Journal of Medicinal Chemistry
Article
flash chromatography using AcOEt−2N ammonia in MeOH (9:1 v/v)
as an eluent to yield pure products as yellowish-orange solids.
1-(3-(5-Methyl-5H-indolo[2,3-b]quinolin-11-ylamino)propyl)-3-
phenylthiourea (17a). Yield 99%; yellow solids; mp 201−203 °C. IR
(KBr) 3335, 3208, 3055, 2938, 1622, 1595, 1568, 1539, 1512, 1485,
1441, 1422, 1406, 1310, 1277, 1242, 1190, 1142, 1103, 1072, 955, 858,
748, 733 cm−1. 1H NMR (600 MHz, DMSO-d6) δ ppm 1.98 (quint, J
= 6.6 Hz, 2H), 3.51 (m, 2H), 3.89 (q, J = 6.6 Hz, 2H), 4.16 (s, 3H),
7.06−7.11 (m, 3H), 7.24 (d, J = 4.2 Hz, 4H), 7.30 (t, J = 7.2 Hz, 1H),
7.43 (t, J = 7.8 Hz, 1H), 7.51 (d, J = 7.8 Hz, 1H), 7.73 (br s, 1H), 7.80
(t, J = 7.2 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.96 (d, J = 7.8 Hz, 1H),
8.55 (d, J = 8.4 Hz, 1H), 9.46 (br s, 1H). 13C NMR (150.8 MHz,
DMSO-d6) δ ppm 30.36, 32.33, 41.39, 45.60, 104.58, 115.09, 115.68,
116.35, 118.22, 120.69, 122.17 (2C), 123.16, 123.93, 124.04 (2C),
124.21, 124.69, 128.66, 130.73, 137.33, 138.87, 148.28, 151.74, 156.11,
180.24. HPLC purity 100%. HRMS (ESI) calcd for C26H24N5S [M −
H]−. Exact mass: 438.1758, found 438.1751.
Hz, 2H), 3.14 (q, J = 6.0 Hz, 2H), 3.84 (q, J = 6.6 Hz, 2H), 4.13 (s,
3H), 6.18 (t, J = 6.0 Hz, 1H), 6.87 (t, J = 7.2 Hz, 1H), 7.07 (t, J = 7.2
Hz, 1H), 7.19 (t, J = 7.2 Hz, 3H), 7.28 (t, J = 7.2 Hz, 1H), 7.35 (d, J =
8.4 Hz, 2H), 7.50 (d, J = 7.8 Hz, 1H), 7.80 (m, 1H), 7.90 (d, J = 7.2
Hz, 2H), 8.41 (s, 1H), 8.78 (d, J = 1.8 Hz, 1H). 13C NMR (150.8
MHz, DMSO-d6) δ ppm 31.46, 32.37, 36.50, 45.38, 105.23, 112.92,
116.74, 117.35, 117.38, 117.70 (2C), 118.28, 121.01, 122.37, 124.02,
124.94, 125.92, 128.59 (2C), 132.94, 136.32, 140.40, 146.99, 152.49,
155.48, 156.32. HPLC purity 96.6%. HRMS (ESI) calcd for
C26H23BrN5O [M − H]−. Exact Mass: 500.1091, found 500.1087.
1-(3-(2-Chloro-5-methyl-5H-indolo[2,3-b]quinolin-11-ylamino)-
propyl)-3-phenylurea (17f). Yield 83%; yellow solids; mp 130−133
°C. IR (KBr) 3347, 3051, 2938, 1680, 1622, 1595, 1557, 1499, 1443,
1422, 1314, 1281, 1246, 1200, 1119, 991, 800, 760, 743, 694 cm−1. 1H
NMR (600 MHz, DMSO-d6) δ ppm 1.89 (quint, J = 6.6 Hz, 2H), 3.14
(q, J = 6.0 Hz, 2H), 3.84 (q, J = 6.6 Hz, 2H), 4.14 (s, 3H), 6.17 (t, J =
6.0 Hz, 1H), 6.87 (t, J = 7.2 Hz, 1H), 7.07 (t, J = 7.2 Hz, 1H), 7.17 (m,
3H), 7.29 (t, J = 7.2 Hz, 1H), 7.34 (d, J = 7.8 Hz, 2H), 7.50 (d, J = 7.8
Hz, 1H), 7.80 (dd, J = 9.0, 2.4 Hz, 1H), 7.86 (d, J = 9.6 Hz, 1H), 7.91
(d, J = 7.2 Hz, 1H), 8.40 (s, 1H), 8.67 (d, J = 2.4 Hz, 1H). 13C NMR
(150.8 MHz, DMSO-d6) δ ppm 31.45, 32.41, 36.49, 45.41, 105.32,
116.70, 116.89, 117.10, 117.69 (2C), 118.27, 121.00, 122.37, 123.02,
123.96, 124.95, 125.14, 128.57 (2C), 130.25, 136.01, 140.39, 147.06,
152.45, 155.46, 156.32. HPLC purity 97.2%. HRMS (ESI) calcd for
C26H25ClN5O [M + H]+. Exact mass: 458.1742, found 458.1747.
1-(3-(2-Fluoro-5-methyl-5H-indolo[2,3-b]quinolin-11-ylamino)-
propyl)-3-phenylurea (17g). Yield 87%; yellow solids; mp 218−220
°C. IR (KBr) 3339, 3053, 2926, 1690, 1613, 1599, 1566, 1499, 1487,
1-Butyl-3-(3-(5-methyl-5H-indolo[2,3-b]quinolin-11-ylamino)-
propyl)urea (17b). Yield 86%; yellow solids; mp 80−81 °C. IR (KBr)
3360, 3312, 2953, 2920, 2870, 1622, 1593, 1568, 1520, 1489, 1443,
1
1416, 1400, 1288, 1250, 1196, 1065, 1022, 841, 750 cm−1. H NMR
(600 MHz, CDCl3) δ ppm 0.86 (t, J = 7.8 Hz, 3H), 1.31 (sext, J = 7.8
Hz, 2H), 1.45 (quint, J = 7.2 Hz, 2H), 1.68 (quint, J = 6.0 Hz, 2H),
3.19 (q, J = 6.6 Hz, 2H), 3.36 (q, J = 6.6 Hz, 2H), 3.85 (q, J = 6.0 Hz,
2H), 4.10 (s, 3H), 5.49 (br s, 1H), 5.79 (br s, 1H), 6.92 (m, 1H), 7.13
(t, J = 7.2 Hz, 1H), 7.31−7.38 (m, 2H), 7.51 (d, J = 7.8 Hz, 1H),
7.63−7.67 (m, 2H), 7.82 (d, J = 7.8 Hz, 1H), 8.39 (dd, J = 9.0, 1.2 Hz,
1H). 13C NMR (150.8 MHz, CDCl3) δ ppm 13.77, 20.04, 32.33,
32.38, 33.07, 36.60, 40.19, 44.25, 105.39, 114.51, 116.07, 116.41,
119.25, 121.44, 121.83, 123.48, 124.28, 125.44, 130.64, 137.45, 149.30,
152.45, 155.40, 159.77. HPLC purity 96.3%. HRMS (ESI) calcd for
C24H28N5O [M − H]−. Exact mass: 402.2299, found 402.2319.
1-(3-(5-Methyl-5H-indolo[2,3-b]quinolin-11-ylamino)propyl)-3-
phenylurea (17c). Yield 99%; yellow solids; mp 215 °C. IR (KBr)
3341, 3048, 3024, 2969, 2930, 1694, 1620, 1591, 1557, 1489, 1443,
1
1445, 1400, 1317, 1281, 1234, 1144, 878, 795, 760, 692 cm−1. H
NMR (600 MHz, DMSO-d6) δ ppm 1.84 (quint, J = 6.6 Hz, 2H), 3.11
(q, J = 6.0 Hz, 2H), 3.82 (q, J = 6.6 Hz, 2H), 4.14 (s, 3H), 6.13 (t, J =
6.0 Hz, 1H), 6.84 (t, J = 7.2 Hz, 1H), 6.99 (t, J = 6.0 Hz, 1H), 7.04 (t,
J = 7.2 Hz, 1H), 7.16 (t, J = 7.8 Hz, 2H), 7.26 (t, J = 7.2 Hz, 1H), 7.31
(dd, J = 8.4, 1.2 Hz, 2H), 7.47 (d, J = 7.8 Hz, 1H), 7.67 (m, 1H), 7.86
(dd, J = 9.6, 4.8 Hz, 1H), 7.89 (d, J = 7.8 Hz, 1H), 8.37 (s, 1H), 8.42
(dd, J = 10.8, 2.4 Hz, 1H). 13C NMR (150.8 MHz, DMSO-d6) δ ppm
31.49, 32.50, 36.49, 45.42, 105.66, 109.04 (d, J = 24.1 Hz), 116.44 (d, J
= 7.8 Hz), 116.55, 117.16 (d, J = 8.4 Hz), 117.69 (2C), 118.08, 118.53
(d, J = 23.5 Hz), 121.00, 122.36, 123.73, 124.99, 128.57 (2C), 134.15,
140.39, 147.27 (d, J = 2.9 Hz), 152.65, 155.44, 156.45, 156.65 (d, J =
237.2 Hz). 19F NMR (564 MHz, DMSO-d6) δ ppm −121.25. HPLC
purity 98.9%. HRMS (ESI) calcd for C26H23FN5O [M − H]−. Exact
mass: 440.1892, found 440.1890.
1-(3-(5-Methyl-2-(trifluoromethyl)-5H-indolo[2,3-b]quinolin-11-
ylamino)propyl)-3-phenylurea (17h). Yield 77%; yellow solids; mp
204−205 °C. IR (KBr) 3335, 3055, 2938, 1688, 1614, 1597, 1553,
1499, 1443, 1435, 1333, 1317, 1277, 1242, 1196, 1148, 1119, 1090,
912, 816, 766, 752, 725 cm−1. 1H NMR (600 MHz, DMSO-d6) δ ppm
1.90 (quint, J = 6.6 Hz, 2H), 3.15 (q, J = 6.0 Hz, 2H), 3.88 (q, J = 6.6
Hz, 2H), 4.19 (s, 3 H), 6.17 (t, J = 6.0 Hz, 1H), 6.87 (t, J = 7.2 Hz,
1H), 7.10 (t, J = 7.2 Hz, 1H), 7.19 (t, J = 7.8 Hz, 2H), 7.29−7.34 (m,
3H), 7.46 (t, J = 6.0 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.94 (d, J = 7.8
Hz, 1H), 8.00 (d, J = 9.0 Hz, 1H), 8.05 (dd, J = 9.0, 1.2 Hz, 1H), 8.39
(s, 1H), 8.94 (s, 1H). 13C NMR (150.8 MHz, DMSO-d6) δ ppm
31.47, 32.55, 36.45, 45.34, 105.04, 115.37, 116.16, 116.97, 117.70
(2C), 118.66, 120.95, 121.03, 121.73, 121.75, 123.22 (q, J = 244.6 Hz),
123.80, 124.98, 126.38, 128.57 (2C), 139.33, 140.39, 147.61, 152.25,
155.52, 156.46. 19F NMR (564 MHz, DMSO-d6) δ ppm −58.57.
HPLC purity 100%. RMS (ESI) calcd for C27H23F3N5O [M − H]−.
Exact mass: 490.1860, found 490.1889.
1
1406, 1314, 1275, 1227, 1177, 1144, 891, 758, 718, 692 cm−1. H
NMR (600 MHz, DMSO-d6) δ ppm 1.86 (quint, J = 6.6 Hz, 2H), 3.14
(q, J = 6.6 Hz, 2H), 3.86 (q, J = 6.6 Hz, 2H), 4.16 (s, 3H), 6.18 (t, J =
6.0 Hz, 1H), 6.87 (t, J = 7.2 Hz, 1H), 7.06 (m, 2H), 7.20 (t, J = 7.8 Hz,
2H), 7.27 (t, J = 7.2 Hz, 1H), 7.35 (d, J = 7.8 Hz, 2H), 7.42 (t, J = 7.2
Hz, 1H), 7.50 (d, J = 7.8 Hz, 1H), 7.79 (t, J = 7.2 Hz, 1H), 7.85 (d, J =
8.4 Hz, 1H), 7.96 (d, J = 7.8 Hz, 1H), 8.42 (s, 1H), 8.54 (d, J = 8.4 Hz,
1H). 13C NMR (150.8 MHz, DMSO-d6) δ ppm 31.62, 32.20, 36.48,
45.43, 105.02, 115.06, 115.62, 116.55, 117.72 (2C), 117.98, 120.55,
121.03, 122.05, 124.00, 124.07, 124.65, 128.59 (2C), 130.63, 137.40,
140.40, 148.23, 152.38, 155.52, 156.40. HPLC purity 98.8%. HRMS
(ESI) calcd for C26H24N5O [M − H]−. Exact mass: 422.1986, found
422.2003.
1-(6-(5-Methyl-5H-indolo[2,3-b]quinolin-11-ylamino)hexyl)-3-
phenylurea (17d). Yield 89%; yellow solids; mp 101−104 °C. IR
(KBr) 3356, 3053, 2930, 2855, 1668, 1622, 1595, 1559, 1499, 1441,
1
1420, 1312, 1279, 1244, 1071, 750, 694 cm−1. H NMR (600 MHz,
DMSO-d6) δ ppm 1.19−1.25 (m, 4H), 1.31 (quint, J = 6.6 Hz, 2H),
1.68 (quint, J = 6.6 Hz, 2H), 2.95 (q, J = 6.0 Hz, 2H), 3.83 (q, J = 6.6
Hz, 2H), 4.16 (s, 3H), 6.03 (t, J = 6.0 Hz, 1H), 6.86 (t, J = 7.2 Hz,
1H), 7.01 (t, J = 5.4 Hz, 1H), 7.08 (t, J = 7.2 Hz, 1H), 7.19 (t, J = 7.2
Hz, 2H), 7.28 (t, J = 7.2 Hz, 1H), 7.34 (d, J = 7.2 Hz, 2H), 7.42 (t, J =
7.8 Hz, 1H), 7.50 (d, J = 7.8 Hz, 1H), 7.78 (t, J = 7.8 Hz, 1H), 7.84 (d,
J = 7.8 Hz, 1H), 7.91 (d, J = 7.8 Hz, 1H), 8.34 (s, 1H), 8.53 (d, J = 8.4
Hz, 1H). 13C NMR (150.8 MHz, DMSO-d6) δ ppm 25.90, 26.03,
29.60, 30.75, 32.22, 38.82, 48.00, 104.48, 115.06, 115.61, 116.50,
117.52 (2C), 117.96, 120.59, 120.86, 121.98, 123.98, 124.09, 124.59,
128.61 (2C), 130.66, 137.37, 140.58, 148.35, 152.10, 155.15, 156.34.
HPLC purity 96.1%. HRMS (ESI) calcd for C29H30N5O [M − H]−.
Exact mass: 464.2456, found 464.2480.
1-(3-(2-Methoxy-5-methyl-5H-indolo[2,3-b]quinolin-11-
ylamino)propyl)-3-phenylurea (17i). Yield 98%; yellow solids; mp
122−124 °C. IR (KBr) 3383, 3050, 2936, 1682, 1614, 1597, 1568,
1532, 1499, 1445, 1314, 1288, 1246, 1142, 1036, 804, 758, 694 cm−1.
1H NMR (600 MHz, DMSO-d6) δ ppm 1.84 (quint, J = 6.6 Hz, 2H),
3.15 (q, J = 6.6 Hz, 2H), 3.85 (q, J = 6.6 Hz, 2H), 3.94 (s, 3H), 4.15
(s, 3H), 6.19 (t, J = 6.0 Hz, 1H), 6.88 (t, J = 7.2 Hz, 1H), 7.02−7.06
(m, 2H), 7.20 (t, J = 7.8 Hz, 2H), 7.27 (t, J = 7.2 Hz, 1H), 7.35 (d, J =
7.2 Hz, 2H), 7.45−7.49 (m, 2H), 7.81 (d, J = 9.6 Hz, 1H), 7.93 (d, J =
7.8 Hz, 1H), 8.00 (d, J = 2.4 Hz, 1H), 8.43 (s, 1H). 13C NMR (150.8
1-(3-(2-Bromo-5-methyl-5H-indolo[2,3-b]quinolin-11-ylamino)-
propyl)-3-phenylurea (17e). Yield 80%; yellow solids; mp 132−135
°C. IR (KBr) 3347, 3050, 2938, 1680, 1616, 1591, 1557, 1499, 1487,
1443, 1424, 1314, 1281, 1246, 1200, 1111, 1086, 885, 799, 760, 741,
694 cm−1. 1H NMR (600 MHz, DMSO-d6) δ ppm 1.88 (quint, J = 6.6
I
dx.doi.org/10.1021/jm300887b | J. Med. Chem. XXXX, XXX, XXX−XXX