2312
A.J.M. Rasras et al. / European Journal of Medicinal Chemistry 45 (2010) 2307–2313
(m, ca 22H, skeletal CH2 and CH); 2.60 (m, 2H, 23-CH2); 3.12 (bs, 1H,
H-3 ); 3.55 (bs, 1H, H-7 ); 3.75 (bs, 1H, H-12
); 3.90 (d, 1H, J ¼ 3.35,
H-3
b
); 3.55 (bs, 1H, H-7
b
); 3.75 (bs, 1H, H-12
b
); 4.00 (d, 1H, J ¼ 3.17,
b
b
b
3-OH); 4.10 (d, 1H, 7-OH); 4.30 (d, 1H, J ¼ 3.76, 12-OH); 6.50–6.90
(m, 3H, skeletal CH-aromatic); 8.00 (8.15) (s, 1H, C]NH); 11.00
(11.20) (s, 1H, CONH). 13C NMR (75 MHz, DMSO-d6, in ppm): 12.85
(C-18); 17.65 (17.59) (C-21); 23.13 (C-19); 23.3 (C-15); 26.71 (C-9);
27.75 (C-16); 29.06 (29.21) (C-11); 30.9 (C-2); 31.1 (C-22); 31.74
(C-23); 34.89 (C-10); 35.36 (C-6); 35.63 (C-1); 35.8 (C-20); 40.55 (C-
4); 40.82 (C-8); 41.88 (C-5); 42 (C-14); 46.23 (C-13); 46.43 (C-17);
66.74 (C-7); 70.92 (C-3); 71.49 (C-12); 149.86 (149.98) (C-20); 112.46
(112.54) (C-30); 113.12 (113.42) (C-40); 145.2 (145.4) (C-50); 133.03
(136.1) (C]N); 169.58 (175.31) (C]O). ESIMS: m/z calculated for
[M þ Naþ]: 523.31479, found 523.320816, difference: 0.00600.
3-OH); 4.10 (d, 1H, J ¼ 3.34, 7-OH); 4.30 (d, 1H, J ¼ 4.05, 12-OH);
7.70–8.30 (m, 3H, skeletal CH-aromatic); covered by aromatic (1H,
C]NH); 11.40 (11.60) (s, 1H, CONH). 13C NMR (75 MHz, DMSO-d6, in
ppm): 12.84 (C-18); 17.66 (17.59) (C-21); 23.12 (C-19); 23.3 (C-15);
26.72 (C-9); 27.87 (C-16); 29.06 (29.58) (C-11); 30.9 (C-2); 31.33 (C-
22); 31.7 (C-23); 34.88 (C-10); 35.38 (C-6); 35.65 (C-1); 35.82
(C-20); 40.53 (C-4); 40.8 (C-8); 41.9 (C-5); 42 (C-14); 46.4 (C-13);
46.51 (C-17); 66.73 (C-7); 70.92 (C-3); 71.48 (C-12); 125.73 (126) (C-
10); 123.5 (123.83) (C-20); 148.28 (148.39) (C-30); 135.58 (135.69)
(C-40); 131.31 (131.81) (C-50); 132.55 (C-60); 139.41 (142.61) (C]N);
170.07 (175.74) (C]O). ESIMS: m/z calculated for [M þ Naþ]:
612.28163, found 612.289643, difference: 0.00801.
4.3.21. (3a, 5b, 7a, 12a)-3, 7, 12-Trihydroxy-N-[(1E)-thiophen-2-
ylmethylene]cholan-24-ohydrazide (4r)
4.3.18. (3
a
, 5
b
, 7
a
, 12
a
)-3, 7, 12-Trihydroxy-N-[(1E)-1H-indole-2-
This derivative was synthesized according to the above general
ylmethylene]cholan-24-ohydrazide (4o)
procedure. Yield 70%, as white solid, m.p.170–171 ꢀC, [
a
]D ¼ þ22.8ꢀ.
This derivative was synthesized according to the above general
procedure. Yield 90%, as yellow solid, m.p. 223–224 ꢀC,
1H NMR (300 MHz, DMSO-d6, in ppm): 0.58 (s, 3H, 18-CH3); 0.80
(s, 3H, 19-CH3); 0.95 (d, 3H, J ¼ 6, 21-CH3); 0.92–2.20 (m, ca 22H,
[
a
]
¼ þ19.0. 1H NMR (300 MHz, DMSO-d6, in ppm): 0.58 (s, 3H, 18-
skeletal CH2 and CH); 2.60 (m, 2H, 23-CH2); 3.12 (bs,1H, H-3b); 3.55
D
CH3); 0.80 (s, 3H, 19-CH3); 0.95 (d, 3H, J ¼ 5.39, 21-CH3); 0.92–2.20
(bs, 1H, H-7b); 3.75 (bs, 1H, H-12b); 4.00 (d, 1H, 3-OH); 4.10 (d, 1H,
(m, ca 22H, skeletal CH2 and CH); 2.60 (m, 2H, 23-CH2); 3.15 (bs, 1H,
J ¼ 2.69, 7-OH); 4.30 (d, 1H, J ¼ 4.07, 12-OH); 7.10–7.60 (m, 3H,
skeletal CH-aromatic); 8.10 (8.30) (s, 1H, C]NH); 11.00 (11.10) (s,
1H, CONH). 13C NMR (75 MHz, DMSO-d6, in ppm): 12.86 (C-18);
17.66 (17.59) (C-21); 23.12 (C-19); 23.31 (C-15); 26.7 (C-9); 27.79
(C-16); 29.05 (29.69) (C-11); 30.9 (C-2); 31 (C-22); 31.9 (C-23);
34.88 (C-10); 35.37 (C-6); 35.37 (C-1); 35.82 (C-20); 40.54 (C-4);
40.82 (C-8); 41.86 (C-5); 42 (C-14); 46.23 (C-13); 46.5 (C-17); 66.73
(C-7); 70.92 (C-3); 71.48 (C-12); 139.72 (C-20); 130.3 (130.95) (C-30);
128.98 (C-40); 128.23 (128.46) (C-50); 137.89 (141.31) (C]N); 169.49
(175.25) (C]O). ESIMS: m/z calculated for [M þ Naþ]: 539.29195,
found 539.294343, difference: 0.00239.
H-3b); 3.60 (bs, 1H, H-7b); 3.80 (bs, 1H, H-12b); 4.00 (bs, 1H, 3-OH);
4.10 (bs, 1H, 7-OH); 4.30 (bs, 1H, 12-OH); 7.00–8.30 (m, 5H, skeletal
CH-aromatic); covered by aromatic (1H, C]NH); 10.80 (11.00)
(s, 1H, CONH); 11.50 (bs, NH). 13C NMR (75 MHz, DMSO-d6, in ppm):
12.88 (C-18); 17.63 (C-21); 23.11 (C-19); 23.33 (C-15); 26.69 (C-9);
27.88 (C-16); 29 (29.93) (C-11); 30.9 (C-2); 31 (C-22); 31.05 (C-23);
34.89 (C-10); 35.37 (C-6); 35.71 (C-1); 35.82 (C-20); 40.55 (C-4);
40.83 (C-8); 41.84 (C-5); 42(C-14); 46.27 (C-13); 46.84 (C-17); 66.76
(C-7); 70.96 (C-3); 71.54 (C-12); 124.81 (C-20); 112.11 (C-30); 120.71
(120.84) (C-40); 124.57 (C-50); 123 (C-60); 130.28 (70); 137.46
(137.52) (C-80); 112.18 (112.33) (C-90); 140.29 (143.28) (C]N);
168.83 (174.75) (C]O). ESIMS: m/z calculated for [M þ Naþ]:
573.35425, found 573.35700, difference: 0.00275.
4.3.22. (3a, 5b, 7a, 12a)-3, 7, 12-Trihydroxy-N-[(1E)-1H-pyrrol-2-
ylmethylene]cholan-24-ohydrazide (4s)
This derivative was synthesized according to the above general
procedure. Yield 38%, as white solid, m.p. 267–268 ꢀC. 1H NMR
(300 MHz, DMSO-d6, in ppm): 0.58 (s, 3H, 18-CH3); 0.80 (s, 3H, 19-
CH3); 0.95 (d, 3H, J ¼ 6, 21-CH3); 0.92–2.20 (m, ca 22H, skeletal CH2
4.3.19. (3a, 5b, 7a, 12a)-3, 7, 12-Trihydroxy-N-[(1E)-5-methoxy-
1H-indole-3-ylmethylene] cholan-24-ohydrazide (4p)
This derivative was synthesized according to the above general
procedure. Yield 95%, as orange solid, m.p. 224–225 ꢀC,
and CH); 2.60 (m, 2H, 23-CH2); 3.12 (bs, 1H, H-3
b
); 3.55 (bs, 1H, H-
[
a
]
¼ þ16.9. 1H NMR (300 MHz, DMSO-d6, in ppm): 0.58 (s, 3H, 18-
7b); 3.75 (bs, 1H, H-12b
); 4.00 (d, 1H, 3-OH); 4.10 (d, 1H, J ¼ 2.69,
D
CH3); 0.80 (s, 3H, 19-CH3); 0.95 (d, 3H, J ¼ 6, 21-CH3); 0.92–2.20
7-OH); 4.30 (d, 1H, J ¼ 4.07, 12-OH); 6.00–6.90 (m, 3H, skeletal CH-
aromatic); 7.80(8.00) (s, 1H, C]NH); 10.80 (11.00) (s, 1H, NH); 11.15
(11.40) (s, 1H, CONH). 13C NMR (75 MHz, DMSO-d6, in ppm): 12.86
(C-18); 17.66 (17.59) (C-21); 23.12 (C-19); 23.31 (C-15); 26.7 (C-9);
27.79 (C-16); 29.05 (29.69) (C-11); 30.9 (C-2); 31 (C-22); 31.9 (C-
23); 34.88 (C-10); 35.37 (C-6); 35.37 (C-1); 35.82 (C-20); 40.54 (C-
4); 40.82 (C-8); 41.86 (C-5); 42 (C-14); 46.23 (C-13); 46.5 (C-17);
66.73 (C-7); 70.92 (C-3); 71.48 (C-12); 127.79 (127.58) (C-20); 111.94
(113.23) (C-30); 109.51 (C-40); 121.92 (122.54) (C-50); 135.89
(139.34) (C]N); 169.07 (174.87) (C]O). ESIMS: m/z calculated for
[M þ Naþ]: 522.33078, found 522.33023, difference: 0.00055.
(m, ca 22H, skeletal CH2 and CH); 2.60 (m, 2H, 23-CH2); 3.12 (bs, 1H,
H-3b); 3.55 (bs, 1H, H-7b); 3.73 (s, 3H, OCH3); 3.75 (bs, 1H, H-12b);
4.00 (bs, 1H, 3-OH); 4.10 (bs, 1H, 7-OH); 4.30 (bs, 1H, 12-OH); 6.70–
8.30 (m, 4H, skeletal CH-aromatic); covered by aromatic (1H,
C]NH); 10.80 (10.90) (s, 1H, CONH); 11.50 (bs, NH). 13C NMR
(75 MHz, DMSO-d6, in ppm): 12.82 (C-18); 17.63 (C-21); 23.13
(C-19); 23.32 (C-15); 26.69 (C-9); 27.88 (C-16); 29 (29.93) (C-11);
30.9 (C-2); 31 (C-22); 31.05 (C-23); 34.89 (C-10); 35.37 (C-6); 35.71
(C-1); 35.82 (C-20); 40.55 (C-4); 40.83 (C-8); 41.84 (C-5); 42(C-14);
46.27 (C-13); 47 (C-17); 55.47 (55.81) (OCH3); 66.73 (C-7); 70.94 (C-
3); 71.5 (C-12); 103.43 (C-20); 132.41 (132.49) (C-30); 104.64 (C-40);
154.79 (C-50); 113.04 (C-60); 130.67 (70); 132.49 (132.73) (C-80);
111.82 (112.58) (C-90); 140.34 (143.5) (C]N); 168.71 (174.35)
(C]O). ESIMS: m/z calculated for [M þ Naþ]: 602.35699, found
602.35649, difference: 0.00050.
4.3.23. (3a, 5b, 7a, 12a)-3, 7, 12-Trihydroxy-N-[(1E)-pyridin-2-
ylmethylene]cholan-24-ohydrazide (4t)
This derivative was synthesized according to the above general
procedure. Yield 67%, as white solid, m.p. 184–186 ꢀC, [
a
]D ¼ þ6.0ꢀ.
1H NMR (300 MHz, DMSO-d6, in ppm): 0.58 (s, 3H, 18-CH3); 0.80
(s, 3H, 19-CH3); 0.95 (d, 3H, J ¼ 6, 21-CH3); 0.92–2.20 (m, ca 22H,
4.3.20. (3a, 5b, 7a, 12a)-3, 7, 12-Trihydroxy-N-[(1E)-furan-2-
ylmethylene]cholan-24-ohydrazide. (4q)
skeletal CH2 and CH); 2.60 (m, 2H, 23-CH2); 3.12 (bs,1H, H-3b); 3.55
This derivative was synthesized according to the above general
procedure. Yield 57.4%, as yellow solid, m.p. 146–147 ꢀC,
(bs,1H, H-7b); 3.75 (bs,1H, H-12b); 4.00 (s,1H, 3-OH); 4.10 (s,1H, 7-
OH); 4.30 (d, 1H, J ¼ 4.01, 12-OH); 7.20–8.60 (m, 4H, skeletal CH-
aromatic); 8.00 (8.15) (s, 1H, C]NH); 11.35 (11.50) (s, 1H, CONH).
13C NMR (75 MHz, DMSO-d6, in ppm): 12.86 (C-18); 17.66 (17.59)
(C-21); 23.12 (C-19); 23.31 (C-15); 26.7 (C-9); 27.79 (C-16); 29.05
[
a]
¼ þ24.0ꢀ. 1H NMR (300 MHz, DMSO-d6, in ppm): 0.58 (s, 3H,
D
18-CH3); 0.80 (s, 3H, 19-CH3); 0.95 (d, 3H, J ¼ 6, 21-CH3); 0.92–2.20
(m, ca 22H, skeletal CH2 and CH); 2.60 (m, 2H, 23-CH2); 3.12 (bs, 1H,