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A. Naganawa et al. / Bioorg. Med. Chem. 14 (2006) 6628–6639
Rf = 0.53 (MeOH/CHCl3, 1/9); 1H NMR (200 MHz,
CDCl3) d 8.10 (d, J = 8.4 Hz, 2H), 7.70–7.60 (m, 2H),
7.50–7.20 (m, 7H), 7.11 (d, J = 1.6 Hz, 1H), 5.00–4.80
(m, 2H), 3.44 (d, J = 7.4 Hz, 2H), 1.70–1.50 (m, 1H),
0.90 (d, J = 6.4 Hz, 6H); IR (KBr) 2963, 1694, 1614,
1510, 1448, 1427, 1331, 1289, 1257, 1213, 1169, 1127,
1086, 1019 cmꢁ1; MS (FAB, Pos.) m/e 508 (M+H)+;
Anal. Calcd for C25H24F3NO5S: C, 59.16; H, 4.77;
N, 2.76; S, 6.32. Found: C, 59.50; H, 4.73; N, 2.75; S,
6.54.
J = 6.6 Hz, 6H); IR (KBr) 3452, 1697, 1613, 1579,
1509, 1428, 1332, 1173, 1127 cmꢁ1; MS (APCI, Neg.)
m/e 507 (MꢁH)ꢁ; HRMS (Pos.) calcd for
C24H24F3N2O5S: 509.1358. Found: 509.1355.
4.7.6. 4-{[2-[(2-Furylsulfonyl)(isobutyl)amino]-5-(trifluo-
romethyl)phenoxy]methyl}benzoic acid (6). Yield 89%;
TLC Rf = 0.20 (EtOAc/hexane, 1:1); 1H NMR
(200 MHz, CDCl3) d 8.18–8.14 (m, 2H), 7.48–7.40 (m,
2H), 7.30–7.26 (m, 3H), 7.16 (dd, J = 2.0, 1.0 Hz, 1H),
6.84 (dd, J = 3.5, 1.0 Hz, 1H), 6.35 (dd, J = 3.5,
2.0 Hz, 1H), 5.07 (s, 2H), 3.54 (d, J = 7.0 Hz, 2H),
1.64 (sept, J = 7.0 Hz, 1H), 0.90 (d, J = 7.0 Hz, 6H);
IR (KBr) 2971, 1687, 1511, 1434, 1332, 1124,
1018 cmꢁ1; MS (FAB, Pos.) m/e 498 (M+H)+; Anal.
Calcd for C23H22F3NO6S: C, 55.53; H, 4.46; N, 2.82;
S, 6.45. Found: C, 55.82; H, 4.66; N, 2.83; S, 6.64.
According to the same procedure as described above, 2–
15 were prepared from 21b–o, respectively.
4.7.2. 4-{[2-[Isobutyl(pyridin-3-ylsulfonyl)amino]-5-(tri-
fluoromethyl)phenoxy]methyl}-benzoic acid (2). Yield
69%; TLC Rf = 0.27 (MeOH/CHCl3, 1:9); 1H NMR
(300 MHz, CD3OD) d 8.63 (m, 1H), 8.53 (dd, J = 5.1,
1.8 Hz, 1H), 7.99–7.94 (m, 3H), 7.56 (d, J = 7.5 Hz,
1H), 7.40–7.29 (m, 3H), 7.23 (d, J = 8.4 Hz, 2H), 5.10–
4.80 (m, 2H), 3.58–3.40 (m, 2H), 1.61 (m, 1H), 0.92
(br d, J = 6.0 Hz, 6H); IR (KBr) 3441, 2924, 1705,
1615, 1587, 1511, 1417, 1362, 1333, 1277, 1171,
1124 cmꢁ1; MS (APCI, Neg.) m/e 507 (MꢁH)ꢁ; Anal.
Calcd for C24H23F3N2O5S: C, 56.69; H, 4.56; N, 5.51;
S, 6.31. Found: C, 56.87; H, 4.54; N, 5.55; S, 6.22.
4.7.7. 4-{[2-[Isobutyl(thien-3-ylsulfonyl)amino]-5-(trifluo-
romethyl)phenoxy]methyl}benzoic acid (7). Yield 75%;
TLC Rf = 0.36 (MeOH/CHCl3, 1:10); 1H NMR
(300 MHz, CDCl3) d 8.14–8.10 (m, 2H), 7.74 (dd,
J = 3.3, 1.5 Hz, 1H), 7.42 (d, J = 8.1 Hz, 1H), 7.35 (d,
J = 8.1 Hz, 2H), 7.27 (m, 1H), 7.20 (dd, J = 4.8,
3.0 Hz, 1H), 7.15 (d, J = 1.2 Hz, 1H), 7.10 (dd, J = 4.8,
1.5 Hz, 1H), 4.99 (s, 2H), 3.45 (d, J = 6.9 Hz, 2H),
1.61 (m, 1H), 0.90 (d, J = 6.9 Hz, 6H); IR (KBr) 2963,
4.7.3.
4-{[2-[Isobutyl(1H-pyrrol-2-ylsulfonyl)amino]-5-
1693, 1511, 1421, 1332, 1210, 1159, 1128, 1017 cmꢁ1
;
(trifluoromethyl)phenoxy]methyl}benzoic acid (3). Yield
58%; TLC Rf = 0.45 (MeOH/CHCl3, 1:5); 1H NMR
(300 MHz, CDCl3) d 8.15–8.10 (m, 2H), 7.47 (dd,
J = 8.1, 0.9 Hz, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.27 (m,
1H), 7.13 (d, J = 1.5 Hz, 1H), 6.63 (dd, J = 4.2, 2.1 Hz,
1H), 6.55 (dd, J = 2.4, 2.1 Hz, 1H), 6.02 (dd, J = 4.2,
2.4 Hz, 1H), 5.01 (br s, 2H), 3.44 (d, J = 7.5 Hz, 2H),
3.41 (s, 3H), 1.59 (m, 1H), 0.89 (d, J = 6.6 Hz, 6H); IR
(KBr) 2961, 1694, 1615, 1511, 1429, 1332, 1295, 1170,
1122, 1086, 1019 cmꢁ1; MS (FAB, Pos.) m/e 511
(M+H)+; Anal. Calcd for C24H25F3N2O5S: C, 56.46;
H, 4.94; N, 5.49; S, 6.28. Found: C, 56.49; H, 4.99; N,
5.32; S, 6.43.
MS (APCI, Neg.) m/e 496 (MꢁH)ꢁ; Anal. Calcd for
C23H22F3NO5S2: C, 53.79; H, 4.32; N, 2.73; S, 12.49.
Found: C, 53.86; H, 4.23; N, 2.69; S, 12.60.
4.7.8. 4-{[2-[(3-Furylsulfonyl)(isobutyl)amino]-5-(trifluo-
romethyl)phenoxy]methyl}benzoic acid (8). Yield 88%;
TLC Rf = 0.37 (MeOH/CHCl3, 1:10); 1H NMR
(300 MHz, CDCl3) d 8.16–8.11 (m, 2H), 7.74 (dd,
J = 1.8, 0.6 Hz, 1H), 7.43 (d, J = 7.5 Hz, 1H), 7.41 (d,
J = 7.8 Hz, 2H), 7.28 (dd, J = 1.8, 1.8 Hz, 1H), 7.27 (d,
J = 7.5 Hz, 1H), 7.18 (d, J = 1.5 Hz, 1H), 6.40 (dd,
J = 1.8, 0.6 Hz, 1H), 5.07 (s, 2H), 3.43 (d, J = 7.5 Hz,
2H), 1.62 (m, 1H), 0.90 (d, J = 6.6 Hz, 6H); IR (KBr)
2961, 1693, 1510, 1431, 1333, 1130, 1081, 1015 cmꢁ1
;
4.7.4. 4-{[2-[Isobutyl(1,3-thiazol-2-ylsulfonyl)amino]-5-
(trifluoromethyl)phenoxy]methyl}benzoic acid (4). Yield
87%; TLC Rf = 0.60 (EtOAc); 1H NMR (300 MHz,
MS (APCI, Neg.) m/e 512 (MꢁH)ꢁ; Anal. Calcd for
C23H22F3NO6S: C, 55.53; H, 4.46; N, 2.82; S, 6.45.
Found: C, 55.55; H, 4.50; N, 2.72; S, 6.37.
DMSO-d6)
d 8.03 (d, J = 3.0 Hz, 1H), 7.95 (d,
J = 8.1 Hz, 2H), 7.90 (d, J = 3.0 Hz, 1H), 7.50–7.45
(m, 2H), 7.45–7.35 (m, 3H), 5.11 (br s, 2H), 3.49 (d,
J = 7.2 Hz, 2H), 1.60–1.45 (m, 1H), 0.83 (d,
J = 6.6 Hz, 6H); IR (KBr) 3413, 3084, 2967, 2872,
1687, 1615, 1579, 1512, 1430, 1360, 1333, 1296, 1174,
1126 cmꢁ1; MS (APCI, Neg.) m/e 513 (MꢁH)ꢁ; Anal.
Calcd for C22H21F3N2O5S2: C, 51.36; H, 4.11; N, 5.44;
S, 12.46. Found: C, 51.63; H, 4.08; N, 5.51; S, 12.17.
4.7.9. 4-{[2-[Isobutyl(1H-pyrrol-3-ylsulfonyl)amino]-5-
(trifluoromethyl)phenoxy]methyl}benzoic acid (9). Yield
65%; TLC Rf = 0.45 (MeOH/CHCl3, 1:5); 1H NMR
(300 MHz, CDCl3)
d 8.45 (br s, 1H), 8.12 (d,
J = 8.1 Hz, 2H), 7.42 (d, J = 8.1 Hz, 2H), 7.38 (d,
J = 7.8 Hz, 1H), 7.24 (m, 1H), 7.16 (d, J = 1.2 Hz,
1H), 7.14 (m, 1H), 6.68 (m, 1H), 6.33 (m, 1H), 5.08 (s,
2H), 3.40 (d, J = 7.5 Hz, 2H), 1.60 (m, 1H), 0.88 (d,
J = 6.6 Hz, 6H); IR (KBr) 3348, 2961, 1697, 1511,
1429, 1333, 1173, 1132, 1083, 1043 cmꢁ1; MS (FAB,
Pos.) m/e 497 (M+H)+; Anal. Calcd for
C23H23F3N2O5S: C, 55.64; H, 4.67; N, 5.64; S, 6.46.
Found: C, 55.55; H, 4.75; N, 5.47; S, 6.58.
4.7.5. 4-{[2-[Isobutyl(pyridin-2-ylsulfonyl)amino]-5-(tri-
fluoromethyl)phenoxy]methyl}benzoic acid (5). Yield
87%; TLC Rf = 0.29 (MeOH/CHCl3, 1:9); 1H NMR
(300 MHz, CD3OD) d 8.39 (br d, J = 4.5 Hz, 1H), 8.00
(d, J = 8.1 Hz, 2H), 7.83 (dt, J = 7.8, 1.8 Hz, 1H), 7.70
(d, J = 7.8 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.40–7.35
(m, 1H), 7.34–7.26 (m, 4H), 5.00–4.90 (m, 2H), 3.61
(br d, J = 6.9 Hz, 2H), 1.68–1.54 (m, 1H), 0.91 (d,
4.7.10. 4-{[2-{Isobutyl[(1-methyl-1H-pyrrol-3-yl)sulfo-
nyl]amino}-5-(trifluoromethyl)phenoxy]-methyl}benzoic acid
(10). Yield 73%; TLC Rf = 0.46 (MeOH/CHCl3, 1:5);