H. Hussain et al. / European Journal of Medicinal Chemistry 54 (2012) 936e942
941
7.25 (d, J ¼ 9.0 Hz, 2H), 6.95 (d, J ¼ 9.0 Hz, 2H), 6.65 (d, J ¼ 9.0 Hz,
4.5.20. 6-(Biphenyl-4,40-diamino)quinoline-5,8-dione (10e)
Red powder. Mp. 276 ꢁC; Yield 13% (47 mg). 1H NMR (500 MHz,
DMSO-d6)
2H); 13C NMR (125 MHz, CDCl3 þ CD3OD)
d 179,3, 176.5, 165.4,
156.3, 147.1, 144.2, 138.4, 135.5, 135.3, 131.2, 127.5, 126.1, 125.0,
124.9, 124.2, 110.4, 106.5; HREIMS m/z C21H13BrN2O3 [M]þ calcd
420.011, found 420.015. Anal. (C21H13BrN2O3). Elemental anal-
ysis: Found C 59.82%, H 3.10%, N 6.63; calcd for C 59.88%, H 3.11%,
N 6.65.
d
9.75 (br s, NH or NH2), 9.85 (d, J ¼ 8.2 Hz, 1H), 8.70 (d,
J ¼ 8.2 Hz, 1H), 7.55 (d, J ¼ 8.2 Hz, 1H), 7.50 (d, J ¼ 9.0 Hz, 2H), 7.45
(d, J ¼ 9.0 Hz, 2H), 7.40 (d, J ¼ 9.0 Hz, 2H), 7.05 (d, J ¼ 9.0 Hz, 2H),
6.22 (s, 1H); 13C NMR (125 MHz, DMSO-d6)
d 180,2, 179.2, 165.7,
155.5, 145.4, 144.1, 138.4, 135.2, 135.0, 131.8, 127.8, 126.1, 126.1, 124.1,
123.3, 111.4, 106.7; HREIMS m/z C21H15N3O2 [M]þ calcd 341.1164,
found 341.1160. Anal. (C21H15N3O2). Elemental analysis: Found C
73.81%, H 4.40%, N 12.27; calcd for C 73.89%, H 4.43%, N 12.31.
4.5.15. 7-Bromo-6-(biphenyl-4,40-diamino)quinoline-5,
8-dione (9e)
Red powder. Mp. 271 ꢁC; Yield 75% (331 mg). 1H NMR
(500 MHz, DMSO-d6)
d
9.70 (br s, NH or NH2), 9.85 (d, J ¼ 8.2 Hz,
4.5.21. 7-Bromo-6-(4-(7-bromo-2-methyl-5,8-dioxo-5,8-
dihydroquinolin-6-ylamino)piperazin-1-ylamino)-2-
methylquinoline-5,8-dione (11)
1H), 8.70 (d, J ¼ 8.2 Hz, 1H), 7.55 (d, J ¼ 8.2 Hz, 1H), 7.50 (d,
J ¼ 9.0 Hz, 2H), 7.45 (d, J ¼ 9.0 Hz, 2H), 7.40 (d, J ¼ 9.0 Hz, 2H), 7.05
(d, J ¼ 9.0 Hz, 2H); 13C NMR (125 MHz, DMSO-d6)
d
180,1, 178.2,
Red powder. Mp. 293 ꢁC; Yield 77% (258 mg). 1H NMR (500 MHz,
165.1, 156.5, 145.7, 144.9, 138.4, 135.2, 135.0, 131.8, 127.9, 126.7,
126.0, 124.0, 123.1, 116.4, 106.9; HREIMS m/z C21H14BrN3O2 [M]þ
calcd 419.0269, found 419.0267. Anal. (C21H14BrN3O2). Elemental
analysis: Found C 60.10%, H 3.33%, N 10.05; calcd for C 60.02%, H
3.36%, N 10.00.
CDCl3 þ CD3OD)
d
8.01 (d, J ¼ 8.2 Hz, 1H), 7.31 (d, J ¼ 8.2 Hz, 1H),
3.15 (br s, 2H), 2.81 (br s, 2H), 2.75 (s, 3H); 13C NMR (125 MHz,
CDCl3 þ CD3OD)
d 182.5, 179.7, 165.0, 152.4, 147.15, 134.7, 128.3,
126.2, 106.7, 56.1, 25.3; HREIMS m/z C24H20Br2N6O4 [M]þ calcd
613.9913, found 613.9903. Anal. (C24H20Br2N6O4). Elemental anal-
ysis: Found C 46.71%, H 3.23%, N 13.62; calcd for C 46.78%, H 3.27%,
N 13.64.
4.5.16. 6-(4-Phenylpiperazin-1-yl)quinoline-5,8-dione (10a)
Red powder. Mp: 221 ꢁC; Yield 11% (55 mg). 1H NMR (500 MHz,
d
CDCl3) 8.25 (d, J ¼ 8.2 Hz, 1H), 7.47 (d, J ¼ 8.2 Hz, 1H), 7.31 (d,
J ¼ 9.0 Hz, 2H), 6.93 (d, J ¼ 9.0 Hz, 2H), 6.92 (m, 1H), 6.23 (s, 1H),
3.71 (t, J ¼ 6.0 Hz, 2H), 3.39 (t, J ¼ 6.0 Hz, 2H); 13C NMR (125 MHz,
4.6. General procedure for synthesis of 13e15
A solution of 2-hydroxynapthoquinone (12) (1 equiv) in 5 mL of
dichloromethane was added dropwise to a solution of appropriate
amine (3 equiv) in 15 mL of EtOH. The reaction was refluxed for 1 h.
After concentration in vacuo, the residue was directly purified by
flash column chromatography (EtOAc/n-hexane 40:60 to 50:50) to
give 13e15.
CDCl3)
d 182.9, 182.3, 164.5, 150.6, 150.3, 147.1, 134.3, 129.4, 127.7,
126.9, 120.1, 116.7, 113.2, 50.0; HREIMS m/z C19H17N3O2 [M]þ calcd
319.1321, found 319.1311. Anal. (C19H17N3O2). Elemental analysis:
Found C 71.33%, H 5.49%, N 13.25; calcd for C 71.46%, H 5.37%, N
13.16.
4.5.17. 6-(4-Propyl-biphenyl-40-amino)quinoline-5,8-dione (10b)
4.6.1. 2(4-Propyl-biphenyl-40-amino)-3-hydroxynaphthalene-1,4-
dione (13)
Red solid. Mp.: 245 ꢁC; Yield 13% (69 mg). 1H NMR (500 MHz,
CDCl3)
d
9.02 (d, J ¼ 8.2 Hz, 1H), 8.37 (d, J ¼ 8.2 Hz, 1H), 7.59 (d,
Red powder. Mp. 257 ꢁC; Yield 73% (220 mg). 1H NMR (500 MHz,
J ¼ 8.2 Hz, 1H), 7.48 (m, 4H), 7.20 (d, J ¼ 9.0 Hz, 2H), 6.91 (d,
J ¼ 9.0 Hz, 2H), 6.21 (s, 1H), 4.90 (br s, NH), 2.60 (t, J ¼ 6.5 Hz, 2H),
1.67 (m, 2H), 0.95 (t, J ¼ 6.5 Hz, 3H); 13C NMR (125 MHz, CDCl3)
DMSO-d6)
d
7.85 (dd, J ¼ 8.2,1.5 Hz,1H), 7.77 (dd, J ¼ 8.2, 1.5 Hz,1H),
7.65 (td, J ¼ 8.2, 1.5 Hz, 1H), 7.50 (td, J ¼ 8.2, 1.5 Hz, 1H), 7.40 (d,
J ¼ 9.0 Hz, 2H), 7.33 (d, J ¼ 9.0 Hz, 2H), 7.17 (d, J ¼ 9.0 Hz, 2H), 6.60
(d, J ¼ 9.0 Hz, 2H), 2.55 (t, J ¼ 6.0 Hz, 2H), 1.62 (m, 2H), 0.90 (t,
d
182.4, 180.5, 157.1, 152.1, 150.5, 147.5, 137.0, 134.0, 129.3, 128.1,
127.3, 126.4, 120.4, 116.4, 116.2, 111.7, 37.8, 24.4, 13.5; HREIMS m/z
C24H20N2O2 [M]þ calcd 368.1525, found 368.1511. Anal.
(C24H20N2O2). Elemental analysis: Found C 78.20%, H 5.42%, N 7.65;
calcd for C 78.24%, H 5.47%, N 7.60.
J ¼ 6.0 Hz, 3H); 13C NMR (125 MHz, DMSO-d6)
d 187.3, 180.3, 173.0,
148.5, 139.9, 138.6, 136.5, 133.5, 132.3, 130.3, 129.1, 128.9, 128.0,
127.3, 126.5, 125.6, 125.1, 115.6, 114.7, 106.9, 37.2, 24.5, 14.2; HREIMS
m/z C25H21NO3 [M]þ calcd 383.1521, found 383.1511. Anal.
(C25H21NO3). Elemental analysis: Found C 18.30%, H 5.57%, N 3.61;
calcd for C 18.31%, H 5.52%, N 3.65.
4.5.18. 6-(4-Aminopiperazin-1-ylamino)quinoline-5,8-dione (10c)
Red solid. Mp. 233 ꢁC; Yield 14% (51 mg). 1H NMR (500 MHz,
CDCl3 þ CD3OD)
d
8.96 (d, J ¼ 8.2 Hz, 1H), 8.30 (d, J ¼ 8.2 Hz, 1H),
4.6.2. 2(4-4-Hydroxybiphenyl-40-amino)-3-hydroxynaphthalene-
1,4-dione (14)
7.51 (d, J ¼ 8.2 Hz, 1H), 6.18 (s, 1H), 3.17 (br s, 2H), 3.13 (br s, 2H); 13C
NMR (125 MHz, CDCl3 þ CD3OD)
d
182.3, 179.7, 153.1, 152.4, 147.15,
Red powder. Mp. 297 ꢁC; Yield 72% (153 mg). 1H NMR (500 MHz,
134.9, 129.3, 125.2, 112.1, 57.2, 53.1; HREIMS m/z C13H15N5O2 [M]þ
calcd 273.1226, found 273.1225. Anal. (C13H15N5O2). Elemental
analysis: Found C 57.19%, H 5.50%, N 25.69; calcd for C 57.13%, H
5.53%, N 25.63.
DMSO-d6)
d
7.85 (dd, J ¼ 8.2,1.5 Hz,1H), 7.77 (dd, J ¼ 8.2, 1.5 Hz,1H),
7.65 (td, J ¼ 8.2, 1.5 Hz, 1H), 7.50 (td, J ¼ 8.2, 1.5 Hz, 1H), 7.40 (d,
J ¼ 9.0 Hz, 2H), 7.33 (d, J ¼ 9.0 Hz, 2H), 7.20 (d, J ¼ 9.0 Hz, 2H), 6.90
(d, J ¼ 9.0 Hz, 2H); 13C NMR (125 MHz, DMSO-d6)
d 187.3, 180.1,
173.1, 153.1, 148.5, 139.1, 137.1, 136.1, 132.5, 132.1, 130.3, 129.1, 128.9,
128.0, 127.3, 126.5, 125.6, 125.2, 115.1, 115.7, 107.9; HREIMS m/z
C22H15NO4 [M]þ calcd 357.1001, found 357.1000. Anal. (C22H15NO4).
Elemental analysis: Found C 73.83%, H 4.20%, N 3.90; calcd for C
73.94%, H 4.23%, N 3.92.
4.5.19. 6-(4-Hydroxybiphenyl-40-amino)quinoline-5,8-dione (10d)
Red powder. Mp. 263 ꢁC; Yield 11% (48 mg). 1H NMR
(500 MHz, CDCl3 þ CD3OD)
d
8.97 (d, J ¼ 8.2 Hz, 1H), 8.31 (d,
J ¼ 8.2 Hz, 1H), 7.52 (d, J ¼ 8.2 Hz, 1H), 7.31 (d, J ¼ 9.0 Hz, 2H),
7.29 (d, J ¼ 9.0 Hz, 2H), 6.93 (d, J ¼ 9.0 Hz, 2H), 6.67 (d, J ¼ 9.0 Hz,
2H), 6.20 (s, 1H); 13C NMR (125 MHz, CDCl3 þ CD3OD)
d
180.2,
4.6.3. 2(4-Phenylpiperazin-1-yl)-3-hydroxynaphthalene-1,4-dione
(15)
177.5, 165.3, 156.3, 147.2, 144.2, 138.4, 135.5, 135.3, 131.2, 127.3,
126.1, 125.2, 125.3, 124.0, 112.4, 107.5; HREIMS m/z C21H14N2O3
[M]þ calcd 342.1004, found 342.1006. Anal. (C21H14N2O3).
Elemental analysis: Found C 73.63%, H 4.10%, N 8.13; calcd for C
73.73%, H 4.12%, N 8.18.
Red powder. Mp. 281 ꢁC; Yield 77% (109 mg). 1H NMR (500 MHz,
DMSO-d6)
d
7.83 (dd, J ¼ 8.2, 1.5 Hz,1H), 7.75 (dd, J ¼ 8.2,1.5 Hz,1H),
7.63 (td, J ¼ 8.2, 1.5 Hz, 1H), 7.51 (td, J ¼ 8.2, 1.5 Hz, 1H), 7.31 (d,
J ¼ 9.0 Hz, 2H), 6.90 (d, J ¼ 9.0 Hz, 2H), 6.90 (m, 1H), 3.73 (t,