F. Mart´ınez-Ramos et al. / European Journal of Medicinal Chemistry 43 (2008) 1432e1437
1435
(relative intensity): 246 (Mþ, 83), 228 (64.6), 184 (100), 156
(33), 105 (42), 77 (22), 45 (18).
Table 4
LD50 determination of tested selenium compounds
Dose
(mg/kg b.w.) animals
Number of Alive
Dead
animals animals (mg/kg b.w.)
LD50
5.1.1.5. 2-(Carboxymethylselenenyl)benzoic acid (2e). Ob-
tained in 95% yield, mp 232e234 ꢀC. 1H NMR (DMSO,
ppm): d 8e7.3 (m, Ar, 4H), 3.6 (s, CH2, 2H) H-10. 13C
NMR (DMSO, ppm): d 172 (C-20, COOH), 168 (C-7, e
COOH), 136.9 (C-1), 132.8 (C-4), 131.3 (C-6), 128.4 (C-2),
128.1 (C-3), 124.9 (C-5), 25.8 (C-10). Mass spectrum, m/z (rel-
ative intensity): 260 (Mþ, 37), 242 (12), 214 (2), 201 (100),
184 (7), 156 (7), 105 (9), 77 (6).
Control vehicle
(bicarbonate)
e
6
6
0
e
Indomethacin
2a
33
6
6
6
6
6
3
0
3
0
6
3
0
3
0
0
33
600
600
600
e
>600
600
>600
e
2c
2e
Control vehicle
(PO/DMSO)
4a
4c
4f
600
600
600
6
6
6
3
0
0
3
0
0
600
>600
>600
5.1.1.6. 2-(Benzylselenenyl)benzoic acid (2f). Obtained in
1
85% yield, mp 202e204 ꢀC. H NMR (DMSO, ppm): d 13.2
(s, COOH, 1H), 8e7 (m, Ar, 9H), 4.2 (s, CH2, 2H) H-70.
13C NMR (DMSO, ppm): d 167.9 (C-7, eCOOH), 138.5 (C-
10), 137.449 (C-1), 132.789 (C-40), 131.373 (C-6), 129.2 (C-
30, C-50), 128.465 (C-40), 128.212 (C-2), 128.059 (C-3),
126.751 (C-5), 124.776 (C-20, C-60), 28.743 (C-70). Mass spec-
trum, m/z (relative intensity): 292 (Mþ, 23), 201 (11), 156
(1.5), 91 (100), 65 (8.5). Crystal data [23]: C14H12O2Se,
FW ¼ 291.20, monoclinic, space group P21/c, a ¼ 8.1055(7),
ppm): d 8.2e7.2 (m, Ar, 4H), 5 (m, 2H), H-30, 3.6 (m, CH2,
2H) H-10, 1.9 (m, CH3, 3H) H-40. 13C NMR (CHCl3 þ DMSO,
ppm): d 172 (C-7, eCOOH), 140.8 (C-20), 139.8 (C-1), 133.3
(C-4), 132.6 (C-6), 128.3 (C-3), 127.3 (C-2), 124.6 (C-5),
114.5 (C-30), 33.2 (C-10), 22.3 (C-40). Mass spectrum, m/z (rel-
ative intensity): 256 (Mþ, 29), 201 (100), 156 (9), 145 (6), 117
(5), 117 (6), 55 (33). Crystal data [22]: C11H12O2Se,
Fw ¼ 255.16, triclinic, space group P1, a ¼ 5.8450(10), b ¼
b ¼ 5.8403(11), c ¼ 26.0203(17) A, b ¼ 94.560(5)ꢀ, V ¼
˚
3
1228.3(3) A , Z ¼ 4, Dx ¼ 1.575 g/cm3, m(Mo Ka) ¼
˚
3.043 mmꢁ1, T ¼ 293 K, R ¼ 0.048, Rw ¼ 0.084, 2144 reflec-
˚
8.1490(10), c ¼ 11.4620(10) A, a ¼ 97.050(10), b ¼ 90.140
(10), g ¼ 90.120(10)ꢀ, Z ¼ 2 , R ¼ 0.047.
tions, GOF ¼ 1.013.
5.1.1.2. 2-(Allylselenenyl)benzoic acid (2b). Obtained in 54%
5.1.1.7. 2-(Phenacylselenenyl)benzoic acid (2g). Obtained in
57% yield, mp 176e178 ꢀC. 1H NMR (CDCl3 þ DMSO,
ppm): d 8e7 (m, Ar, 9H), 4.17 (s, CH2, 2H) H-80. 13C NMR
(CDCl3 þ DMSO, ppm): d 195.3 (C-70, C]O), 168.3 (C-7,
eCOOH), 136.8 (C-10), 135.1 (C-1), 132.9 (C-40), 132.4 (C-
4), 131.4 (C-6), 128.2 (C-2, C-20, C-30, C-50, C-60), 127.4
(C-3), 124.6 (C-5), 29.3 (C-80). Crystal data: C15H12O3Se,
Fw ¼ 319.21, monoclinic, space group: P21/n, a ¼ 5.080(1),
1
yield, mp 136e138 ꢀC: H NMR (CDCl3, ppm): d 8.2e7.2
(m, Ar, 4H), 6 (m, 1H) H-20, 5.2 (m, 2H) H-30, 3.6 (m, CH2,
2H) H-10. 13C NMR (CDCl3, ppm): 172.1 (C-7, eCOOH),
139.1 (C-1), 133.3 (C-4), 133.188 (C-20), 132.698 (C-6),
128.137 (C-3), 127.3 (C-2), 124.724 (C-5), 118.34 (C-30),
28.2 (C-10). Mass spectrum, m/z (relative intensity): 242
(Mþ, 22), 201 (100), 156 (7), 145 (6.8), 117 (3.7), 77 (3.7),
41 (11.8).
b ¼ 10.709(1), c ¼ 24.102(3) A, Z ¼ 4, Dx ¼ 1.617 g/cm3,
˚
m(Mo Ka) ¼ 2.865 mmꢁ1, T ¼ 293 K, R ¼ 0.038, Rw ¼ 0.052,
5.1.1.3. 2-(Propargylselenenyl)benzoic acid (2c). Obtained in
2375 reflections, GOF ¼ 0.926.
1
57% yield, mp 183e185 ꢀC. H NMR (DMSO, ppm): d 13.4
5.1.1.8. 2-(40-Bromophenacylselenenyl)benzoic acid (2h). Ob-
(s, COOH, 1H) H-7, 8.5e7.8 (m, Ar, 4H), 4.1 (d,
J ¼ 2.6 Hz, CH2, 2H) H-10, 3.4 (dd, J ¼ 2.5, J ¼ 1.6 Hz, CH,
1H) H-30. 13C NMR (DMSO, ppm): 168.3 (C-7, eCOOH),
137.5 (C-1), 132.8 (C-4), 131.5 (C-6), 128.4 (C-2), 127.8
(C-3), 124.9 (C-5), 81.2 (C-20), 72.9 (C-30), 9.3 (C-10). 77Se
NMR: d 372. Mass spectrum, m/z (relative intensity): 240
(Mþ, 20), 210 (100), 184(9.4), 156 (13), 105 (8), 77 (11).
Crystal data: C10H8O2Se, FW ¼ 239.12, triclinic, space group
1
tained in 51% yield, mp 200 ꢀC (decomposition). H NMR
(DMSO, ppm): d 8e7 (m, Ar, 8H), 4.4 (s, CH2, 2H) H-80.
13
NMR C (DMSO, ppm): d 197 (C-70, C]O), 168.3 (C-7,
eCOOH), 136.4 (C-10), 135.1 (C-1), 133.4 (C-4), 131.6 (C-
3), 131.4 (C-6), 130.5 (C-20, C-60), 129.4 (C-30, C-50), 128.2
(C-40), 126.4 (C-5), 125.2 (C-2), 29.3 (C-80). Mass spectrum,
m/z (relative intensity): 398 (Mþ, 14), 381 (11), 300 (32),
184 (26), 183 (100), 156 (14), 155 (22), 104 (5), 76 (12).
˚
P1, a ¼ 4.345(1), b ¼ 7.827(2), c ¼ 13.831(4) A, a ¼ 88.93(1),
b ¼ 85.32(1), g ¼ 75.14(1)ꢀ, Z ¼ 2 y, R ¼ 0.042.
5.1.2. General procedure for the synthesis of alkylaryl
selenides 4 from 4,40-diselenide-bisbenzamide 3
5.1.1.4. 2-(20-Hydroxyethylselenenyl)benzoic acid (2d). Ob-
tained in 34% yield, mp 116e118 ꢀC. 1H NMR (CDCl3,
ppm): d 8e7.2 (m, Ar, 4H), 6.2 (s, OH, 1H), 3.9 (t,
J ¼ 6.9 Hz, CH2, 2H) H-20, 3.08 (t, J ¼ 6.9 Hz, CH2, 2H) H-
10. 13C NMR (CDCl3, ppm): d 168.5 (C-7, COOH), 136.2
(C-2), 132.2 (C-4), 131.8 (C-6), 129.2 (C-2), 127.4 (C-3),
124.3 (C-5), 60.6 (C-20), 27.4 (C-10). Mass spectrum, m/z
To a mixture of diselenide 3 (213 mg, 0.5 mmol) with
10 ml of ethanol and 10 ml of water, followed by the addition
of NaBH4 (114 mg, 3 mmol), in portions. After 15e30 min the
corresponding alkyl halide (1 mmol). The reaction was stirred
at room temperature for 3 h. Addition to water and extraction
(ethyl acetate), charcoal and filtered. The purification was by