J. Dong, X. Pan, Y. Yang et al.
European Journal of Medicinal Chemistry 223 (2021) 113631
4.21.9. N-(2-(40-methoxy-1,10,3-trimethyl-2,5,70,110-tetraoxo-
50,70,100,110-tetrahydrospiro[imidazolidine-4,60-naphtho [2,1-f]
indol]-80-yl)ethyl)-3-(trifluoromethyl)benzamide 22i
4.21.14. N-(2-(40-methoxy-1,10,3-trimethyl-2,5,70,110-tetraoxo-
50,70,100,110-tetrahydrospiro[imidazolidine-4,60-naphtho [2,1-f]
indol]-80-yl)ethyl)quinoline-2-carboxamide 22n
Mp: 179e181 ꢁC; 1H NMR (400 MHz, CD3OD)
d
8.09 (s, 1H), 8.00
Mp: 180e182 ꢁC; 1H NMR (400 MHz, CD3OD)
d 8.44 (d,
(dd, J ¼ 8, 0.8 Hz, 1H), 7.81 (dd, J ¼ 8, 0.8 Hz, 1H), 7.66 (t, J ¼ 8 Hz,
1H), 7.22 (d, J ¼ 8.8 Hz, 1H), 7.07e7.05 (m, 2H), 3.86 (s, 3H),
3.69e3.59 (m, 2H), 3.40 (d, J ¼ 16.8 Hz, 1H), 3.13 (s, 3H), 3.07e2.98
J ¼ 8.4 Hz, 1H), 8.16e8.11 (m, 2H), 7.97 (d, J ¼ 8.4 Hz, 1H), 7.80 (t,
J ¼ 7.2 Hz, 1H), 7.66 (t, J ¼ 7.2 Hz, 1H), 7.21 (d, J ¼ 8.4 Hz, 1H), 7.09 (s,
1H), 7.05 (d, J ¼ 8.4 Hz, 1H), 3.85 (s, 3H), 3.76 (dd, J ¼ 13.6, 6.8 Hz,
1H), 3.69 (dd, J ¼ 13.6, 6.8 Hz, 1H), 3.38 (d, J ¼ 16.8 Hz, 1H),
3.16e3.11 (m, 4H), 3.05 (dd, J ¼ 14, 6.8 Hz, 1H), 2.99 (d, J ¼ 16.8 Hz,
(m, 3H), 2.21 (s, 6H); 13C NMR (100 MHz, CD3OD)
d 182.6, 178.1,
176.7, 168.5, 157.3, 156.9, 155.7, 148.4, 138.9, 136.8, 133.0, 132.4,
131.8, 130.7, 130.6, 130.6, 129.1, 126.9, 125.3, 124.8, 123.5, 114.3, 63.4,
56.4, 41.4, 33.4, 27.1, 26.4, 25.8, 23.2; HRMS calcd. for C32H28F3N4O6
[MþH]þ 621.1955, found 621.1964.
1H), 2.21 (s, 3H), 2.13 (s, 3H); 13C NMR (100 MHz, CD3OD)
d 182.5,
178.1, 176.7, 166.9, 157.2, 155.7, 154.2, 151.1, 148.3, 148.0, 139.0, 138.9,
132.4, 131.5, 130.8, 130.8, 130.6, 130.5, 129.3, 129.0, 126.9, 124.7,
123.5, 119.5, 114.2, 63.4, 56.4, 40.8, 33.4, 27.1, 26.6, 25.8, 23.2; HRMS
calcd. for C34H30N5O6 [MþH]þ 604.2191, found 604.2177.
4.21.10. 3,4,5-Trimethoxy-N-(2-(40-methoxy-1,10,3-trimethyl-
2,5,70,110-tetraoxo-50,70,100,110-tetrahydrospiro[imidazolidine-4,60-
naphtho [2,1-f]indol]-80-yl)ethyl)benzamide 22j
4.21.15. N-(2-(40-methoxy-1,10,3-trimethyl-2,5,70,110-tetraoxo-
50,70,100,110-tetrahydrospiro[imidazolidine-4,60-naphtho [2,1-f]
indol]-80-yl)ethyl)benzofuran-2-carboxamide 22o
Mp: 151e153 ꢁC; 1H NMR (400 MHz, CD3OD)
d
7.22 (d, J ¼ 8.8 Hz,
1H), 7.11 (s, 2H), 7.07e7.04 (m, 2H), 3.87 (s, 6H), 3.86 (s, 3H), 3.79 (s,
3H), 3.65e3.56 (m, 2H), 3.39 (d, J ¼ 16.8 Hz, 1H), 3.13 (s, 3H),
Mp: 191e193 ꢁC; 1H NMR (400 MHz, CD3OD)
d
7.70 (dd, J ¼ 8,
0.8 Hz, 1H), 7.56 (dt, J ¼ 8, 0.8 Hz, 1H), 7.45e7.41 (m, 2H), 7.31e7.27
(m, 1H), 7.21 (d, J ¼ 8.4 Hz, 1H), 7.06e7.04 (m, 2H), 3.85 (s, 3H),
3.70e3.61 (m, 2H), 3.39 (d, J ¼ 16.8 Hz, 1H), 3.14 (s, 3H), 3.10e2.97
(m, 3H), 2.21 (s, 3H), 2.17 (s, 3H); 13C NMR (100 MHz, CD3OD)
3.07e2.97 (m, 3H), 2.21 (s, 6H); 13C NMR (125 MHz, CD3OD)
d 181.0,
176.6, 175.3, 168.2, 155.8, 154.3, 153.0, 146.9, 140.6, 137.4, 134.7,
131.6,131.0,129.7,129.2,129.1,125.5,125.3,123.4,122.1,122.0,112.8,
104.4, 61.9, 59.7, 55.3, 55.3, 55.0, 39.7, 32.0, 25.7, 25.1, 24.4, 21.8;
HRMS calcd. for C34H35N4O9 [MþH]þ 643.2399, found 643.2385.
d
182.6, 178.1, 176.7, 161.3, 157.3, 156.5, 155.7, 150.1, 148.3, 138.9,
133.0, 132.4, 130.6, 130.5, 128.9, 128.1, 126.9, 124.9, 124.7, 123.8,
123.5, 114.2, 112.9, 111.1, 63.4, 56.4, 40.7, 33.4, 27.1, 26.5, 25.8, 23.2;
HRMS calcd. for C33H29N4O7 [MþH]þ 593.2031, found 593.2035.
4.21.11. N-(2-(40-methoxy-1,10,3-trimethyl-2,5,70,110-tetraoxo-
50,70,100,110-tetrahydrospiro[imidazolidine-4,60-naphtho [2,1-f]
indol]-80-yl)ethyl)-2-(3-(trifluoromethyl)phenyl)acetamide 22k
4.21.16. N-(2-(40-methoxy-1,10,3-trimethyl-2,5,70,110-tetraoxo-
50,70,100,110-tetrahydrospiro[imidazolidine-4,60-naphtho [2,1-f]
indol]-80-yl)ethyl)benzo[b]thiophene-2-carboxamide 22p
Mp: 171e173 ꢁC; 1H NMR (400 MHz, CD3OD)
d 7.58 (s, 1H),
7.55e7.47 (m, 3H), 7.22 (d, J ¼ 8.4 Hz, 1H), 7.07 (d, J ¼ 8.4 Hz, 1H),
6.92 (s, 1H), 3.86 (s, 3H), 3.52 (s, 2H), 3.47 (dd, J ¼ 13.2, 6.4 Hz, 1H),
3.42e3.37 (m, 2H), 3.14 (s, 3H), 3.00 (d, J ¼ 16.8 Hz, 1H), 2.90 (t,
J ¼ 6.8 Hz, 2H), 2.23 (s, 3H), 2.21 (s, 3H); 13C NMR (100 MHz, CD3OD)
Mp: 177e179 ꢁC; 1H NMR (400 MHz, CD3OD)
d 7.91e7.88 (m,
2H), 7.84 (d, J ¼ 0.8 Hz, 1H), 7.42e7.38 (m, 2H), 7.20 (d, J ¼ 8.4 Hz,
1H), 7.07e7.04 (m, 2H), 3.85 (s, 3H), 3.65e3.61 (m,2H), 3.39 (d,
J ¼ 16.8 Hz, 1H), 3.14 (s, 3H), 3.10e2.97 (m, 3H), 2.20 (s, 3H), 2.14 (s,
d
182.6, 178.0, 176.7, 173.2, 157.3, 155.8, 148.4, 138.8, 138.5, 133.9,
133.0, 132.5, 130.6, 130.5, 130.3, 126.9, 126.8, 124.7, 124.6, 123.5,
123.5, 114.3, 63.4, 56.4, 43.5, 40.9, 33.4, 27.1, 26.4, 25.8, 23.3; HRMS
calcd. for C33H30F3N4O6 [MþH]þ 635.2112, found 635.2094.
3H); 13C NMR (100 MHz, CD3OD)
d 181.2, 176.6, 175.2, 163.3, 155.8,
154.2, 146.9, 140.9, 139.3, 138.6, 137.4, 130.9, 129.0, 125.9, 125.5,
125.1, 124.9, 124.8, 124.5, 123.3, 122.2, 122.0, 112.7, 61.9, 54.9, 40.1,
31.9, 25.6, 24.9, 24.3, 21.7; HRMS calcd. for C33H29N4O6S [MþH]þ
609.1802, found 609.1796.
4.21.12. N-(2-(40-methoxy-1,10,3-trimethyl-2,5,70,110-tetraoxo-
50,70,100,110-tetrahydrospiro[imidazolidine-4,60-naphtho [2,1-f]
indol]-80-yl)ethyl)-2-(4-methoxyphenyl)acetamide 22l
4.21.17. N-(2-(40-methoxy-1,10,3-trimethyl-2,5,70,110-tetraoxo-
50,70,100,110-tetrahydrospiro[imidazolidine-4,60-naphtho [2,1-f]
indol]-80-yl)ethyl)thiophene-2-carboxamide 22q
Mp: 157e159 ꢁC; 1H NMR (400 MHz, CD3OD)
d 7.22 (d,
J ¼ 8.4 Hz,1H), 7.14e7.10 (m, 2H), 7.06 (d, J ¼ 8.4 Hz,1H), 6.90 (s,1H),
6.84e6.81 (m, 2H), 3.86 (s, 3H), 3.74 (s, 3H), 3.48e3.38 (m, 3H), 3.35
(s, 2H), 3.13 (s, 3H), 3.20 (d, J ¼ 16.8 Hz, 1H), 2.88 (t, J ¼ 6.8 Hz, 2H),
Mp: >250 ꢁC; 1H NMR (400 MHz, CD3OD)
d
7.59 (dd, J ¼ 5.2,
1.2 Hz, 1H), 7.56 (dd, J ¼ 3.6, 1.2 Hz, 1H), 7.21 (d, J ¼ 8.4 Hz, 1H), 7.09
(dd, J ¼ 5.2, 3.6 Hz, 1H), 7.07e7.04 (m, 2H), 3.86 (s, 3H), 3.62e3.54
(m, 2H), 3.40 (d, J ¼ 16.8 Hz, 1H), 3.14 (s, 3H), 3.07e2.95 (m, 3H),
2.23 (s, 3H), 2.21 (s, 3H); 13C NMR (100 MHz, CD3OD)
d 181.1, 176.5,
175.2, 173.1, 158.7, 155.8, 154.2, 146.9, 137.3, 131.5, 130.9, 129.6, 129.1,
129.0, 127.5, 125.4, 123.2, 122.0, 122.0, 113.5, 112.8, 61.9, 54.9, 54.2,
41.7, 39.1, 31.9, 25.6, 24.8, 24.3, 21.8; HRMS calcd. for C33H33N4O7
[MþH]þ 597.2344, found 597.2336.
2.20 (s, 6H); 13C NMR (100 MHz, CD3OD)
d 176.5, 175.2, 163.0, 154.2,
137.4,134.9,131.5,130.9,130.0,129.1,128.1,127.4,125.5,125.3,123.4,
122.0, 118.7, 116.8, 115.1, 112.8, 61.9, 54.9, 40.1, 31.9, 25.7, 24.9, 24.3,
21.7; HRMS calcd. for C29H27N4O6S [MþH]þ 559.1646, found
559.1637.
4.21.13. N-(2-(40-methoxy-1,10,3-trimethyl-2,5,70,110-tetraoxo-
50,70,100,110-tetrahydrospiro[imidazolidine-4,60-naphtho [2,1-f]
indol]-80-yl)ethyl)-1H-indole-2-carboxamide 22m
4.21.18. N-(2-(40-methoxy-1,10,3-trimethyl-2,5,70,110-tetraoxo-
50,70,100,110-tetrahydrospiro[imidazolidine-4,60-naphtho [2,1-f]
indol]-80-yl)ethyl)furan-2-carboxamide 22r
Mp: 231e233 ꢁC; 1H NMR (400 MHz, CD3OD)
1H), 7.41 (d, J ¼ 8 Hz,1H), 7.22e7.17 (m, 2H), 7.06e7.00 (m, 3H), 6.96
(s, 1H), 3.86 (s, 3H), 3.63 (t, J ¼ 7.2 Hz, 2H), 3.40 (d, J ¼ 16.8 Hz, 1H),
3.15 (s, 3H), 3.10e2.98 (m, 3H), 2.20 (s, 3H), 2.18 (s, 3H); 13C NMR
d
7.62 (d, J ¼ 8 Hz,
Mp: 226e228 ꢁC; 1H NMR (400 MHz, CD3OD)
1H), 7.21 (d, J ¼ 8.4 Hz, 1H), 7.07e7.03 (m, 3H), 6.54 (dd, J ¼ 3.2,
1.6Hz, 1H), 3.86 (s, 3H), 3.63e3.54 (m, 2H), 3.40 (d, J ¼ 16.8 Hz, 1H),
3.14 (s, 3H), 3.05e2.95 (m, 3H), 2.22 (s, 3H), 2.21 (s, 3H); 13C NMR
d
7.62 (d, J ¼ 2 Hz,
(100 MHz, CD3OD)
d 178.1, 177.6, 176.7, 164.2, 157.3, 155.7, 148.4,
138.9, 138.3, 132.4, 132.2, 130.6, 130.5, 129.1, 127.0, 125.0, 124.9,
123.5, 122.9, 121.1, 114.2, 113.0, 104.2, 63.4, 56.4, 41.1, 33.4, 27.1, 26.5,
25.9, 23.2; HRMS calcd. for C33H30N5O6 [MþH]þ 592.2191, found
592.2182.
(100 MHz, CD3OD) d 182.7, 178.1, 176.7, 161.0, 157.3, 155.7, 149.1,
148.4, 146.3, 138.9, 133.0, 132.4, 130.6, 130.6, 126.9, 124.8, 123.5,
123.5, 115.1, 114.3, 112.9, 63.4, 56.4, 40.7, 33.4, 27.2, 26.4, 25.8, 23.3;
HRMS calcd. for C29H27N4O7 [MþH]þ 543.1874, found 543.1870.
13