F. Wei et al. / Bioorg. Med. Chem. Lett. 16 (2006) 6342–6347
6347
CH ),
0
0
0
0
Ethyl 1-(3 -(4 -chlorophenoxy)-2 -hydroxypropyl)-3-(4 -
chlorophenyl)-1H-pyrazole-5-carboxylate Compound 3g:
Pale yellowish oil; IR (film) m: 3431 (OH), 3068, 2981,
9.6 Hz, 1H, CH
2
), 4.38 (q, J = 7.1 Hz, 2H, OCH
2
3
0
0
4.41–4.49 (m, 3H, 2 -H and 3 -H), 6.75 (d, J = 8.8 Hz, 2H,
ArH), 6.79 (s, 1H, 4-H), 6.92 (d, J = 7.4 Hz, 2H, ArH), 6.95
(t, J = 7.4 Hz, 1H, ArH), 7.24 (t, J = 7.4 Hz, 2H, ArH),
2
1
935, 1723 (C@O), 1597 (C@C), 1492(C@N), 1244, 1213,
ꢀ
1 1
093 (C–Cl), 1029, 823, 779, 671 cm
;
H
NMR
), 2.93
br s, OH), 3.75 (dd, J = 6.1, 9.5 Hz, 1H, CH ), 3.91 (dd,
7.30 (d, J = 8.8 Hz, 2H, ArH); HRMS (EI) calcd for
O
+
(M) 396.1685, found 396.1685.
(
(
CDCl
3
, 400 MHz) d:1.41 (t, J = 7.1 Hz, 3H, CH
3
C
22
H
24
N
2
5
0
0
0
0
Ethyl 1-(3 -(4 -chlorophenoxy)-2 -hydroxypropyl)-3-(4 -
methoxyphenyl)-1H-pyrazole-5-carboxylate. Compound
3l: Pale yellowish oil; IR (film) m: 3425 (OH), 3068, 2975,
2936, 1720 (C@O), 1613 (C@C), 1492 (C@N), 1250, 1212,
2
2
J = 4.8, 9.5 Hz, 1H, CH ), 4.38 (q, J = 7.1 Hz, 2H,
OCH CH ), 4.41–4.49 (m, 3H, 2 -H and 3 -H), 6.65 (d,
J = 8.9 Hz, 2H, ArH), 6.82 (s, 1H, 4-H), 7.20 (d,
J = 8.9 Hz, 2H, ArH), 7.31 (d, J = 8.5 Hz, 2H, ArH),
0
0
2
3
ꢀ1
1
1093, 1034, 824, 779,671 cm
400 MHz) d:1.40 (t, J = 7.1 Hz, 3H, CH
J = 5.7, 9.4 Hz, 1H, CH ), 3.85 (s, 3H, OCH
3
;
H
NMR (CDCl
), 3.74 (dd,
), 3.90 (dd,
3
,
7
C
.39 (d, J = 8.5 Hz, 2H, ArH); HRMS (EI) calcd for
3
+
(M) 434.0800, found 434.0782.
21
H
20Cl
2
N
2
O
4
2
0
0
0
0
Ethyl 3-(4 -chlorophenyl)-1-(2 -hydroxy-3 -(4 -nitrophen-
oxy)propyl)-1H-pyrazole-5-carboxylate. Compound 3h:
Pale yellowish oil; IR (film) m: 3425 (OH), 3085, 2936,
J = 4.5, 9.4 Hz, 1H, CH ), 4.11 (br s, OH), 4.39 (q,
2
0
J = 7.1 Hz, 2H, OCH
0
2
CH
3
), 4.41–4.48 (m, 3H, 2 -H and
3 -H), 6.66 (d, J = 9.0 Hz, 2H, ArH), 6.78 (s, 1H, 4-H), 6.92
(d, J = 8.7 Hz, 2H, ArH), 7.12 (d, J = 9.0 Hz, 2H, ArH),
7.28 (d, J = 8.7 Hz, 2H, ArH); HRMS (EI) calcd for
1
1
4
714 (C@O), 1593 (C@C), 1513 (N@O), 1343 (N@O),
ꢀ
1 1
261, 1215, 1093, 1029, 845, 752 cm ; H NMR (CDCl ,
3
+
00 MHz) d:1.40 (t, J = 7.1 Hz, 3H, CH
OH), 3.88 (dd, J = 6.0, 9.6 Hz, 1H, CH
J = 4.9, 9.6 Hz, 1H, CH ), 4.40 (q, J = 7.1 Hz, 2H,
3
), 2.96 (br s,
), 4.03 (dd,
C
Ethyl
22
H
23ClN
2
O
5
0
(M) 430.1295, found 430.1287.
0
0
0
2
1-(2 -hydroxy-3 -(4 -nitrophenoxy)propyl)-3-(4 -
methoxyphenyl)-1H-pyrazole-5-carboxylate. Compound
3m: Pale yellowish oil; IR (film) m: 3408 (OH), 3083,
2936, 2839, 1714 (C@O), 1593 (C@C), 1513 (N@O), 1343
2
0
OCH CH ), 4.42–4.54 (m, 3H, 2 -H and 3-H), 6.79 (d,
2
3
J = 9.2 Hz, 2H, ArH), 6.83 (s, 1H, 4-H), 7.32
d,J = 8.5 Hz, 2H, ArH), 7.39 (d, J = 8.5 Hz, 2H, ArH),
.22 (d, J = 9.2 Hz, 2H, ArH); HRMS (EI) calcd for
ꢀ
1
;
1
(
8
C
(N@O), 1254, 1215, 1033, 845, 753 cm
H NMR
(CDCl , 400 MHz) d:1.40 (t, J = 7.2 Hz, 3H, CH ), 2.96
3
3
+
21
H
20ClN
3
0
O
6
(M) 445.1041, found 445.1057.
(br s, OH), 3.84 (s, 3H, OCH
1H, CH ), 4.08 (dd, J = 4.5, 9.8 Hz, 1H, CH
3
), 4.02 (dd, J = 5.2, 9.8 Hz,
), 4.36 (q,
), 4.41–4.51 (m, 3H, 2 -H and
0
0
0
Ethyl 3-(4 -chlorophenyl)-1-(2 -hydroxy-3 -(2 -nitrophen-
oxy)propyl)-1H-pyrazole-5-carboxylate. Compound 3i:
White solid, mp 121–124 °C; IR (KBr) m: 3342 (OH),
2
2
0
J = 7.2 Hz, 2H, OCH
2
CH
3
0
3 -H), 6.79 (s, 1H, 4-H), 6.80 (d, J = 9.2 Hz, 2H, ArH), 6.92
(d, J = 8.6 Hz, 2H, ArH), 7.27 (d, J = 8.6 Hz, 2H, ArH),
8.15 (d, J = 9.2 Hz, 2H, ArH); HRMS (EI) calcd for
3
130, 2988, 2947, 1727 (C@O), 1610 (C@C), 1534 (N@O),
ꢀ
364 (N@O), 1250, 1212, 1092, 1035, 823, 745, 672 cm ;
1
1
1
+
H NMR (CDCl , 400 MHz) d:1.38 (t, J = 7.2 Hz, 3H,
C H N O [(M-CH OC H NO ) ] 289.1190, found
2
3
15 17
2
4
2
6
4
CH ), 3.26 (br s, OH), 4.00 (dd, J = 5.8, 9.4 Hz, 1H, CH ),
289.0764.
0 0 0 0
Ethyl 1-(2 -hydroxy-3 -(2 -nitrophenoxy)propyl)-3-(4 -
3
2
4
2
1
1
.08 (dd, J = 4.7, 9.4 Hz, 1H, CH
H, OCH CH ), 4.44–4.54 (m, 3H, 2 -H and 3 -H), 6.80 (s,
H, 4-H), 6.97 (d, J = 8.3 Hz, 1H, ArH), 7.04 (t, J = 8.3Hz,
H, ArH), 7.31 (d, J = 8.5 Hz, 2H, ArH), 7.36 (d,
2
), 4.39 (q, J = 7.2 Hz,
0
0
2
3
methoxyphenyl)-1H-pyrazole-5-carboxylate. Compound
3n: Pale yellowish oil; IR (film) m: 3426 (OH), 3074, 2939,
2839, 1717 (C@O), 1609 (C@C), 1525 (N@O), 1350
ꢀ
1
1
J = 8.5 Hz, 2H, ArH), 7.50 (t, J = 8.3 Hz, 1H, ArH), 7.85
(
(N@O), 1254, 1212, 1032, 840, 746 cm
(CDCl , 400 MHz) d: 1.40 (t, J = 7.2 Hz, 3H, CH
(br s, OH), 3.85 (s, 3H, OCH ), 3.96 (dd, J = 5.8, 9.4 Hz,
;
H NMR
1
d, J = 8.3 Hz, 1H, ArH); C NMR (CDCl
3
3
, 100 MHz)
3
3
), 3.61
d:14.4, 51.7, 61.1, 69.1, 69.9, 109.1, 114.6, 121.1, 126.1,
3
1
1
4
27.3, 129.3, 130.3, 134.5, 135.7, 139.4, 143.7, 145.4, 151.6,
O
1H, CH
J = 7.2 Hz, 2H, OCH
6.79 (s, 1H, 4-H), 6.91 (d, J = 8.8 Hz, 2H, ArH), 6.97 (d,
J = 8.3 Hz, 1H, ArH), 7.04 (t, J = 8.3 Hz, 1H, ArH), 7.26
(d, J = 8.8 Hz, 2H, ArH), 7.51 (t, J = 8.3 Hz, 1H, ArH),
7.86 (d, J = 8.3 Hz, 1H, ArH); HRMS (EI) calcd for
2
), 4.10 (dd, J = 4.1, 9.4 Hz, 1H, CH
0
2
), 4.41 (q,
0
+
[(M-O) ]
62.0; HRMS (EI) calcd for C21
29.1091, found 429.0859.
H20ClN
3
5
2
),4.47–4.54 (m, 3H, 2 -H and 3 -H),
0
0
0
0
Ethyl 3-(4 -chlorophenyl)-1-(2 -hydroxy-3 -(2 -methoxy-
phenoxy)propyl)-1H- pyrazole-5-carboxylate. Compound
3
2
1
4
3
3
2
j: White solid, mp 96–99 °C; IR (KBr) m: 3447 (OH), 3063,
+
935, 2835, 1720 (C@O), 1593 (C@C), 1506(C@N), 1254,
C H N O (M) 441.1536, found 441.1542.
2
2
23
3
7
ꢀ
1
210, 1124, 1092, 1027, 837, 743 cm ; H NMR (CDCl ,
00 MHz) d:1.40 (t, J = 7.1 Hz, 3H, CH
.76 (s, 3H, OCH ), 3.86 (dd, J = 5.8, 9.9 Hz, 1H, CH
.99 (dd, J = 5.2, 9.9 Hz, 1H, CH ), 4.41 (q, J = 7.1 Hz,
1
0
0
0
0
Ethyl 1-(2 -hydroxy-3 -(2 -methoxyphenoxy)propyl)-3-(4 -
methoxyphenyl)-1H-pyrazole-5-carboxylate. Compound
3o: Pale yellowish oil; IR (film) m: 3445 (OH), 3052, 2934,
2836, 1719 (C@O), 1613 (C@C), 1505 (C@N), 1254, 1211,
3
3
), 3.27 (br s, OH),
3
2
),
2
0
0
ꢀ1
1
H, OCH
2
CH
3
), 4.42–4.53 (m, 3H, 2 -H and 3 -H), 6.80 (d,
1029, 838, 744 cm ; H NMR (CDCl
(t, J = 7.1 Hz, 3H, CH ), 3.48 (br s, OH), 3.75 (s, 3H,
OCH ), 3.84 (s, 3H, OCH ), 3.90 (dd, J = 5.6, 9.9 Hz, 1H,
3
, 400 MHz) d:1.41
J = 7.6 Hz, 2H, ArH), 6.82 (s, 1H, 4-H), 6.88 (t, J = 7.6 Hz,
H, ArH), 6.97 (t, J = 7.6 Hz, 1H, ArH), 7.34–7.39 (m, 4H,
3
1
3
3
13
ArH); C NMR (CDCl , 100 MHz) d:14.4, 51.9, 55.6,
CH ), 4.00 (dd, J = 5.3, 9.9 Hz, 1H, CH ), 4.39 (q, J = 7.1
2
3
2
0
0
6
1.1, 69.4, 70.3, 109.0, 111.8, 114.7, 120.9, 122.3, 127.7,
29.0, 130.6, 135.3, 143.6, 145.2, 147.6, 149.7, 162.1;
Hz, 2H, OCH
2
CH
3
), 4.42–4.50 (m, 3H, 2 -H and 3 -H),
1
HRMS (EI) calcd for C H ClN O (M) 430.1295,
found 430.1282.
6.79 (s, 1H, 4-H), 6.84 (d, J = 9.1 Hz, 2H, ArH), 6.87 (d,
J = 9.1 Hz, 2H, ArH), 6.93 (d, J = 8.8 Hz, 2H, ArH), 7.34
(d, J = 8.8 Hz, 2H, ArH); HRMS (EI) calcd for
+
2
2
23
2
5
0
0
0
+
Ethyl 1-(2 -hydroxy-3 -phenoxypropyl)-3-(4 -methoxyphe-
nyl)-1H-pyrazole-5-carboxylate Compound 3k: Pale yel-
lowish oil; IR (film) m: 3444 (OH), 3063, 2980, 2936, 1721
C
23
H
26
N
2
O
6
(M) 426.1791, found 426.1786.
30. A549 cells were cultured in the medium with or without the
compounds 3a–3o 12.5–100 lM for 24 or 48 h, respective-
ly. Then, the morphological changes of the cells were
observed under phase contrast microscope (Nikon, Japan).
31. Ono, K.; Wang, X.; Han, J. Mol. Cell. Biol. 2001, 21,
8276.
(
7
C@O), 1599 (C@C), 1499 (C@N), 1251, 1211, 1035, 839,
ꢀ1
1
55, 692 cm
;
H NMR (CDCl
), 3.33 (br s, OH), 3.80 (dd, J = 6.0,
.6 Hz, 1H, CH ), 3.85 (s, 3H, OCH ), 3.96 (dd, J = 4.8,
3
, 400 MHz) d:1.40 (t,
J = 7.1 Hz, 3H, CH
9
3
2
3