S. Schenone et al. / Il Farmaco 55 (2000) 495–498
497
Table 1
Yields, physical and spectroscopic data of compounds 2a–2h
a
Comp. B.p. (°C
mmHg))
Yield (%)
1H NMR l (ppm)
Formula
(C, H, N)
(
2
2
2
2
2
2
2
2
a
b
c
d
e
f
155–160 (0.2)
160–165 (0.2)
145–150 (0.2)
170–175 (0.3)
160–165 (0.3)
155–160 (0.3)
m.p. 97–98
87
75
75
76
80
68
45
65
0.81, 0.92 and 1.02 (3s, 9H, 3CH ), 1.03 (t, J=6.6, 6H, 2CH Et), 1.35–2.02
C17H32N O2
3
3
2
(
(
m, 6H, 3CH ), 2.14 (near s, 1H, CH), 2.30–2.85 (m, 6H, 3CH N), 3.45–3.70
2
2
m, 1H, OH, disappears with D O), 3.90–4.21 (m, 3H, CHO+CH O)
2
2
0.79, 0.92 and 1.00 (3s, 9H, 3CH ), 1.06 (d, J=7.2, 6H, 2CH isopr.)
C16H30N O2
3
3
2
1
.35–2.01 (m, 6H, 3CH ), 2.11 (near s, 1H, CH), 2.28–3.11 (m, 3H,
2
CHN+CH N), 3.80–4.20 (m, 3H, CHO+CH O), NH and OH not detectable
2
2
0.80, 0.91 and 1.00 (3s, 9H, 3CH ), 1.15–2.02 (m, 10H, 5CH ), 2.15 (near s,
C17H30N O2
3
2
2
1
H, CH), 2.25–2.80 (m, 6H, 3CH N), 3.40–3.60 (m, 1H, OH, disappears with
2
D O), 3.90–4.20 (m, 3H, CHO+CH O)
2
2
0.80, 0.92 and 1.00 (3s, 9H, 3CH ), 1.15–2.05 (m, 12H, 6CH ), 2.15 (near s,
C18H32N O2
3
2
2
1
H, CH), 2.25–2.80 (m, 6H, 3CH N), 3.90–4.20 (m, 3H, CHO+CH O), 4.68
2
2
(
near s, 1H, OH, disappears with D O)
2
0.80, 0.92 and 1.00 (3s, 9H, 3CH ), 1.10–2.00 (m, 6H, 3CH ), 2.11 (near s,
C17H30N O3
3
2
2
1
H, CH), 2.20–2.80 (m, 6H, 3CH N), 3.20–3.50 (m, 1H, OH, disappears with
2
D O), 3.60–3.80 (m, 4H, 2CH O morph.), 3.90–4.20 (m, 3H, CHO+CH O)
2
2
2
0.80, 0.92 and 1.00 (3s, 9H, 3CH ), 1.12–2.00 (m, 14H, 7CH ), 2.12 (near s,
C19H34N O2
3
2
2
1
H, CH), 2.30–2.90 (m, 6H, 3CH N), 3.65–3.85 (m, 1H, OH, disappears with
2
D O), 3.95–4.20 (m, 3H, CHO+CH O)
2
2
g
h
0.80, 0.91 and 1.00 (3s, 9H, 3CH ), 1.08 (d, J=6, 6H, 2CH pip), 1.29–2.00
C20H36N O2
3
3
2
(
m, 10H, 4CH +2CH pip), 2.01 (near s, 1H, CH), 2.27–3.03 (m, 6H,
2
3
CH N), 3.70–4.14 (m, 4H, CHO+CH O+OH, 1H disappears with D O)
2 2 2
175–180 (0.3)
0.80, 0.92 and 1.01 (3s, 9H, 3CH ), 1.15 (d, J=6.6, 6H, 2CH morph),
C19H34N O3
3
3
2
1
.40–2.02 (m, 6H, 3CH ), 2.13 (near s, 1H, CH), 2.20–3.00 (m, 6H, 3CH N),
2
2
3
.40–4.30 (m, 6H, 3CHO+CH O+OH, 1H disappears with D O)
2
2
a
−1
All of 2a–2h have an O–H absorption at 3420 and a CꢀN absorption at 1660 cm
in the IR spectra.
Table 2
a
Activity against ventricular fibrillation caused by aconitine in albino rats
Comp.
Dose (mg/kg p.o.)
Appearance time (s9SE) of extrasystoles
178918.2
Death time (s9SE)
669920.6
b
Control (aconitine HCl)
Quinidine
d
d
25
50
50
50
50
50
50
50
12.5
421921.5
294926.2
981923.5
789921.3
731928.7
814922.5
d
d
2
2
2
2
2
2
2
2
a
b
c
d
e
f
c
212927.4
316923.2
233928.1
d
d
c
d
811927.1
194929.6
208923.5
239922.6
701924.2
707926.9
802925.3
c
c
g
h
189918.7
206919.3
287927.1
715922.7
806920.8
902929.1
2
5
5
0
d
d
a
b
c
Ten animals (200–250 g) per group.
5 mg/kg i.v. until death.
Statistically significant value calculated in comparison with the test performed with aconitine only (PB0.05).
Statistically significant value calculated in comparison with the test performed with aconitine only (PB0.01).
1
d
Once again the antinociceptive activity is present in
almost all compounds 2a–2h, likewise their analogues
; a maximum of activity is elicited by the piperidine
harrhytmic and analgesic features of the earlier
analogues 1 without substantial strengthening of
potency.
1
derivative 2d with an ED50 of 57.12 (38.18–85.46)
mg/kg o.s. in the acetic acid writhing test (Table 3).
In conclusion this series of terpenoid hydrox-
yaminoethers 2a–2h seems to maintain only the anti-
In any case the antinociceptive action of these cam-
phor oxime derivatives is superior to that shown by the
other carbocyclic oxime derivatives recently reported
[4].