JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
689
125.31, 126.08, 127.59, 132.40, 138.79, 140.96, 143.29, 148.78, C20H17ClN4O: C, 65.84; H, 4.70; N, 15.36; Found C, 66.09; H, 4.74; N,
163.23, 165.58 (C¼O); Anal. calcd. For C18H13ClN4O: C, 64.20; H, 15.53.
3.89; N, 16.64; Found C, 64.43; H, 3.93; N, 16.87.
5-Bromo-3-(((1-propyl-1H-indol-3-yl)methylene)hydrazono)indolin-
2-one (6k). Yield 83%, m.p. 126–128 ꢀC; IR (KBr, ꢀ cmꢁ1): 3381
5-Bromo-3-(((Z)-(1-methyl-1H-indol-3-yl)methylene)hydrazono)indo-
lin-2-one (6g). Yield 77%, m.p. 295–297 ꢀC; IR (KBr, ꢀ cmꢁ1): 3390 (NH), 1697 (C¼O); 1H NMR (DMSO-d6) d (ppm): 0.88 (t, 3H,
(NH), 1695 (C¼O); 1H NMR (DMSO-d6) d (ppm): 3.91 (s, 3H, CH3), –CH2–CH2–CH3, J ¼ 7.2 Hz), 1.84 (sextet, 2H, –CH2–CH2–CH3,
6.86 (d, 1H, Ar-H, J ¼ 7.6 Hz), 7.33–7.38 (m, 2H, Ar-H), 7.54 (d, 1H, J ¼ 7.2 Hz), 4.27 (t, 2H, –CH2–CH2–CH3, J ¼ 7.2 Hz), 6.86 (d, 1H, Ar-H,
Ar-H, J ¼ 7.2 Hz), 7.63 (d, 1H, Ar-H, J ¼ 7.2 Hz), 8.24–8.29 (m, 2H, J ¼ 8.0 Hz), 7.31–7.36 (m, 2H, Ar-H), 7.54 (d, 1H, Ar-H, J ¼ 8.0 Hz),
-CH¼N- and Ar-H), 8.66 (s, 1H, Ar-H), 8.97 (s, 1H, H-2 indole), 10.87 7.69 (d, 1H, Ar-H, J ¼ 8.0 Hz), 8.29–8.31 (m, 2H, -CH¼N- and Ar-H),
(s, 1H, NH isatin, D2O exchangeable); 13C NMR (DMSO-d6) d ppm:
8.66 (s, 1H, Ar-H), 8.97 (s, 1H, H-2 indole), 10.87 (s, 1H, NH isatin,
D2O exchangeable); 13C NMR (DMSO-d6)
d
ppm: 11.05
33.84 (N-CH3), 111.71, 111.79, 112.92, 113.69, 119.22, 121.75,
122.64, 124.16, 125.23, 130.43, 135.06, 138.75, 141.07, 143.56,
148.70, 163.38, 165.45 (C¼O); Anal. calcd. For C18H13BrN4O: C,
56.71; H, 3.44, N, 14.70; Found C, 57.02; H, 3.48; N, 14.96.
(–CH2–CH2–CH3), 23.22 (–CH2–CH2–CH3), 48.32 (–CH2–CH2–CH3),
111.82, 111.90, 112.98, 113.69, 119.22, 121.89, 122.61, 124.17,
125.32, 130.42, 135.12, 138.15, 140.32, 143.59, 148.77, 163.41,
165.44 (C¼O); Anal. calcd. For C20H17BrN4O: C, 58.69; H, 4.19; N,
13.69; Found C, 58.95; H, 4.26; N, 14.02.
5-Methoxy-3-(((1-methyl-1H-indol-3-yl)methylene)hydrazono)indo-
lin-2-one (6h). Yield 82%, m.p. 281–283 ꢀC; IR (KBr, ꢀ cmꢁ1): 3427
(NH), 1705 (C¼O); 1H NMR (DMSO-d6) d (ppm): 3.79 (s, 3H, OCH3),
3.92 (s, 3H, CH3), 6.79 (d, 1H, Ar-H, J ¼ 8.0 Hz), 6.93 (dd, 1H, Ar-H,
J ¼ 8.0, 2.4 Hz), 7.21 (t, 1H, Ar-H, J ¼ 8.0 Hz), 7.32 (t, 1H, Ar-H,
J ¼ 8.0 Hz), 7.55 (d, 1H, Ar-H, J ¼ 8.4 Hz), 8.06 (d, 1H, Ar-H,
J ¼ 2.4 Hz), 8.19 (s, 1H, -CH¼N-), 8.34 (d, 1H, Ar-H, J ¼ 8.4 Hz), 8.96
(s, 1H, H-2 indole), 10.49 (s, 1H, NH isatin, D2O exchangeable); 13C
NMR (DMSO-d6) d ppm: 33.74 (N-CH3), 55.92 (OCH3), 111.64 (2 C),
111.71, 112.68, 117.87, 119.77, 121.94, 122.43, 124.01, 125.29,
138.46, 138.65, 140.35, 149.99, 155.02, 162.30, 165.97 (C¼O); MS
m/z [%]: 332 [Mþ, 67.77], 289 [100]; Anal. calcd. For C19H16N4O2: C,
68.66; H, 4.85, N, 16.86; Found C, 68.91; H, 4.92; N, 17.09.
5-Methoxy-3-(((1-propyl-1H-indol-3-yl)methylene)hydrazono)indo-
lin-2-one (6l). Yield 80%, m.p. 122–124 ꢀC; IR (KBr, ꢀ cmꢁ1): 3361
(NH), 1696 (C¼O); 1H NMR (DMSO-d6) d (ppm): 0.86 (t, 3H,
–CH2–CH2–CH3, J ¼ 7.2 Hz), 1.81 (sextet, 2H, –CH2–CH2–CH3,
J ¼ 7.2 Hz), 3.78 (s, 3H, OCH3), 4.24 (t, 2H, –CH2–CH2–CH3,
J ¼ 7.2 Hz), 6.81 (d, 1H, Ar-H, J ¼ 8.0 Hz), 6.94 (d, 1H, Ar-H,
J ¼ 8.0 Hz), 7.22 (t, 1H, Ar-H, J ¼ 8.0 Hz), 7.35 (t, 1H, Ar-H, J ¼ 8.0 Hz),
7.55 (d, 1H, Ar-H, J ¼ 8.4 Hz), 8.09 (s, 1H, Ar-H), 8.22 (s, 1H, -CH¼N-
), 8.33 (d, 1H, Ar-H, J ¼ 8.4 Hz), 8.97 (s, 1H, H-2 indole), 10.81 (s, 1H,
NH isatin, D2O exchangeable); 13C NMR (DMSO-d6) d ppm: 11.51
(–CH2–CH2–CH3), 23.25 (–CH2–CH2–CH3), 48.27 (–CH2–CH2–CH3),
55.96 (OCH3), 111.76, 111.80 (2C), 112.74, 117.90, 119.83, 122.11,
122.32, 124.03, 125.43, 138.06, 138.51, 139.53, 150.07, 155.07,
162.32, 166.00; Anal. calcd. For C21H20N4O2: C, 69.98; H, 5.59; N,
15.55; Found C, 76.21; H, 5.66; N, 15.80.
3-(((1-Propyl-1H-indol-3-yl)methylene)hydrazono)indolin-2-one (6i).
Yield 75%, m.p. 118–120 ꢀC; IR (KBr, ꢀ cmꢁ1): 3415 (NH), 1698
(C¼O); 1H NMR (DMSO-d6) d (ppm): 0.85 (t, 3H, –CH2–CH2–CH3,
J ¼ 7.2 Hz), 1.81 (sextet, 2H, –CH2–CH2–CH3, J ¼ 7.2 Hz), 4.24 (t, 2H,
–CH2–CH2–CH3, J ¼ 7.2 Hz), 6.88 (d, 1H, Ar-H, J ¼ 8.0 Hz), 7.04 (t, 1H,
Ar-H, J ¼ 8.0 Hz), 7.33–7.38 (m, 3H, Ar-H), 7.66–7.68 (m, 1H, Ar-H),
8.26 (s, 1H, -CH¼N-), 8.28–8.30 (m, 1H, Ar-H), 8.36 (d, 1H, Ar-H,
J ¼ 7.6 Hz), 8.92 (s, 1H, H-2 indole), 10.73 (s, 1H, NH isatin, D2O
exchangeable); 13C NMR (DMSO-d6) d ppm: 11.53 (–CH2–CH2–CH3),
23.28 (–CH2–CH2–CH3), 48.26 (–CH2–CH2–CH3), 111.05, 111.70,
111.74, 117.64, 121.93, 122.49, 122.62, 123.92, 125.56, 128.15,
133.18, 138.01, 139.08, 144.70, 149.61, 161.80, 165.83 (C¼O); Anal.
calcd. For C20H18N4O: C, 72.71; H, 5.49, N, 16.96; Found C, 72.88; H,
5.56; N, 17.24.
5-Fluoro-3-(((1-propyl-1H-indol-3-yl)methylene)hydrazono)indolin-
2-one (6m). Yield 75%, m.p. 135–137 ꢀC; IR (KBr, ꢀ cmꢁ1): 3420
(NH), 1702 (C¼O); 1H NMR (DMSO-d6) d (ppm): 0.86 (t, 3H,
–CH2–CH2–CH3, J ¼ 7.6 Hz), 1.83 (sextet, 2H, –CH2–CH2–CH3,
J ¼ 7.2 Hz), 4.23 (t, 2H, –CH2–CH2–CH3, J ¼ 7.2 Hz), 6.98–7.02 (m, 1H,
Ar-H), 7.31–7.36 (m, 2H, Ar-H), 7.42 (dd, 1H, Ar-H, J ¼ 8.0, 2.4 Hz),
7.59 (d, 1H, Ar-H, J ¼ 8.0 Hz), 8.27–8.30 (m, 2H, -CH¼N- and Ar-H),
8.45 (d, 1H, Ar-H, J ¼ 2.4 Hz), 8.96 (s, 1H, H-2 indole), 10.83 (s, 1H,
NH isatin, D2O exchangeable); MS m/z [%]: 348 [Mþ, 25.60], 143
[100]; 13C NMR (DMSO-d6) d ppm: 11.49 (–CH2–CH2–CH3), 23.26
(–CH2–CH2–CH3), 48.25 (–CH2–CH2–CH3), 111.13, 111.41, 112.55,
113.96, 117.90, 119.08, 121.47, 122.35, 124.03, 125.52, 132.78,
136.62, 138.97, 143.07, 149.21, 161.83, 165.90; Anal. calcd. For
C20H17FN4O: C, 68.95; H, 4.92; N, 16.08; Found C, 69.18; H, 4.97; N,
16.24.
5-Chloro-3-(((1-propyl-1H-indol-3-yl)methylene)hydrazono)indolin-
2-one (6j). Yield 80%, m.p. 141–142 ꢀC; IR (KBr, ꢀ cmꢁ1): 3406 (NH),
1712 (C¼O); 1H NMR (DMSO-d6) d (ppm): 0.85, 1.02 (2t, 3H,
–CH2–CH2–CH3, J ¼ 7.6 Hz), 1.80, 3.40 (2sextet, 2H, –CH2–CH2–CH3,
J ¼ 7.2 Hz), 4.25, 4.31 (2t, 2H, –CH2–CH2–CH3, J ¼ 7.2 Hz), 6.83, 6.90
(2d, 1H, Ar-H, J ¼ 8.4 Hz), 7.14, 7.41 (2dd, 1H, Ar-H, J ¼ 8.4, 2.0 Hz),
7.29–7.38 (m, 3H, Ar-H), 7.60, 7.69 (2d, 1H, Ar-H, J ¼ 8.0 Hz), 8.29,
8.30 (2 s, 1H, -CH¼N-), 8.48 (d, 1H, Ar-H, J ¼ 2.4 Hz), 8.97, 8.99 (2 s,
7-Fluoro-3-(((1-propyl-1H-indol-3-yl)methylene)hydrazono)indolin-
2-one (6n). Yield 79%, m.p. 129–131 ꢀC; IR (KBr, ꢀ cmꢁ1): 3418
(NH), 1705 (C¼O); 1H NMR (DMSO-d6) d (ppm): 0.85 (t, 3H,
1H, H-2 indole), 10.78, 10.87 (2 s, 1H, NH isatin, D2O exchangeable); –CH2–CH2–CH3, J ¼ 7.6 Hz), 1.81 (sextet, 2H, –CH2–CH2–CH3,
13C NMR (DMSO-d6) d ppm: 11.45, 11.51 (–CH2–CH2–CH3), 23.15, J ¼ 7.2 Hz), 4.24 (t, 2H, –CH2–CH2–CH3, J ¼ 7.2 Hz), 7.09–7.12 (m, 1H,
23.24 (–CH2–CH2–CH3), 48.28, 48.33 (–CH2–CH2–CH3), 111.82, Ar-H), 7.29–7.376 (m, 3H, Ar-H), 7.67–7.69 (m, 1H, Ar-H), 8.23–8.30
111.84, 111.95, 112.49, 117.40, 117.52, 118.74, 121.51, 121.64, (m, 3H, –CH¼N– and 2 Ar-H), 8.95 (s, 1H, H-2 indole), 11.27 (s, 1H,
121.89, 122.58, 122.85, 123.91, 124.15, 124.53, 125.15, 125.40, NH isatin, D2O exchangeable); 13C NMR (DMSO-d6) d ppm: 11.52
125.51, 126.10, 126.80, 127.60, 132.38, 137.52, 137.62, 138.15, (–CH2–CH2–CH3), 23.29 (–CH2–CH2–CH3), 48.23 (–CH2–CH2–CH3),
140.11, 143.27, 148.84, 163.08, 163.22, 165.60, 184.89; MS m/z [%]: 111.13, 111.41, 112.98, 116.87, 119.16, 121.23, 123.85, 125.48,
366 [(M þ 2)þ, 24.47], 364 [Mþ, 69.06], 143 [100]; Anal. calcd. For 127.04, 131.23, 135.47, 138.56, 142.61, 147.08, 152.32, 162.72,