M. Teresa Cocco et al. / European Journal of Medicinal Chemistry 38 (2003) 513ꢀ
/518
517
Table 2
IR and 1H-NMR data of compounds 1ꢀ
/
11
Comp. IR (n, cmꢁ1 1H-NMR (d, ppm)
)
1
3266, 3197, 1666, 1591
3037, 1695, 1606, 1585
3274, 3148, 1668, 1613, 1568
0.87 (d, Jꢂ
7.1 Hz, 2H, CH2), 3.67 (q, Jꢂ
Ar), 7.84 (s, 1H, NH)
0.86 (d, Jꢂ6.7 Hz, 6H, CH3), 1.54 (d, Jꢂ
7.1 Hz, 2H, CH2), 3.69 (q, Jꢂ7.1 Hz, 1H, CH), 7.16, 8.08, 8.22, 8.36 (m, 4H, Py), 7.09, 7.21 (d, Jꢂ
4H, Ar), 7.66 (s, 1H, NH)
0.86 (d, Jꢂ6.7 Hz, 6H, CH3), 1.54 (d, Jꢂ
CH3), 2.42 (d, Jꢂ7.1 Hz, 2H, CH2), 3.68 (q, Jꢂ
(d, Jꢂ8.0 Hz, 4H, Ar), 8.23 (s, 1H, NH)
3275, 3053, 1690, 1668, 1613, 0.86 (d, Jꢂ6.7 Hz, 6H, CH3), 1.54 (d, Jꢂ
1567 CH3), 2.41 (d, Jꢂ7.1 Hz, 2H, CH2), 3.66 (q, Jꢂ
(d, Jꢂ8.0 Hz, 4H, Ar), 7.99 (s, 1H, NH)
3301, 3253, 3087, 3048, 1672, 0.89 (d, Jꢂ6.3 Hz, 6H, CH3), 1.51 (d, Jꢂ
CH3), 2.43 (d, Jꢂ7.1 Hz, 2H, CH2), 3.70 (q, Jꢂ
3H, Py), 7.09, 7.28 (d, Jꢂ8.0 Hz, 4H, Ar)
0.89 (d, Jꢂ6.7 Hz, 6H, CH3), 1.51 (d, Jꢂ7.1 Hz, 3H, CH3), 1.84 (hept, Jꢂ
CH3), 2.43 (d, Jꢂ7.1 Hz, 2H, CH2), 3.69 (q, Jꢂ
3H, Py), 7.09, 7.28 (d, Jꢂ8.0 Hz, 4H, Ar)
3204, 3051, 1702, 1688, 1616, 0.87 (d, Jꢂ4.9 Hz, 6H, CH3), 1.54 (d, Jꢂ5.5 Hz, 3H, CH3), 1.82 (hept, Jꢂ
CH3), 2.32 (s, 3H, CH3), 2.43 (d, Jꢂ5.5 Hz, 2H, CH2), 3.63 (q, Jꢂ5.5 Hz, 1H, CH), 6.66, 7.87 (s, 2H, Py),
7.09, 7.22 (d, Jꢂ8.0 Hz, 4H, Ar), 7.70 (s, 1H, NH)
0.87 (d, Jꢂ6.6 Hz, 6H, CH3), 1.64 (d, Jꢂ7.0 Hz, 3H, CH3), 1.86 (hept, Jꢂ
7.0 Hz, 2H, CH2), 3.78 (q, Jꢂ7.0 Hz, 1H, CH), 7.20, 7.28 (m, 4H, Ar), 7.60, 8.08, 8.18 (m, 3H, Py), 7.83 (s,
1H, NH)
0.90 (d, Jꢂ
7.1 Hz, 2H, CH2), 3.67 (q, Jꢂ
Py), 7.62 (s, 1H, NH)
0.90 (d, Jꢂ6.7 Hz, 6H, CH3), 1.52 (d, Jꢂ
7.1 Hz, 2H, CH2), 3.72 (q, Jꢂ7.1 Hz, 1H, CH), 7.11, 7.24 (d, Jꢂ
Pyrim), 7.80 (s, 1H, NH)
0.86 (d, Jꢂ5.0 Hz, 6H, CH3), 1.54 (d, Jꢂ5.5 Hz, 3H, CH3), 1.81 (m, 1H, CH), 2.37 (s, 6H, CH3), 2.42 (d,
/
6.7 Hz, 6H, CH3), 1.55 (d, Jꢂ
/
7.1 Hz, 3H, CH3), 1.82 (hept, Jꢂ
/
6.7 Hz, 1H, CH), 2.42 (d, Jꢂ
/
/7.1 Hz, 1H, CH), 6.95, 7.64, 8.17 (m, 4H, Py), 7.10, 7.20 (d, Jꢂ
/8.0 Hz, 4H,
2
/
/
7.1 Hz, 3H, CH3), 1.82 (hept, Jꢂ
/
6.7 Hz, 1H, CH), 2.43 (d, Jꢂ
/
/
/8.0 Hz,
3
/
/
7.1 Hz, 3H, CH3), 1.82 (hept, Jꢂ
/6.7 Hz, 1H, CH), 2.30 (s, 3H,
/
/7.1 Hz, 1H, CH), 6.78, 7.98, 8.07 (m, 3H, Py), 7.23, 7.28
/
4
/
/
7.1 Hz, 3H, CH3), 1.80 (hept, Jꢂ
/6.7 Hz, 1H, CH), 2.31 (s, 3H,
/
/7.1 Hz, 1H, CH), 6.79, 8.03, 8.18 (m, 3H, Py), 7.09, 7.21
/
5
/
/
7.1 Hz, 3H, CH3), 1.84 (hept, Jꢂ
/6.3 Hz, 1H, CH), 2.10 (s, 3H,
1631, 1568
/
/7.1 Hz, 1H, CH), 6.20 (s, 1H, NH), 6.57, 7.32, 7.75 (m,
/
6
3281, 1666, 1601, 1578, 1538
/
/
/6.7 Hz, 1H, CH), 2.36 (s, 3H,
/
/7.1 Hz, 1H, CH), 5.80 (s, 1H, NH), 6.30, 6.42, 7.35 (m,
/
7
/
/
/4.9 Hz, 1H, CH), 2.27(s, 3H,
1569
/
/
/
8
3279, 3025, 1668, 1587, 1571
/
/
/
6.6 Hz, 1H, CH), 2.48 (d, Jꢂ
/
/
9
3373, 1697, 1582 a
/6.7 Hz, 6H, CH3), 1.54 (d, Jꢂ
/
7.1 Hz, 3H, CH3), 1.82 (hept, Jꢂ
/
6.7 Hz, 1H, CH), 2.42 (d, Jꢂ
/
/7.1 Hz, 1H, CH), 7.10, 7.20 (d, Jꢂ
/8.0 Hz, 4H, Ar), 7.04, 8.03 8.72 (m, 3H,
10
11
3240, 1731, 1579 a
/
/
7.1 Hz, 3H, CH3), 1.83 (hept, Jꢂ
/
6.7 Hz, 1H, CH), 2.44 (d, Jꢂ
/
/
/7.9 Hz, 4H, Ar), 7.16, 8.81 (m, 3H,
3260, 3195, 1689, 1601, 1564
/
/
Jꢂ
/
5.5 Hz, 2H, CH2), 4.04 (m, 1H, CH), 6.67 (s, 1H, Pyrim), 7.08, 7.24 (m, 4H, Ar), 7.78 (s, 1H, NH)
a
Neat.
Table 3
Ulcerogenic effect of amides 2, 5, 6, 9, 10
5.3.2. Acute ulcerogenesis
Acute ulcerogenesis test was done according to Verna
et al. and Suleyman et al. [48,49]. Ulcerogenic activity
Compounds
Lesion index (mm)
was evaluated after p.o. administration of the test
compound or ibuprofen at the dose of 100 mg kgꢁ1
Vehicle
Ibuprofen
0
.
36.759
0 *
0.59
391 *
0 *
0 *
/
5
Control rats received p.o. administration of vehicle
(suspension of 0.5% methylcellulose). Food but not
water was removed 24 h before administration of the
test compound. Eight hours after p.o. administration of
the test compound, rats were anaesthetized with chloral
hydrate and the stomach was extracted and dipped in
1% formaldehyde solution for about 15 min and then
cut out along its great curvature. The number and the
length of ulcers were detected using a microscope. The
severity of the gastric lesion was measured along its
2
5
/
0.2 *
6
/
9
10
Significance was evaluated by Newmanꢀ
per group.
* P B0.01 as compared to ibuprofen lesion index.
/
Keuls post hoc test. Nꢂ6
/
/
greatest length (1 mmꢂ
/
rating of 1, 1ꢀ
/
2 mmꢂrating of
/
ence drug. The analgesic activity was expressed also, in
terms of percentage of inhibition:
2, 2 mmꢂrating according to their length in mm). The
/
overall total of length was designated as the ‘ulcer
index’. Each experimental group consisted of six rats.
% analgesic activityꢂnꢁn?=nꢃ100
where nꢂ
(vehicle-injected animals) and n?ꢂ
/
mean number of writhes of control group
mean number of
/
5.3.3. Statistics
Mean and mean standard error (S.E.M.) of writhes
and index ulcers were calculated for each experimental
writhes of test group. Each experimental group con-
sisted of eight rats.