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E. Rezníckova et al. / European Journal of Medicinal Chemistry 182 (2019) 111663
15
(qui, J ¼ 5.0 Hz, 1H, CH), 4.71 (qui, J ¼ 5.0 Hz, 1H, CH), 6.35 (bs, 1H,
132.57, 133.17, 136.98, 138.63, 146.86, 152.58, 154.81, 158.73.
NH), 6.89 (d, J ¼ 7.5 Hz, 1H, ArH), 7.19 (t, J ¼ 7.5 Hz, 1H, ArH), 7.78 (s,
1H, ArH), 7.87e8.01 (m, 2H, ArH, CH), 9.33 (bs, 1H, NH). 13C NMR
(126 MHz, DMSO‑d6) d ppm: 23.94, 31.60, 34.24, 34.71, 41.91, 50.12,
52.88, 53.76, 63.32, 66.76, 70.92, 114.32, 119.27, 121.01, 122.82,
128.56, 137.33, 138.39, 140.80, 152.57, 158.66.
4.2.5.34. 3-(2-((4-aminobutyl)amino)-6-((4-(4-benzylpiperazin-1-
yl)phenyl)amino)-9H-purin-9-yl)cyclopentan-1-ol (14n). Yield: 81%,
mp: 271e273 ꢀC. Elemental analysis: Calcd for C31H41N9O (555.73):
C, 67.00; H, 7.44; N, 22.68. Found: C, 66.95; H, 7.01; N, 22.39. HPLC-
MS (ESIþ): 557.28 (97.7%). 1H NMR (500 MHz, DMSO‑d6)
d ppm:
4.2.5.30. 3-(2-((4-aminocyclohexyl)amino)-6-((4-(morpholino-
1.42 (qui, J ¼ 6.5 Hz, 2H, CH2), 1.53 (qui, J ¼ 6.5 Hz, 2H, CH2),
1.72e1.77 (m, 2H), 1.79e1.84 (m, 1H), 2.01e2.15 (m, 2H), 2.32e2.38
(m, 1H, CH), 2.47e2.49 (m, 2H), 2.58 (t, J ¼ 7.0 Hz, 2H, CH2),
3.02e3.05 (m, 4H), 3.22 (q, J ¼ 6.5 Hz, 4H, 2xCH2), 3.49 (s, 2H, CH2),
4.19 (qui, J ¼ 4.5 Hz, 1H, CH), 4.72 (qui, J ¼ 7.5 Hz, 1H, CH), 6.48 (t,
J ¼ 6.0 Hz, 1H, NH), 6.82 (d, J ¼ 9.0 Hz, 2H, ArH), 7.21e7.25 (m, 1H,
ArH), 7.29e7.31 (m, 4H, ArH), 7.76 (d, J ¼ 9.0 Hz, 2H, ArH), 7.87 (s,
methyl)phenyl)amino)-9H-purin-9-yl)cyclopentan-1-ol
(14j).
Yield: 75%, mp: 197e198 ꢀC. Elemental analysis: Calcd for
C
27H38N8O2 (506.65): C, 64.01; H, 7.56; N, 22.12. Found: C, 64.28; H,
7.14; N, 22.27. HPLC-MS (ESIþ): 508.07 (99.9%). 1H NMR (500 MHz,
DMSO‑d6)
d ppm: 1.70e1.83 (m, 5H), 1.90e1.97 (m, 2H), 2.05e2.16
(m, 1H), 2.26e2.39 (m, 5H), 2.52e2.62 (m, 2H), 3.13 (s, 2H, CH2),
3.52e3.54 (m, 4H), 3.56e3.63 (m, 1H, CH), 4.20 (qui, J ¼ 5,0 Hz, 1H,
CH), 4.71 (qui, J ¼ 7.5 Hz, 1H, CH), 5.08 (bs, 1H, OH), 6.38 (d,
J ¼ 7.5 Hz, 1H, NH), 7.15 (d, J ¼ 8.0 Hz, 2H, ArH), 7.88e7.94 (m, 3H,
1H, CH), 9.11 (bs, 1H, NH). 13C NMR (126 MHz, DMSO‑d6)
d ppm:
27.15, 29.34, 31.11, 34.79, 41.15, 41.89, 49.12, 49.53, 52.92, 53.19,
62.64, 70.97, 114.28, 116.16, 121.75, 127.51, 128.74, 129.45, 133.05,
136.05, 138.64, 146.86, 151.63, 152.60, 159.43.
ArH, CH), 9.36 (bs, 1H, NH). 13C NMR (126 MHz, DMSO‑d6)
d ppm:
31.70, 34.72, 35.02, 41.90, 49.09, 49.69, 50.41, 53.65, 56.55, 62.68,
66.74, 70.95, 120.25, 129.45, 130.13, 131.40, 137.27, 139.86, 152.54,
152.53, 157.60, 158.66.
4.2.5.35. 3-(6-((4-(4-benzylpiperazin-1-yl)phenyl)amino)-2-((4-
hydroxybutyl)amino)-9H-purin-9-yl)cyclopentan-1-ol
(14o).
Yield: 74%, mp: 218e220 ꢀC. Elemental analysis: Calcd for
4.2.5.31. 3-(2-((4-aminobutyl)amino)-6-((4-(morpholinomethyl)
phenyl)amino)-9H-purin-9-yl)cyclopentan-1-ol (14k). Yield: 80%,
mp: 142e144 ꢀC. Elemental analysis: Calcd for C25H36N8O2
(480.62): C, 62.48; H, 7.55; N, 23.32. Found: C, 62.74; H, 7.29; N,
23.01. HPLC-MS (ESIþ): 481.9 (98%). 1H NMR (500 MHz, DMSO‑d6)
C31H40N8O2 (556.72): C, 66.88; H, 7.24; N, 20.13. Found: C, 66.62; H,
7.19; N, 20.46. HPLC-MS (ESIþ): 558.03 (95.4%). 1H NMR (500 MHz,
DMSO‑d6)
d
ppm: 1.44 (qui, J ¼ 7.5 Hz, 2H, CH2), 1.53 (qui, J ¼ 7.5 Hz,
2H, CH2), 1.72e1.76 (m, 2H), 1.79e1.84 (m, 1H, CH), 1.99e2.15 (m,
2H), 2.32e2.38 (m, 1H, CH), 2.47e2.49 (m, 2H), 2.98e3.08 (m, 4H),
3.22 (q, J ¼ 6.5 Hz, 2H, CH2), 3.37 (q, J ¼ 6.5 Hz, 2H, CH2), 3.47e3.53
(m, 2H), 4.19 (sex, J ¼ 4.0 Hz, 1H, CH), 4.34 (t, J ¼ 5.0 Hz, 1H, OH),
4.72 (qui, J ¼ 7.5 Hz, 1H, CH), 5.12 (d, J ¼ 4.0 Hz, 1H, OH), 6.47 (t,
J ¼ 5.5 Hz, 1H, NH), 6.82 (d, J ¼ 9.0 Hz, 2H, ArH), 7.21e7.26 (m, 1H,
ArH), 7.29e7.33 (m, 4H, ArH), 7.77 (d, J ¼ 9.0 Hz, 2H, ArH), 7.87 (s,
d
ppm: 1.93 (qui, J ¼ 6.0 Hz, 2H, CH2), 2.40e2.45 (m, 4H), 3.39 (q,
J ¼ 6.0 Hz, 2H, CH2), 3.66 (s, 2H, CH2), 3.73e3.75 (m, 4H), 4.19 (t,
J ¼ 7.0 Hz, 2H, CH2), 4.64 (t, J ¼ 5.0 Hz, 1H, OH), 7.02 (td, J ¼ 7.5 Hz,
Jꢁ¼ 1.0 Hz, 1H, ArH), 7.22 (dd, J ¼ 8.0 Hz, Jꢁ¼ 1.5 Hz, 1H, ArH), 7.33 (td,
J ¼ 7.8 Hz, 1H, ArH), 8.28 (s, 1H, CH), 8.34 (d, J ¼ 8.0 Hz, 1H, ArH),
11.59 (bs, 1H, NH). 13C NMR (126 MHz, DMSO‑d6)
d
ppm: 32.75,
1H, CH), 9.11 (bs, 1H, NH). 13C NMR (126 MHz, DMSO‑d6)
d ppm:
41.30, 53.01, 58.17, 61.68, 66.41, 119.91, 120.78, 123.50, 126.46,
128.52, 130.60, 138.96, 143.52, 150.92, 152.38, 152.79.
26.51, 30.74, 31.13, 34.78, 41.73, 41.91, 49.49, 52.89, 53.12, 61.25,
62.60, 70.97, 116.20, 121.70, 127.55, 128.76, 129.50, 131.98, 132.60,
133.12, 136.88, 146.80, 151.65, 152.58, 159.45.
4.2.5.32. 3-(2-((4-hydroxybutyl)amino)-6-((4-(morpholinomethyl)
phenyl)amino)-9H-purin-9-yl)cyclopentan-1-ol (14l). Yield: 78%,
mp: 222e224 ꢀC. Elemental analysis: Calcd for C25H35N7O3
(481.60): C, 62.35; H, 7.33; N, 20.36. Found: C, 62.58; H, 6.94; N,
20.69. HPLC-MS (ESIþ): 482.92 (98.4%). 1H NMR (500 MHz,
4.2.5.36. N2-(4-Amino-cyclohexyl)-N6-[4-(4-benzyl-piperazin-1-yl)-
phenyl]-9-cyclopentyl-9H-purine-2,6-diamine (14p). Yield: 92%.
m.p.: 149e150 ꢀC. Elemental analysis: Calcd.for C33H43N9 (565.77):
C, 70.06; H, 7.66; N, 22.28. Found: C, 69.82; H, 7.48; N, 22.01. HPLC-
DMSO‑d6)
d
ppm: 1.73e1.77 (m, 2H), 1.80e1.84 (m, 1H), 1.99e2.15
MS (ESIþ): 568.8 (99.9%). 1H NMR (500 MHz, DMSO‑d6)
d ppm
(m, 2H), 2.22e2.38 (m, 5H), 3.25 (q, J ¼ 7.0 Hz, 2H, CH2), 3.35e3.40
(m, 4H), 3.50e3.61 (m, 4H), 4.20 (sex, J ¼ 4.5 Hz, 1H, CH), 4.36 (t,
J ¼ 5.5 Hz, 1H, OH), 4.74 (qui, J ¼ 8.0 Hz, 1H, CH), 5.10 (d, J ¼ 4.0 Hz,
1H, OH), 6.59 (t, J ¼ 6.0 Hz, 1H, NH), 7.15 (d, J ¼ 8.0 Hz, 2H, ArH),
7.91e7.93 (m, 3H, ArH, CH), 9.34 (bs, 1H, NH). 13C NMR (126 MHz,
1.28e1.12 (m, 8H), 1.70e1.58 (m, 4H), 2.11e1.74 (m, 19H), 2.65e2.57
(m, 2H), 3.02 (t, J ¼ 9.8 Hz, 7H), 3.49 (d, J ¼ 3.3 Hz, 9H), 3.62e3.54
(m, 4H), 4.69e4.59 (m, 2H), 6.29 (bs, 1H), 6.82 (d, J ¼ 8.8 Hz, 4H),
7.26e7.19 (m, 2H), 7.32e7.28 (m, 8H), 7.84e7.74 (m, 6H), 9.10 (bs,
1H). 13C NMR (126 MHz, DMSO‑d6)
d ppm 31.49, 32.29, 34.18, 49.62,
DMSO‑d6)
d
ppm: 23.05, 26.50, 30.75, 31.16, 34.76, 41.92, 52.90,
50.29, 53.16, 62.61, 116.25, 121.62, 127.51, 128.73, 128.73, 129.47,
133.19, 138.60, 146.85, 158.66.
53.62, 61.23, 62.60, 66.71, 70.97, 114.37, 120.31, 129.49, 137.04,
139.90, 151.93, 152.52, 159.39, 172.11.
4.2.5.37. N2-(4-Amino-cyclohexyl)-9-cyclopentyl-N6-(4-morpholin-
4-ylmethyl-phenyl)-9H-purine-2,6-diamine (14q). Yield: 94%. m.p.:
133e135 ꢀC. Elemental analysis: Calcd.for C27H38N8O (490.64): C,
66.09; H, 7.81; N, 22.84. Found: C, 66.04; H, 7.59; N, 22.61. HPLC-MS
4. 2. 5. 33. 3-(2-((4-aminocyclohexyl)amino)-6-((4-(4-
benzylpiperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclopentan-1-ol
(14m). Yield: 65%, mp: 176e178 ꢀC. Elemental analysis: Calcd for
C
33H43N9O (581.77): C, 68.13; H, 7.45; N, 21.67. Found: C, 68.24; H,
(ESIþ): 491.65 (98.2%). 1H NMR (500 MHz, DMSO‑d6)
d ppm
7.49; N, 21.22. HPLC-MS (ESIþ): 583.23 (99.9%). 1H NMR (500 MHz,
1.30e1.05 (m, 4H),1.69e1.56 (m, 2H), 2.12e1.72 (m,10H), 2.27e2.32
(m, 4H), 2.53 (t, J ¼ 10.4 Hz, 1H), 3.36 (s, 2H), 3.50e3.56 (m, 4H),
3.68e3.56 (m, 1H), 4.72e4.59 (sep, J ¼ 7.5 Hz, 1H), 6.39 (bs, 1H), 7.15
(d, J ¼ 8.0 Hz, 2H), 7.84 (s, 1H), 7.92 (d, J ¼ 8.0 Hz, 2H), 9.32 (bs), 1H).
DMSO‑d6)
d ppm: 1.09e1.26 (m, 4H), 1.72e1.80 (m, 4H), 1.90e1.93
(m, 2H), 2.01e2.13 (m, 2H), 2.31e2.37 (m, 1H, CH), 2.51e2.57 (m,
1H, CH), 3.02e3.04 (m, 4H), 3.49 (s, 2H, CH2), 3.54e3.61 (m, 1H,
CH), 4.19 (qui, J ¼ 4.5 Hz, 1H, CH), 4.70 (qui, J ¼ 7.5 Hz, 1H, CH), 5.08
(bs, 1H, OH), 6.25 (d, J ¼ 7.5 Hz, 1H, NH), 6.81 (d, J ¼ 9.0 Hz, 2H, ArH),
7.21e7.25 (m, 1H, ArH), 7.27e7.32 (m, 4H, ArH), 7.78 (d, J ¼ 9.0 Hz,
2H, ArH), 7.87 (s, 1H, CH), 9.12 (bs, 1H, NH). 13C NMR (126 MHz,
13C NMR (126 MHz, DMSO‑d6)
d ppm 24.31, 31.76, 32.29, 35.57,
50.53, 53.65, 55.34, 62.67, 66.74, 114.51, 120.25, 129.42, 131.24,
137.12, 139.90, 152.50, 158.63.
DMSO‑d6)
d
ppm: 31.72, 34.81, 35.03, 41.89, 48.31, 49.08, 49.63,
4.2.5.38. 4-[9-Cyclopentyl-6-(4-morpholin-4-ylmethyl-phenyl-
50.43, 53.71, 62.62, 70.96, 116.22, 121.62, 127.49, 128.73, 129.45,
amino)-9H-purin-2-ylamino]-butan-1-ol (14r). Yield: 88%. m.p.: