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P. Sengupta et al. / European Journal of Medicinal Chemistry 46 (2011) 5549e5555
J ¼ 6.8 Hz), 7.92 (d, 1H, J ¼ 7.7 Hz), 7.75 (d, 1H, J ¼ 7.8 Hz), 7.50e7.42
(m, 3H), 5.93 (s, 2H), 4.33 (m, 1H), 4.04e3.99 (m, 1H), 3.83e3.81 (m,
1H), 3.64e3.61 (m, 1H), 3.56e3.55 (m, 1H), 2.72e2.68 (m, 1H),
134.72, 128.40, 126.81, 121.73, 121.53, 118.34, 109.99, 66.69, 64.85,
41.67, 28.81,13.55; ESI-MS (m/z): 415.1 (M þ H)þ.
2.10e2.09 (m, 1H), 1.68e1.67 (m, 1H); 13C NMR (
d
, DMSO-d6):
7.4.8. N-[(3R, 4R)-3-(hydroxycarbamoyl)tetrahydro-2H-pyran-4-
yl]-5-[(2-trifluoromethyl-1H-benzimidazol-1-yl)methyl]thiophene-
2-carboxamide (17)
171.39, 167.69, 159.15, 150.02, 142.16, 140.18, 138.03, 131.44, 127.39,
125.69, 122.16, 122.09, 122.05, 113.08, 68.23, 67.14, 50.60, 48.61,
43.43, 30.11; ESI-MS (m/z): 464.43 (M þ H)þ.
Rf: 0.3 (CH2Cl2-methanol, 9:1); 1H NMR (
d, DMSO-d6): 10.47 (s,
1H), 8.75 (s, 1H), 8.29 (d, 1H, J ¼ 7.0 Hz), 7.93e7.89 (m, 1H),
7.74e7.73 (m, 1H), 7.58e7.54 (m, 1H), 7.49e7.45 (m, 1H), 7.19e7.18
(m, 1H), 5.95 (s, 2H), 4.19 (m, 1H), 4.01e3.97 (m, 1H), 3.87e3.84 (m,
1H), 3.53e3.49 (m, 1H), 2.66e2.61 (m, 1H), 2.25e2.22 (m, 1H),
7.4.3. N-[(1S, 2R)-3-(hydroxycarbamoyl)cyclohexyl]-6-[(2-methyl-
1H-benzimidazol-1-yl)methyl]nicotinamide (12)
Rf: 0.3 (CH2Cl2-methanol, 9:1); 1H NMR (
d, DMSO-d6): 10.51 (s,
1H), 8.90 (s, 1H), 8.76 (s, 1H), 8.48 (d, 1H, J ¼ 7.0 Hz), 8.15 (d, 1H,
J ¼ 7.5 Hz), 7.61e7.57 (m, 1H), 7.51e7.47 (m, 1H), 7.39 (d, 1H,
J ¼ 8.0 Hz), 7.20e7.16 (m, 2H), 5.67 (s, 2H), 4.33 (m, 1H), 4.07e3.98
(m, 1H), 3.83e3.72 (m, 1H), 3.68e3.55 (m, 3H), 2.21e2.10 (m, 1H),
1.61e1.59 (m, 1H); 13C NMR (
d, DMSO-d6): 168.25, 160.16, 142.66,
140.48, 139.76, 139.07, 135.06, 128.30, 127.54, 125.75, 124.00, 121.04,
112.12, 66.69, 64.86, 43.36, 28.80; ESI-MS (m/z): 469.0 (M þ H)þ.
1.72e1.64 (m, 1H); 13C NMR (
d
, DMSO-d6): 170.06, 164.38, 158.26,
7.4.9. N-[(1S, 2R)-3-(hydroxycarbamoyl)cyclopentyl]-5-[(2-
methyl-1H-benzimidazol-1-yl)methyl]thiophene-2-carboxamide
(18)
152.29, 148.59, 142.37, 136.31, 135.31, 129.72, 121.51, 121.28, 120.96,
118.20, 109.90, 48.22, 47.87, 41.23, 28.97, 24.91, 22.90, 21.71, 13.70;
ESI-MS (m/z): 408.15 (M þ H)þ.
Rf: 0.1 (CH2Cl2-methanol, 9:1); 1H NMR (
d, DMSO-d6): 10.46 (s,
1H), 8.69 (s,1H), 8.15 (d,1H, J ¼ 6.9 Hz), 7.63e7.58 (m, 3H), 7.26e7.19
(m, 2H), 7.14e7.13 (m, 1H), 5.71 (s, 2H), 4.31 (d, 1H, J ¼ 7.0 Hz),
2.71e2.67 (m,1H), 2.62 (s, 3H),1.90e1.84 (m, 5H),1.54e1.52 (m,1H);
7.4.4. N-[(1S, 2R)-3-(hydroxycarbamoyl)cyclohexyl]-6-[(2-
trifluoromethyl-1H-benzimidazol-1-yl)methyl]nicotinamide (13)
Rf: 0.3 (CH2Cl2-methanol, 9:1); 1H NMR (
d, DMSO-d6): 10.51 (s,
13C NMR (
d, DMSO-d6): 169.71, 160.20, 151.41, 144.36, 142.31, 139.48,
1H), 8.90 (s, 1H), 8.76 (s, 1H), 8.48 (d, 1H, J ¼ 7.0 Hz), 8.15 (d, 1H,
J ¼ 7.5 Hz), 7.61e7.57 (m, 1H), 7.51e7.47 (m, 1H), 7.39 (d, 1H,
J ¼ 8.0 Hz), 7.20e7.16 (m, 2H), 5.67 (s, 2H), 4.33 (m, 1H), 4.07e3.98
(m, 1H), 3.83e3.72 (m, 1H), 368e3.55 (m, 3H), 2.21e2.10 (m, 1H),
134.73, 128.03, 126.75, 123.73, 121.52, 118.33, 110.00, 52.74, 43.54,
41.66, 31.55, 28.04, 22.36, 13.55; ESI-MS (m/z): 399.10 (M þ H)þ.
7.4.10. N-[(1S, 2R)-3-(hydroxycarbamoyl)cyclopentyl]-5-[(2-
trifluoromethyl-1H-benzimidazol-1-yl)methyl]thiophene-2-
carboxamide (19)
1.72e1.64 (m, 1H); 13C NMR (
d, DMSO-d6): 170.04, 164.30, 156.99,
148.43,140.45,140.16,139.86,136.35,135.95,129.88,125.43,123.64,
120.81, 120.66, 120.12, 117.97, 112.06, 64.91, 48.82, 48.19, 41.27,
29.00, 24.82, 22.93, 21.55, 15.16; ESI-MS (m/z): 462.09 (M þ H)þ.
Rf: 0.1 (CH2Cl2-methanol, 9:1); 1H NMR (
d, DMSO-d6): 10.45 (s,
1H), 8.68 (s, 1H), 8.19 (d, 1H, J ¼ 7.3 Hz), 7.93e7.90 (m, 2H),
7.65e7.64 (m, 1H), 7.58e7.54 (m, 1H), 7.49e7.45 (m, 1H), 7.17e7.16
(m, 1H), 5.94 (s, 2H), 4.34e4.27 (m, 1H), 2.72e2.67 (m, 1H),
7.4.5. N-[(1S, 2R)-2-(hydroxycarbamoyl)cyclopentyl]-6-[(2-
methyl-1H-benzimidazol-1-yl)methyl]nicotinamide (14)
1.92e1.79 (m, 5H), 1.56e1.52 (m, 1H); 13C NMR (
d, DMSO-d6):
Rf: 0.3 (CH2Cl2-methanol, 9:1); 1H NMR (
d, DMSO-d6): 10.48 (s,
169.69, 160.10, 142.35, 140.47, 140.00, 135.03, 127.90, 127.46, 125.72,
123.97, 121.01, 112.10, 52.75, 43.56, 43.32, 31.52, 28.02, 22.35; ESI-
MS (m/z): 453.04 (M þ H)þ.
1H), 8.85 (s, 1H), 8.69 (s, 1H), 8.34 (d, 1H, J ¼ 7.7 Hz), 8.11 (dd, 1H,
J1 ¼ 8.1 Hz, J2 ¼ 2.0 Hz), 7.59e7.57 (m, 1H), 7.50e7.48 (m, 1H), 7.36
(d, 1H, J ¼ 8.1 Hz), 7.19e7.17 (m, 2H), 5.65 (s, 2H), 4.45e4.40 (m, 1H),
2.74 (dd, 1H, J1 ¼ 15.3 Hz, J2 ¼ 7.7 Hz), 2.62 (s, 3H), 2.00e1.93 (m,
7.4.11. N-[(1S, 2R)-3-(hydroxycarbamoyl)cyclopentyl]-5-[(2-
1H), 1.86e1.78 (m, 4H), 1.56e1.55 (m, 1H); 13C NMR (
d, DMSO-d6):
methyl-1H-benzimidazol-1-yl)methyl]furan-2-carboxamide (20)
169.50, 164.28, 158.28, 152.29, 148.46, 142.37, 136.16, 135.31, 129.59,
121.53, 121.29, 120.95, 118.21, 109.91, 52.60, 47.87, 43.90, 31.57,
27.74, 22.56, 13.71; ESI-MS (m/z): 394.13 (M þ H)þ.
Rf: 0.5 (CH2Cl2-methanol, 9:1); 1H NMR (
d, DMSO-d6): 10.64 (s,
1H), 8.91 (s, 1H), 7.95 (d, 1H, J ¼ 6.9 Hz), 7.70 (d, 1H, J ¼ 7.7 Hz), 7.57
(d, 1H, J ¼ 7.7 Hz), 7.28e7.18 (m, 2H), 7.07 (d, 1H, J ¼ 3.3 Hz), 6.66 (d,
1H, J ¼ 3.2 Hz), 5.56 (s, 2H), 4.31e4.24 (m, 1H), 2.74 (s, 3H),
7.4.6. N-[(1S, 2R)-2-(hydroxycarbamoyl)cyclopentyl]-6-[(2-
2.72e2.68 (m, 1H), 2.00e1.70 (m, 6H); 13C NMR (
d, DMSO-d6):
trifluoromethyl-1H-benzimidazol-1-yl)methyl]nicotinamide (15)
170.02, 156.74, 151.93, 151.82, 147.54, 142.16, 134.82, 121.78, 121.54,
118.23, 114.10,110.63, 110.13, 52.23, 43.14, 32.52, 28.33, 22.28,13.55;
ESI-MS (m/z): 383.13 (M þ H)þ.
Rf: 0.3 (CH2Cl2-methanol, 9:1); 1H NMR (
d, DMSO-d6): 10.47 (s,
1H), 8.76 (s, 1H), 8.68 (s, 1H), 8.35 (d, 1H, J ¼ 7.8 Hz), 8.14 (dd, 1H,
J1 ¼ 8.0 Hz, J2 ¼ 1.8 Hz), 7.91 (d, 1H, J ¼ 7.7 Hz), 7.75 (d, 1H,
J ¼ 7.9 Hz), 7.50e7.42 (m, 3H), 5.92 (s, 2H), 4.47e4.40 (m, 1H), 2.73
(dd, 1H, J1 ¼ 15.2 Hz, J2 ¼ 7.7 Hz), 1.98e1.93 (m, 1H), 1.89e1.78 (m,
7.4.12. N-[(1S, 2R)-3-(hydroxycarbamoyl)cyclopentyl]-5-[(2-
trifluoromethyl-1H-benzimidazol-1-yl)methyl]furan-2-
carboxamide (21)
4H), 1.55e1.51 (m, 1H); 13C NMR (
d, DMSO-d6): 169.45, 164.21,
156.99, 148.28, 140.44, 140.15, 139.85, 136.71, 135.93, 129.80, 125.44,
123.64, 120.81, 120.64, 120.11, 117.96, 112.35, 52.60, 48.81, 43.94,
31.55, 27.69, 22.53; ESI-MS (m/z): 448.07 (M þ H)þ.
Rf:0.3(CH2Cl2-methanol, 9:1); 1HNMR(
d, DMSO-d6):10.61(s,1H),
8.84(s,1H), 8.04 (d,1H, J ¼ 8.2 Hz), 7.90 (d, 2H, J ¼ 7.6 Hz), 7.60 (m,1H),
7.47 (m,1H), 7.09 (d,1H, J ¼ 2.8 Hz), 6.66 (d,1H, J ¼ 2.5 Hz), 5.79(s, 2H),
4.31e4.28 (m, 1H), 2.72e2.67 (m, 1H), 1.92e1.76 (m, 5H), 1.60e1.50
7.4.7. N-[(3R, 4R)-3-(hydroxycarbamoyl)tetrahydro-2H-pyran-4-
yl]-5-[(2-methyl-1H-benzimidazol-1-yl)methyl]thiophene-2-
carboxamide (16)
(m,1H); 13C NMR (
d, DMSO-d6): 169.88,156.63,150.40,147.73,140.32,
135.22, 125.83, 123.92, 120.87, 114.10, 112.32, 110.23, 52.26, 43.19,
41.13, 32.42, 28.16, 22.18; ESI-MS (m/z): 437.07 (M þ H)þ.
Rf: 0.14 (CH2Cl2-methanol, 9:1); 1H NMR (
d, DMSO-d6): 10.46 (s,
1H), 8.76 (s,1H), 8.25 (d,1H, J ¼ 7.0 Hz), 7.73e7.58 (m, 2H), 7.26e7.19
(m, 2H), 7.16e7.15 (m,1H), 5.72 (s, 2H), 4.19e4.18 (m,1H), 4.01e3.97
(m, 1H), 3.87e3.84 (m, 1H), 3.63e3.59 (m, 1H), 3.53e3.49 (m, 1H),
2.66e2.64 (m,1H), 2.62 (s, 3H), 2.25e2.23 (m,1H),1.61e1.58 (m,1H);
7.4.13. N-[(1S, 2R)-3-(hydroxycarbamoyl)cyclohexyl]-5-[(2-
methyl-1H-benzimidazol-1-yl)methyl]thiophene-2-carboxamide
(22)
Rf: 0.1 (CH2Cl2-methanol, 9:1); 1H NMR (
d, DMSO-d6): 10.43 (s,
13C NMR (
d, DMSO-d6): 168.26,160.23,151.41,144.34,142.32,139.20,
1H), 8.65 (s, 1H), 7.98e7.96 (m, 1H), 7.85e7.72 (m, 1H), 7.63e7.58