Journal of Medicinal Chemistry
Article
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a green-yellow solid. Mp > 200 °C. H NMR (400 Hz, DMSO-d6): δ
(E )-1 -M e thyl-4 -(4- methylpip era zin- 1- yl) -2- (4-
morpholinostyryl)quinolin -1-ium Iodide (22). Following general
procedure B for (2-aromatic vinyl)-1-N-methylquinolinium derivatives,
8.95 (d, 1H, J = 8.0), 8.87 (s, 1H), 8.61 (d, 1H, J = 8.0), 8.49 (t, 2H, J
= 8.0), 8.30−8.24(m, 2H), 8.13 (t, 2H, J = 8.0), 7.96−7.88 (m, 2H),
7.78 (dd, 2H, J = 8.0, J = 12.0), 7.54 (t, 1H, J = 8.0), 7.33 (t, 1H, J =
8.0), 4.58 (s, 3H), 4.50 (d, 2H, J = 8.0), 1.36 (s, 3H). 13C NMR (100
MHz, DMSO-d6): δ 156.1, 149.0, 142.8, 141.5, 140.1, 138.9, 134.3,
129.7, 128.3, 127.9, 127.0, 126.6, 126.0, 122.7, 122.4, 122.1, 120.6,
120.4, 119.8, 118.8, 115.2, 109.8, 109.7, 39.6, 37.3, 13.8. Purity: 99.5%
by HPLC. ESI-HRMS (C26H23N2): calcd, 363.1856 [M]+; found,
363.1866.
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the product was obtained as a green-yellow solid. Mp > 200 °C. H
NMR (400 Hz, DMSO-d6): δ 8.27 (d, 1H, J = 8.0), 8.12 (d, 1H, J =
8.0), 8.01−7.95 (t, 1H, J = 8.0), 7.88 (d, 1H, J = 12.0), 7.79 (d, 2H, J =
12.0), 7.72 (t, 1H, J = 8.0), 7.48 (t, 2H, J = 8.0),7.05 (d, 2H, J = 8.0),
4.22 (s, 3H), 3.75 (s, 8H), 3.32 (s, 4H), 2.63 (s, 4H), 2.31 (s, 3H). 13C
NMR (100 MHz, DMSO-d6): δ 159.0, 154.4, 152.4, 143.7, 140.7,
133.5, 130.3, 126.3, 126.0, 125.1, 119.6, 119.1, 115.0, 113.9, 104.7,
65.8, 54.2, 51.5, 47.0, 45.5, 38.1. Purity: 96.6% by HPLC. ESI-HRMS
(C27H33N4O): calcd, 429.2649 [M]+; found, 429.2649.
(E)-1-Methyl-4-(4-methylpiperazin-1-yl)-2-styrylquinolin-1-
ium Iodide (17). Following general procedure B for (2-aromatic
vinyl)-1-N-methylquinolinium derivatives, the product was obtained as
(E)-2-(2-(1H-Indol-2-yl)vinyl)-1-methyl-4-(4-methylpipera-
zin-1-yl)quinolin 1-ium Iodide (23). Following general procedure B
for (2-aromatic vinyl)-1-N-methylquinolinium derivatives, the product
was obtained as a green-yellow solid. Mp > 200 °C. 1H NMR (400 Hz,
DMSO-d6): δ 12.01 (s, 1H), 8.27 (t, 2H, J = 8.0), 8.17 (s, 2H), 8.12
(d, 1H, J = 8.0), 8.00 (t,1H, J = 8.0), 7.72 (t, 1H, J = 8.0), 7.53 (s, 2H),
7.41 (d, 1H, J = 16.0), 7.28 (d, 2H, J = 4.0), 4.25 (s, 3H), 3.72(s, 4H),
2.65 (s, 4H), 2.32 (s, 3H). 13C NMR (100 MHz, DMSO-d6): δ 158.8,
155.2, 140.7, 138.8, 137.4, 133.4, 132.5, 126.3, 126.0, 125.0, 122.9,
121.2, 120.2, 119.8, 119.1, 113.6, 112.6, 104.3, 54.2, 51.5, 48.5, 45.5,
37.9. Purity: 97.8% by HPLC. ESI-HRMS (C25H27N4): calcd,
383.2230 [M]+; found, 383.2212.
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a green-yellow solid. Mp > 200 °C. H NMR (400 Hz, DMSO-d6): δ
8.32−8.28 (m, 1H), 8.18−8.15 (m, 1H), 8.04 (t, 1H, J = 12.0), 7.92−
7.85 (m, 3H), 7.76−7.71 (m, 2H), 7.99 (d, 1H, J = 8.0), 7.50 (s, 4H),
4.24 (s, 3H), 3.84 (s, 4H), 2.65 (s, 4H), 2.32 (s, 3H). 13C NMR (100
MHz, DMSO-d6) δ 159.5, 153.7, 142.6, 140.8, 135.1, 133.8, 132.6,
130.3, 129.2, 128.9, 128.4, 126.7, 126.2, 120.2, 119.5, 119.2, 105.2,
54.2, 51.6, 45.4, 38.3. Purity: 96.1% by HPLC. ESI-HRMS
(C23H26N3): calcd, 344.2121 [M]+; found, 344.2115.
(E)-2-(4-Fluoro-3-methoxystyryl)-1-methyl-4-(4-methylpi-
perazin-1-yl) quinolin-1-ium Iodide (18). Following general
procedure B for (2-aromatic vinyl)-1-N-methylquinolinium derivatives,
(E)-2-(2-(9-Ethyl-9H-carbazol-3-yl)vinyl)-1-methyl-4-(4-meth-
yl piperazin-1-yl)quinolin-1-ium Iodide (24). Following general
procedure B for (2-aromatic vinyl)-1-N-methylquinolinium derivatives,
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the product was obtained as a green-yellow solid. Mp > 200 °C. H
NMR (400 Hz, DMSO-d6): δ 8.30 (d, 1H, J = 8.0), 8.15 (d, 1H, J =
8.0), 8.04 (t, 1H, J = 8.0), 7.83 (d,1H, J = 20.0), 7.78 (d, 1H, J = 16.0),
7.74 (s, 1H), 7.70−7.68 (m, 1H),7.46 (s, 2H), 7.34 (t, 1H, J = 12.0),
4.24 (s, 3H), 3.95 (s, 3H), 3.82 (s, 4H), 2.61 (s, 4H), 2.29(s, 2H). 13C
NMR (100 MHz, DMSO-d6) δ 159.4, 153.9, 153.6, 151.4, 147.5,
147.3, 141.8, 140.7, 133.8, 132.2, 126.6, 126.2, 122.1, 120.0, 119.4,
119.2, 116.3, 116.1, 113.3, 105.3, 56.5, 54.3, 51.7, 45.4, 38.5. Purity:
95.3% by HPLC. ESI-HRMS (C24H27N3OF): calcd, 392.2133 [M]+;
found, 392.2114.
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the product was obtained as a green-yellow solid. Mp > 200 °C. H
NMR (400 Hz, DMSO-d6): δ 8.73 (s, 1H), 8.31 (d, 1H, J = 12.0), 8.23
(d, 1H, J = 8.0), 8.16 (d, 1H, J = 8.0), 8.13 (s, 1H), 8.07−8.01 (m, 2H,
J = 8.0, J = 8.0), 7.75 (t, 3H, J = 8.0), 7.69 (d, 1H, J = 8.0), 7.57−7.51
(m, 2H, J = 8.0, J = 8.0), 7.30 (t, 1H, J = 8.0), 4.53−4.48 (m, 2H, J =
4.0, J = 8.0), 4.29 (s, 3H), 3.78 (s, 4H), 2.65 (s, 4H), 2.32 (s, 3H), 1.36
(t, 3H, J = 8.0). 13C NMR (100 MHz, DMSO-d6) δ 159.1, 154.2,
144.8, 140.8, 140.6, 140.0, 133.4, 126.7, 126.3, 126.2, 126.1, 126.0,
122.5, 122.1, 121.7, 120.5, 119.6, 119.0, 116.1, 109.6, 109.5, 104.8,
54.2, 51.6, 45.5, 38.2, 37.2, 13.8. Purity: 98.6% by HPLC. ESI-HRMS
(C31H33N4): calcd, 461.2700 [M]+; found, 461.2703.
(E)-1-Methyl-4-(4-methylpiperazin-1-yl)-2-(3,4,5-
trimethoxystyryl)quinolin-1-ium Iodide (19). Following general
procedure B for (2-aromatic vinyl)-1-N-methylquinolinium derivatives,
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the product was obtained as a green-yellow solid. Mp > 200 °C. H
(E)-2-(2-(9-Ethyl-9H-carbazol-3-yl)vinyl)-4-(4-(2-
hydroxyethyl)piperazin-1-yl)-1-methylquinolin-1-ium Iodide
(25). Following general procedure B for (2-aromatic vinyl)-1-N-
methylquinolinium derivatives, the product was obtained as a green-
yellow solid. Mp > 200 °C. 1H NMR (400 Hz, DMSO-d6): δ 8.73 (s,
1H), 8.31 (d, 1H, J = 8.0), 8.23 (d, 1H, J = 8.0), 8.13 (t, 2H, J = 8.0),
8.07−8.00 (m, 2H), 7.76−7.72 (m, 3H), 7.68 (d, 1H, J = 8.0), 7.56−
7.51(m, 2H), 7.30 (t, 1H, J = 8.0), 4.51(t, 2H, J = 4.0), 4.29 (s, 3H),
3.80 (s, 4H), 3.60 (t, 2H, J = 8.0, J = 4.0), 2.76 (s, 4H), 2.55 (t, 2H, J =
8.0), 1.36 (t, 3H, J = 8.0). 13C NMR (100 MHz, DMSO-d6): δ 159.0,
154.2, 144.7, 140.8, 140.6, 140.1, 133.5, 126.7, 126.4, 126.3, 126.2,
126.0, 122.6, 122.2, 121.7, 120.6, 119.6, 119.5, 119.0, 116.1, 109.6,
109.5, 104.7, 59.8, 58.5, 52.8, 51.7, 38.2 37.2, 13.8. Purity: 96.7% by
HPLC. ESI-HRMS (C32H35N4O): calcd, 491.2805 [M]+; found,
491.2778.
(E)-4-(4-(2-(Dimethylamino)ethyl)piperazin-1-yl)-2-(2-(9-
ethyl-9H-carbazol-3 -yl)vinyl)-1-methylquinolin-1-ium Iodide
(26). Following general procedure B for (2-aromatic vinyl)-1-N-
methylquinolinium derivatives, the product was obtained as a green-
yellow solid. Mp > 200 °C. 1H NMR (400 Hz, DMSO-d6): δ 8.75 (s,
1H), 8.32 (d, 1H, J = 8.0), 8.23 (d, 1H, J = 8.0), 8.16 (t, 2H, J = 8.0),
8.07 (d, 1H, J = 12.0), 8. 01 (t, 1H, J = 8.0), 7.81−7.73 (m, 3H), 7.70
(d, 1H, J = 8.0),7.59 (s, 1H), 7.57−7.52 (m, 1H, J = 4.0, J = 8.0), 7.31
(t, 1H, J = 8.0), 4.55−4.50 (m, 2H, J = 8.0, J = 8.0), 4.31 (s, 3H), 3.82
(s, 4H), 3.32 (s, 2H), 3.15 (t, 2H, J = 4.0), 2.83 (s, 6H), 2.73 (s, 4H),
1.88 (s, 2H), 1.36 (t, 3H, J = 8.0). 13C NMR (100 MHz, DMSO-d6): δ
159.1, 154.4, 144.9, 141.0, 140.8, 140.1, 133.6, 126.7, 126.4, 126.2,
126.1, 122.6, 122.2, 121.7, 120.8, 120.5, 120.1, 119.7, 119.6, 119.2,
116.3, 109.9, 109.7, 109.6, 109.6, 104.9, 55.5, 54.2, 52.2, 51.6, 42.4,
38.2, 37.2, 20.9, 13.8. Purity: 99.7% by HPLC. ESI-HRMS
(C34H40N5): calcd, 518.3278 [M]+; found, 518.3160.
NMR (400 Hz, CDCl3): δ 8.00−7.88 (m, 4H), 7.71 (d, 1H, J = 16.0),
7.64−7.61 (m, 1H), 7.41 (s, 1H), 7.21 (s, 2H), 4.37 (s, 3H), 3.93 (m,
4H), 3.91 (s, 6H), 3.75 (s, 3H), 2.76 (m, 4H), 2.41 (s, 3H). 13C NMR
(100 Hz, CDCl3): δ 159.7, 155.1, 153.1, 144.8, 141.2, 140.0, 134.3,
130.2, 126.7, 126.1, 118.6, 118.4, 106.7, 106.1, 60.8, 57.4, 54.7, 52.4,
45.8, 40.4. Purity: 99.4% by HPLC. ESI-HRMS (C26H32N3O3): calcd,
434.2438 [M]+; found, 434.2411.
(E)-2-(4-Hydroxystyryl)-1-methyl-4-(4-methylpiperazin-1-yl)-
quinolin-1-ium Iodide (20). Following general procedure B for (2-
aromatic vinyl)-1-N-methylquinolinium derivatives, the product was
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obtained as a green-yellow solid. Mp > 200 °C. H NMR (400 Hz,
DMSO-d6): δ 8.29 (d, 1H, J = 8.0), 8.14 (d, 1H, J = 8.0), 8.02 (t, 1H, J
= 8.0), 7.85 ( d, 1H, J = 16.0), 7.75 (m, 3H), 7.49 (m, 2H), 6.90 (d,
2H, J = 8.0), 4.22 (s, 3H), 3.79 (s, 4H), 2.68 (s, 4H), 2.34 (s, 3H). 13C
NMR (100 Hz, DMSO-d6): δ 160.0, 159.1, 154.3, 143.6, 140.6, 133.6,
130.7, 126.4, 126.3, 126.2, 119.6, 119.1, 116.0, 115.8, 105.0, 54.0, 51.3,
45.1, 42.8. Purity: 97.2% by HPLC. ESI-HRMS (C23H26N3O): calcd,
360.2070 [M]+; found, 360.2083.
(E)-2-(3-Methoxy-4-morpholinostyryl)-1-methyl-4-(4- meth-
ylpiperazin-1-yl)quinolin-1-ium Iodide (21). Following general
procedure B for (2-aromatic vinyl)-1-N-methylquinolinium derivatives,
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the product was obtained as a green-yellow solid. Mp > 200 °C. H
NMR (400 Hz, DMSO-d6): δ 8.28 (d, 1H, J = 12.0), 8.13 (d, 1H, J =
8.0), 8.02 (t, 1H, J = 8.0), 7.88 (t, 1H, J = 16.0), 7.73 (t, 1H, J = 8.0),
7.59 (d, 1H, J = 16.0), 7.48 (d, 2H, J = 4.0), 7.42 (d, 1H, J = 8.0), 6.95
(d, 1H, J = 8.0), 4.23 (s, 3H), 3.91 (s, 3H), 3.77 (s, 4H), 3.73 (s, 4H),
3.07 (s, 4H), 2.63 (s, 4H), 2.30 (s, 3H). 13C NMR (100 MHz, DMSO-
d6) δ 159.3, 154.2, 151.7, 143.5, 140.8, 136.6, 133.7, 129.2, 126.5,
126.2, 123.2, 119.7, 119.2, 117.5, 117.3, 111.2, 105.0, 66.2, 55.8, 54.2,
51.5, 50.2, 45.4, 38.2. Purity: 99.0% by HPLC. ESI-HRMS
(C28H35N4O2): calcd, 459.2755 [M]+; found, 459.2746.
(E)-4-(4-(3-Dimethylamino)propyl)piperazin-1-yl)-2-(2-(9-
ethyl-9H-carbazol-3-yl) vinyl)-1-methylquinolin-1-ium Iodide
M
J. Med. Chem. XXXX, XXX, XXX−XXX