Journal of Medicinal Chemistry
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(t, J = 8.0 Hz, 2H), 4.84 (t, J = 7.8 Hz, 2H), 3.03 (t, J = 8.0 Hz, 2H),
2.92 (t, J = 7.8 Hz, 2H), 2.71 (m, 8H), 1.09 (m, 12H). 13C NMR (101
MHz, CDCl3) δC (ppm) 169.13, 139.70, 139.65, 131.38, 130.62,
127.32, 126.86, 124.89, 122.69, 122.60, 120.95, 119.52, 115.14, 114.11,
110.63, 53.17, 50.87, 47.69, 47.35, 43.10, 11.85. Anal. (C, H, N): Calcd
for C27H36N4O·2.2HCl: C, 63.24, H, 7.51, N, 10.93, found: C, 63.25,
2.62 (q, J = 7.1 Hz, 4H), 2.47 (q, J = 7.1 Hz, 6H), 2.23−2.14 (m, 2H),
2.04−1.93 (m, 2H), 1.08 (t, J = 7.1 Hz, 6H), 0.96 (t, J = 7.1 Hz, 6H).
13C NMR (100 MHz, CDCl3) δC (ppm) 154.53, 147.13, 141.47,
138.04, 135.73, 133.78, 128.62, 127.20, 124.79, 123.45, 122.50, 121.11,
115.61, 112.71, 77.21, 50.96, 50.35, 48.51, 44.13, 26.63, 26.37, 9.54,
9.38. ESI-MS: [M + H]+ m/z 461.24.
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H, 7.34, N, 10.55. (3a) H NMR (400 MHz, CDCl3) δH (ppm) 8.55
5,10-Bis[3-(piperidin-1-yl)propyl]-5H-indolo[3,2-b]quinolin-11-
(10H)-one (2d) and 11-[3-(Piperidin-1-yl)propoxy]-10-[3-(piperidin-
1-yl)propyl]-10H-indolo[3,2-b]quinoline (3d). A solution of 7a (70
mg, 0.29 mmol), K2CO3 (619.8 mg, 4.35 mmol, 15 equiv) in dried
acetone (20 mL), and 1-(3-chloropropyl)piperidine hydrochloride
(237.0 mg, 1.20 mmol, 4 equiv) was reacted and purified according to
procedure D, using as eluent Hex:AcOEt (1:1) to give 2d (45.2 mg,
(d, J = 7.7 Hz, 1H), 8.40 (d, J = 8.2 Hz, 1H), 8.33 (d, J = 8.5 Hz, 1H),
7.70 (dd, J = 8.5, 6.8 Hz, 1H), 7.66 (dd, J = 8.2, 7.4 Hz, 1H), 7.58 (dd,
J = 8.2, 6.80 Hz, 1H), 7.52 (d, J = 8.2 Hz, 1H), 7.35 (dd, J = 7.7, 7.4
Hz, 1H), 4.73 (t, J = 7.70 Hz, 2H), 4.32 (t, J = 6.3 Hz, 2H), 3.10 (t, J =
6.3 Hz, 2H), 2.79 (t, J = 7.70 Hz, 2H), 2.70 (q, J = 7.1 Hz, 4H), 2.62
(q, J = 7.1 Hz, 4H), 1.13 (t, J = 7.1 Hz, 6H), 1.00 (t, J = 7.1 Hz, 6H).
13C NMR (101 MHz, CDCl3) δC (ppm) 148.59, 145.83, 144.80,
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31%) and 3d (56.3 mg, 38%). (2d) H NMR (400 MHz, CDCl3) δH
(ppm) 8.68 (d, J = 8.1 Hz, 1H), 8.24 (d, J = 8.3 Hz, 1H), 7.80 (d, J =
8.6 Hz, 1H), 7.68 (dd, J = 8.6, 7.3 Hz, 1H), 7.65 (d, J = 8.4 Hz, 1H),
7.52 (dd, J = 8.4, 7.4 Hz, 1H), 7.34 (dd, J = 8.1, 7.3 Hz, 1H), 7.22 (dd,
J = 8.3, 7.4 Hz, 1H), 4.96 (t, J = 7.1 Hz, 2H), 4.81 (t, J = 7.2 Hz, 2H),
2.53 (t, J = 6.3 Hz, 2H), 2.47 (m, 4H), 2.35 (m, 6H), 2.18 (m, 2H),
2.12 (quint, J = 7.1 Hz, 2H), 1.69 (quint, J = 5.5 Hz, 4H), 1.58 (quint,
J = 5.6 Hz, 4H), 1.51 (m, 2H), 1.42 (m, 2H),. 13C NMR (100 MHz,
CDCl3) δC (ppm) 169.03, 139.79, 139.53, 131.21, 130.66, 127.05,
126.73, 124.91, 122.73, 122.70, 120.84, 119.33, 115.08, 114.37, 110.91,
55.97, 55.91, 55.07, 54.54, 54.46, 53.83, 46.25, 42.78, 28.19, 26.20,
25.98, 24.48. Anal. (C, H, N): Calcd for C31H40N4O·2HCl·5H2O: C,
144.58, 129.69, 129.31, 126.65, 124.87, 124.68, 122.46, 122.23, 122.08,
121.27, 119.86, 109.17, 74.51, 52.93, 51.71, 47.69, 47.62, 43.51, 12.06.
Anal. (C, H, N): Calcd for C27H36N4O·2.8HCl: C, 60.65, H, 7.31, N,
10.48, found: C, 61.07, H, 7.61, N, 10.12.
5,10-Bis[2-(pyrrolidin-1-yl)ethyl]-5H-indolo[3,2-b]quinolin-11-
(10H)-one (2b) and 11-[2-(Pyrrolidin-1-yl)ethoxy]-10-[2-(pyrrolidin-
1-yl)ethyl]-10H-indolo[3,2-b]quinoline (3b). A solution of 7a (70 mg,
0.29 mmol), K2CO3 (619.8 mg, 4.35 mmol, 15 equiv) in dried acetone
(20 mL), and 1-(2-chloroethyl)pyrrolidine hydrochloride (203.4 mg,
1.20 mmol, 4 equiv) was refluxed and purified according to procedure
D, using as eluent Hex:AcOEt (1:1) to give 2b (27.3 mg, 21%) and 3b
(45.5 mg, 35%). (2b) 1H NMR (400 MHz, CDCl3) δH (ppm) 8.68 (d,
J = 7.8 Hz, 1H), 8.24 (d, J = 8.4 Hz, 1H), 7.72 (m, 2H), 7.69 (d, J =
8.5 Hz, 1H), 7.57 (dd, J = 8.5, 7.2 Hz, 1H), 7.37 (m, 1H), 7.28 (dd, J =
8.4, 7.2 Hz, 1H), 5.13 (t, J = 7.7 Hz, 2H), 4.89 (t, J = 7.8 Hz, 2H), 3.11
(m, 4H), 2.85 (m, 4H), 2.78 (m, 4H), 1.92 (m, 4H), 1.89 (m, 4H).
13C NMR (100 MHz, CDCl3) δC (ppm) 169.05, 139.61, 139.51,
131.62, 130.81, 127.70, 126.78, 124.88, 122.50, 122.46, 121.18, 119.95,
115.10, 114.11, 110.65, 55.82, 54.75, 54.24, 53.44, 47.20, 43.21, 23.62,
23.58. Anal. (C, H, N): Calcd for C27H32N4O·2HCl·2H2O: C, 60.33,
H, 7.13, N, 10.42, found: C, 60.76, H, 7.53, N, 10.32. (3b): 1H NMR
(400 MHz, CDCl3) δH (ppm) 8.44 (d, J = 7.6 Hz, 1H), 8.22 (d, J = 8.0
Hz, 1H), 8.20 (d, J = 8.0 Hz, 1H), 7.62−7.54 (m, 2H), 7.49 (d, J = 8.0
Hz, 1H), 7.48 (dd, J = 8.0, 8.0 Hz, 1H) 7.25 (ddd, 1H), 4.79 (t, J = 7.5
Hz, 2H), 4.30 (t, J = 5.8 Hz, 2H), 3.03 (t, J = 5.8 Hz, 2H), 2.86 (t, J =
7.5 Hz, 2H), 2.63 (m, 8H), 1.79 (m, 4H), 1.75 (m, 4H). 13C NMR
(100 MHz, CDCl3) δC (ppm) 148.59, 145.92, 144.58, 144.43, 129.95,
129.37, 126.78, 124.88, 124.62, 122.41, 122.14, 122.09, 121.10, 120.13,
109.24, 74.64, 55.81, 54.76, 54.41, 43.43, 23.60, 23.56. Anal. (C, H,
N): Calcd for C27H32N4O·2HCl·3H2O: C, 58.37, H, 7.26, N, 10.09,
found: C, 58.79, H, 7.74, N, 9.72.
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57.49, H, 8.09, N, 8.65, found: C, 57.45, H, 8.04, N, 8.43. (3d) H
NMR (400 MHz, CDCl3) δH (ppm) 8.53 (d, J = 7.7 Hz, 1H), 8.32 (d,
J = 7.9 Hz, 1H), 8.31 (d, J = 7.8 Hz, 1H), 7.66−7.58 (m, 2H), 7.53
(dd, J = 8.4, 7.8 Hz, 1H), 7.51 (d, J = 7.8 Hz, 1H), 7.30 (dd, J = 7.7,
7.2 Hz, 1H), 4.57 (t, J = 6.9 Hz, 2H), 4.22 (t, J = 6.2 Hz, 2H), 2.65 (t,
J = 7.2 Hz, 2H), 2.47 (m, 4H), 2.26 (m, Hz, 6H), 2.20 (quint, J =, 6.2
Hz, 2H), 2.02 (quint, J = 6.9 Hz, 2H), 1.64 (quint, J = 5.6 Hz, 4H),
1.54 (quint, J = 5.6 Hz, 4H), 1.49 (m, 2H), 1.40 (m, 2H). 13C NMR
(100 MHz, CDCl3) δC (ppm) 148.58, 145.76, 144.82, 144.53, 129.54,
129.29, 126.55, 124.74, 124.59, 122.34, 122.18, 121.92, 121.25, 119.68,
109.36, 74.13, 56.12, 55.35, 54.68, 54.53, 42.75, 27.58, 26.91, 26.09,
25.97, 24.52, 24.45. Anal. (C, H, N): Calcd for C31H40N4O·3HCl·
3.5H2O: C, 56.36, H, 8.01, N, 8.55, found: C, 56.66, H, 7.67, N, 8.53.
7-Chloro-5,10-bis[2-(diethylamino)ethyl]-5H-indolo[3,2-b]-
quinolin-11(10H)-one (2e) and 2-{[7-Chloro-10-(2-(diethylamino)-
ethyl)-10H-indolo[3,2-b]quinolin-11-yl]oxy}-N,N-diethylethanamine
(3e). According to general procedure D, 7b (100 mg, 0.372 mmol) was
reacted with 2-chloro-N,N-diethylethanaminium chloride (256.1 mg,
1.488 mmol, 4 equiv). The crude mixture was purified by preparative
thin layer chromatography using as eluent Hex:AcOEt (1:1) to give 2e
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(40.0 mg, 23%) and 3e (26.1 mg, 15%). (2e): H NMR (400 MHz,
5,10-Bis[3-(diethylamino)propyl]-5H-indolo[3,2-b]quinolin-11-
(10H)-one (2c) and 3-[11-(3-(Diethylamino)propoxy)-10H-indolo-
[3,2-b]quinolin-10-yl]-N,N-diethylpropan-1-amine (3c). According
to general procedure D, 7a (100 mg, 0.427 mmol) was reacted with
3-chloro-N,N-diethylpropan-1-amine (31.9 mg, 1.71 mmol, 4 equiv).
The crude mixture was purified by preparative thin layer
chromatography using as eluent Hex:AcOEt (1:1) to give 2c (53.1
CD3OD) δH (ppm) 8.54 (dd, J = 8.2, 1.4 Hz, 1H), 8.43 (d, J = 1.4 Hz,
1H), 8.07 (d, J = 8.8 Hz, 1H), 7.88 (ddd, J = 8.8, 7.8, 1.4 Hz, 1H), 7.82
(d, J = 9.1 Hz, 1H), 7.66 (dd, J = 9.1, 1.4 Hz, 1H), 7.43 (dd, J = 8.2,
7.8 Hz, 1H), 5.37 (t, J = 7.9 Hz, 2H), 5.14 (t, J = 6.4 Hz, 2H), 3.65 (t,
J = 6.4 Hz, 2H), 3.56 (t, J = 7.9 Hz, 2H), 3.44−3.36 (m, 8H), 1.42 (t, J
= 7.1 Hz, 6H), 1.36 (t, J = 7.3 Hz, 6H). 13C NMR (100 MHz,
CD3OD) δC (ppm) 170.40, 140.58, 139.90, 134.46, 132.06, 130.45,
127.98, 127.34, 125.53, 124.25, 123.84, 122.91, 117.11, 116.10, 113.40,
53.68, 49.64, 49.40, 49.05, 43.98, 41.50, 9.36. Anal. (C, H, N): Calcd
for C27H35ClN4O·3.7 HCl: C, 53.87, H, 6.49, N, 9.31, found: C, 53.59,
H, 6.58, N, 9.23 (3e): 1H NMR (400 MHz, CDCl3) δH (ppm) 8.48 (d,
J = 1.9 Hz, 1H), 8.36 (dd, J = 8.5, 1.1 Hz, 1H), 8.28 (d, J = 8.3 Hz,
1H), 7.66 (ddd, J = 8.3, 7.7, 1.1 Hz, 1H), 7.58−7.53 (m, 2H), 7.41 (d,
J = 8.7 Hz, 1H), 4.66 (t, J = 7.3 Hz, 2H), 4.28 (t, J = 6.2 Hz, 2H), 3.05
(t, J = 6.2 Hz, 2H), 2.77 (t, J = 7.3 Hz, 2H), 2.67 (q, J = 7.2 Hz, 4H),
2.56 (q, J = 7.2 Hz, 4H), 1.09 (t, J = 7.2 Hz, 6H), 0.93 (t, J = 7.2 Hz,
6H). 13C NMR (100 MHz, CDCl3) δC (ppm) 147.28, 146.03, 144.92,
143.03, 129.58, 129.41, 126.97, 125.44, 125.23, 125.03, 123.61, 122.33,
121.64, 121.30, 110.42, 74.57, 52.97, 51.75, 47.64, 47.55, 43.57, 11.81,
11.77. Anal. (C, H, N): Calcd for C27H35ClN4O·4.5HCl: C, 51.38, H,
6.31, N, 8.88, found: C, 51.32, H, 6.58, N, 8.9.
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mg, 27%) and 3c (43.3 mg, 22%, <95% purity). (2c): H NMR (400
MHz, CDCl3) δH (ppm) 8.66 (dd, J = 8.3, 1.5 Hz, 1H), 8.25 (d, J = 8.5
Hz, 1H), 7.72 (d, J = 8.6 Hz, 1H), 7.66 (ddd, J = 8.6, 7.5, 1.5 Hz, 1H),
7.57 (d, J = 8.3 Hz, 1H), 7.50 (dd, J = 8.3, 7.6 Hz, 1H), 7.31 (ddd, J =
8.3, 7.5, 0.7 Hz, 1H), 7.20 (ddd, J = 8.5, 7.6, 0.7 Hz, 1H), 4.93 (t, J =
7.3 Hz, 2H), 4.77 (t, J = 8.0 Hz, 2H), 2.68 (t, J = 6.3 Hz, 2H), 2.64−
2.56 (m, 6H), 2.53 (q, J = 7.3 Hz, 4H), 2.14 (quint, J = 8.0 Hz, 2H),
2.05 (quint, J = 7.3 Hz, 2H), 1.11 (t, J = 7.1 Hz, 6H), 1.00 (t, J = 7.3
Hz, 6H). 13C NMR (100 MHz, CDCl3) δC (ppm) 169.06, 139.64,
139.48, 131.30, 130.69, 127.21, 126.83, 125.00, 122.88, 122.72, 120.89,
119.41, 115.20, 114.29, 110.74, 50.38, 50.14, 47.14, 46.71, 46.60,
43.01, 28.20, 26.51, 11.98, 11.63. ESI-MS: [M + H]+ m/z 461.27. Anal.
(C, H, N): Calcd for C29H40N4O.4.2HCl: C, 56.75, H, 7.26, N, 9.13,
found: C, 56.76, H, 7.46, N, 8.79. (3c): 1H NMR (400 MHz, CDCl3)
δH (ppm) 8.53 (d, J = 7.9 Hz, 1H), 8.31 (d, J = 8.2 Hz, 1H), 8.27 (dd,
J = 8.5, 0.8 Hz, 1H), 7.68−7.60 (m, 2H), 7.55 (ddd, J = 8.4, 7.6, 0.7
Hz, 1H), 7.49 (d, J = 8.3 Hz, 1H), 7.32 (dd, J = 7.9, 7.4 Hz, 1H), 4.59
(t, J = 7.5 Hz, 2H), 4.26 (t, J = 6.5 Hz, 2H), 2.80 (t, J = 7.3 Hz, 2H),
5,10-Bis[2-(diethylamino)ethyl]-7-methoxy-5H-indolo[3,2-b]-
quinolin-11(10H)-one (2f) and 2-{11-[2-(Diethylamino)ethoxy]-7-
methoxy-10H-indolo[3,2-b]quinolin-10-yl}-N,N-diethylethanamine
(3f). According to general procedure D, 7c (100 mg, 0.378 mmol) was
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dx.doi.org/10.1021/jm500075d | J. Med. Chem. 2014, 57, 3295−3313