ORIGINAL ARTICLES
2.31–2.63 (m, 4 H, CH2), 3.48 (m, 2 H, CH2), 3.68 (m, 1 H, CH2), 3.72 (s,
Ar––H), 8.15 (d, 1 H, J ¼ 7.6 Hz, Ar––H), 8.46 (s, 1 H, Ar––H), 9.43 (s, 1 H,
NH) ppm; MS (FABþ): m/z (%): 491 (MHþ, 29), 126 (100); IR (KBr):
3224, 2979, 1730, 1542, 1434, 1235, 1208, 1040, 892, 647 cmꢁ1; mp:
145–152 ꢀC; yield: 28%.
3 H, COO––CH3), 3.87 (m, 2 H, CH2), 4.13 (m, 1 H, CH2), 7.63 (dqu, 2 H,
J1 ¼ 7.5 Hz, J2 ¼ 1.7 Hz, Ar––H), 7.85 (dd, 1 H, J1 ¼ 8.6 Hz, J2 ¼ 1.8 Hz,
Ar––H), 7.98 (d, 1 H, J ¼ 7.6 Hz, Ar––H), 8.08 (d, 1 H, J ¼ 8.4 Hz,
Ar––H), 8.14 (d, 1 H, J ¼ 7.6 Hz, Ar––H), 8.44 (s, 1 H, Ar––H), 9.37 (s,
1 H, NH) ppm; MS (FABþ): m/z (%): 503 (MHþ, 56), 55 (100); IR
(KBr): 3434, 2927, 2852, 1668, 1438, 1239, 1166, 970, 751 cmꢁ1; mp:
91–95 ꢀC; yield: 29%.
3.4.7.8. Methyl 4-{[1-(4-morpholinylcarbonyl)-2-(2-naphthylsulfo-
nyl)hydrazino]methyl}-1-piperidinecarboxylate (6h)
1H NMR (DMSO-d6): d 0.92 (m, 2 H, CH2), 1.51 (m, 2 H, CH2), 1.88 (m,
1 H, CH), 2.69 (m, 2 H, CH2), 2.91 (m, 4 H, CH2), 3.12 (m, 6 H, CH2),
3.55 (s, 3 H, COO––CH3), 3.90 (d, 2 H, J ¼ 11.3 Hz, CH2), 7.71 (dqu, 2 H,
J1 ¼ 6.7 Hz, J2 ¼ 1.8 Hz, Ar––H), 7.78 (d, 1 H, J ¼ 8.7 Hz, Ar––H), 8.06
(d, 1 H, J ¼ 7.9 Hz, Ar––H), 8.13 (d, 1 H, J ¼ 8.7 Hz, Ar––H), 8.18 (d,
1 H, J ¼ 7.7 Hz, Ar––H), 8.45 (s, 1 H, Ar––H), 9.64 (s, 1 H, NH) ppm; MS
(FABþ): m/z (%): 491 (MHþ, 22), 93 (100); IR (KBr): 3373, 2981, 1718,
1690, 1528, 1412, 1274, 1168, 1099, 988, 654 cmꢁ1; mp: 80–84 ꢀC;
yield: 22%.
3.4.7.2. Methyl 4-{[1-[(4-methyl-1-piperidinyl)carbonyl]-2-(2-naphthylsul-
fonyl)hydrazino]methyl}-1-piperidinecarboxylate (6b)
1H NMR (DMSO-d6): d 0.46 (d, 3 H, J ¼ 6.03 Hz, CH3), 0.87–1.24 (m,
7 H, CH2, CH), 1.48–1.70 (m, 4 H, CH2), 1.94 (m, 1 H, CH), 2.70 (m,
4 H, CH2), 2.91 (m, 2 H, CH2), 3.56 (s, 3 H, COO––CH3), 3.92 (d, 2 H,
J ¼ 10.3 Hz, CH2), 7.69 (dqu, 2 H, J1 ¼ 6.8 Hz, J2 ¼ 1.8 Hz, Ar––H), 7.77
(dd, 1 H, J1 ¼ 8.6 Hz, J2 ¼ 1.6 Hz, Ar––H), 8.04 (d, 1 H, J ¼ 7.7 Hz, Ar––H),
8.09 (d, 1 H, J ¼ 8.7 Hz, Ar––H), 8.15 (d, 1 H, J ¼ 7.7 Hz, Ar––H), 8.43
(s, 1 H, Ar––H), 9.45 (s, 1 H, NH) ppm; MS (FABþ): m/z (%): 503
(MHþ, 48), 93 (100); IR (KBr): 2926, 2855, 1801, 1699, 1448, 1242,
1166, 970 cmꢁ1; mp: 60–64 ꢀC; yield: 17%.
3.4.7.9. Methyl 3-{[1-[(cycloheptylamino)carbonyl]-2-(2-naphthylsulfo-
nyl)hydrazino]methyl}-1-piperidinecarboxylate (6i)
1H NMR (DMSO-d6): d 1.02 (m, 2 H, CH2), 1.22 (m, 4 H, CH2), 1.69 (m,
5 H, CH, CH2), 1.83 (m, 4 H, CH2), 2.35 (m, 5 H, CH, CH2), 3.52 (d, 1 H,
J ¼ 11.6 Hz, CH2), 3.74 (s, 3 H, COO––CH3), 3.81 (m, 3 H, CH2, NH),
4.12 (d, 1 H, J ¼ 10.5 Hz, CH2), 7.66 (dqu, 2 H, J1 ¼ 7.7 Hz, J2 ¼ 1.7 Hz,
Ar––H), 7.80 (dd, 1 H, J1 ¼ 8.5 Hz, J2 ¼ 1.8 Hz, Ar––H), 7.97 (d, 1 H,
J ¼ 8.6 Hz, Ar––H), 8.04 (d, 1 H, J ¼ 8.6 Hz, Ar––H), 8.11 (d, 1 H,
J ¼ 7.5 Hz, Ar––H), 8.42 (s, 1 H, Ar––H), 9.40 (s, 1 H, NH) ppm; MS
(FABþ): m/z (%): 517 (MHþ, 34), 126 (100); IR (KBr): 3413, 3186,
2937, 1685, 1430, 1335, 1168, 1026, 858, 754, 552 cmꢁ1; mp: 77–82 ꢀC;
yield: 35%.
3.4.7.3. Methyl 3-{[2-(2-naphthylsulfonyl)-1-(1-piperidinylcarbonyl)hydra-
zino]methyl}-1-piperidinecarboxylate (6c)
1H NMR (DMSO-d6): d 1.04 (m, 2 H, CH2), 1.32 (m, 4 H, CH2), 1.52 (m,
2 H, CH2), 1.67 (m, 2 H, CH2), 1.76–2.01 (m, 3 H, CH, CH2), 2.88 (m,
2 H, CH2), 3.02 (m, 2 H, CH2), 3.46 (m, 1 H, CH2), 3.71 (s, 3 H,
COO––CH3), 3.85 (d, 2 H, J ¼ 11.6 Hz, CH2), 4.01 (m, 1 H, CH2), 7.62
(dqu, 2 H, J1 ¼ 7.6 Hz, J2 ¼ 1.8 Hz, Ar––H), 7.79 (dd, 1 H, J1 ¼ 8.5 Hz,
J2 ¼ 1.6 Hz, Ar––H), 8.01 (d, 1 H, J ¼ 7.6 Hz, Ar––H), 8.11 (d, 1 H, J ¼
8.5 Hz, Ar––H), 8.17 (d, 1 H, J ¼ 7.5 Hz, Ar––H), 8.46 (s, 1 H, Ar––H),
9.53 (s, 1 H, NH) ppm; MS (FABþ): m/z (%): 499 (MHþ, 16), 112 (100);
IR (KBr): 3411, 3023, 1693, 1435, 1240, 1167, 1075, 856, 750 cmꢁ1; mp:
76–85 ꢀC; yield: 37%.
3.4.7.10. Methyl 4-{[1-(1-azepanylcarbonyl)-2-(2-naphthylsulfonyl)hydra-
zino]methyl}-1-piperidinecarboxylate (6j)
1H NMR (DMSO-d6): d 0.94 (m, 4 H, CH2), 1.13 (m, 2 H, CH2) 1.27 (m,
8 H, CH2), 1.71 (m, 2 H, CH2), 1.89 (m, 1 H, CH), 2.70 (m, 3 H, CH2),
2.96 (m, 1 H, CH), 3.53 (s, 3 H, COO––CH3), 3.82 (s, 1 H, NH), 3.90 (d,
2 H, J ¼ 10.5 Hz, CH2), 4.07 (s, 1 H, CH2), 7.67 (dqu, 2 H, J1 ¼ 7.3 Hz,
J2 ¼ 1.7 Hz, Ar––H), 7.80 (dd, 1 H, J1 ¼ 8.5 Hz, J2 ¼ 1.7 Hz, Ar––H), 8.01
(d, 1 H, J ¼ 7.6 Hz, Ar––H), 8.11 (d, 1 H, J ¼ 8.5 Hz, Ar––H), 8.16 (d,
1 H, J ¼ 7.3 Hz, Ar––H), 8.42 (s, 1 H, Ar––H), 9.44 (s, 1 H, NH) ppm; MS
(FABþ): m/z (%): 517 (MHþ, 27), 93 (100); IR (KBr): 3420, 2980, 1720,
1688, 1521, 1449, 1251, 1087, 854 cmꢁ1; mp: 76–80 ꢀC; yield: 24%.
3.4.7.4. Methyl 4-{[2-(2-naphthylsulfonyl)-1-(1-piperidinylcarbonyl)hydra-
zino]methyl}-1-piperidinecarboxylate (6d)
1H NMR (DMSO-d6): d 0.85–1.05 (m, 6 H, CH2), 1.24 (m, 2 H, CH2),
1.54 (m, 2 H, CH2), 1.89 (m, 1 H, CH), 2.66 (m, 2 H, CH2), 2.89 (d, 2 H,
J ¼ 6.7 Hz, CH2), 2.89 (m, 2 H, CH2), 2.99 (m, 2 H, CH2), 3.55 (s, 3 H,
COO––CH3), 3.90 (d, 2 H, J ¼ 12.4 Hz, CH2), 7.69 (dqu, 2 H, J1 ¼ 7.5 Hz,
J2 ¼ 1.8 Hz, Ar––H), 7.77 (dd, 1 H, J1 ¼ 8.6 Hz, J2 ¼ 1.8 Hz, Ar––H), 8.04
(d, 1 H, J ¼ 7.5 Hz, Ar––H), 8.10 (d, 1 H, J ¼ 8.6 Hz, Ar––H), 8.16 (d,
1 H, J ¼ 7.5 Hz, Ar––H), 8.43 (s, 1 H, Ar––H), 9.45 (s, 1 H, NH) ppm; MS
(FABþ): m/z (%): 489 (MHþ, 10), 93 (100); IR (KBr): 3413, 3160, 2931,
2853, 1692, 1475, 1255, 1170, 1085, 914, 753, 697 cmꢁ1; mp: 72–77 ꢀC;
yield: 35%.
3.4.7.11. Methyl 3-{[1-[(cyclopentylamino)carbonyl]-2-(2-naphthylsulfo-
nyl)hydrazino]methyl}-1-piperidinecarboxylate (6k)
1H NMR (DMSO-d6): d 1.17–1.35 (m, 6 H, CH2), 1.69 (m, 4 H, CH2),
1.92 (m, 3 H, CH, CH2), 2.14 (m, 2 H, CH2), 2.37 (m, 1 H, CH), 3.11 (m,
1 H, CH2), 3.48 (s, 1 H, CO––NH), 3.62 (s, 3 H, COO––CH3), 3.75 (m,
1 H, CH2), 4.01 (d, 2 H, J ¼ 9.1 Hz, CH2), 7.65 (dqu, 2 H, J1 ¼ 7.5 Hz,
J2 ¼ 1.8 Hz, Ar––H), 7.80 (dd, 1 H, J1 ¼ 8.6 Hz, J2 ¼ 1.7 Hz, Ar––H), 8.00
(d, 1 H, J ¼ 7.6 Hz, Ar––H), 8.10 (d, 1 H, J ¼ 8.6 Hz, Ar––H), 8.14 (d,
1 H, J ¼ 7.4 Hz, Ar––H), 8.44 (s, 1 H, Ar––H), 9.45 (s, 1 H, NH) ppm; MS
(FABþ): m/z (%):489 (MHþ, 25), 168 (100); IR (KBr): 3437, 1693, 1441,
1350, 1240, 1166, 864, 753 cmꢁ1; mp: 83–88 ꢀC; yield: 28%.
3.4.7.5. Methyl 3-{[1-(1-azepanylcarbonyl)-2-(2-naphthylsulfonyl)hydra-
zino]methyl}-1-piperidinecarboxylate (6e)
1H NMR (DMSO-d6): d 1.26 (m, 4 H, CH2), 1.71 (m, 4 H, CH2), 1.81 (m,
1 H, CH), 1.92 (m, 2 H, CH2), 2.17 (m, 2 H, CH2), 2.83 (m, 2 H, CH2),
3.46 (m, 1 H, CH2), 3.70 (m, 9 H, CH2, COO––CH3), 4.10 (d, 1 H,
J ¼ 6.8 Hz, CH2), 7.67 (dqu, 2 H, J1¼ 7.8 Hz, J2 ¼ 1.6 Hz, Ar––H), 7.77
(dd, 1 H, J1 ¼ 8.6 Hz, J2 ¼ 1.6 Hz, Ar––H), 7.98 (d, 1 H, J ¼ 8.3 Hz, Ar––H),
8.03 (d, 1 H, J ¼ 8.7 Hz, Ar––H), 8.12 (d, 1 H, J ¼ 7.8 Hz, Ar––H), 8.47
(s, 1 H, Ar––H), 9.41 (s, 1 H, NH) ppm; MS (FABþ): m/z (%): 503
(MHþ, 24), 126 (100); IR (KBr): 2933, 2857, 1693, 1434, 1383, 1239,
1167, 867 cmꢁ1; mp: 76–79 ꢀC; yield: 39%.
3.4.7.12. Methyl 4-{[1-[(cyclopentylamino)carbonyl]-2-(2-naphthylsulfo-
nyl)hydrazino]methyl}-1-piperidinecarboxylate (6l)
1H NMR (DMSO-d6): d 1.03–1.31 (m, 6 H, CH2), 1.60 (m, 4 H, CH2),
1.81 (m, 1 H, CH), 2.71 (m, 4 H, CH2), 3.23 (m, 1 H, CH), 3.58 (s, 3 H,
COO––CH3), 3.62 (s, 1 H, NH), 4.02 (d, 2 H, J ¼ 11.7 Hz, CH2), 4.16 (q,
2 H, J ¼ 7.3 Hz, CH2), 7.72 (dqu, 2 H, J1 ¼ 6.5 Hz, J2 ¼ 1.8 Hz, Ar––H),
7.75 (d, 1 H, J ¼ 8.5 Hz, Ar––H), 8.01 (d, 1 H, J ¼ 8.0 Hz, Ar––H), 8.15
(d, 1 H, J ¼ 8.6 Hz, Ar––H), 8.21 (d, 1 H, J ¼ 7.6 Hz, Ar––H), 8.44 (s, 1 H,
Ar––H), 9.64 (s, 1 H, NH) ppm; MS (FABþ): m/z (%): 489 (MHþ, 34),
126 (100); IR (KBr): 3309, 2956, 1716, 1537, 1426, 1208, 1036, 972,
815 cmꢁ1; mp: 71–74 ꢀC; yield: 23%.
3.4.7.6. Methyl 4-{[1-(1-azepanylcarbonyl)-2-(2-naphthylsulfonyl)hydra-
zino]methyl}-1-piperidinecarboxylate (6f)
1H NMR (DMSO-d6): d 0.69 (m, 2 H, CH2), 0.88–1.13 (m, 6 H, CH2),
1.32 (m, 2 H, CH2), 1.50–1.65 (m, 2 H, CH2), 1.89 (m, 1 H, CH), 2.57–
2.73 (m, 2 H, CH2), 2.87 (m, 4 H, CH2), 3.07 (m, 2 H, CH2), 3.55 (s, 3 H,
COO––CH3), 3.90 (d, 2 H, J ¼ 11.5 Hz, CH2), 7.68 (dqu, 2 H, J1 ¼ 5.9 Hz,
J2 ¼ 1.8 Hz, Ar––H), 7.79 (dd, 1 H, J1 ¼ 6.9 Hz, J2 ¼ 1.6 Hz, Ar––H), 8.02
(d, 1 H, J ¼ 7.7 Hz, Ar––H), 8.09 (d, 1 H, J ¼ 8.7 Hz, Ar––H), 8.15 (d,
1 H, J ¼ 7.6 Hz, Ar––H), 8.44 (s, 1 H, Ar––H), 9.38 (s, 1 H, NH) ppm; MS
(FABþ): m/z (%): 503 (MHþ, 19), 126 (100); IR (KBr): 3415, 1647,
1455, 1166, 872, 658 cmꢁ1; mp: 64–67 ꢀC; yield: 13%.
3.4.7.13. Methyl 3-{[1-{[cyclohexyl(methyl)amino]carbonyl}-2-(2-naphthyl-
sulfonyl)hydrazino]methyl}-1-piperidinecarboxylate (6m)
1H NMR (DMSO-d6): d 0.98 (m, 6 H, CH2), 1.25 (m, 4 H, CH2), 1.63 (m,
4 H, CH2), 1.71 (m, 1 H, CH), 1.86 (m, 2 H, CH2), 2.88 (s, 3 H, CH3),
3.11 (m, 1 H, CH), 3.54 (m, 1 H, CH2), 3.70 (s, 3 H, COO––CH3), 3.86
(m, 2 H, CH2), 4.05 (m, 1 H, CH2), 7.69 (dqu, 2 H, J1 ¼ 7.8 Hz,
J2 ¼ 1.8 Hz, Ar––H), 7.82 (dd, 1 H, J1 ¼ 8.6 Hz, J2 ¼ 1.8 Hz, Ar––H), 7.99
(d, 1 H, J ¼ 8.5 Hz, Ar––H), 8.05 (d, 1 H, J ¼ 8.7 Hz, Ar––H), 8.12 (d,
1 H, J ¼ 7.9 Hz, Ar––H), 8.44 (s, 1 H, Ar––H), 9.37 (s, 1 H, NH) ppm; MS
(FABþ): m/z (%): 517 (MHþ, 37), 126 (100); IR (KBr): 3414, 3145,
2957, 1675, 1432, 1342, 1167, 1042, 858, 748, 644, 553 cmꢁ1; mp: 133–
136 ꢀC; yield: 24%.
3.4.7.7. Methyl 3-{[1-(4-morpholinylcarbonyl)-2-(2-naphthylsulfo-
nyl)hydrazino]methyl}-1-piperidinecarboxylate (6g)
1H NMR (DMSO-d6): d 1.22 (m, 2 H, CH2), 1.59 (m, 2 H, CH2), 1.83 (m,
1 H, CH), 1.90 (m, 2 H, CH2), 2.13 (m, 2 H, CH2), 3.22 (t, 4 H,
J ¼ 6.5 Hz, CH2), 3.38 (t, 4 H, J ¼ 6.4 Hz, CH2), 3.59 (m, 1 H, CH2), 3.78
(s, 3 H, COO––CH3), 4.12 (d, 1 H, J ¼ 11.3 Hz, CH2), 7.68 (dqu, 2 H, J1 ¼
7.6 Hz, J2 ¼ 1.9 Hz, Ar––H), 7.83 (dd, 1 H, J1 ¼ 8.6 Hz, J2 ¼ 1.8 Hz,
Ar––H), 8.01 (d, 1 H, J ¼ 8.5 Hz, Ar––H), 8.07 (d, 1 H, J ¼ 8.7 Hz,
250
Pharmazie 62 (2007) 4