ArꢀH), 6.46 (2 H, s, ArꢀH), 6.78 (2 H, t, J = 7.6 Hz,
ArꢀH), 7.03 (2 H, d, J = 7.1 Hz, ArꢀH), 7.25 (1 H, s,
ArꢀH), 7.43 (1 H, m, ArꢀH), 12.46 (1 H, s, NH);
121.98, 128.89, 129.04, 130.17, 132.91, 135.67, 136.32,
154.83. Anal. calculated for C18H12Cl2N2: C, 66.07;
H, 3.70 and N, 8.56; found: C, 66.12; H, 3.75 and N, 8.59.
13C NMR (DMSOꢀd6
) δ (ppm): 40.02 (CH2), 103.01,
2ꢀ(3,4ꢀDimethoxybenzyl)ꢀ1
2.29 g (72%); mp: 265 C (decomp.); H NMR
(ppm): 3.68 (3 H, s, OCH3), 3.80 (3 H, s, OCH3), 3.89
(2 H, s, CH2), 6.88 (2H, m, ArꢀH), 6.94 (1 H, d,
8.4 Hz, ArꢀH), 7.20–7.28 (5 H, m, ArꢀH), 7.47 (1 H,
s, ArꢀH); 13C NMR (DMSOꢀd6
(ppm): 37.07
(CH2), 56.00, 56.19 (OCH3),108.37, 112.50, 113.95,
120.54, 121.85, 122.10, 126.23, 128.95, 134.19, 134.70,
148.90, 149.30, 160.57. Anal. calculated for C20H18N2O2:
C, 75.45; H, 5.70 and N, 8.80; found: C, 75.48; H, 5.74
and N, 8.85.
Hꢀperimidine (2d). Yield:
107.89, 114.21, 122.89, 128.06, 135.87, 138.30,
144.89, 148.60, 150.02, 157.29. Anal. calculated for
C18H13BrN2: C, 64.11; H, 3.89 and N, 8.31; found,
C, 64.14; H, 3.88 and N, 8.38.
1
°
δ
J
=
5,6ꢀDichloroꢀ2ꢀ(3,4ꢀdichlorobenzyl)ꢀ1
dazole (3a). Yield: 3.11 g (90%); mp: 208–209
1H NMR
(ppm): 4.23 (2 H, s, CH2), 7.25–7.33
(1 H, m, ArꢀH); 7.56–7.63 (2 H, m, ArꢀH), 7.76 (2 H, s,
ArꢀH), 12.67 (1 H, s, NH, D2O exchangeable);
13C NMR (DMSOꢀd6
(ppm): 34.11 (CH2), 124.41,
H
ꢀbenzimiꢀ
)
δ
°
C;
δ
)
δ
129.89, 129.94, 129.96, 130.44, 130.81, 131.07,
131.44, 132.01, 135.99, 138.46 (ArꢀC), 156.07
(C=N). Anal. calculated for C18H13Cl4N2: C, 48.59;
H, 2.33 and N, 8.10; found: C, 48.55; H, 2.36 and N, 8.14.
2ꢀ(3,4,5ꢀTrimethoxybenzyl)ꢀ1
Yield: 2.57 g (74%); mp: 135–136
(ppm): 3.50 (2 H, s, CH2), 3.61 (3 H, s, OCH3), 3.75
(6 H, s, OCH3), 6.44 (2 H, = 7.0 Hz, ArꢀH), 6.72
(2 H, s, ArꢀH), 7.05 (2 H, t, J = 7.4 Hz, ArꢀH), 7.11
(2 H, d, J = 7.0 Hz, ArꢀH); 13C NMR (DMSOꢀd6
Hꢀperimidine (2e).
1
°
C; H NMR
δ
d, J
5,6ꢀDichloroꢀ2ꢀ(2,4ꢀdichlorobenzyl)ꢀ1
dazole (3b). Yield: 3.11 g (90%); mp: 188–189
1H NMR
(ppm): 4.32 (2 H, s, CH2), 7.42–7.47
(2 H, m, ArꢀH), 7.63 (1 H, s, ArꢀH), 7.75 (2 H, s, ArꢀH),
12.65 (1 H, s, NH); 13C NMR (DMSOꢀd6
(ppm):
H
ꢀbenzimiꢀ
°
C;
)
δ
δ
(ppm): 40.72 (CH2), 55.81 (OCH3), 59.84 (OCH3),
106.11, 118.62, 121.06, 128.34, 131.76, 134.82,
136.33, 152.71, 156.24. Anal. calculated for
C21H20N2O3: C, 72.40; H, 5.79 and N, 8.04; found:
C, 72.43; H, 5.72 and N, 8.00.
)
δ
32.66 (CH2), 124.36, 127.97, 129.23, 132.96, 133.42,
134.20, 134.81 (ArꢀC), 155.35 (C=N). Anal. calculated
for C18H13Cl4N2: C, 48.59; H, 2.33 and N, 8.10; found:
C, 48.56; H, 2.38 and N, 8.10.
2ꢀ[3ꢀ(Bromomethyl)phenyl]ꢀ1
Yield: 2.32 g (69%); mp: 180
C (decomp.); 1H NMR
(ppm): 4.45 (2 H, s, CH2), 6.35 (2 H, d, = 7.0 Hz,
Hꢀperimidine (2f).
°
5,6ꢀDichloroꢀ2ꢀ(2,6ꢀdichlorobenzyl)ꢀ1
dazole (3c). Yield: 3.21 g (93%); mp: 293–294
H
ꢀbenzimiꢀ
δ
J
°
C;
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 40
No. 3
2014