A. Foroumadi et al. / Bioorg. Med. Chem. Lett. 18 (2008) 3315–3320
3319
9. Foroumadi, A.; Mansouri, S.; Kiani, Z.; Rahmani, A.
Eur. J. Med. Chem. 2003, 38, 851.
10. Foroumadi, A.; Emami, S.; Pournourmohammadi, S.;
Kharazmi, A.; Shafiee, A. Eur. J. Med. Chem. 2005, 40,
1346.
CH2S, J = 8.6 Hz), 2.67 (q, 2H, SCH2–Me, J = 7.3 Hz),
1.31 (t, 3H, CH3, J = 7.3 Hz); MS: m/z (%) 327 (M+, 20),
239 (100), 163 (60), 88 (60); Anal. Calcd for
C12H13N3O2S3: C, 44.02; H, 4.00; N, 12.83. Found: C,
43.96; H, 3.91; N, 12.72.
11. Foroumadi, A.; Pournourmohammadi, S.; Soltani, F.;
Rezaee, M. A.; Dabiri, S.; Kharazmi, A.; Shafiee, A.
Bioorg. Med. Chem. Lett. 2005, 15, 1983.
12. Foroumadi, A.; Asadipour, A.; Mirzaei, M.; Karimi, J.;
Emami, S. Il Farmaco 2002, 57, 765.
13. Foroumadi, A.; Mirzaei, M.; Shafiee, A. Pharmazie 2001,
56, 610.
14. General procedure for the synthesis of 2-[2-(ethylthio)eth-
ylthio]-5-(nitroaryl)-1,3,4-thiadiazole (6a–f). To a mixture
15. General procedure for the synthesis of 2-[2-(ethylsulfo-
nyl)ethylthio]-5-(nitroaryl)-1,3,4-thiadiazole (7a–f). To a
mixture of 5-(nitroaryl)-1,3,4-thiadiazole-2-thiol
(1.65 mmol) and 2-(ethylsulfonyl)ethyl chloride
5
(1.8 mmol) in ethanol (10 mL), KOH solution (1.8 mmol
in 2 mL H2O) was added dropwise, and the mixture stirred
at room temperature overnight. After adding water, the
separated solid was filtered off, washed with water, and
crystallized from EtOH, to give compounds 7a–f.
of 5-(nitroaryl)-1,3,4-thiadiazole-2-thiol
5
(1.65 mmol)
Compound 7a. Yield 42%; mp 122–124 ꢁC; IR (KBr): mmax
and 2-(ethylthio)ethyl chloride (1.8 mmol) in ethanol
(10 mL), KOH solution (1.8 mmol in 2 mL H2O) was
added dropwise, and the mixture stirred at room temper-
ature overnight. Then, water was added, and the separated
solid filtered off, washed with water and crystallized from
EtOH, to give compounds 6a–f.
3100 (thiophene), 1536, 1348 (NO2) cmÀ1 1H NMR
;
(CDCl3) d 7.88 (d, 1H, thiophene, J = 4.3 Hz), 7.23 (d, 1H,
thiophene, J = 4.3 Hz), 3.64 (t, 2H, SCH2, J = 8.30 Hz),
3.09–2.60 (m, 4H, CH2SO2CH2), 1.30 (t, 3H, CH3,
J = 7.33 Hz); MS: m/z (%) 365 (M+, 40), 273 (100), 197
(50), 83 (50). Anal. Calcd for C10H11N3O4S4: C, 36.86; H,
3.03; N, 11.50. Found: C, 36.75; H, 3.15; N, 11.41.
Compound 7b. Yield 55%; mp 72–74 ꢁC; IR (KBr): mmax
3134 (furan), 1536, 1362 (NO2) cmÀ1; 1H NMR (CDCl3) d
7.45 (d, 1H, furan, J = 4.1 Hz), 7.30 (d, 1H, furan,
J = 4.1 Hz), 3.64 (t, 2H, SCH2, J = 7.35 Hz), 3.20–2.50
(m, 4H, CH2SO2CH2), 1.31 (t, 3H, CH3, J = 7.26 Hz);
MS: m/z (%) 349 (M+, 10), 227 (90), 150 (80), 66 (100).
Anal. Calcd for C10H11N3O5S3: C, 34.37; H, 3.17; N,
12.03. Found: C, 34.46; H, 3.22; N, 11.91.
Compound 6a. Yield 45%; mp 94–96 ꢁC; IR (KBr): mmax
3098 (thiophene), 1516, 1342 (NO2) cmÀ1 1H NMR
;
(CDCl3) d 7.95 (d, 1H, thiophene, J = 4.3 Hz), 7.47 (d, 1H,
thiophene, J = 4.3 Hz), 3.72 (t, 2H, SCH2, J = 6.35 Hz),
2.89–2.43 (m, 4H, CH2SCH2), 1.26 (t, 3H, CH3,
J = 7.34 Hz); MS: m/z (%) 333 (M+, 20), 246 (40), 172
(50), 127 (40), 88 (100), 59 (80). Anal. Calcd for
C10H11N3O2S4: C, 36.02; H, 3.32; N, 12.60. Found: C,
36.16; H, 3.21; N, 12.49.
Compound 6b. Yield 70%; mp 79–81 ꢁC; IR (KBr): mmax
3144 (furan), 1536, 1347 (NO2) cmÀ1; 1H NMR (CDCl3) d
7.43 (d, 1H, furan, J = 4.0 Hz), 7.14 (d, 1H, furan,
J = 4.0 Hz), 3.65 (t, 2H, SCH2, J = 6.35 Hz), 2.75–2.61
(m, 4H, CH2SCH2), 1.30 (t, 3H, CH3, J = 7.26 Hz); MS:
m/z (%) 317 (M+, 10), 229 (40), 153 (50), 88 (100), 60 (55).
Anal. Calcd for C10H11N3O3S3: C, 37.84; H, 3.49; N,
13.24. Found: C, 37.69; H, 3.55; N, 13.17.
Compound 7c. Yield 50%; mp 123–125 ꢁC; IR (KBr): mmax
3119 (imidazole), 1516, 1342 (NO2) cmÀ1 1H NMR
;
(CDCl3) d 8.07 (s, 1H, imidazole), 4.55 (s, 3H, NCH3),
3.64 (t, 2H, SCH2, J = 7.80 Hz), 3.10–2.57 (m, 4H,
CH2SO2CH2), 1.31 (t, 3H, CH3, J = 7.50 Hz); MS: m/z
(%) 363 (M+, 10), 244 (100), 171 (45); Anal. Calcd for
C10H13N5O4S3: C, 33.05; H, 3.61; N, 19.27. Found: C,
32.90; H, 3.54; N, 19.12.
Compound 6c. Yield 76%; mp 102–104 ꢁC; IR (KBr): mmax
Compound 7d. Yield 41%; mp 113–115 ꢁC; IR (KBr): mmax
1
3446 (imidazole), 1522, 1332 (NO2) cmÀ1
;
1H NMR
3090 (phenyl), 1518, 1338(NO2) cmÀ1; H NMR (CDCl3)
(CDCl3) d 8.70 (s, 1H, imidazole), 4.55 (s, 3H, NCH3),
3.63 (t, 2H, SCH2, J = 7.35 Hz), 2.99 (t, 2H, CH2S,
J = 8.0 Hz), 2.66 (q, 2H, SCH2–Me, J = 7.40 Hz) 1.31 (t,
3H, CH3, J = 7.40 Hz); MS: m/z (%) 331 (M+, 10), 244
(40), 168 (30), 89 (100), 59 (85); Anal. Calcd for
C10H13N5O2S3: C, 36.24; H, 3.95; N, 21.13. Found: C,
36.35; H, 3.83; N, 21.22.
Compound 6d. Yield 65%; mp 105–108 ꢁC; IR (KBr):mmax
3118 (phenyl), 1536, 1485 (NO2) cmÀ1; 1H NMR (CDCl3)
d 8.10 (d, 1H, phenyl, J = 7.9 Hz), 7.76 (t, 1H, phenyl,
J = 8.0 Hz), 7.65 (t, 1H, phenyl, J = 8.0 Hz), 7.40 (d, 1H,
phenyl, J = 7.9 Hz), 3.64 (t, 2H, SCH2, J = 8.0 Hz), 2.75–
2.61 (m, 4H, CH2SCH2), 1.31 (t, 3H, CH3, J = 7.10 Hz);
MS: m/z (%) 327 (M+, 10), 239 (100), 164 (65), 89 (70);
Anal. Calcd for C12H13N3O2S3: C, 44.02; H, 4.00; N,
12.83. Found: C, 43.94; H, 3.93; N, 12.96.
Compound 6e. Yield 45%; mp 92–94 ꢁC; IR (KBr): mmax
3068 (phenyl), 1526, 1347 (NO2) cmÀ1; 1H NMR (CDCl3)
d 8.71 (s, 1H, phenyl), 8.23 (m, 2H, phenyl), 7.70 (t, 1H,
phenyl, J = 8.0 Hz), 3.64 (t, 2H, SCH2, J = 7.4 Hz), 2.99
(t, 2H, CH2S, J = 7.6 Hz), 2.67 (q, 2H, SCH2–Me,
J = 7.4 Hz), 1.31 (t, 3H, CH3, J = 7.4 Hz). MS: m/z (%)
327 (M+, 80), 266 (20), 239 (90), 193 (15), 163 (100), 87
(80). Anal. Calcd for C12H13N3O2S3: C, 44.02; H, 4.00; N,
12.83. Found: C, 44.16; H, 4.12; N, 12.96.
Compound 6f. Yield 61%; mp 102–104 ꢁC; IR (KBr): mmax
3073 (phenyl), 1531, 1342 (NO2) cmÀ1; 1H NMR (CDCl3)
d 8.34 (d, 2H, phenyl, J = 8.9 Hz), 8.06 (d, 2H, phenyl,
J = 8.9 Hz), 3.65 (t, 2H, SCH2, J = 8.6 Hz), 3.00 (t, 2H,
d 8.08 (d, 1H, phenyl, J = 8.0 Hz), 7.70 (t, 1H, phenyl,
J = 8.0 Hz), 7.56 (t, 1H, phenyl, J = 8.0 Hz), 7.38 (d, 1H,
phenyl, J = 8.09 Hz), 3.64 (t, 2H, SCH2, J = 7.9 Hz), 2.97
(t, 2H, CH2SO2, J = 7.9 Hz), 2.56 (q, 2H, SO2CH2–Me,
J=7.20 Hz), 1.31 (t, 3H, CH3, J = 7.20 Hz); MS: m/z (%)
359 (M+, 10), 239 (100), 163 (85), 77 (40). Anal. Calcd for
C12H13N3O4S3: C, 40.10; H, 3.65; N, 11.69. Found: C,
40.21; H, 3.54; N, 11.72.
Compound 7e. Yield 36%; mp 98–100 ꢁC; IR (KBr): mmax
3062 (phenyl), 1534, 1346 (NO2) cmÀ1; 1H NMR (CDCl3)
d 8.73 (s, 1H, phenyl), 8.29 (d, 1H, phenyl, J = 8.0 Hz),
8.10 (d, 1H, phenyl, J = 8.0 Hz), 7.72 (t, 1H, phenyl,
J = 8.0 Hz), 3.64 (t, 2H, SCH2, J = 7.4 Hz), 3.00–2.67 (m,
4H, CH2SO2CH2), 1.31 (t, 3H, CH3, J = 7.4 Hz); MS: m/z
(%) 359 (M+, 85), 266 (20), 239 (85), 193 (15), 163 (100), 87
(90); Anal. Calcd for C12H13N3O4S3: C, 40.10; H, 3.65; N,
11.69. Found: C, 40.19; H, 3.74; N, 11.57.
Compound 7f. Yield 44%; mp 156–158 ꢁC; IR (KBr): mmax
3073 (phenyl), 1531, 1342 (NO2) cmÀ1; 1H NMR (CDCl3)
d 8.28 (d, 2H, phenyl, J = 8.9 Hz), 7.95 (d, 2H, phenyl,
J = 8.9 Hz), 3.90 (t, 2H, SCH2, J = 8.4 Hz), 3.41 (t, 2H,
CH2SO2, J = 8.4 Hz), 3.10 (q, 2H, SO2CH2–Me,
J = 7.5 Hz), 1.57 (t, 3H, CH3, J = 7.5 Hz); MS: m/z (%)
359 (M+, 20), 238 (100), 162 (80), 75 (25). Anal. Calcd for
C12H13N3O4S3: C, 40.10; H, 3.65; N, 11.69. Found: C,
40.23; H, 3.74; N, 11.77.
16. Antibacterial activity. Twofold serial dilutions of the
compounds were prepared in Mueller–Hinton agar. Drugs
(6.4 mg) were dissolved in DMSO (1 mL) and the solution