1270
L.F.C. da Costa Leite et al. / European Journal of Medicinal Chemistry 42 (2007) 1263e1271
1H NMR (d ppm, DMSO-d6): 2.27 (s, CH3), 2.36 (s, CH3),
4.79 (s, CH2), 7.15 (d, 2H, benzyl, J ¼ 8.1 Hz), 7.2 (d, 2H,
benzyl, J ¼ 8.4 Hz), 7.36 (d, 2H, benzylidene, J ¼ 8.1 Hz),
7.53 (d, 2H, benzylidene, J ¼ 8.1 Hz), 7.93 (s, CH). MS, m/z
(%): 323 (Mþꢅ 100), 324 (18.7), 325 (7.3), 105 (45.3), 91 (6.3).
7.5. (Z ) 5-(3-Bromo-benzylidene)-3-(4-methyl-benzyl)-
thiazolidine-2,4-dione 8
C18H14BrNO2S, yield: 48%. Mp: 109e111 ꢄC. TLC (ben-
zene/ethyl acetate; 95:5) Rf: 0.9. IR (KBr; n cmꢁ1) 2911,
1
1743, 1692, 1600, 1427, 1376, 1325, 758. H NMR (d ppm,
DMSO-d6): 2.28 (s, CH3), 4.79 (s, CH2), 7.16 (d, 2H, benzyl,
J ¼ 8.1 Hz), 7.22 (d, 2H, benzyl, J ¼ 8.1 Hz), 7.4e7.45 (m,
1H, benzylidene), 7.54e7.6 (m, 2H, benzylidene), 7.82 (d,
1H, benzylidene, J ¼ 8.4 Hz), 8.02 (s, CH). MS, m/z (%):
ꢅ
387 (Mþ 34.6), 389 (21.6), 308 (25.7), 212 (6.1), 132
(19.8), 105 (100), 89 (80.4), 77 (14.4).
Fig. 6. Docking poses for ligands 1, 3 and 6 in PPAR-g. Important residues are
labelled to facilitate the localization of these poses on the active site region.
7.6. (Z ) 3-(4-methyl-benzyl)-5-(4-nitro-benzylidene)-
thiazolidine-2,4-dione 12
C18H14N2O4S, yield: 39%. Mp: 189e191 ꢄC. TLC (n-hex-
ane/ethyl acetate; 70:30) Rf: 0.56. IR (KBr; n cmꢁ1) 2360,
(s, CH3), 4.76 (s, NCH2), 7.85 (s, CH), 7.16 (m, 4H benzyl), 6.92
(d, 2H benzylidene, J ¼ 8.1 Hz), 7.48 (d, 2H benzylidene,
ꢅ
J ¼ 8.4 Hz), 10.4 (sl, OH). MS, m/z (%): 325 (Mþ 100), 326
1
1743, 1692, 1614, 1509, 1380, 1148, 840. H NMR (d ppm,
(29.1), 312 (6.3), 105 (61.7).
DMSO-d6): 2.28 (s, CH3), 4.81 (s, CH2), 7.16 (d, 2H, benzyl,
J ¼ 8.1 Hz), 7.22 (d, 2H, benzyl, J ¼ 7.8 Hz), 7.9 (d, 2H, ben-
zylidene, J ¼ 9 Hz), 8.35 (d, 2H, benzylidene, J ¼ 9 Hz), 8.08
7.3. (Z ) 5-(3-Chloro-benzylidene)-3-(4-methyl-benzyl)-
thiazolidine-2,4-dione 6
ꢅ
(s, CH). MS, m/z (%): 354 (Mþ 100), 355 (13.5), 326 (5.6),
105 (35.7), 89 (6.6).
C18H14ClNO2S, yield: 50%. Mp: 143e145 ꢄC. TLC
(n-hexane/ethyl acetate; 70:30) Rf: 0.8. IR (KBr; n cmꢁ1
)
Acknowledgments
3040, 2935, 1730, 1675, 1605, 1420, 1370, 1320, 1135, 920.
1H NMR (d ppm, DMSO-d6): 2.27 (s, CH3), 4.79 (s, CH2),
7.16 (d, 2H, benzyl, J ¼ 8.4 Hz), 7.21 (d, 2H, benzyl,
J ¼ 8.4 Hz), 7.58 (m, 3H, benzylidene), 7.73 (s, 1H, benzyli-
We thank the CNPq (Conselho Nacional de Desenvolvi-
´
mento Cientıfico e Tecnologico, Brasil) and the CAPES/CO-
FECUB (Fundac¸ao Coordenac¸ao de Aperfeic¸oamento de
´
~
~
ꢅ
dene), 7.96 (s, CH). MS, m/z (%): 343 (Mþ 55.4), 344
´
´
Pessoal de Ensino Superior/Comite Franc¸ais d’Evaluation de
la Cooperation Universitaire avec le Bresil) for their support.
(11.6), 345 (16.6), 105 (100).
´
´
7.4. (Z ) 3-(4-Methyl-benzyl)-5-(4-methyl-benzylidene)-
thiazolidine-2,4-dione 7
References
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C19H17NO2S, yield: 45%. Mp: 139e140 ꢄC. TLC (n-hex-
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2930, 1730, 1675, 1590, 1425, 1370, 1320, 1135, 805.
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Table 3
Effective doses for a 40% reduction (ED40) of GP and TG in case of ATZDs
1e4 and 9 in mice with alloxan-induced diabetes and free energy of binding
(DG) to PPAR-g and PPAR-a
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ATZD #
MW
ED40
PG, 10ꢁ5
mol/L
DG
(kcal/mol),
PPAR-g
ED40 TG,
10ꢁ5 mol/L
DG
(kcal/mol),
PPAR-a
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1
2
3
4
9
343
325
343
339
352
6.9
4.2
3.3
5.6
4.3
ꢁ8.36
ꢁ8.90
ꢁ8.61
ꢁ8.36
ꢁ8.85
5.8
e
ꢁ8.56
ꢁ8.13
ꢁ7.95
ꢁ7.63
ꢁ8.69
[8] Y. Iwata, S. Miyamoto, M. Takamura, H. Yanagisawa, A. Kasuya, J. Mol.
Graph. Model. 19 (2001) 536e542.
8.8
0.97
5.8
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J. Martin, Clin. Ther. 24 (2002) 378e396.