Vol. 25, No. 15 (2013)
Synthesis and Anticoccidial Activities of Quinoline Carboxylate Derivatives 8511
TABLE-1
DATA FOR ANTICOCCIDIAL ACTIVITIES OF COMPOUNDS 7a–7h AND THE
COMPOUND DECOQUINATE AGAINST Eimeria tenella AT 27 mg/Kg
Test groups
Test compounds
(mg/Kg)
Rate of relative
body weight gain
Survival
rate (%)
Lesion
scores
Oocyst
scores
ACIa
1
2
3
4
5
6
7
8
75.8
70.3
87.7
86.7
88.7
72.8
73.4
73.8
91.3
60.0
100.0
85
85
30
30
20
20
10
30
20
20
10
30
0
20
20
20
20
10
20
20
20
1
110.8
105.3
137.7
137.7
168.7
107.8
123.4
108.8
180.3
80
7a (27)
7b (27)
7c (27)
7d (27)
7e (27)
7f (27)
7g (27)
7h (27)
90
90
100
85
90
85
9
Decoquinate (27)
INGb
100
80
10
30
0
11
NNGc
100
200
aAnticoccidial activity index; bInfected non-medicated group; cNon-infected non-medicated group
carboxylic acid ethyl ester (7c): Light yellow solid; yield:
1
42 %; m.p. 132-134 ºC; H NMR spectrum (400 MHz;
J = 6.8 Hz), 6.964 (1H, s) 7.22-7.45 (5H, m), 7.489 (1H, s),
7.823 (1H, s), 8.718 (1H, s), 8.864 (1H, s). IR (KBr, νmax, cm-1)
3055, 2926, 2853, 1706, 1618, 1551, 1450, 1395, 1267, 1218,
1131, 1098, 1025, 992, 943, 881, 802, 764, 723, 688, 615.
HR-MS (ESI): calcd. for C40H50N3O8 [M+H]+: 700.3598.
Found: 700.3573.
d1-CDCl3; TMS): δ (ppm) = 0.884 (3H, t, J = 6.4 Hz), 1.278
(16H, m), 1.838 (3H, t, J = 6.4 Hz), 2.306 (3H, s), 3.617 (3H,
s), 3.782 (3H, s), 4.107 (2H, t, J = 6.8 Hz), 4.408 (2H, q, J =
6.8 Hz), 6.999 (1H, s), 7.26-7.52 (6H, m), 7.824 (1H, s), 8.723
(1H, s), 8.866 (1H, s). IR (KBr, νmax, cm-1): 3054, 2958, 2925,
2853, 1706, 1618, 1550, 1449, 1395, 1262, 1217, 1096, 1023,
942, 874, 801, 687, 614, 551. HR-MS (ESI): calcd. for
C38H46N3O8 [M+H]+: 672.3285. Found: 672.3264.
6-Benzyloxy-4-{6-[2-(2-methoxy-1-methoxycar-
bonyl-vinyl)-phenoxy]-pyrimidin-4-yloxy}-7-methyl-
quinoline-3-carboxylic acid ethyl ester (7g): Light yellow
1
solid; yield: 40 %; m.p. 156-158 ºC; H NMR spectrum
4-{6-[2-(2-Methoxy-1-methoxycarbonyl-vinyl)-phenoxy]-
pyrimidin-4-yloxy}-7-methyl-6-octyloxy-quinoline-3-
carboxylic acid ethyl ester (7d) : Light yellow solid; yield:
(400 MHz; d1-CDCl3; TMS): δ (ppm) = 1.424 (3H, t, J =
7.2 Hz), 2.374 (3H, s), 3.621 (3H, s), 3.788 (3H, s), 4.419
(2H, t, J = 7.2 Hz), 4.402 (2H, q, J = 6.8 Hz), 5.231 (2H, s),
7.000 (1H, s), 7.22-7.54 (11H, m), 7.950 (1H, s), 8.752
(1H, s), 8.870 (1H, s). IR (KBr, νmax, cm-1) 3060, 2936, 1732,
1707, 1627, 1558, 1489, 1447, 1384, 1252, 1213, 1168,
1134, 1101, 1021, 946, 855, 804, 758, 699, 622, 588, 461.
HR-MS (ESI): calcd. for C35H31N3O8Na [M+Na]+: 644.2009.
Found:644.2009.
1
45 %; m.p. 130-132 ºC; H NMR spectrum (400 MHz; d1-
CDCl3; TMS): δ (ppm.) = 0.886 (3H, t, J = 6.4 Hz), 1.248
(12H, m), 1.833 (3H, t, J = 6.8 Hz), 2.297 (3H, s), 3.608 (3H,
s), 3.772 (3H, s), 4.100 (2H, t, J = 6.8 Hz), 4.398 (2H, q, J =
6.4 Hz), 6.955 (1H, s) 7.22-7.44 (6H, m), 7.817 (1H, s), 8.712
(1H, s), 8.858 (1H, s). IR (KBr, νmax, cm-1) 3052, 2963, 2926,
2855, 1707, 1617, 1551, 1449, 1398, 1262, 1217, 1022, 866,
801, 692, 613. HR-MS (ESI): calcd. for C36H42N3O8 [M+H]+:
644.2972. Found: 644.2950.
6-Benzyloxy-7-methoxy-4-{6-[2-(2-methoxy-1-
methoxycarbonyl-vinyl)-phenoxy]-pyrimidin-4-yloxy}-
quinoline-3-carboxylic acid ethyl ester (7h): Light yellow
solid; yield: 40 %; m.p. 184-187 ºC; 1H NMR spectrum (400
MHz; d1-CDCl3; TMS): δ (ppm) = 1.412 (3H, t, J = 6.4 Hz),
3.573 (3H, s), 3.778 (3H, s), 3.818 (3H, s), 4.410 (2H, q, J = 7.2
Hz), 5.265 (2H, s), 6.911 (1H, s), 7.059 (1H, s), 7.22-7.50 (10H,
6-Decyloxy-7-ethoxy-4-{6-[2-(2-methoxy-1-methoxy-
carbonyl-vinyl)-phenoxy]-pyrimidin-4-yloxy}-quinoline-3-
carboxylic acid ethyl ester (7e) : Light yellow solid; yield: 40
%; m.p. 140-142 ºC; 1H NMR spectrum (400 MHz; d1-CDCl3;
TMS): δ (ppm) = 0.873 (3H, t, J = 7.2 Hz), 1.264 (16H, m),
1.407 (3H, t, J = 6.8 Hz), 1.450 (3H, t, J = 6.8 Hz), 3.573 (3H,
s), 3.761 (3H, s), 3.961 (2H, q, J = 6.8 Hz), 4.124 (2H, t, J =
6.4Hz), 4.396 (2H, q, J = 7.2 Hz), 6.875 (1H, s), 6.994 (1H, s)
7.249 (1H, s) 7.32-7.47 (4H, m), 7.863 (1H, s), 8.706 (1H, s),
8.863 (1H, s). IR (KBr, νmax, cm-1) 3054, 2927, 2854, 1707,
1620, 1553, 1507, 1451, 1382, 1270, 1226, 1131, 1097, 1025,
992, 952, 877, 801, 723, 691, 621, 592, 560. HR-MS (ESI):
calcd. for C39H47N3O9Na [M+Na]+: 724.3216. Found: 724.3210.
6-Dodecyloxy-4-{6-[2-(2-methoxy-1-methoxy-
carbonyl-vinyl)-phenoxy]-pyrimidin-4-yloxy}-7-methyl-
quinoline-3-carboxylic acid ethyl ester (7f) : Light yellow
solid; yield: 42 %; m.p. 135-136 ºC; 1H NMR spectrum (400
MHz; d1-CDCl3; TMS): δ (ppm) = 0.881 (3H, t, J = 6.4 Hz),
1.228 (20H, m), 1.838 (3H, t, J = 6.8 Hz), 2.303 (3H, s), 3.616
(3H, s), 3.779 (3H, s), 4.105 (2H, t, J = 6.4 Hz), 4.406 (2H, q,
m), 7.964 (1H, s), 8.733 (1H, s), 8.874 (1H, s). IR (KBr, νmax
,
cm-1) 3059, 2952, 1621, 1586, 1551, 1450, 1387, 1265, 1218,
1132, 1098, 1024, 944, 857, 802, 696, 462. HR-MS (ESI): calcd.
for C35H31N3O9Na [M+Na]+: 660.1958. Found: 660.1959.
Biological assay: The anticoccidial activities of 7a-7h
were evaluated according to the anticoccidial index method,
using decoquinate as a reference drug15,16. The chickens used
to test the anticoccidial activity of compounds were 15-day-
old broiler chickens, which fed by the feedstuff without any
anticoccidial drugs and drank clean water by Guangdong
province academy of agricultural sciences. Then these chickens
were randomly divided into 11 groups, 20 in each group.
Groups 1-9 of these chickens were fed the diet with the comp-
ounds 7a-7h or decoquinate in 27 mg/Kg. Groups 1-10 of
these chickens were infected factitiously with the Eimeria
tenella. After 7 days, recorded the weight gain, mortality,