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K. Manjunatha et al. / European Journal of Medicinal Chemistry 45 (2010) 5225e5233
176.84; LC-MS (m/z): 350 (Mþ, 82%); Anal. Calcd. (%) for
C16H22N4OS2: C, 54.83; H, 6.33; N, 15.98; S, 18.30. Found: C, 54.81;
H, 6.30; N, 15.95; S, 18.28.
(400 MHz, CDCl3,
d
ppm): 0.88 (d, 6H, CH3, J ¼ 8 Hz), 1.66 (d, 3H,
CH3, J ¼ 8 Hz), 1.80e1.88 (m, lH, CH), 2.45 (d,2H, CH2, J ¼ 8 Hz), 2.94
(t, 4H, piperazine-CH2, J ¼ 4.4 Hz), 3.43 (t, 4H, piperazine-CH2,
J ¼ 4.4 Hz), 4.02 (q, lH, CH, J ¼ 8 Hz), 4.95 (s, 2H, NeCH2eN),
6.77e6.90 (m, 4H, Ar-H), 7.00e7.11 (m, 4H, NO2eAreH); 13C NMR
6.3.10. 5-(4-Methylthiobenzyl)-3-(piperidin-1-ylmethyl)-1,3,4-
oxadiazole-2(3H)-thione, 4j
(100 MHz, CDCl3,
d ppm): 19.02, 19.72, 23.48, 31.24, 38.17, 46.35,
IR (KBr, gmax, cmꢁ1): 3037 (ArC-H), 2951 (CeH), 1635 (C]N),
46.59, 70.43, 117.94, 119.63, 127.53, 127.72, 132.13, 137.48, 142.82,
149.13, 160.04, 179.97; LC-MS (m/z): 481 (Mþ, 60%); Anal. Calcd. (%)
for C25H31N5O3S: C, 62.35; H, 6.49; N,14.54; S, 6.66. Found: C, 62.37;
H, 6.51; N, 14.56; S, 6.64.
1324 (C]S), 1250 (CeOeC); 1H NMR (400 MHz, CDCl3,
d ppm): 2.47
(s, 3H, SCH3), 2.75e3.45 (m, 10H, piperazine-CH2), 4.35 (s, 2H, CH2),
4.93 (s, 2H, NeCH2eN), 7.08 (d, 2H, Ar-H, J ¼ 8.4 Hz), 7.16 (d, 2H, Ar-
H, J ¼ 8.4 Hz); 13C NMR (100 MHz, CDCl3,
d ppm): 16.17, 25.84, 27.62,
32.25, 46.38, 67.47,126.82,129.65,139.08,142.14,162.62,177.34; LC-
MS (m/z): 335 (Mþ, 72%); Anal. Calcd. (%) for C15H20N4OS2: C, 57.28;
H, 6.13; N, 12.53; S, 19.12. Found: C, 57.26; H, 6.11; N, 12.51; S, 19.09.
6.3.15. 5-(4-Isobutylphenyl)ethyl-3-{[4-(4-fluorophenyl)piperazin-
1-yl]methyl}-1,3,4-oxadiazole-2 (3H)-thione, 5e
IR (KBr, gmax, cmꢁ1): 3078 (Ar-H), 2986 (CeH), 1617 (C]N), 1327
(C]S), 1256 (CeOeC), 957 (CeF); 1H NMR (400 MHz, CDCl3,
6.3.11. 5-(4-Isobutylphenyl)ethyl-3-{[4-(4-methoxyphenyl)
piperazin-1-yl]methyl}-1,3,4-oxadiazole-2(3H)-thione, 5a
IR (KBr, gmax, cmꢁ1): 3071 (ArC-H), 2978(CeH), 1697 (C]N), 1328
d
ppm): 0.82 (d, 6H, CH3, J ¼ 8 Hz), 1.59 (d, 3H, CH3, J ¼ 8 Hz),
1.73e1.78 (m, lH, CH), 2.37 (d,2H, CH2, J ¼ 8 Hz), 2.88 (t, 4H,
piperazine-CH2, J ¼ 4.4 Hz), 3.03 (t, 4H, piperazine-CH2, J ¼ 4.4 Hz),
4.11 (q, lH, CH, J ¼ 8 Hz), 5.06 (s, 2H, NeCH2eN), 7.09e7.14 (m, 4H,
Ar-H), 7.52e7.65 (m, 4H, FeAreH); 13C NMR (100 MHz, CDCl3,
(C]S),1252 (CeOeC), 1116 (CeO); 1H NMR (400 MHz, CDCl3,
d ppm):
0.85 (d, 6H, CH3, J ¼ 8 Hz),1.66 (d, 3H, CH3, J ¼ 8 Hz,),1.80e1.88 (m, lH,
CH), 2.45 (d,2H, CH2, J ¼ 8 Hz), 3.87 (s, 3H, OCH3), 3.04 (t, 4H, piper-
azine-CH2, J ¼ 5.2 Hz), 3.10 (t, 4H, piperazine-CH2, J ¼ 5.2 Hz), 4.11 (q,
lH, CH, J ¼ 8 Hz), 4.83 (s, 2H, NeCH2eN), 7.09 (d, 2H, Ar-H, J ¼ 8 Hz),
7.14 (d, 2H, Ar-H, J ¼ 8 Hz), 7.43e7.52 (m, 4H, OCH3-Ar-H); 13C NMR
d
ppm): 18.80, 19.20, 22.88, 30.67, 37.70, 45.05, 46.47, 70.39, 116.17,
118.63, 127.82, 127.26, 136.34, 141.55, 142.00, 148.30, 164.80, 179.30;
LC-MS (m/z): 454 (Mþ, 56%); Anal. Calcd. (%) for C25H31N4OFS: C,
66.05; H, 6.87; N, 12.32; S, 7.05. Found: C, 66.03; H, 6.84; N, 12.31; S,
7.03.
(100 MHz, CDCl3,
d ppm): 18.07, 18.77, 22.48, 29.46, 36.32, 45.04,
45.50, 70.26, 116.41, 119.36, 128.32, 130.54, 136.51, 141.84, 142.17,
148.96, 164.96, 178.05; LC-MS (m/z): 466 (Mþ, 39%); Anal. Calcd. (%)
for C26H34N4O2S:C, 66.92;H, 7.34;N,12.01;S, 6.87. Found: C, 66.89; H,
7.31; N, 12.00; S, 6.85.
6.3.16. 5-(4-Isobutylphenyl)ethyl-3-{[4-(2-ethoxyphenyl)
piperazin-1-yl]methyl}-1,3,4-oxadiazole-2 (3H)-thione, 5f
IR (KBr, gmax, cmꢁ1): 3038 (Ar-H), 2962 (CeH), 1728 (C]O), 1606
(C]N), 1326 (C]S), 1258 (CeOeC), 1126 (CeO); 1H NMR (400 MHz,
6.3.12. 5-(4-Isobutylphenyl)ethyl-3-{[4-(4-chlorophenyl)piperazin-
1-yl]methyl}-1,3,4-oxadiazole-2(3H)-thione, 5b
CDCl3,
d
ppm): 0.85 (d, 6H, CH3, J ¼ 8 Hz), 1.25(t, 3H, CH3, J ¼ 8 Hz),
1.66 (d, 3H, CH3, J ¼ 8 Hz), 1.80e1.88 (m, lH, CH), 2.41 (q, 2H, CH2 of
ethyl, J ¼ 4.4 Hz), 2.45 (d, 2H, CH2, J ¼ 8 Hz), 4.11 (q, lH, CH, J ¼ 8 Hz),
2.77 (t, 4H, piperazine-CH2, J ¼ 4.4 Hz) 3.49 (t, 4H, piperazine-CH2,
J ¼ 4.4 Hz) 5.11 (s, 2H, NeCH2eN), 7.09e7.14 (m, 4H, Ar-H),
IR (KBr, gmax, cmꢁ1): 3023 (ArC-H), 2972 (CeH), 1618 (C]N),
1329 (C]S), 1256 (CeOeC), 750 (CeCl); 1H NMR (400 MHz, CDCl3,
d
ppm): 0.81 (d, 6H, CH3, J ¼ 8 Hz), 1.66 (d, 3H, CH3, J ¼ 8 Hz),
1.80e1.88 (m, lH, CH), 2.45 (d, 2H, CH2, J ¼ 8 Hz), 2.87 (t, 4H,
piperazine-CH2, J ¼ 4 Hz), 3.43 (t, 4H, piperazine-CH2, J ¼ 4 Hz), 4.11
(q, lH, CH, J ¼ 8 Hz), 4.95 (s, 2H, NeCH2eN), 7.09 (d, 2H, Ar-
H, J ¼ 8.2 Hz), 7.14 (d, 2H, Ar-H, J ¼ 8.2 Hz), 7.89 (d, 2H,
CleAreH, J ¼ 8 Hz), 7.81 (d, 2H, CleAreH, J ¼ 8 Hz); 13C NMR
7.52e7.65 (m, 4H, Ar-H); 13C NMR (100 MHz, CDCl3,
d ppm): 16.05,
18.26, 18.83, 21.51, 29.80, 36.72, 41.38, 45.74, 45.98, 67.72, 116.34,
119.20, 128.16, 128.68, 135.46, 141.36, 142.45, 148.24, 164.34, 178.42;
LC-MS (m/z): 480 (Mþ, 35%); Anal. Calcd. (%) for C27H36N4O2S: C,
67.47; H, 7.55; N, 11.66; S, 6.67. Found: C, 67.45; H, 7.53; N, 11.62; S,
6.63.
(100 MHz, CDCl3,
d ppm): 18.67, 19.42, 22.65, 30.28, 37.48, 44.78,
45.47, 69.73, 116.87, 118.51, 127.05, 130.96, 136.02, 141.23, 141.65,
147.15,164.34,178.43; LC-MS (m/z): 471(Mþ, 42%), 473 (M þ 2,14%);
Anal. Calcd. (%) for C25H31N4OSCl: C, 63.74; H, 6.63; N, 11.89; S, 6.81.
Found: C, 63.73; H, 6.65; N, 11.87; S, 6.79.
6.3.17. 5-(4-Methylthiobenzyl)-3-{[4-(4-methoxyphenyl)piperazin-
1-yl]methyl}-1,3,4-oxadiazole-2 (3H)-thione, 5g
IR (KBr, gmax, cmꢁ1): 3073 (ArC-H), 2960 (CeH), 1628 (C]N),
1328 (C]S), 1253 (CeOeC), 1118 (CeO); 1H NMR (400 MHz, CDCl3,
6.3.13. 5-(4-Isobutylphenyl)ethyl-3-{[4-(3-chlorophenyl)piperazin-
1-yl]methyl}-1,3,4-oxadiazole-2 (3H) -thione, 5c
d
ppm): 2.47 (s, 3H, SCH3), 2.73 (t, 4H, piperazine-CH2, J ¼ 4.4 Hz),
3.03 (t, 4H, piperazine-CH2, J ¼ 4.4 Hz), 3.83 (s, 3H, OCH3), 4.13
(s, 2H, CH2), 4.79 (s, 2H, NeCH2eN), 6.71 (d, 2H, Ar-H, J ¼ 7.2 Hz),
6.73 (d, 2H, Ar-H, J ¼ 7.2 Hz), 7.01e7.03 (m, 4H, CH3eAreH); 13C
IR (KBr, gmax, cmꢁ1): 3041 (ArC-H), 2965 (CeH),1620 (C]N),1327
(C]S),1258 (CeOeC), 735 (CeCl); 1H NMR (400 MHz, CDCl3,
d ppm):
0.88 (d, 6H, CH3, J ¼ 8 Hz),1.65 (d, 3H, CH3, J ¼ 8 Hz),1.78e1.85 (m, lH,
CH), 2.43 (d,2H, CH2, J ¼ 8 Hz), 3.07 (t, 4H, piperazine-CH2, J ¼ 5.2 Hz),
3.14 (t, 4H, piperazine-CH2, J ¼ 5.2 Hz), 4.10 (q, lH, CH, J ¼ 8 Hz), 5.07
(s, 2H, NeCH2eN), 7.09 (d, 2H, Ar-H, J ¼ 8 Hz), 7.14 (d, 2H, Ar-
H, J ¼ 8 Hz), 7.89 (d, 2H, CleAreH, J ¼ 4 Hz), 7.81 (d, 2H, CleAreH,
NMR (100 MHz, CDCl3, d ppm): 16.21, 32.13, 34.86, 46.88, 47.02,
69.58, 116.23, 119.46, 127.32, 128.52, 138.58, 139.20, 142.45, 148.24,
164.34, 178.42; LC-MS (m/z): 442 (Mþ, 48%); Anal. Calcd. (%) for
C22H26N4O2S2 : C, 59.70; H, 5.92; N, 12.66; S, 14.49. Found: C, 59.69;
H, 5.89; N, 12.64; S, 14.47.
J ¼ 4 Hz); 13C NMR (100 MHz, CDCl3,
d ppm): 18.14,19.28, 22.57, 30.04,
37.26, 44.12, 44.38, 69.86, 116.58, 118.46, 127.24, 128.56, 135.56,
142.58,148.34,157.12,165.05,177.96; LC-MS (m/z): 471(Mþ, 54%), 473
(M þ 2, 18%); Anal. Calcd. (%) for C25H31N4OSCl: C, 63.74; H, 6.63; N,
11.89; S, 6.81. Found: C, 63.71; H, 6.61; N, 11.85; S, 6.78.
6.3.18. 5-(4-Methylthiobenzyl)-3-{[4-(4-chlorophenyl)piperazin-1-
yl]methyl}-1,3,4-oxadiazole-2(3H)-thione, 5h
IR (KBr, gmax, cmꢁ1): 3028 (ArC-H), 2968 (CeH), 1603 (C]N),
1326 (C]S), 1257 (CeOeC), 740 (CeCl); 1H NMR (400 MHz, CDCl3,
d
ppm): 2.47 (s, 3H, SCH3), 2.81 (t, 4H, piperazine-CH2, J ¼ 4.4 Hz),
6.3.14. 5-(4-Isobutylphenyl)ethyl-3-{[4-(4-nitrophenyl)piperazin-
1-yl]methyl}-1,3,4-oxadiazole-2 (3H)-thione, 5d
3.17 (t, 4H, piperazine-CH2, J ¼ 4.4 Hz), 4.19 (s, 2H, CH2), 5.07 (s, 2H,
NeCH2eN), 6.82 (d, 2H, Ar-H, J ¼ 7.2 Hz), 6.84 (d, 2H, Ar-
H, J ¼ 7.2 Hz), 7.68 (d, 2H, CleAreH, J ¼ 8.4 Hz), 7.72 (d, 2H,
IR (KBr, gmax, cmꢁ1): 3103 (ArC-H), 2942 (CeH), 1610 (C]N),
1445 (NO2), 1317 (C]S), 1254 (CeOeC), 1163 (NO2); 1H NMR
CleAreH, J ¼ 8.4 Hz); 13C NMR (100 MHz, CDCl3,
d ppm): 16.04,