A. Naganawa et al. / Bioorg. Med. Chem. 14 (2006) 7774–7789
7785
1049 cmꢀ1; MS (FAB, Pos.) m/e 546 (M+H)+; HRMS
(Pos.) calcd for C24H24ClF3NO6S: 546.0965; found:
546.0927.
Anal. Calcd for C25H29NO6S: C, 63.68; H, 6.20;
N, 2.97; S, 6.80. Found: C, 63.80; H, 6.25; N,
3.05; S 6.98.
Compounds 4–5, 7–13, and 15–18 were prepared from
26b–c, 38a–d, 47, and 38e–j, respectively, according to
the same procedure as described for the preparation of
3 from 26a.
4.22.6.
4-{[(6-{Isobutyl[(5-methyl-2-furyl)sulfonyl]ami-
no}-2,3-dihydro-1H-inden-5-yl)oxy]methyl}benzoic acid
(9). Yield 72%; TLC Rf = 0.45 (MeOH/CHCl3, 1:9);
1H NMR (300 MHz, CDCl3) d 8.11 (d, J = 8.1 Hz,
2H), 7.43 (d, J = 8.1 Hz, 2H), 7.12 (s, 1H), 6.77 (s,
1H), 6.73 (d, J = 3.3 Hz, 1H), 5.94 (m, 1H), 5.15–4.85
(br, 2H), 3.60–3.40 (br, 2H), 2.86 (t, J = 7.2 Hz, 4H),
2.14 (s, 3H), 2.13–2.00 (m, 2H), 1.68 (m, 1H), 1.02–
0.82 (br, 6H); IR (KBr) 3417, 2959, 1689, 1614, 1496,
4.22.2. 3-Chloro-4-{[2-{isobutyl[(5-methyl-2- furyl)sulfo-
nyl]amino}-5-(trifluoromethyl)phenoxy]methyl}benzoic
acid (4). Yield 87%; TLC Rf = 0.28 (MeOH/CHCl3, 1:9);
1H NMR (300 MHz, CDCl3) d 8.14 (d, J = 1.5 Hz, 1H),
8.05 (dd, J = 8.1, 1.5 Hz, 1H), 7.65 (d, J = 8.1 Hz, 1H),
7.42 (d, J = 8.1 Hz, 1H), 7.32–7.15 (m, 2H), 6.78 (d,
J = 3.3 Hz, 1H), 6.00 (d, J = 3.3 Hz, 1H), 5.23–5.09
(m, 2H), 3.52 (d, J = 7.5 Hz, 2H), 2.19 (s, 3H), 1.63–
1.59 (m, 1H), 0.90 (d, J = 6.9 Hz, 6H); IR (KBr) 2963,
1692, 1510, 1430, 1334, 1132, 1043 cmꢀ1; MS (FAB,
Pos.) m/e 546 (M+H)+; Anal. Calcd for
C24H23ClF3NO6S: C, 52.80; H, 4.25; N, 2.57; S, 5.87.
Found: C, 53.08; H, 4.26; N, 2.42; S, 5.84.
1414, 1356, 1282, 1218, 1178, 1135, 1056, 1021 cmꢀ1
;
MS (APCI, Neg.) m/e 482 (MꢀH)ꢀ; Anal. Calcd for
C26H29NO6S: C, 64.58; H, 6.04; N, 2.90; S, 6.63. Found:
C, 64.61; H, 6.13; N, 2.98; S 6.70.
4.22.7. 4-{[(3-{Isobutyl[(5-methyl-2-furyl)sulfonyl]ami-
no}-5,6,7,8-tetrahydronaphthalen-2-yl)oxy]methyl}benzo-
ic acid (10). Yield 78%; TLC Rf = 0.45 (MeOH/CHCl3,
d
1:9); 1H NMR (300 MHz, CDCl3)
8.10 (d,
J = 8.1 Hz, 2H), 7.42 (d, J = 8.1 Hz, 2H), 6.95 (s, 1H),
6.73 (d, J = 3.3 Hz, 1H), 6.57 (s, 1H), 5.93 (m, 1H),
5.15–4.82 (br, 2H), 3.48 (d, J = 7.2 Hz, 2H), 2.77–2.60
(m, 4H), 2.13 (s, 3H), 1.82–1.60 (m, 5H), 0.92 (d,
J = 6.6 Hz, 6H); IR (KBr) 2926, 1685, 1613, 1508,
1420, 1350, 1313, 1287, 1259, 1219, 1189, 1179, 1135,
1067, 1018 cmꢀ1; MS (FAB, Pos.) m/e 498 (M+H)+;
HRMS (Pos.) calcd for C27H32NO6S: 498.1950; found:
498.1955.
4.22.3. 4-{[2-{Isobutyl[(5-methyl-2-furyl)sulfonyl]amino}-
5-(trifluoromethyl)phenoxy]methyl}-3-methylbenzoic acid
(5). Yield 61%; TLC Rf = 0.40 (MeOH/CHCl3, 1:10); 1H
NMR (300 MHz, CDCl3) d 7.97 (d, J = 8.4 Hz, 1H),
7.96 (s, 1H), 7.46 (d, J = 8.4 Hz, 1H), 7.42 (d,
J = 8.4 Hz, 1H), 7.28 (d, J = 8.4 Hz, 1H), 7.20 (s, 1H),
6.76 (d, J = 3.6 Hz, 1H), 5.99 (dd, J = 3.6, 1.2 Hz, 1H),
5.05 (s, 2H), 3.50 (d, J = 7.5 Hz, 2H), 2.41 (s, 3H),
2.15 (s, 3H), 1.64 (m, 1H), 0.88 (d, J = 6.6 Hz, 6H); IR
(KBr) 2964, 1685, 1509, 1429, 1334, 1217, 1164, 1133,
1046 cmꢀ1; MS (APCI, Neg.) m/e 524 (MꢀH)ꢀ; Anal.
Calcd for C25H26F3NO6S: C, 57.14; H, 4.99; N, 2.67;
S, 6.10. Found: C, 57.30; H, 5.05; N, 2.62; S, 6.25.
4.22.8.
4-{[(3-{Isobutyl[(5-methyl-2-furyl)sulfonyl]ami-
no}-2-naphthyl)oxy]methyl}benzoic acid (11). Yield
78%; TLC Rf = 0.33 (MeOH/CHCl3, 1:9); 1H NMR
(300 MHz, CDCl3) d 8.05 (d, J = 8.4 Hz, 2H), 7.82–
7.75 (m, 3H), 7.53 (d, J = 8.4 Hz, 2H), 7.51–7.35
(m, 3H), 6.71 (d, J = 3.3 Hz, 1H), 6.05 (m, 1H),
5.42–4.95 (br, 2H), 3.62 (d, J = 7.5 Hz, 1H), 2.13 (s,
3H), 1.79–1.61 (m, 2H), 0.94 (d, J = 6.3 Hz, 6H);
IR (KBr) 2961, 1697, 1505, 1474, 1362, 1257, 1181,
1136, 1060, 1020 cmꢀ1; MS (APCI, Neg.) m/e 492
(MꢀH)ꢀ; Anal. Calcd for C27H27NO6S: C, 65.70;
H, 5.51; N, 2.84; S, 6.50. Found: C, 65.78; H, 5.47;
N, 2.92; S, 6.60.
4.22.4. 4-[(2-{Isobutyl[(5-methyl-2-furyl)sulfonyl]amino}-
5-methylphenoxy)methyl]benzoic acid (7). Yield 67%;
TLC Rf = 0.56 (MeOH/CHCl3, 1:9); 1H NMR
(300 MHz, CDCl3) d 8.12 (d, J = 8.4 Hz, 2H), 7.45 (d,
J = 8.4 Hz, 2H), 7.15 (d, J = 8.1 Hz, 1H), 6.79 (m,
1H), 6.75–6.69 (m, 2H), 5.94 (m, 1H), 5.20–4.85 (m,
2H), 3.51 (d, J = 7.2 Hz, 2H), 2.33 (s, 3H), 2.14 (s,
3H), 1.67 (m, 1H), 0.91 (d, J = 6.6 Hz, 6H); IR (KBr)
3434, 2962, 2924, 2870, 1687, 1608, 1506, 1420, 1359,
1314, 1287, 1180, 1129, 1072, 1044, 1019 cmꢀ1; MS
(APCI, Neg.) m/e 524 (MꢀH)ꢀ; Anal. Calcd for
C24H27NO6S: C, 63.00; H, 5.95; N, 3.06; S, 7.01. Found:
C, 62.69; H, 5.97; N, 3.19; S, 6.96.
4.22.9. 4-[(2-{Isobutyl[(5-methyl-2-furyl)sulfonyl]amino}-
4,5-dimethylphenoxy)methyl]-3-methylbenzoic acid (12).
Yield 85%; TLC Rf = 0.35 (MeOH/CHCl3, 1:19); 1H
NMR (300 MHz, CDCl3) d 7.94 (d, J = 7.8 Hz, 1H),
7.93 (s, 1H), 7.44 (d, J = 7.8 Hz, 1H), 7.04 (s, 1H),
6.74–6.70 (m, 2H), 5.94 (dd, J = 3.3, 0.9 Hz, 1H), 4.94
(br, 2H), 3.48 (d, J = 6.6 Hz, 2H), 2.37 (s, 3H), 2.24 (s,
3H), 2.19 (s, 3H), 2.11 (s, 3H), 1.68 (sept, J = 6.6 Hz,
1H), 0.91 (d, J = 6.6 Hz, 6H); IR (KBr) 3442, 2961,
1687, 1612, 1578, 1514, 1347, 1271, 1185, 1136,
1063 cmꢀ1; MS (APCI, Neg.) m/e 484 (MꢀH)ꢀ; Anal.
Calcd for C26H31NO6S: C, 64.31; H, 6.43; N, 2.88; S,
6.60. Found: C, 64.42; H, 6.54; N, 2.98; S 6.72.
4.22.5. 4-[(2-{Isobutyl[(5-methyl-2-furyl)sulfonyl]amino}-
4,5- dimethylphenoxy)methyl]benzoic acid (8). Yield
77%; TLC Rf = 0.38 (MeOH/CHCl3, 1:109); 1H
NMR (300 MHz, CDCl3)
d 8.11 (d, J = 8.1 Hz,
2H), 7.42 (d, J = 8.1 Hz, 2H), 7.04 (s, 1H), 6.72
(d, J = 3.3 Hz, 1H), 6.69 (s, 1H), 5.95–5.92 (m,
1H), 5.01 (br s, 2H), 3.50 (br d, J = 6.9 Hz, 2H),
2.22 (s, 3H), 2.18 (s, 3H), 2.13 (s, 3H), 1.78–1.60
(m, 1H), 0.92 (br d, J = 6.3 Hz, 6H); IR (KBr)
3434, 2962, 2924, 2870, 1687, 1608, 1506, 1420,
1359, 1314, 1287, 1180, 1129, 1072, 1044,
1019 cmꢀ1; MS (APCI, Neg.) m/e 524 (MꢀH)ꢀ;
4.22.10. 4-{[(6-{Isobuty[(5-methyl-2-furyl)sulfonyl]ami-
no}-2,3-dihydro-1H-inden-5-yl)oxy]methyl}-3-methylben-
zoic acid (13). Yield 83%; TLC Rf = 0.53 (MeOH/