Page 161 - 《精细化工》2021年第3期

第 3 期 卢言菊，等: N-杂环异海松酰基磺酰胺的制备及其抗肿瘤活性 ·581·

187.0, 176.5, 153.5, 151.0, 149.9, 149.8, 133.5, 135.1, (C==O), 1630 (C==C), 1342, 1290, 1166 (—SO 2 —);
134.6, 132.9, 132.6, 132.4, 130.4, 127.4, 126.6, 121.2, 1 HNMR (DMSO-d 6 , 400 MHz), δ: 9.15 (s, 1H), 8.60 (s,
121.0, 109.7, 51.4, 46.3, 44.8, 40.1, 36.4, 34.7, 21.2, 1H), 8.41 (s, 1H), 7.53, 7.51 (d, J = 8.93 Hz, 2H), 7.03,
+
17.2, 15.0; ESIMS [M+H] , m/Z: 实测值（计算值） 7.01 (d, J = 8.91 Hz, 2H), 5.83~5.75 (t, J = 9.54、6.91
600.0 (600.8)。 Hz, 1H), 5.29~5.27 (t, J = 4.29、4.29 Hz, 1H), 4.95,
N-[4-(异海松酰胺基)苯基]-3-氯喹啉磺酰胺（Ⅴc）： 4.90 (d, J = 10.55 Hz, 1H), 4.88, 4.85 (d, J = 8.91 Hz,
浅红色固体，收率 50.7%；熔点：193.7~194.9 ℃。 IR 1H), 3.97 (s, 1H), 1.92~1.86 (t, J = 13.71、13.71 Hz,
–1
(ν/cm ): 3223 (N—H), 3082 (N—H), 1802, 1735, 1692 1H), 1.86 (s, 2H), 1.82, 1.80 (d, J = 9.14 Hz, 2H),
(C==O), 1638 (C==C), 1365, 1215, 1114 (—SO 2 —); 1.77~1.74 (t, J = 5.33、5.59 Hz, 2H), 1.54~1.50 (t, J =
1 9.40、10.16 Hz, 1H), 1.46~1.42 (m, 2H), 1.36~1.31 (t,
HNMR (DMSO-d 6 , 400 MHz), δ: 9.25 (s, 1H), 9.09 (s,
1H), 8.39, 8.37 (d, J = 6.86 Hz, 1H), 8.31, 8.29 (d, J = J = 11.94、8.13 Hz, 2H), 1.26 (s, 3H), 1.21~1.14 (m,
8.25 Hz, 1H), 8.22 (s, 1H), 7.96~7.93 (t, J = 7.12、7.04 2H), 1.08~1.04 (t, J = 6.35、6.60 Hz, 2H), 0.82 (s, 3H);
Hz, 1H), 7.28, 7.26 (d, J = 7.41 Hz, 2H), 6.71, 6.70 (d, 13 CNMR (DMSO-d 6 , 400 MHz), δ: 176.6, 153.4, 149.8,
J = 3.70 Hz, 2H), 5.83~5.78 (t, J = 8.43、11.50 Hz, 145.8, 140.4, 136.9, 135.9, 135.1, 131.3, 124.9, 122.3,
1H), 5.36~5.32 (t, J = 8.11、5.09 Hz, 1H), 4.96, 4.91 121.6, 121.0, 120.3, 112.6, 109.7, 51.4, 46.4, 36.4,
+
(d, J = 10.81 Hz, 1H), 4.90, 4.87 (d, J = 11.73 Hz, 1H), 34.7, 21.2, 17.3, 15.0; ESIMS [M+H] , m/Z: 实测值
4.09 (s, 1H), 1.97~1.90 (t, J = 11.30、15.20 Hz, 1H), （计算值）646.5 (647.0)。
1.82, 1.80 (d, J = 9.74 Hz, 2H), 1.76~1.74 (t, J = N-[4-(异海松酰胺基)苯基]-3-吡啶-磺酰胺（Ⅴf）：
3.59、3.85 Hz, 2H), 1.68 (s, 2H), 1.60~1.55 (t, J = 白色固体，收率 65.4%；熔点：148.6~149.7 ℃。IR
18.32、6.55 Hz, 1H), 1.45~1.43 (m, 2H), 1.39~1.34 (t, (ν/cm ): 3439 (N—H), 3083 (N—H), 1731 (C==O),
–1
J = 12.47、7.02 Hz, 2H), 1.24 (s, 3H), 1.18 (s, 3H), 1638 (C==C), 1383, 1203, 1176 (—SO 2 —); HNMR
1
1.10~1.03 (m, 2H), 1.03~0.98 (t, J = 9.74、7.02 Hz, 2H), (DMSO-d 6 , 400 MHz), δ: 10.13 (s, 1H), 8.98, 8.95 (d,
13
0.87 (s, 3H); CNMR (DMSO-d 6 , 400 MHz), δ: 180.0, J = 11.76 Hz, 1H), 8.83, 8.77 (d, J = 26.33 Hz, 1H),
173.8, 150.4, 150.1, 135.9, 135.7, 121.3, 120.8, 110.2, 8.06 (s, 1H), 7.60, 7.58, 7.55 (t, J = 7.84、8.40 Hz, 1H),
110.1, 52.3, 48.2, 46.1, 45.1, 38.8, 36.9, 36.2, 36.0, 7.47, 7.45 (d, J = 7.84 Hz, 1H), 7.02, 7.00 (d, J =
35.0, 25.4, 21.9, 20.1, 17.7, 17.3, 15.1; ESIMS 8.40 Hz, 1H), 5.84~5.78 (t, J = 10.85、11.45 Hz, 1H),
+
[M+H] , m/Z: 实测值（计算值）617.5 (618.2)。
5.36~5.35 (t, J = 3.01、3.01 Hz, 1H), 4.96, 4.91 (d, J =
N-[4-(异海松酰胺基)苯基]-2-氯-5-吡啶磺酰胺
18.08 Hz, 1H), 4.90, 4.87 (d, J = 11.05 Hz, 1H), 3.82
（Ⅴd）：白色固体，收率 88.7%；熔点：225.6~226.3 ℃。 (s, 1H), 1.97~1.87 (t, J = 11.94、13.17 Hz, 1H), 1.86
–1
IR (ν/cm ): 3385 (N—H), 3122 (N—H), 1645 (C==O), (s, 2H), 1.86, 1.83 (d, J = 13.17 Hz, 2H), 1.68~1.56 (t,
1
1336, 1280, 1170 (—SO 2 —); HNMR (DMSO-d 6 , J = 27.87、16.54 Hz, 2H), 1.56~1.51 (t, J = 13.17、
400 MHz), δ: 10.35 (s, 1H), 9.14 (s, 1H), 8.56, 8.64 (d, 11.02 Hz, 1H), 1.49~1.47 (m, 2H), 1.36~1.34 (t, J =
J = 2.49 Hz, 1H), 8.08、8.05 (d, J = 8.39 Hz, 1H), 7.74, 6.74、5.51 Hz, 2H), 1.24 (s, 3H), 1.22~1.16 (m, 2H),
7.72 (d, J = 8.76 Hz, 1H), 7.51, 7.49 (d, J = 8.39 Hz, 1.01~0.97 (t, J = 7.66、6.74 Hz, 2H), 0.87 (s, 3H), 0.84
1H), 7.01, 6.99 (d, J = 8.70 Hz, 2H), 5.83~5.76 (t, J = (s, 3H); CNMR (DMSO-d 6, 400 MHz), δ: 173.7, 150.1,
13
10.82、6.68 Hz, 1H), 5.29~5.28 (t, J = 5.76、5.76 Hz, 135.9, 120.8, 110.2, 52.3, 48.2, 46.1, 45.1, 38.8, 36.9,
1H), 4.95, 4.90 (d, J = 18.19 Hz, 1H), 4.88, 4.85 (d, 36.2, 36.0, 35.0, 25.4, 21.9, 20.1, 17.7, 17.3, 15.1;
J = 9.90 Hz, 1H), 3.98 (s, 1H), 3.98 (s, 1H), 1.93~1.89 ESIMS [M+H] , m/Z: 实测值（计算值）533.0 (533.8)。
+
(t, J = 13.89、8.01 Hz, 1H), 1.86 (s, 2H), 1.82, 1.81 (d,
1.3 抗肿瘤活性实验
J = 7.66 Hz, 2H), 1.79, 1.77, 1.74 (t, J = 7.86、8.53 Hz,
采用噻唑蓝（MTT）法测定 N-[4-(异海松酰胺
2H), 1.55~1.50 (t, J = 10.21、10.87 Hz, 1H), 1.46~1.42
基)苯基]-杂环磺酰胺类化合物的抗肿瘤活性：（1）细
(m, 2H), 1.37~1.31 (t, J = 13.89、8.37 Hz, 2H), 1.26
胞株培养，将待测人体肿瘤细胞株用胰蛋白酶-EDTA
(s, 3H), 1.21~1.13 (m, 2H), 1.03~0.97 (t, J = 9.54、 （质量分数 0.25%）消化液消化后，与质量分数 10%
13
10.87 Hz, 2H), 0.88 (s, 3H), 0.82 (s, 3H); CNMR 胎牛血清、磷酸缓冲盐溶液（PBS）和含各种氨基酸
(DMSO-d 6 , 400 MHz), δ: 176.6, 154.1, 152.5, 149.8,
147.8, 138.0, 136.6, 135.1, 131.6, 127.8, 125.2, 122.7, 和葡萄糖（DMEM）的培养基制成细胞悬浮液，置
122.1, 121.6, 121.0, 109.7, 51.4, 46.4, 44.8, 35.4, 34.7, 于 37 ℃、体积分数 5% CO 2 饱和水汽 CO 2 培养箱中
+
21.2, 17.3, 15.1; ESIMS [M+H] , m/Z: 实测值（计算 培养，3~4 d 传代一次；（2）受试化合物溶液的配制，
值）567.5 (568.2)。 用二甲基亚砜（DMSO）分别配制 N-[4-(异海松酰胺
N-[4-(异海松酰胺基)苯基]-3-溴-2-氯吡啶-5-磺 基)苯基]-杂环磺酰胺类化合物母液 100 mmol/L，稀释
酰胺（Ⅴe）：白色固体，收率 79.2%；熔点：162.3~ 配制成 100 和 10 µmol/L 的待测液；（3）MTT 法测
–1
162.8 ℃。IR (ν/cm ): 3438 (N—H), 3250 (N—H), 1665 试化合物对肿瘤细胞的抑制活性，细胞经消化、计