5464 Journal of Medicinal Chemistry, 2010, Vol. 53, No. 15
Zhou et al.
1
4.21-4.15 (m, 2H), 4.08-4.04 (m, 4H), 3.98-3.95 (m, 1H),
2.74-2.52 (m, 20H), 2.33 (s, 6H), 1.56 (d, J=6.9 Hz, 3H). 13C
NMR (100 MHz, CDCl3): δ 151.2, 143.5, 131.6, 118.2, 74.9, 66.1,
60.2, 55.0, 52.5, 45.9, 42.6, 21.4. LRMS (EI) m/z 842 [M]þ. HRMS
(EI) m/z calcd for C30H42Br4N4O4 [M]þ 837.9940, found
837.9894.
CH3OH = 20/1). Yield: 78%. H NMR (300 MHz, CDCl3):
δ 6.85 (s, 4H), 4.10-4.04 (m, 2H), 3.76 (d, J=5.1 Hz, 4H), 2.71-
2.44 (m, 20H), 2.30 (s, 6H), 2.23 (s, 12H), 2.17 (br, 4H), 1.50 (br,
6H). 13C NMR (100 MHz, CDCl3): δ 152.7, 143.7, 129.6, 127.3,
73.8, 66.3, 60.3, 54.9, 53.0, 45.7, 44.7, 37.1, 26.2, 22.7, 16.4. LRMS
(EI) m/z 636 [M]þ. HRMS (EI) m/z calcd for C38H60N4O4 [M]þ
636.4615, found 636.4612.
3,30-(4,40-(Cyclopentane-1,1-diyl)bis(2,6-dibromo-4,1-phenylene))-
bis(oxy)bis(1-morpholinopropan-2-ol) (34). By the same manner as
described for the preparation of 1, compound 34 was prepared
from the intermediate 16 and morpholine and purified by silica
3,30-(4,40-(Cyclohexane-1,1-diyl)bis(2-bromo-4,1-phenylene))-
bis(oxy)bis(1-(4-methylpiperazin-1-yl)propan-2-ol) (40). By the
same manner as described for the preparation of 1, compound
40 was prepared from the intermediate 21 and1-methylpiperazine
and purified by silica gel chromatography (CH2Cl2/CH3OH=
20/1). Yield: 78%. 1H NMR (300 MHz, CDCl3): δ 7.41 (d, J=1.8
Hz, 2H), 7.09 (dd, J=8.7 Hz, 1.8 Hz, 2H), 6.82 (d, J=8.7 Hz, 2H),
4.13 (m, 2H), 4.01 (m, 4H), 2.54-2.76 (m, 22H), 2.34 (s, 6H), 2.17
(br, 4H), 1.50 (br, 6H). 13C NMR (100 MHz, CDCl3): δ 152.7,
142.3, 131.7, 127.1, 113.2, 112.1, 71.3, 65.6, 60.3, 54.9, 53.1, 45.8,
44.8, 37.0, 26.0, 22.6. LRMS (EI) m/z 738 [M]þ. HRMS (EI) m/z
calcd for C34H50Br2N4O4 [M]þ 736.2199, found 736.2195.
3,30-(4,40-(Cycloheptane-1,1-diyl)bis(2,6-dimethyl-4,1-pheny-
lene))bis(oxy)bis(1-morpholinopropan-2-ol) (41). By the same
manner as described for the preparation of 1, compound 41
was prepared from the intermediate 18c and morpholine and
purified by silica gel chromatography (CH2Cl2/CH3OH=20/1).
Yield: 80%. 1H NMR (300 MHz, CDCl3): δ 6.75 (s, 4H) 4.12-
4.07 (m, 2H), 3.78 (d, J=5.1 Hz, 4H), 3.73 (t, 8H), 2.70-2.63 (m,
4H), 2.61-2.56 (m, 4H), 2.52-2.45 (m, 4H), 2.22 (s, 12H), 2.18
(br, 4H), 1.66 (br, 4H), 1.56 (br, 4H). 13C NMR (100 MHz,
CDCl3): δ 152.6, 146.5, 129.5, 127.6, 73.7, 66.9, 66.2, 61.0, 53.7,
48.8, 40.3, 30.2, 24.3, 16.6. LRMS (EI) m/z 624 [M]þ. HRMS (EI)
m/z calcd for C37H56N2O6 [M]þ 624.4138, found 624.4116.
3,30-(4,40-(Cycloheptane-1,1-diyl)bis(2,6-dimethyl-4,1-pheny-
lene))bis(oxy)bis(1-(4-methylpiperazin-1-yl)propan-2-ol) (42). By
the same manner as described for the preparation of 1, compound
42 was prepared from the intermediate 18c and 1-methylpiper-
azine and purified by silica gel chromatography (CH2Cl2/
1
gel chromatography (CH2Cl2/CH3OH=20/1). Yield: 80%. H
NMR (300 MHz, CDCl3): δ 7.32 (s, 4H), 4.23-4.14 (m, 2H), 4.05
(m, 4H), 3.73 (t, 8H), 2.72-2.63 (m, 8H), 2.56-2.46 (m, 4H),
2.20-2.13 (br, 4H), 1.73-1.67 (br, 4H). 13C NMR (100 MHz,
CDCl3): δ 150.9, 146.2, 131.2, 118.0, 75.0, 67.0, 66.2, 61.0, 54.7,
53.8, 38.6, 22.6. LRMS (EI) m/z 856 [M]þ. HRMS (EI) m/z calcd
for C31H40Br4N2O6 [M]þ 851.9620, found 851.9620.
3,30-(4,40-(Cyclopentane-1,1-diyl)bis(2,6-dibromo-4,1-pheny-
lene))bis(oxy)bis(1-(4-methylpiperazin-1-yl)propan-2-ol) (35). By
the same manner as described for the preparation of 1, compound
35was preparedfrom the intermediate16and 1-methylpiperazine
and purified by silica gel chromatography (CH2Cl2/CH3OH=
20/1). Yield: 78%. 1H NMR (300 MHz, CDCl3): δ 7.31 (s, 4H),
4.20-4.11 (m, 2H), 4.06-4.01 (m, 4H), 2.75-2.61(m, 8H), 2.60-
2.35 (m, 12H), 2.89 (s, 6H), 2.19-2.13 (br, 4H), 1.73-1.66 (br,
4H). 13C NMR (100 MHz, CDCl3): δ 151.0, 146.2, 131.2, 118.0,
75.1, 66.3, 60.3, 55.2, 54.7, 53.3, 46.0, 38.6, 22.6. LRMS (EI) m/z
882 [M]þ. HRMS (EI) m/z calcd for C33H46Br4N4O4 [M]þ
878.0253, found 878.0290.
3,30-(4,40-(Cyclopentane-1,1-diyl)bis(2,6-dimethyl-4,1-pheny-
lene))bis(oxy)bis(1-morpholinopropan-2-ol) (36). By the same
manner as described for the preparation of 1, compound 36
was prepared from the intermediate 18a and morpholine and
purified by silica gel chromatography (CH2Cl2/CH3OH=20/1).
Yield: 80%. 1H NMR (300 MHz, CDCl3): δ 6.87 (s, 4H), 4.12-
4.04 (m, 2H), 3.78-3.68 (m, 12H), 2.69-2.62 (m, 4H), 2.60-2.55
(m, 4H), 2.50-2.45 (m, 4H), 2.23 (s, 12H), 2.19 (br, 4H), 1.65 (br,
4H). 13C NMR (100 MHz, CDCl3): δ 152.9, 144.3, 129.7, 127.4,
73.7, 66.9, 66.2, 61.1, 54.5, 53.8, 38.8, 22.9, 16.5. LRMS (EI) m/z
596 [M]þ. HRMS (EI) m/z calcd for C35H52N2O6 [M]þ 596.3825,
found 596.3818.
3,30-(4,40-(Cyclopentane-1,1-diyl)bis(2,6-dimethyl-4,1-pheny-
lene))bis(oxy)bis(1-(4-methylpiperazin-1-yl)propan-2-ol) (37). By
the same manner as described for the preparation of 1, compound
37 was prepared from the intermediate 18a and 1-methylpiper-
azine and purified by silica gel chromatography (CH2Cl2/CH3OH
=20/1). Yield: 78%. 1H NMR (300 MHz, CDCl3): δ 6.85 (s, 4H),
4.09-4.03 (m, 2H), 3.75 (d, J=4.8 Hz, 4H), 2.70-2.43 (m, 20H),
2.28 (s, 6H), 2.22 (s, 12H), 2.18 (br, 4H), 1.64 (br, 4H). 13C NMR
(100 MHz, CDCl3): δ 153.0, 144.3, 129.7, 127.3, 73.8, 66.3, 60.3,
55.1, 54.5, 46.0, 38.7, 22.9, 16.5. LRMS (EI) m/z 622 [M]þ.
HRMS (EI) m/z calcd for C37H58N4O4 [M]þ 622.4458, found
622.4462.
3,30-(4,40-(Cyclohexane-1,1-diyl)bis(2,6-dimethyl-4,1-pheny-
lene))bis(oxy)bis(1-morpholinopropan-2-ol) (38). By the same
manner as described for the preparation of 1, compound 38 was
prepared from the intermediate 18b and morpholine and purified
by silica gel chromatography (CH2Cl2/CH3OH=20/1). Yield:
80%. 1H NMR (300 MHz, CDCl3): δ 6.87 (s, 4H), 4.13-4.08 (m,
2H), 3.78 (d, J=4.8 Hz, 4H), 3.74 (t, 8H), 2.72-2.63 (m, 4H),
2.62-2.58 (m, 4H), 2.53-2.46 (m, 4H), 2.24 (s, 12H), 2.18 (br,
4H), 1.51 (br, 6H). 13C NMR (100 MHz, CDCl3): δ 152.8, 144.0,
129.8, 127.5, 73.7, 67.0, 66.2, 61.0, 53.7, 45.0, 37.2, 26.4, 22.9, 16.6.
LRMS (EI) m/z 610 [M]þ. HRMS (EI) m/z calcd for C36H54N2O6
[M]þ 610.3982, found 610.3990.
3,30-(4,40-(Cyclohexane-1,1-diyl)bis(2,6-dimethyl-4,1-pheny-
lene))bis(oxy)bis(1-(4-methylpiperazin-1-yl)propan-2-ol) (39). By
the same manner as described for the preparation of 1, compound
39 was prepared from the intermediate 18b and 1-methylpiper-
azine and purified by silica gel chromatography (CH2Cl2/
1
CH3OH =20/1). Yield: 78%. H NMR (300 MHz, CDCl3): δ
6.74 (s, 4H), 4.12-4.02 (m, 2H), 3.77 (d, J=5.1 Hz, 4H), 2.70-
2.42 (m, 20H), 2.29 (s, 6H), 2.21 (s, 12H), 2.18 (br, 4H), 1.65 (br,
4H), 1.54 (br, 4H). 13C NMR (100 MHz, CDCl3): δ 152.7, 146.4,
129.6, 127.6, 73.8, 66.3, 60.4, 55.1, 53.5, 48.8, 46.0, 40.3, 30.2, 24.3,
16.6. LRMS (EI) m/z 650 [M]þ. HRMS (EI) m/z calcd for
C39H62N4O4 [M]þ 650.4771, found 650.4781.
3,30-(4,40-(Propane-2,2-diyl)bis(2,6-dibromo-4,1-phenylene))-
bis(oxy)bis(1-(3,5-dimethylpiperidin-1-yl)propan-2-ol) (43). By
the same manner as described for the preparation of 1, compound
43 was prepared from 3,5-dimethylpiperidine and purified by
silica gel chromatography (CH2Cl2/CH3OH=20/1). Yield: 75%.
1H NMR (300 MHz, CDCl3): δ 7.27 (s, 4H), 4.38 (m, 2H), 4.05
(m, 4H), 2.93(m, 8H), 1.90(s, 8H), 1.58 (s, 6H), 1.01 (m, 4H), 0.88
(m, 12H). 13C NMR (100 MHz, CDCl3): δ 150.0, 148.4, 131.1,
117.2, 74.4, 63.8, 59.7, 57.8, 42.0, 38.6, 29.5, 28.1, 18.3. LRMS
(ESI) m/z 883 [M þ H]þ. HRMS (ESI) m/z calcd C35H51Br4N2O4
[M þ H]þ 879.0582, found 879.0563.
3,30-(4,40-(Propane-2,2-diyl)bis(2,6-dibromo-4,1-phenylene))-
bis(oxy)bis(1-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)propan-2-ol)
(44). By the same manner as described for the preparation of 1,
compound 44 was prepared from 1,4-dioxa-8-azaspiro[4.5]decane
and purified by silica gel chromatography (CH2Cl2/CH3OH=
20/1). Yield: 75%. 1H NMR (300 MHz, CDCl3): δ 7.30 (s, 4H),
4.15-4.18 (m, 2H), 4.08 (d, J=5.1 Hz, 4H), 3.97 (s, 8H), 2.74-
2.80 (m, 4H), 2.68 (d, J=6.6 Hz, 4H), 2.56-2.61 (m, 4H), 1.75-
1.79 (m, 8H), 1.60 (s, 6H). 13C NMR (100 MHz, CDCl3): δ 151.0,
147.9, 131.0, 118.0, 107.0, 75.0, 66.3, 64.2, 59.9, 51.6, 42.2, 34.9,
30.4. LRMS (ESI) m/z 943 [M þ H]þ. HRMS (ESI) m/z calcd
C35H47Br4N2O8 [M þ H]þ 939.0066, found 939.0060.
3,30-(4,40-(Propane-2,2-diyl)bis(2,6-dibromo-4,1-phenylene))-
bis(oxy)bis(1-(dibutylamino)propan-2-ol) (45). By the same man-
ner as described for the preparation of 1, compound 45 was
prepared from 1,4-dioxa-8-azaspiro[4.5]decane and purified by