B. Bonnet et al. / Bioorg. Med. Chem. 8 (2000) 95±103
101
53.00, 48.55, 25.13, 21.68; m/z 556; biological assays
were performed using the hydrochloride salt of this
compound.
NMR (CD2Cl2) d 134.88, 130.01, 129.85, 129.67,
127.90, 127.22, 58.98, 53.86, 51.83, 48.51, 30.31, 27.30;
m/z 665; biological assays were performed using the hy-
drochloride salt of this compound.
1,4-Bis(3-{N-[4-(benzyloxy)benzyl]amino}propyl)piper-
ꢀ
1
azine (6e). White solid (40%); mp 86±88 C; H NMR
(CD2Cl2) d 7.46±7.37 (m, 10H, aromatic H), 7.30±7.26
(m, 4H, aromatic H), 6.97±6.94 (m, 4H, aromatic H),
5.08 (s, 4H, CH2), 3.73 (s, 4H, CH2), 2.71±2.66 (m, 4H,
CH2), 2.41±2.35 (m, 12H, CH2), 1.80 (s, 2H, NH), 1.71±
1.68 (m, 4H, CH2); 13C NMR (CD2Cl2) d 130.89,
129.98, 129.38, 129.01, 70.31, 57.39, 53.70, 53.11, 48.48,
26.99; m/z 592; biological assays were performed using
the oxalate salt of this compound.
1,4-Bis{3-[N-(3-phenylpropyl)amino]propyl}piperazine (6k).
1
Colourless oil (33%); H NMR (D2O) d 7.39±7.24 (m,
10H, aromatic H), 3.59±3.52 (m, 8H, CH2), 3.30±3.24
(m, 4H, CH2), 3.09±2.99 (m, 8H, CH2), 2.71±2.66 (m,
4H, CH2), 2.17±2.08 (m, 4H, CH2), 1.99±1.94 (m, 4H,
CH2); 13C NMR (D2O) d 128.89, 126.93, 53.91, 49.48,
47.66, 44.55, 32.17, 27.54, 22.43, 21.23; m/z 436; biolo-
gical assays were performed using the hydrochloride salt
of this compound.
1,4-Bis{3-[N-(napht-2-ylmethyl)amino]propyl}piperazine
(6f). White solid (97%); mp 50±52 ꢀC; 1H NMR
(CD2Cl2) d 7.87±7.80 (m, 8H, aromatic H), 7.54±7.46
(m, 6H, aromatic H), 3.97 (s, 4H, CH2), 2.76±2.71 (m,
4H, CH2), 2.42±2.34 (m, 12H, CH2), 1.79 (s, 2H, NH),
1.75±1.67 (m, 4H, CH2); 13C NMR (CD2Cl2) d 128.24,
127.99, 127.93, 127.04, 126.68, 126.34, 125.87, 57.39,
54.19, 53.68, 48.62, 27.01; m/z 480; biological assays
were performed using the hydrochloride salt of this
compound.
1,4±Bis{3-[N-(cinnamyl)amino]propyl}piperazine (6l).
1
Yellow oil (96%); H NMR (CD2Cl2) d 7.43±7.23 (m,
10H, aromatic H), 6.58±6.53 (m, 1H, CH), 6.38±6.30
(m, 1H, CH), 3.42±3.39 (m, 4H, CH2), 2.71±2.66 (m,
4H, CH2), 2.45±2.36 (m, 12H, CH2), 1.72±1.62 (m, 6H,
NH and CH2); 13C NMR (CD2Cl2) d 130.81, 129.62,
128.87, 127.56, 126.53, 57.32, 53.82, 52.17, 48.48, 27.54;
m/z 432; biological assays were performed using the hy-
drochloride salt of this compound.
1,4-Bis{3-[N-(pyrid-3-ylmethyl)amino]propyl}piperazine
1
1,4-Bis{3-[N-(anthr-9-ylmethyl)amino]propyl}piperazine
(6g). Yellow solid (25%); mp 65±67 ꢀC; 1H NMR
(CD2Cl2) d 8.44±8.38 (m, 6H, aromatic H), 8.06±8.02
(m, 4H, aromatic H), 7.60±7.49 (m, 8H, aromatic H),
4.72 (s, 4H, CH2), 2.97±2.92 (m, 4H, CH2), 2.36±2.31
(m, 14H, NH and CH2), 1.77±1.67 (m, 4H, CH2); 13C
NMR (CD2Cl2) d 131.94, 130.62, 129.37, 127.28,
126.29, 125.32, 124.80, 59.00, 53.84, 49.77, 46.30, 27.29;
m/z 580; biological assays were performed using the hy-
drochloride salt of this compound.
(6m). Yellow oil (91%); H NMR (CD2Cl2) d 8.56±8.54
(m, 2H, aromatic H), 8.49±8.46 (m, 2H, aromatic H),
7.77±7.68 (m, 2H, aromatic H), 7.29±7.24 (m, 2H, aro-
matic H), 3.79 (s, 4H, CH2), 2.69±2.64 (m, 4H, CH2),
2.40±2.35 (m, 12H, CH2), 1.71±1.62 (m, 6H, NH and
CH2); 13C NMR (CD2Cl2) d 150.06, 148.58, 135.85,
123.57, 57.26, 54.20, 53.78, 51.64, 48.52, 27.36; m/z 382;
biological assays were performed using the hydrochlo-
ride salt of this compound.
1,4-Bis{3-[N-(quinol-2-ylmethyl)amino]propyl}piperazine
1
1,4-Bis{3-[N-(¯uoren-2-ylmethyl)amino]propyl}piperazine
(6h). White solid (70%); mp 112±114 ꢀC; 1H NMR
(CD2Cl2) d 7.82±7.75 (m, 4H, aromatic H), 7.59±7.55
(m, 4H, aromatic H), 7.40±7.31 (m, 6H, aromatic H),
3.93 (s, 4H, CH2), 3.85 (s, 4H, CH2), 2.72±2.67 (m, 4H,
CH2), 2.42±2.36 (m, 12H, CH2), 1.71±1.64 (m, 6H, NH
and CH2); 13C NMR (CD2Cl2) d 127.08, 127.02, 126.80,
125.39, 125.31, 119.99, 57.35, 54.39, 53.83, 48.57, 37.19,
27.53; m/z 556; biological assays were performed using
the hydrochloride salt of this compound
(6n). Orange oil (99%); H NMR (CD2Cl2) d 8.87±8.85
(m, 2H, aromatic H), 8.16±8.09 (m, 4H, aromatic H),
7.74±7.70 (m, 2H, aromatic H), 7.63±7.57 (m, 2H, aro-
matic H), 7.51±7.49 (m, 2H, aromatic H), 4.28 (s, 4H,
CH2), 2.83±2.78 (m, 4H, CH2), 2.44±2.39 (m, 12H,
CH2), 1.87 (s, 2H, NH), 1.78±1.69 (m, 4H, CH2); 13C
NMR (CD2Cl2) d 150.74, 130.43, 129.24, 126.64,
123.87, 120.11, 57.29, 53.83, 50.52, 49.12, 27.28; m/z
482; biological assays were performed using the hydro-
chloride salt of this compound.
1,4-Bis(3-{N-[2-(phenylsulfanyl)benzyl]amino}propyl)-
piperazine (6i). Colourless oil (68%); 1H NMR
(CD2Cl2) d 7.40±7.20 (m, 16H, aromatic H), 3.90 (s, 4H,
CH2), 2.71±2.64 (m, 4H, CH2), 2.45±2.36 (m, 12H,
CH2), 1.82 (s, 2H, NH), 1.69±1.62 (m, 4H, CH2); 13C
NMR (CD2Cl2) d 136.15, 135.13, 134.80, 132.08, 131.11,
130.53, 130.27, 129.78, 127.97, 59.04, 53.86, 51.83, 48.55,
30.50, 28.50; m/z 596; biological assays were performed
using the hydrochloride salt of this compound.
1,4-Bis{3-[N-(indol-3-ylmethyl)amino]propyl}piperazine
(6o). White solid (31%); mp 130±132 ꢀC; 1H NMR
(CD3OD) d 7.74±7.70 (m, 2H, aromatic H), 7.49 (s, 2H,
aromatic H), 7.45±7.41 (m, 2H, aromatic H), 7.21±7.11
(m, 4H, aromatic H), 4.36 (m, 4H, CH2), 3.18±3.13 (m,
4H, CH2), 2.34±2.29 (m, 12H, CH2), 1.83±1.73 (m, 6H,
NH and CH2); 13C NMR (CD3OD) d 126.47, 122.37,
120.03, 118.01, 111.88, 56.23, 52.25, 47.99, 42.53, 22.29;
m/z 458; biological assays were performed using the hy-
drochloride salt of this compound.
1,4-Bis(3-{N-[5-chloro-2-(phenylsulfanyl)benzyl]amino}-
1
propyl)piperazine (6j). Colourless oil (33%); H NMR
1,4-Bis{3-[N-(fur-2-ylmethyl)amino]propyl}piperazine (6p).
1
(CD2Cl2) d 7.32±7.21 (m, 16H, aromatic H), 3.87 (s, 4H,
CH2), 2.66±2.61 (m, 4H, CH2), 2.44±2.34 (m, 12H,
CH2), 1.79 (s, 2H, NH), 1.66±1.61 (m, 4H, CH2); 13C
Yellow oil (78%); H NMR (CD2Cl2) d 7.38 (s, 2H,
aromatic H), 6.35±6.34 (m, 2H, aromatic H), 6.20±6.19
(m, 2H, aromatic H), 3.76 (s, 4H, CH2), 2.67±2.62