8206 Journal of Medicinal Chemistry, 2005, Vol. 48, No. 26
Mahindroo et al.
4.74 (s, 2H), 6.39 (d, J ) 3.0 Hz, 1H), 6.81 (dd, J ) 2.4, 8.7
Hz, 1H), 6.94 (d, J ) 8.7 Hz, 1H), 6.97 (d, J ) 3.3 Hz, 1H),
7.01-7.06 (m, 2H), 7.40-7.46 (m, 3H), 7.56 (d, J ) 8.7 Hz,
1H), 7.83-7.86 (m, 2H). MS (ESI m/z) 499.1 (M + H)+.
2-{4-[3-(3-Phenyl-7-propylbenzo[d]isoxazol-6-yloxy)-
propoxy]indol-1-yl}ethanoic Acid (28). This compound was
prepared as described in the case of 14, starting from 28b,
1
giving a 98% yield. H NMR (400 MHz, CDCl3) δ 0.97 (t, J )
7.2 Hz, 3H), 1.71-1.77 (m, 2H), 2.42-2.45 (m, 2H), 2.93 (t, J
) 7.2 Hz, 2H), 4.34 (q, J ) 4.8 Hz, 4H), 4.88 (s, 2H), 6.60 (d,
J ) 7.6 Hz, 1H), 6.68 (d, J ) 2.8 Hz, 1H), 6.88 (d, J ) 8.8 Hz,
1H), 6.99 (d, J ) 2.8 Hz, 1H), 7.03 (d, J ) 8.8 Hz, 1H), 7.16 (t,
J ) 8.0 Hz, 2H), 7.51-7.56 (m, 2H), 7.65 (d, J ) 8.8 Hz, 1H),
7.93 (dd, J ) 1.2, 7.2 Hz, 2H). HRMS (EI+ m/z) calcd for
C29H28N2O5 484.1998, found 484.1987.
Methyl 2-{5-[3-(7-Propyl-1H-indol-6-yloxy)propoxy]in-
dol-1-yl}ethanoate (30b). This compound was prepared as
described in the case of 14a, starting from 30a, giving a 62%
1
yield. H NMR (300 MHz, CDCl3) δ 0.89 (t, J ) 7.5 Hz, 3H),
1.51-1.65 (m, 2H), 2.23 (quintet, J ) 6.0 Hz, 2H), 2.73 (t, J )
7.5 Hz, 2H), 3.60 (s, 3H), 4.13-4.17 (m, 4H), 4.74 (s, 2H), 6.38-
6.39 (m, 2H), 6.76-6.83 (m, 2H), 6.96-7.04 (m, 4H), 7.32 (d,
J ) 8.4 Hz, 1H), 7.92 (br s, 1H). MS (ESI m/z) 421.2 (M +
H)+.
2-{5-[3-(3-Phenyl-7-propylbenzo[d]isoxazol-6-yloxy)-
propoxy]indol-1-yl}ethanoic Acid (29). This compound was
prepared as described in the case of 14, starting from 29b,
Methyl 2-{5-[3-(3-Cyano-7-propyl-1H-indol-6-yloxy)-
propoxy]indol-1-yl}ethanoate (31b). This compound was
prepared as described in the case of 14a, starting from 31a,
1
giving a 97% yield. H NMR (300 MHz, CDCl3) δ 0.97 (t, J )
7.2 Hz, 3H), 1.66-1.79 (m, 2H), 2.34 (quintet, J ) 6.0 Hz, 2H),
2.93 (t, J ) 7.5 Hz, 2H), 4.24 (t, J ) 6.0 Hz, 2H), 4.31 (t, J )
6.0 Hz, 2H), 4.76 (s, 2H), 6.39 (d, J ) 3.0 Hz, 1H), 6.88 (dd, J
) 2.4, 8.7 Hz, 1H), 7.02-7.06 (m, 2H), 7.12-7.16 (m, 2H),
7.51-7.67 (m, 3H), 7.65 (d, J ) 8.7 Hz, 1H), 7.91-7.94 (m,
2H). HRMS (EI+ m/z) calcd for C29H28O5N2 484.1998, found
484.2012.
1
giving a 62% yield. H NMR (300 MHz, CDCl3) δ 0.94 (t, J )
7.5 Hz, 3H), 1.40-1.55 (m, 2H), 2.48 (quintet, J ) 6.0 Hz, 2H),
2.69-2.74 (m, 2H), 3.69 (s, 3H), 4.14-4.20 (m, 4H), 4.88 (s,
2H), 6.38-6.39 (m, 1H), 6.78 (dd, J ) 2.4, 8.7 Hz, 1H), 6.93
(d, J ) 8.7 Hz, 1H), 7.04 (d, J ) 2.1 Hz, 1H), 7.10 (t, J ) 3.0
Hz, 1H), 7.17 (s, 1H), 7.20 (d, J ) 8.7 Hz, 1H), 7.44 (d, J ) 8.7
Hz, 1H), 7.99 (br s, 1H). MS (ESI m/z) 446.1 (M + H)+.
2-{5-[3-(7-Propyl-1H-indol-6-yloxy)propoxy]indol-1-yl}-
ethanoic Acid (30). This compound was prepared as de-
scribed in the case of 14, starting from 30b, giving a 94% yield.
1H NMR (300 MHz, CDCl3) δ 0.89 (t, J ) 7.5 Hz, 3H), 1.51-
1.65 (m, 2H), 2.21 (quintet, J ) 6.0 Hz, 2H), 2.73 (t, J ) 7.5
Hz, 2H), 3.60 (s, 3H), 4.08-4.19 (m, 4H), 4.76 (s, 2H), 6.39-
6.40 (m, 2H), 6.78 (d, J ) 8.7 Hz, 1H), 6.82 (dd, J ) 2.4, 9.0
Hz, 1H), 6.95 (d, J ) 3.0 Hz, 1H), 7.03-7.05 (m, 3H), 7.32 (d,
J ) 8.7 Hz, 1H), 7.87 (br s, 1H). HRMS (EI+ m/z) calcd for
C24H26O4N2 406.1893, found 406.1888.
Methyl 2-(5-{3-[3-(2,2,2-Trifluoroethyl-1-one)-7-propyl-
1H-indol-6-yloxy]propoxy}indol-1-yl)ethanoate (32b). This
compound was prepared as described in the case of 14a,
starting from 32a, giving a 62% yield. 1H NMR (300 MHz,
CDCl3) δ 1.00 (t, J ) 7.5 Hz, 3H), 1.42-1.63 (m, 2H), 2.25
(quintet, J ) 6.0 Hz, 2H), 3.02 (t, J ) 7.8 Hz, 2H), 3.73 (s,
3H), 3.93 (t, J ) 5.4 Hz, 2H), 4.50 (t, J ) 6.9 Hz, 2H), 4.65 (s,
2H), 6.37-6.39 (m, 1H), 6.77-6.82 (m, 2H), 7.00 (d, J ) 2.4
Hz, 1H), 7.10 (t, J ) 2.7 Hz, 1H), 7.21 (d, J ) 8.7 Hz, 1H),
7.81 (d, J ) 1.5 Hz, 1H), 8.06 (br s, 1H), 8.15 (d, J ) 9.0 Hz,
1H). MS (ESI m/z) 517.2 (M + H)+.
Ethyl 2-{4-[3-(2-phenyl-7-propyl-1H-indol-6-yloxy)pro-
poxy]indol-1-yl}ethanoate (33b). This compound was pre-
pared as described in the case of 14a, by reacting 33a with
ethyl-2-bromoacetate, giving a 70% yield. 1H NMR (400 MHz,
CDCl3) δ 1.00 (t, J ) 7.2 Hz, 3H), 1.24 (t, J ) 7.6 Hz, 3H),
1.70-1.74 (m, 2H), 2.38-2.41 (m, 2H), 2.85-2.88 (m, 2H), 4.20
(q, J ) 4.8, 9.6 Hz, 2H), 4.28-4.30 (m, 2H), 4.39 (t, J ) 4.0
Hz, 2H), 4.80 (s, 2H), 6.61 (d, J ) 5.2 Hz, 1H), 6.70 (dd, J )
0.4, 2.0 Hz, 1H), 6.76 (d, J ) 1.6 Hz, 1H), 6.88 (dd, J ) 1.2,
5.6 Hz, 2H), 6.99 (d, J ) 2.0 Hz, 1H), 7.15 (t, J ) 5.2 Hz, 1H),
7.28-7.31 (m, 2H), 7.39-7.44 (m, 2H), 7.65 (dd, J ) 0.8, 5.6
Hz, 2H), 8.09 (br s, 1H). HRMS (EI+ m/z) calcd for C32H34N2O4:
510.2519, found 510.2522.
2-{5-[3-(3-Cyano-7-propyl-1H-indol-6-yloxy)propoxy]-
indol-1-yl}ethanoic Acid (31). This compound was prepared
as described in the case of 14, starting from 31b, giving a 95%
1
yield. H NMR (300 MHz, CDCl3) δ 0.95 (t, J ) 7.5 Hz, 3H),
1.36-1.51 (m, 2H), 2.40 (quintet, J ) 6.0 Hz, 2H), 2.73 (t, J )
7.8 Hz, 2H), 4.14-4.18 (m, 4H), 4.89 (s, 2H), 6.37-6.39 (m,
1H), 6.80 (dd, J ) 2.4, 8.7 Hz, 1H), 6.93 (d, J ) 8.7 Hz, 1H),
7.04 (d, J ) 2.4 Hz, 1H), 7.10 (t, J ) 2.7 Hz, 1H), 7.19 (d, J )
8.7 Hz, 1H), 7.29 (s, 1H), 7.43 (d, J ) 8.7 Hz, 1H), 8.02 (br s,
1H). HRMS (EI+ m/z) calcd for C25H25O4N3 431.1845, found
431.1832.
2-(5-{3-[3-(2,2,2-Trifluoroethyl-1-one)-7-propyl-1H-in-
dol-6-yloxy]propoxy}indol-1-yl)ethanoic acid (32). This
compound was prepared as described in the case of 14, starting
1
from 32b, giving a 92% yield. H NMR (300 MHz, CDCl3) δ
1.00 (t, J ) 7.5 Hz, 3H), 1.56-1.64 (m, 2H), 2.25 (quintet, J )
6.0 Hz, 2H), 3.01 (t, J ) 7.8 Hz, 2H), 3.95 (t, J ) 5.4 Hz, 2H),
4.52 (t, J ) 6.9 Hz, 2H), 4.68 (s, 2H), 6.37-6.39 (m, 1H), 6.79
(dd, J ) 2.1, 8.7 Hz, 1H), 6.85 (d, J ) 8.7 Hz, 1H), 7.00 (d, J
) 2.4 Hz, 1H), 7.13 (t, J ) 2.7 Hz, 1H), 7.23 (d, J ) 8.7 Hz,
1H), 7.82 (d, J ) 1.5 Hz, 1H), 8.05 (br s, 1H), 8.17 (d, J ) 8.7
Hz, 1H). HRMS (EI+ m/z) calcd for C26H25O5N2F3 502.1716,
found 502.1711.
Ethyl 2-{4-[3-(3-phenyl-7-propylbenzo[b]furan-6-yl-
oxy)propoxy]indol-1-yl}ethanoate (34b). This compound
was prepared as described in the case of 14a, by reacting 34a
1
with ethyl-2-bromoacetate, giving a 92% yield. H NMR (600
MHz, CDCl3) δ 0.95 (t, J ) 7.2 Hz, 3H), 1.23 (t, J ) 7.6 Hz,
3H), 1.67-1.71 (m, 2H), 2.37-2.40 (m, 2H), 2.89-2.91 (m, 2H),
4.20 (q, J ) 4.8, 9.6 Hz, 2H), 4.27 (t, J ) 6.0 Hz, 2H), 4.35 (t,
J ) 6.0 Hz, 2H), 4.83 (s, 2H), 6.58 (d, J ) 7.8 Hz, 1H), 6.67
(dd, J ) 0.6, 3.0 Hz, 1H), 6.85 (d, J ) 8.4 Hz, 1H), 6.94 (d, J
) 2.4 Hz, 1H), 6.95 (d, J ) 3.0 Hz, 1H), 7.13 (t, J ) 8.4 Hz,
1H), 7.32-7.35 (m, 1H), 7.43-7.46 (m, 2H), 7.55 (d, J ) 8.4
Hz, 1H), 7.61-7.62 (m, 2H), 7.70 (s, 1H).
2-{4-[3-(2-Phenyl-7-propyl-1H-indol-6-yloxy)propoxy]-
indol-1-yl}ethanoic Acid (33). This compound was prepared
as described in the case of 14, starting from 33b, giving an
1
85% yield. H NMR (400 MHz, CDCl3) δ 0.92 (t, J ) 7.2 Hz,
3H), 1.65-1.71 (m, 2H), 2.33-2.39 (m, 2H), 2.81-2.86 (m, 2H),
4.27 (q, J ) 6.0, 12.8 Hz, 2H), 4.36 (q, J ) 6.0, 12.4 Hz, 2H),
4.83 (s, 2H), 6.57 (t, J ) 7.2 Hz, 1H), 6.67 (d, J ) 3.2 Hz, 1H),
6.73 (s, 1H), 6.83-6.86 (m, 2H), 7.01-7.15 (m, 2H), 7.28 (t, J
) 8.0 Hz, 1H), 7.36-7.43 (m, 3H), 7.63 (d, J ) 7.2 Hz, 2H),
8.02 (br s, 1H). HRMS (EI+ m/z) calcd for C30H30N2O4 482.2206,
found 482.2198.
Ethyl 2-{4-[3-(2-phenyl-7-propylbenzo[b]furan-6-yl-
oxy)propoxy]indol-1-yl}ethanoate (35b). This compound
was prepared as described in the case of 14a, by reacting 35a
1
with ethyl-2-bromoacetate, giving a 92% yield. H NMR (400
MHz, CDCl3) δ 0.97 (t, J ) 7.6 Hz, 3H), 1.23 (t, J ) 7.2 Hz,
3H), 1.70-1.76 (m, 2H), 2.38 (quintet, J ) 2.4, 6.0 Hz, 2H),
2.94 (t, J ) 7.6 Hz, 2H), 4.19 (q, J ) 7.2 Hz, 2H), 4.27 (t, J )
6.4 Hz, 2H), 4.36 (t, J ) 6.0 Hz, 2H), 4.80 (s, 2H), 6.58 (d, J )
7.6 Hz, 1H), 6.66 (d, J ) 3.2 Hz, 1H), 6.87 (t, J ) 8.0 Hz, 2H),
6.92 (s, 1H), 6.98 (d, J ) 3.2 Hz, 1H), 7.12 (t, J ) 8.0 Hz, 1H),
7.28-7.31 (m, 2H), 7.41 (t, J ) 8.0 Hz, 2H), 7.81 (dd, J ) 1.2,
8.4 Hz, 2H). HRMS (EI+ m/z) calcd for C32H33NO5 511.2359,
found 511.2364.
2-{4-[3-(3-Phenyl-7-propylbenzo[b]furan-6-yloxy)pro-
poxy]indol-1-yl}ethanoic Acid (34). This compound was
prepared as described in the case of 14, starting from 34b,
1
giving a 92% yield. H NMR (600 MHz, CDCl3) δ 0.95 (t, J )
7.2 Hz, 3H), 1.67-1.71 (m, 2H), 2.37-2.40 (m, 2H), 2.89-2.91
(m, 2H), 4.27 (t, J ) 6.0 Hz, 2H), 4.35 (t, J ) 6.0 Hz, 2H), 4.83
(s, 2H), 6.58 (d, J ) 7.8 Hz, 1H), 6.67 (dd, J ) 0.6, 3.0 Hz,
1H), 6.85 (d, J ) 8.4 Hz, 1H), 6.94 (d, J ) 2.4 Hz, 1H), 6.95 (d,