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Vol. 59, No. 11
3H, –NHCOCH3), 2.30 (s, 3H, –COCH3), 3.84 (s, 3H, –OCH3), 6.89 (s, 1H,
C5-H), 7.11—7.47 (m, 3H, Ar-H), 9.13 (s, 1H, –OH), 11.82 (s, 1H, –NH–).
IR (KBr) cmꢀ1: 3203, 1704, 1639, 1605, 1496, 1441. EI-MS m/z (%): 310
(Mꢄ, 100), 266 (45), 214 (20). Anal. Calcd for C13H15N3O4S: C, 50.47; H,
4.89; N, 13.58. Found: C, 50.53; H, 4.85; N, 13.62.
Cytotoxicity Assay Cytotoxicity after treatment of the tumor cells with
the test materials was determined using the SRB (sulforhodamine-B)
method, currently adopted in the NCI’s in vitro anti-cancer drug screening,18)
i.e., the inhibition rate of cell proliferation was estimated after continuous
exposure to the test materials for 48 h. All samples were tested in triplicate
and the mean IC50 values (mg/ml) (the concentration of the compound that
resulted in a 50% inhibition of cell proliferation) and the S.E.M. were calcu-
lated, respectively.
C13H15N3O2S: C, 56.30; H, 5.45; N, 15.15. Found: C, 56.33; H, 5.41; N,
15.19.
N-(4-Acetyl-5-(4-nitrophenyl)-4,5-dihydro-1,3,4-thiadiazol-2-yl)-
acetamide 2c: Yield 70%. mp 218—219 °C (lit.13) mp 210—211 °C). 1H-
NMR d: 2.07 (s, 3H, –NHCOCH3), 2.28 (s, 3H, –COCH3), 6.87 (s, 1H, H-
5), 7.54—8.28 (m, 4H, Ar-H), 11.89 (s, 1H, –NH–). IR (KBr) cmꢀ1: 3217,
1697, 1612, 1521, 1446. EI-MS m/z (%): 309 (Mꢄ, 100), 267 (20). Anal.
Calcd for C12H12N4O4S: C, 46.75; H, 3.92; N, 18.17. Found: C, 46.78; H,
3.91; N, 18.20.
N-(4-Acetyl-5-(3-nitrophenyl)-4,5-dihydro-1,3,4-thiadiazol-2-yl)-
acetamide 2d: Yield 67%. mp 233—234 °C. 1H-NMR d: 2.08 (s, 3H,
–NHCOCH3), 2.26 (s, 3H, –COCH3), 6.82 (s, 1H, H-5), 7.69—8.21 (m, 4H,
Ar-H), 11.78 (s, 1H, –NH–). IR (KBr) cmꢀ1: 3222, 1695, 1631, 1601, 1526,
1489. EI-MS m/z (%): 309 (Mꢄ, 85), 267 (100). Anal. Calcd for
C12H12N4O4S: C, 46.75; H, 3.92; N, 18.17. Found: C, 46.79; H, 3.89; N,
18.15.
References
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N-(4-Acetyl-5-(3-(dimethylamino)phenyl)-4,5-dihydro-1,3,4-thiadiazol-2-
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yl)acetamide 2e: Yield 70%. mp 239—240 °C (lit.13) mp 222 °C). H-NMR
d: 2.07 (s, 3H, –NHCOCH3), 2.19 (s, 3H, –COCH3), 2.90 (s, 6H,
–N(CH3)2), 6.68—7.70 (m, 2H, Ar-H), 6.75 (s, 1H, H-5), 7.08—7.10 (m,
2H, Ar-H), 11.73 (s, 1H, –NH–). IR (KBr) cmꢀ1: 3207, 1695, 1633, 1608,
1519, 1485. EI-MS m/z (%): 307 (Mꢄ, 100), 265 (30). Anal. Calcd for
C14H18N4O2S: C, 54.88; H, 5.92; N, 18.29. Found: C, 54.85; H, 5.94; N,
18.26.
5) Schenone S. S., Brullo C. C., Bruno O. O., Bondavalli F. F., Ranise A.
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N-(4-Acetyl-5-(4-chlorophenyl)-4,5-dihydro-1,3,4-thiadiazol-2-yl)-
acetamide 2f: Yield 73%. mp 233—234 °C (lit.13) mp 229—233 °C). 1H-
NMR d: 2.12 (s, 3H, –NHCOCH3), 2.23 (s, 3H, –COCH3), 6.88 (s, 1H, H-5)
7.29—7.47 (m, 4H, Ar-H), 11.85 (s, 1H, –NH–). IR (KBr) cmꢀ1: 3215,
1701, 1637, 1612, 1542, 1492. EI-MS m/z (%): 299 (Mꢄ2, 39), 297 (Mꢄ,
100), 252 (80), 144 (20). Anal. Calcd for C12H12ClN3O2S: C, 48.40; H, 4.06;
N, 14.11. Found: C, 48.45; H, 4.02; N, 14.14.
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Oncol., 14, 33—35 (1991).
13) Kubota S., Ueda Y., Fujikane K., Toyooka F., Shibuya M., J. Org.
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Chem. Pharm. Bull., 39, 2837—2841 (1991).
N-(4-Acetyl-5-(4-bromophenyl)-4,5-dihydro-1,3,4-thiadiazol-2-yl)-
acetamide 2g: Yield 78%. mp 132—133 °C. 1H-NMR d: 2.10 (s, 3H,
–NHCOCH3), 2.25 (s, 3H, –COCH3), 6.89 (s, 1H, H-5) 7.30—7.49 (m, 4H,
Ar-H), 11.78 (s, 1H, –NH–). IR (KBr) cmꢀ1: 3215, 1699, 1631, 1612, 1542,
1492. EI-MS m/z (%): 344 (Mꢄ3, 37), 343 (Mꢄ2, 100), 342 (Mꢄ1, 35),
341 (Mꢄ, 98), 296 (77), 188 (25). Anal. Calcd for C12H12BrN3O2S: C, 42.12;
H, 3.53; N, 12.28. Found: C, 42.16; H, 3.51; N, 12.31.
N-(4-Acetyl-5-(4-hydroxyphenyl)-4,5-dihydro-1,3,4-thiadiazol-2-yl)-
acetamide 2h: Yield 80%. mp 210—211 °C. 1H-NMR d: 2.06 (s, 3H,
–NHCOCH3), 2.23 (s, 3H, –COCH3), 6.81 (s, 1H, H-5), 6.91—6.99 (m, 4H,
Ar-H), 11.63 (s, 1H, –NH–). IR (KBr) cmꢀ1: 3217, 1712, 1701, 1633, 1608,
1454. EI-MS m/z (%): 280 (Mꢄ, 100), 256 (30). Anal. Calcd for
C12H13N3O3S: C, 51.60; H, 4.69; N, 15.04. Found: C, 51.64; H, 4.67; N,
15.08.
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N-(4-Acetyl-5-(4-methoxyphenyl)-4,5-dihydro-1,3,4-thiadiazol-2-yl)-
acetamide 2i: Yield 78%. mp 156—158 °C (lit.13) mp 168—169 °C). 1H-
NMR d: 2.07 (s, 3H, –NHCOCH3), 2.24 (s, 3H, –COCH3), 3.77 (s, 3H,
–OCH3), 6.81 (s, 1H, H-5), 6.96—7.16 (m, 4H, Ar-H), 11.72 (s, 1H, –NH–).
IR (KBr) cmꢀ1: 3222, 1698, 1636, 1609, 1572, 1490. EI-MS m/z (%): 294
(Mꢄ, 100), 252 (80), 144(20). Anal. Calcd for C13H15N3O3S: C, 53.23; H,
5.15; N, 14.32. Found: C, 53.25; H, 5.11; N, 14.35.
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Inst., 82, 1107—1112 (1990).
N-(4-Acetyl-5-(4-hydroxy-3-methoxyphenyl)-4,5-dihydro-1,3,4-thiadia-
zol-2-yl)acetamide 2j: Yield 67%. mp 228—230 °C. 1H-NMR d: 2.02 (s,