M. Asada et al. / Bioorg. Med. Chem. 18 (2010) 80–90
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5.1.15. 3-[2-({[(1R)-1-(1-Naphthyl)ethyl]amino}carbonyl)-4-
(phenoxymethyl)phenyl]propanoic acid (15)
2956, 1719, 1637, 1601, 1531, 1496, 1300, 1244, 1034, 941, 843,
753, 697 cmꢁ1; MS (APCI, Neg.) m/e 430 (MꢁH)ꢁ; HRMS (Pos.)
calcd for C27H30NO4: 432.2175; found: 432.2174.
The titled compound was synthesized in the same manner as
described for 3 using 30 instead of 28 as a white powder. Yield
95% in two steps; 1H NMR (300 MHz, CDCl3) d 8.23 (d, J = 7.8 Hz,
1H), 7.89 (d, J = 7.5 Hz, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.62–7.25 (m,
9H), 6.98–6.88 (m, 3H), 6.36 (d, J = 8.4 Hz, 1H), 6.14 (m, 1H), 4.97
(s, 2H), 3.10 (t, J = 7.2 Hz, 2H), 2.78 (t, J = 7.2 Hz, 2H), 1.80 (d,
J = 6.6 Hz, 3H); IR (KBr) 3290, 2923, 1705, 1636, 1541, 1496,
1304, 1244, 775, 752, 474 cmꢁ1; MS (FAB, Pos.) m/e 454 (M+H)+;
HRMS (Pos.) calcd for C29H28NO4: 454.2018; found: 454.2017.
5.1.21. 3-[2-{[(3-Methyl-1-phenylbutyl)amino]carbonyl}-4-
(phenoxymethyl)phenyl]propanoic acid (8)
The titled compound was synthesized in the same manner as
described for 3 using 40 instead of 28 as a white powder. Yield
82% in two steps; 1H NMR (300 MHz, DMSO-d6) d 8.82 (d,
J = 8.4 Hz, 1H), 7.44–7.16 (m, 10H), 7.04–6.88 (m, 3H), 5.08 (s,
2H), 5.03 (m, 1H), 2.90–2.75 (m, 2H), 2.45 (t, J = 8.4 Hz, 2H),
1.80–1.56 (m, 2H), 1.43 (m, 1H), 0.92 (d, J = 6.9 Hz, 3H), 0.90 (d,
J = 6.9 Hz, 3H); IR (KBr) 3292, 2955, 1703, 1636, 1601, 1531,
1496, 1451, 1301, 1244, 1173, 1080, 1033, 944 cmꢁ1; MS (APCI,
Neg.) m/e 444 (MꢁH)ꢁ; HRMS (Pos.) calcd for C28H32NO4:
446.2331; found: 446.2339.
5.1.16. 3-[2-({[(1S)-1-(1-Naphthyl)ethyl]amino}carbonyl)-4-
(phenoxymethyl)phenyl]propanoic acid (16)
The titled compound was synthesized in the same manner as
described for 3 using 31 instead of 28 as a white powder. Yield
96% in two steps; 1H NMR (300 MHz, CDCl3) d 8.22 (d, J = 7.8 Hz,
1H), 7.89 (d, J = 7.8 Hz, 1H), 7.83 (d, J = 8.1 Hz, 1H), 7.62–7.25 (m,
9H), 6.98–6.88 (m, 3H), 6.36 (d, J = 7.8 Hz, 1H), 6.14 (m, 1H), 4.97
(s, 2H), 3.09 (t, J = 7.5 Hz, 2H), 2.78 (t, J = 7.5 Hz, 2H), 1.80 (d,
J = 6.9 Hz, 3H); IR (KBr) 3290, 2977, 1704, 1636, 1541, 1496,
1302, 1244, 775, 753 cmꢁ1; MS (FAB, Pos.) m/e 454 (M+H)+; HRMS
(Pos.) calcd for C29H28NO4: 454.2018; found: 454.2018.
5.1.22. 3-[2-{[(2-Cyclopropyl-1-phenylethyl)amino]carbonyl}-
4-(phenoxymethyl)phenyl]propanoic acid (9)
The titled compound was synthesized in the same manner as
described for 3 using 41 instead of 28 as a white powder. Yield
98% in two steps; 1H NMR (300 MHz, CDCl3) d 7.74 (m, 1H),
7.48–7.22 (m, 9H), 7.00–6.93 (m, 3H), 6.62 (d, J = 7.2 Hz, 1H),
5.25 (m, 1H), 5.02 (s, 2H), 3.03 (t, J = 7.2 Hz, 2H), 2.74 (t,
J = 7.2 Hz, 2H), 1.88–1.72 (m, 2H), 0.66 (m, 1H), 0.55–0.40 (m,
2H), 0.20–0.01 (m, 2H); IR (KBr) 3296, 2915, 1717, 1634, 1602,
1530, 1497, 1449, 1292, 1245, 941, 846, 750, 698 cmꢁ1; MS (APCI,
Neg.) m/e 442 (MꢁH)ꢁ; HRMS (Pos.) calcd for C28H30NO4:
444.2175; found: 444.2164.
5.1.17. 3-[2-[(Benzylamino)carbonyl]-4-
(phenoxymethyl)phenyl]propanoic acid (4)
The titled compound was synthesized in the same manner as
described for 3 using 36 instead of 28 as a white powder. Yield
38% in two steps; 1H NMR (300 MHz, CDCl3) d 7.46–7.25 (m,
10H), 6.99–6.92 (m, 3H), 6.48 (m, 1H), 5.00 (s, 2H), 4.61 (d,
J = 5.7 Hz, 2H), 3.10 (t, J = 7.5 Hz, 2H), 2.77 (t, J = 7.5 Hz, 2H); IR
(KBr) 3292, 3031, 2924, 1704, 1640, 1599, 1540, 1496, 1455,
1304, 1239 cmꢁ1; MS (APCI, Neg.) m/e 388 (MꢁH)ꢁ; HRMS (Pos.)
calcd for C24H24NO4: 390.1705; found: 390.1704.
5.1.23. 3-[2-{[(3-Hydroxy-3-methyl-1-
phenylbutyl)amino]carbonyl}-4-
(phenoxymethyl)phenyl]propanoic acid (10)
The titled compound was synthesized in the same manner as
described for 3 using 42 instead of 28 as a white powder. Yield
55% in two steps; 1H NMR (300 MHz, CDCl3) d 7.56 (s, 1H), 7.47–
7.17 (m, 11H), 7.00–6.86 (m, 3H), 5.04 (s, 2H), 4.98 (d, J = 10 Hz,
1H), 3.10 (t, J = 7.2 Hz, 2H), 2.78 (t, J = 7.2 Hz, 2H), 2.15 (dd,
J = 15, 10 Hz, 1H), 1.73 (d, J = 15 Hz, 1H), 1.62 (s, 3H), 1.57 (s,
3H); IR (KBr) 3296, 2915, 1717, 1634, 1602, 1530, 1497, 1449,
1292, 1245, 941, 846, 750, 698 cmꢁ1; MS (APCI, Neg.) m/e 460
(MꢁH)ꢁ; HRMS (Pos.) calcd for C28H32NO5: 462.2280; found:
462.2285.
5.1.18. 3-(4-(Phenoxymethyl)-2-{[(1-
phenylethyl)amino]carbonyl}phenyl)propanoic acid (5)
The titled compound was synthesized in the same manner as
described for 3 using 37 instead of 28 as a white powder. Yield
58% in two steps; 1H NMR (300 MHz, DMSO-d6) d 8.92 (d,
J = 7.8 Hz, 1H), 7.48–7.20 (m, 10H), 7.07–6.91 (m, 3H), 5.13 (m,
1H), 5.09 (s, 2H), 2.87 (t, J = 7.9 Hz, 2H), 2.60–2.40 (m, 2H), 1.44
(d, J = 7.2 Hz, 3H); IR (KBr) 3296, 1716, 1637, 1524, 1496, 1249,
754, 698 cmꢁ1; MS (APCI, Neg.) m/e 402 (MꢁH)ꢁ; HRMS (Pos.)
calcd for C25H26NO4: 404.1862; found: 404.1873.
5.1.24. 3-[2-[(Benzhydrylamino)carbonyl]-4-
(phenoxymethyl)phenyl]propanoic acid (11)
5.1.19. 3-(4-(Phenoxymethyl)-2-{[(1-
The titled compound was synthesized in the same manner as
described for 3 using 43 instead of 28 as a white powder. Yield
87% in two steps; 1H NMR (300 MHz, DMSO-d6) d 9.39 (d,
J = 8.7 Hz, 1H), 7.43–7.20 (m, 15H), 7.03–6.90 (m, 3H), 6.36 (d,
J = 8.7 Hz, 1H), 5.07 (s, 2H), 2.85 (t, J = 7.8 Hz, 2H), 2.44 (m, 2H);
IR (KBr) 3288, 3030, 1716, 1639, 1600, 1524, 1495, 1245, 1031,
753, 693 cmꢁ1; MS (APCI, Neg.) m/e 464 (MꢁH)ꢁ; HRMS (Pos.)
calcd for C30H28NO4: 466.2018; found: 466.2015.
phenylpropyl)amino]carbonyl}phenyl)propanoic acid (6)
The titled compound was synthesized in the same manner as
described for 3 using 38 instead of 28 as a white powder. Yield
82% in two steps; 1H NMR (300 MHz, DMSO-d6) d 8.83 (d,
J = 8.4 Hz, 1H), 7.44–7.18 (m, 10H), 7.03–6.90 (m, 3H), 5.08 (s,
2H), 4.86 (m, 1H), 2.84 (t, J = 7.8 Hz, 2H), 2.46 (t, J = 7.8 Hz, 2H),
1.82–1.64 (m, 2H), 0.90 (t, J = 7.5 Hz, 3H); IR (KBr) 3294, 2961,
1703, 1637, 1533, 1496, 1456, 1303, 1241, 1033, 820 752,
700 cmꢁ1; MS (APCI, Neg.) m/e 416 (MꢁH)ꢁ; HRMS (Pos.) calcd
for C26H28NO4: 418.2018; found: 418.2017.
5.1.25. 3-(4-(Phenoxymethyl)-2-{[(2-
phenylethyl)amino]carbonyl}phenyl)propanoic acid (12)
The titled compound was synthesized in the same manner as
described for 3 using 52 instead of 28 as a white powder. Yield
75% in two steps; 1H NMR (300 MHz, CDCl3) d 7.42–7.20 (m,
10H), 7.00–6.90 (m, 3H), 6.25 (m, 1H), 4.98 (s, 2H), 3.72 (dt,
J = 6.0, 6.9 Hz, 2H), 3.01 (t, J = 7.2 Hz, 2H), 2.94 (t, J = 6.9 Hz, 2H),
2.74 (t, J = 7.2 Hz, 2H); IR (KBr) 3328, 2921, 2521, 1704, 1598,
1557, 1492, 1454, 1383, 1287, 1219, 1196 cmꢁ1; MS (APCI, Neg.)
m/e 402 (MꢁH)ꢁ; HRMS (Pos.) calcd for C25H26NO4: 404.1862;
found: 404.1861.
5.1.20. 3-(4-(Phenoxymethyl)-2-{[(1-
phenylbutyl)amino]carbonyl}phenyl)propanoic acid (7)
The titled compound was synthesized in the same manner as
described for 3 using 39 instead of 28 as a white powder. Yield
76% in two steps; 1H NMR (300 MHz, CDCl3) d 7.47–7.24 (m,
10H), 7.02–6.91 (m, 3H), 6.41 (d, J = 8.1 Hz, 1H), 5.15 (m, 1H),
5.03 (s, 2H), 3.08–2.97 (m, 2H), 2.78–2.69 (m, 2H), 1.98–1.74 (m,
2H), 1.52–1.23 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H); IR (KBr) 3290,