Luận án Tổng hợp và thử tác dụng sinh học của một số acid hydroxamic mang khung 2 - Oxoindolin

; 113,80; 110,40; 64,60; 55,69; 42,42. * (E)-3-(4-((7-Cloro-3-(methoxyimino)-2-oxoindolin-1-yl)methyl)phenyl)-N- hydroxypropenamid (IIg) IR (KBr, cm-1): 3307 (NH), 3204 (OH), 3018 (C-H, aren), 2938 (CH, CH2), 1722, 1662 (C=O), 1624 (C=N), 1601, 1514, 1470 (C=C). CTPT: C19H16ClN3O4, KLPT = 385; ESI-MS (m/z): 384 [M-H]-. 1H-NMR (500 MHz, DMSO-d6, ppm): δ 10,74 (1H, s, NH), 9,01 (1H, s, OH), 7,98 (1H, d, J = 7,75 Hz, H-4”), 7,51 (2H, d, J = 8,0 Hz, H-2’, H-6’), 7,44-7,41 (2H, m, H- 3, H-6”), 7,25 (2H, d, J = 8,0 Hz, H-3’, H-5’), 7,12 (1H, t, J = 7,75 Hz, H-5”), 6,42 (1H, d, J = 16,0 Hz, H-2), 5,28 (2H, s, H-7’a, H-7’b), 4,27 (3H, s, -NOCH3). 13C-NMR (125 MHz, DMSO-d6, ppm): δ 163,12; 162,69; 141,91; 139,06; 138,74; 137,85; 134,68; 133,70; 127,76; 126,50; 126,44; 124,49; 118,94; 117,98; 114,79; 64,95; 44,14. 3.1.3.3. Phân tích phổ (E)-N-hydroxy-3-(4-((2’-oxospiro[[1,3]dioxolan-2,3’-indolin]- 1’-yl)methyl)phenyl)propenamid và dẫn xuất (IIIa-g) * (E)-N-Hydroxy-3-(4-((2’-oxospiro[[1,3]dioxolan-2,3’-indolin]-1’-yl)methyl) phenyl)propenamid (IIIa) IR (KBr, cm-1): 3211 (NH), 3060 (C-H, aren), 2925, 2855 (C-H, CH2), 1728, 1666 (C=O), 1618, 1489, 1469 (C=C). CTPT: C20H18N2O5, KLPT = 366; ESI-MS (m/z): 389 [M+Na]+, 367,0 [M+H]+. 1H-NMR (500 MHz, DMSO-d6, ppm): δ 10,78 (1H, s, NH), 9,10 (1H, s, OH), 7,54 (2H, d, J = 8,0 Hz, H-3’, H-6’), 7,42 (1H, d, J = 15,5 Hz, H-3), 7,39 (1H, d, J = 7,5 Hz, H-4”), 7,35 (1H, t, J = 7,5 Hz, H-6”), 7,31 (2H, d, J = 8,0 Hz, H-3’, H-5’), 7,08 87 (1H, t, J = 7,5 Hz, H-5”), 6,95 (1H, d, J = 8,0 Hz, H-7”), 6,43 (1H, d, J = 16,0 Hz, H- 2), 4,85 (2H, s, H-7’a, H-7’b), 4,43 - 4,40 (2H, m, H-10”a, H-11”a), 4,32 – 4,30 (2H, m, H-10”b, H-11”b); 13C-NMR (125 MHz, DMSO-d6, ppm): 172,77; 162,75; 143,13; 137,87; 137,24; 134,25; 131,73; 127,96; 127,78; 124,83; 124,14; 123,32; 119,24; 109,95; 101,57; 65,73; 42,20. * (E)-N-Hydroxy-3-(4-((5’-fluoro-2’-oxospiro[[1,3]dioxolan-2,3’-indolin]-1’-y l) methyl)phenyl)propenamid (IIIb) IR (KBr, cm-1): 3544 (OH), 3189 (NH), 2920 (C-H, CH2), 1717, 1671 (C=O), 1631 (C=N), 1514, 1493 (C=C). CTPT: C20H17FN2O5, KLPT = 384; ESI-MS (m/z): 383 [M-H]-. 1H-NMR (500 MHz, DMSO-d6, ppm): 10,76 (1H, s, NH), 9,01 (1H, s, OH), 7,54 (2H, d, J = 8,0 Hz, H-2’, H-6’), 7,42 (1H, d, J = 16,0 Hz, H-3), 7,37 (1H, dd, JF-H4” = 7,5 Hz, J’ = 2,5 Hz, H-4”), 7,31 (2H, d, J = 8,0 Hz, H-3’, H-5’), 7,22 (1H, td, JF-H6” = 9,0 Hz, JH7”-H6” = 8,5 Hz, J’ = 2,5 Hz, H-6”), 6,98 (1H, dd, J = 8,5 Hz, J’F-H7” = 4,0 Hz, H-7”), 6,42 (1H, d, J = 15,5 Hz, H-3), 4,87 (2H, s, H-7’a, H-7’b), 4,41 -4,37 (2H, m, H-10”a, H-11”a), 4,36 – 4,31 (2H, m, H-10”b, H-11”b); 13C-NMR (125 MHz, DMSO-d6, ppm): 172,55; 162,60; 157,81; 139,12; 137,71; 136,94; 134,24; 127,89; 127,71; 126,08; 126,02; 119,24; 118,00; 117,81; 112,76; 112,56; 111,18; 111,12; 101,23; 65,90; 42,25. * (E)-N-Hydroxy-3-(4-((5’-cloro-2’-oxospiro[[1,3]dioxolan-2,3’-indolin]-1’-yl) methyl)phenyl)propenamid (IIIc) IR (KBr, cm-1): 3588 (OH), 3280 (NH), 3004 (C-H, aren), 2905 (C-H, CH2), 1744, 1706, 1661 (C=O), 1488 (C=C). CTPT: C20H17ClN2O5, KLPT = 400; ESI-MS (m/z): 399 [M-H]-. 1H-NMR (500 MHz, DMSO-d6, ppm): 10,78 (1H, s, NH), 9,05 (1H, s, OH), 7,55 (2H, d, J = 8,5 Hz, H-2’, H-6’), 7,54 (1H, s, H-4”), 7,44 (1H, d, J = 7,75 Hz, H-6”), 7,42 (1H, d, J = 15,5 Hz, H-3), 7,31 (2H, d, J = 8,0 Hz, H-3’, H-5’), 7,02 (1H, d, J = 7,75 Hz, H-7”), 6,43 (1H, d, J = 15,5 Hz, H-2), 4,88 (2H, s, H-7’a, H-7’b), 4,41 – 4,39 (2H, m, H-10”a, H-11”a), 4,37 – 4,35 (2H, m, H-10”b, H-11”b); 13C-NMR (125 MHz, DMSO-d6, ppm): 172,82; 163,10; 142,34; 138,21; 137,34; 134,76; 131,92; 129,14; 128,43; 128,20; 128,12; 127,99; 126,84; 125,43; 119,75; 112,12; 101,60; 66,49; 42,76. * (E)-N-Hydroxy-3-(4-((5’-bromo-2’-oxospiro[[1,3]dioxolan-2,3’-indolin]-1’-yl) methyl)phenyl)propenamid (IIId) 88 IR (KBr, cm-1): 3216 (NH), 3051 (C-H, aren), 2973, 2906, 2855 (C-H, CH2), 1732, 1661 (C=O), 1613, 1515, 1485 (C=C). CTPT: C20H17BrN2O5, KLPT = 445; ESI-MS (m/z): 443 [M-H]- (đồng vị 79Br) 1H-NMR (500 MHz, DMSO-d6, ppm): 10,79 (1H, s, NH), 9,05 (1H, s, OH), 7,64 (1H, s, H-4”), 7,56 (1H, d, J = 9,0 Hz, H-6”), 7,55 (2H, d, J = 8,5 Hz, H-2’, H-6’), 7,43 (1H, d, J = 15,75 Hz, H-3), 7,30 (2H, d, J = 8,5 Hz, H-3’, H-5’), 6,96 (1H, d, J = 9,0 Hz, H-7”), 6,43 (1H, d, J = 15,75 Hz, H-2), 4,88 (2H, s, H-7’a, H-7’b), 4,41 – 4,38 (2H, m, H-10”a, H-11”a), 4,37 – 4,33 (2H, m, H-10”b, H-11”b); 13C-NMR (125 MHz, DMSO-d6, ppm): 172,69; 163,10; 143,89; 142,78; 138,21; 137,31; 134,78; 129,14; 128,43; 128,19; 128,14; 127,14; 119,75; 115,60; 112,60; 101,55; 66,51; 42,74. * (E)-N-Hydroxy-3-(4-((5’-methyl-2’-oxospiro[[1,3]dioxo lan-2,3’-indolin]-1’-yl) methyl)phenyl)propenamid (IIIe) IR (KBr, cm-1): 3474 (NH), 3209 (OH), 3029 (C-H, aren), 2921 (C-H, CH2), 1708 1670 (C=O), 1630 (C=N), 1498 (C=C). CTPT: C21H20N2O5, KLPT = 380; ESI-MS (m/z): 379 [M-H]-. 1H-NMR (500 MHz, DMSO-d6, ppm): 10,80 (1H, s, NH), 9,05 (1H, s, OH), 7,53 (2H, d, J = 8,0 Hz, H-2’, H-6’), 7,41 (1H, d, J = 15,5 Hz, H-3), 7,29 (2H, d, J = 8,0 Hz, H- 3’, H-5’), 7,22 (1H, s, H-4”), 7,14 (1H, d, J = 8,0 Hz, H-7”), 6,82 (1H, d, J = 8,0 Hz, H-6”), 6,43 (1H, d, J = 15,5 Hz, H-2), 4,82 (2H, s, H-7’a, H-7’b), 4,41 – 4,37 (2H, m, H-10”a, H- 11”a), 4,32 – 4,28 (2H, m, H-10”b, H-11”b), 2,24 (3H, s, CH3); 13C-NMR (125 MHz, DMSO-d6, ppm): 172,77; 163,52; 140,70; 137,33; 134,22; 132,64; 131,79; 127,95; 127,75; 127,67; 125,43; 124,18; 119,21; 109,75; 101,76; 65,74; 42,22; 20,42. * (E)-N-Hydroxy-3-(4-((5’-methoxy-2’-oxospiro[[1,3]dioxolan-2,3’-indolin]-1’- yl) methyl)phenyl)propenamid (IIIf) IR (KBr, cm-1): 2960, 2839 (C-H, CH2), 1723 (C-O), 1633 (C=N), 1608, 1497 (C=C). CTPT: C21H20N2O6, KLPT = 396; ESI-MS (m/z): 397 [M+H]+. 1H-NMR (500 MHz, DMSO-d6, ppm): 10,78 (1H, s, NH), 9,04 (1H, s, OH), 7,54 (2H, d, J = 8,0 Hz, H-2’, H-6’), 7,42 (1H, d, J = 16,0 Hz, H-3), 7,31 (2H, d, J = 8,0 Hz, H-3’, H- 5’), 7,03 (1H, s, H-4”), 6,96 – 6,90 (2H, m, H-6”, H-7”), 6,43 (1H, d, J =16,0 Hz, H-2), 4,83 (2H, s, H-7’a, H-7’b), 4,41 – 4,32 (4H, m, H-10”a, H-10”b, H-11”a, H-11”b), 3,71 (3H, s, OCH3). 13C-NMR (125 MHz, DMSO-d6, ppm): 172,56; 162,65; 155,97; 137,77; 137,27; 89 136,12; 134,15; 127,86; 127,70; 125,31; 119,17; 116,41; 111,29; 110,65; 101,72; 65,71; 55,67; 42,16. * (E)-N-Hydroxy-3-(4-((7’-cloro-2’-oxospiro[[1,3]dioxolan-2,3’-indolin]-1’-yl) methyl)phenyl)propenamid (IIIg) IR (KBr, cm-1): 2971, 2903 (C-H, CH2), 1735, 1685 (C=O), 1617, 1514, 1455 (C=C). CTPT: C20H17ClN2O5, KLPT = 400; ESI-MS (m/z): 399 [M-H]-. 1H-NMR (500 MHz, DMSO-d6, ppm): 7,54 (2H, d, J = 8,0 Hz, H-2’, H-6’), 7,45 (1H, d, J = 7,5 Hz, H-6”), 7,42 (1H, d, J = 15,75 Hz, H-3), 7,40 (1H, d, J = 7,5 Hz, H- 4”), 7,19 (2H, d, J = 8,0 Hz, H-3’, H-5’), 7,15 (1H, t, J = 7,5 Hz, H-5”), 6,43 (1H, d, J = 15,75 Hz, H-3), 5,21 (2H, s, H-7’a, H-7’b), 4,44 – 4,41 (2H, m, H-10”a, H-11”a), 4,39 – 4,35 (2H, m, H-10”b, H-11”b); 13C-NMR (125 MHz, DMSO-d6, ppm): 173,45; 162,56; 138,88; 138,36; 133,84; 127,85; 127,43; 126,33; 124,95; 124,02; 119,05; 114,89; 100,46; 65,94; 43,77. 3.1.3.6. Phân tích phổ N-Hydroxy-3-(4-((3-(hydroxyimino)-2-oxoindolin-1- yl)methyl)-1H-1,2,3-triazol-1-yl)propanamid, các dẫn xuất và các dãy chất tương tự (IVa-c, Va-g, VIa-g, VIIa-g, VIIIa-g) * N-Hydroxy-3-(4-((3-(hydroxyimino)-2-oxoindolin-1-yl)methyl)-1H-1,2,3-triazol- 1-yl)propanamid (IVa) IR (KBr, cm-1): 3423 (NH), 3287, 3192 (OH), 3064 (C-H, aren), 2895 (CH, CH2), 1723, 1672 (C=O), 1609, 1549, 1462 (C=C). CTPT: C14H14N6O4, KLPT = 330; ESI-MS (m/z): 353 [M+Na]+. 1H-NMR (500 MHz, DMSO-d6, ppm): δ 10,47 (1H, s, NH); 8,82 (1H, s, OH); 8,02 (1H, s, H-5’); 7,99 (1H, d, J = 8,0 Hz, H-4”); 7,39 (1H, t, J = 8,0 Hz, H-6”); 7,11 (1H, t, J = 8,5 Hz, H-5”); 7,07 (1H, d, J = 8,5 Hz, H-7”); 4,96 (2H, s, H-6’a, H-6’b); 4,51 (2H, t, J = 7,0 Hz, H-3a, H-3b); 2,57 (2H, t, J = 7,0 Hz, H-2a, H-2b). 13C NMR (125 MHz, DMSO-d6, ppm): δ 165,82; 162,75; 143,39; 142,54; 141,69; 131,88; 126,77; 123,51; 122,69; 115,27; 109,73; 109,62; 45,58; 34,57; 32,49. * 3-(4-((5-Fluoro-3-(hydroxyimino)-2-oxoindolin-1-yl)methyl)-1H-1,2,3-triazol - 1-yl)-N-hydroxypropanamid (IVb) 90 IR (KBr, cm-1): 3294 (OH), 3070 (C-H, aren), 2921, 2858 (CH, CH2), 1719 (C=O), 1617, 1480 (C=C). CTPT: C14H13FN6O4, KLPT = 348; ESI-MS (m/z): 347 [M-H]- . 1H-NMR (500 MHz, DMSO-d6, ppm): δ 10,38 (1H, s, NH); 8,05 (1H, s, H-5’); 7,74 (1H, dd, JF-H4” = 8,0 Hz, J’ = 2,0 Hz, H-4”); 7,28 (1H, td, JF-H6” = 9,0 Hz, JH7”-H6” = 8,5 Hz, J’ = 2,0 Hz, H-6”); 7,13 (1H, dd, J = 8,5 Hz, J’F-H7” = 4,0 Hz, H-7”); 4,97 (2H, s, H-6’a, H-6’b); 4,50 (2H, t, J = 6,75 Hz, H-3a, H-3b); 2,57 (2H, t, J = 6,75 Hz, H-2a, H-2b). 13C NMR (125 MHz, DMSO-d6, ppm): δ 165,85; 162,64; 158,95; 157,06; 143,07; 141,62; 141,55; 138,90; 123,62; 118,25; 118,05; 115,81; 115,74; 113,91; 113,70; 110,82; 110,75; 45,65; 34,72; 32,55. * 3-(4-((5-Cloro-3-(hydroxyimino)-2-oxo indolin-1-yl)methyl)-1H-1,2,3-triazol- 1-yl)-N-hydroxypropanamid (IVc) IR (KBr, cm-1): 3421 (NH), 3256, 3151 (OH), 3035 (C-H, aren), 2852 (CH, CH2), 1714, 1647 (C=O), 1609, 1464 (C=C). CTPT: C14H13ClN6O4, KLPT = 364; ESI-MS (m/z): 365 [M + H]+. 1H-NMR (500 MHz, DMSO-d6, ppm): δ 14,70 (1H, s, NOH); 10,48 (1H, s, NH); 8,83 (1H, s, OH); 8,03 (1H, s, H-5’); 7,96 (1H, d, J = 1,75 Hz, H-4”); 7,48 (1H, dd, J = 8,5 Hz, J’ = 1,75 Hz, H-6”); 7,14 (1H, d, J = 8,5 Hz, H-7”); 4,98 (2H, s, H-6’a, H- 6’b); 4,52 (2H, t, J = 6,75 Hz, H-3a, H-3b); 2,57 (2H, t, J = 6,75 Hz, H-2a, H-2b). 13C NMR (125 MHz, DMSO-d6, ppm): δ 165,83; 162,40; 142,66; 141,43; 141,31; 131,37; 126,55; 126,08; 123,59; 116,40; 111,27; 45,62; 34,72; 32,51. * N-Hydroxy-4-(4-((3-(hydroxyimino)-2-oxoindolin-1-yl)methyl)-1H-1,2,3- triazol-1-yl)butanamid (Va) IR (KBr, cm-1): 3136 (OH), 3023 (C-H, aren), 2918, 2859 (CH, CH2), 1722, 1640 (C=O), 1609, 1463 (C=C). CTPT: C15H16N6O4, KLPT = 344; ESI-MS (m/z): 343 [M - H]-. 1H-NMR (500 MHz, DMSO-d6, ppm): δ 13,58 (1H, s, NOH); 10,40 (1H, s, NH); 8,12 (1H, s, H-5’); 7,97 (1H, d, J = 7,5 Hz, H-4”); 7,39 (1H, td, J = 7,5 Hz, J’ = 1,0 91 Hz, H-6”); 7,11 (1H, d, J = 7,5 Hz, H-7”); 7,07 (1H, t, J = 7,5 Hz, H-5”); 4,97 (2H, s, H-6’a, H-6’b); 4,30 (2H, t, J = 6,5 Hz, H-4a, H-4b); 1,99-1,95 (4H, m, H-3a, H-3b, H- 2a, H-2b). 13C NMR (125 MHz, DMSO-d6, ppm): δ 168,16; 162,83; 143,36; 142,60; 141,87; 131,94; 126,83; 123,39; 122,77; 115,32; 109,68; 48,93; 34,67; 29,01; 25,85. * 4-(4-((5-Fluoro-3-(hydroxyimino)-2-oxoindolin-1-yl)methyl)-1H-1,2,3-triazol - 1-yl)-N-hydroxybutanamid (Vb) IR (KBr, cm-1): 3411 (NH), 3208, 3137 (OH), 3029 (C-H, aren), 2872 (CH, CH2), 1722, 1640 (C=O), 1477 (C=C). CTPT: C15H15FN6O4, KLPT = 362; ESI-MS (m/z): 361 [M - H]-. 1H-NMR (500 MHz, DMSO-d6, ppm): δ 10,40 (1H, s, NH); 8,72 (1H, s, OH); 8,11 (1H, s, H-5’); 7,75 (1H, dd, JF-H4” = 7,5 Hz, J’ = 2,5 Hz, H-4”); 7,28 (1H, td, JF-H6” = 9,0 Hz, JH7”-H6” = 8,5 Hz, J’ = 2,5 Hz, H-6”); 7,13 (1H, dd, J = 8,5 Hz, J’F-H7” = 4,0 Hz, H- 7”); 4,98 (2H, s, H-6’a, H-6’b); 4,30 (2H, t, J = 6,5 Hz, H-4a, H-4b); 1,99-1,92 (4H, m, H- 3a, H-3b, H-2a, H-2b). 13C NMR (125 MHz, DMSO-d6, ppm): δ 168,05; 162,64; 158,95; 157,06; 143,13; 141,73; 138,92; 123,34; 118,20; 118,02; 115,83; 115,76; 113,90; 113,70; 110,75; 48,91; 39,00; 34,79; 28,96; 25,77. * 4-(4-((5-Cloro-3-(hydroxyimino)-2-oxo indolin-1-yl)methyl)-1H-1,2,3-triazol- 1-yl)-N-hydroxybutanamid (Vc) IR (KBr, cm-1): 3417 (NH), 3219, 3138 (OH), 3044 (C-H, aren), 2874 (CH, CH2), 1721, 1643 (C=O), 1611, 1463 (C=C). CTPT: C15H15ClN6O4, KLPT = 378; ESI-MS (m/z): 401 [M + Na]+. 1H-NMR (500 MHz, DMSO-d6, ppm): δ 13,82 (1H, s, NOH); 10,38 (1H, s, NH); 8,71 (1H, s, OH); 8,10 (1H, s, H-5’); 7,96 (1H, d, J = 1,75 Hz, H-4”); 7,47 (1H, dd, J = 8,0 Hz, J’ = 1,75 Hz, H-6”); 7,14 (1H, d, J = 8,0 Hz, H-7”); 4,98 (2H, s, H-6’a, H- 6’b); 4,30 (2H, t, J = 6,5 Hz, H-4a, H-4b); 2,00-1,92 (4H, m, H-3a, H-3b, H-2a, H-2b). 13C NMR (125 MHz, DMSO-d6, ppm): δ 168,05; 162,41; 142,71; 141,63; 141,38; 131,40; 126,56; 126,12; 123,33; 116,43; 111,28; 48,92; 34,82; 28,96; 25,76. * 4-(4-((5-Bromo-3-(hydroxyimino)-2-oxoindolin-1-yl)methyl)-1H-1,2,3-triazol-1- yl)-N-hydroxybutanamid (Vd) IR (KBr, cm-1): 3407 (NH), 3139 (OH), 3024 (C-H, aren), 2968, 2853 (CH, CH2), 1732, 1704 (C=O), 1606, 1464 (C=C). CTPT: C15H15BrN6O4, KLPT = 423; ESI-MS (m/z): 421 [M - H]- (đồng vị 79Br) 92 1H-NMR (500 MHz, DMSO-d6, ppm): δ 10,42 (1H, s, NH); 8,72 (1H, s, OH); 8,10 (1H, s, H-5’); 8,08 (1H, d, J = 1,5 Hz, H-4”); 7,60 (1H, dd, J = 8,5 Hz, J’ = 1,5 Hz, H-6”); 7,10 (1H, d, J = 8,0 Hz, H-7”); 4,98 (2H, s, H-6’a, H-6’b); 4,30 (2H, t, J = 6,5 Hz, H-4a, H-4b); 2,00-1,94 (4H, m, H-3a, H-3b, H-2a, H-2b). 13C NMR (125 MHz, DMSO-d6, ppm): δ 168,07; 162,34; 142,52; 141,72; 141,60; 134,17; 128,76; 123,35; 116,88; 114,20; 111,78; 48,92; 34,79; 28,97; 25,78. * N-Hydroxy-4-(4-((3-(hydroxyimino)-5-methyl-2-oxoindolin-1-yl)methyl)-1H - 1,2,3-triazol-1-yl)butanamid (Ve) IR (KBr, cm-1): 3280, 3184 (OH), 3068 (C-H, aren), 2908 (CH, CH2), 1714, 1673 (C=O), 1624 (C=N), 1552, 1476 (C=C). CTPT: C16H18N6O4, KLPT = 358; ESI-MS (m/z): 381 [M+Na]+ 1H-NMR (500 MHz, DMSO-d6, ppm): δ 13,44 (1H, s, NOH); 10,38 (1H, s, NH); 8,71 (1H, s, OH); 8,08 (1H, s, H-5’); 7,83 (1H, s, H-4”); 7,20 (1H, d, J = 8,0 Hz, H- 6”); 6,99 (1H, d, J = 8,0 Hz, H-7”); 4,95 (2H, s, H-6’a, H-6’b); 4,30 (2H, t, J = 6,5 Hz, H-4a, H-4b); 2,27 (3H, s, -CH3); 1,98-1,93 (4H, m, H-3a, H-3b, H-2a, H-2b). 13C NMR (125 MHz, DMSO-d6, ppm): δ 168,07; 162,77; 143,59; 141,93; 140,39; 132,14; 131,77; 127,38; 123,26; 115,35; 109,42; 48,89; 34,67; 28,97; 25,78; 20,51. * N-Hydroxy-4-(4-((3-(hydroxyimino)-5-methoxy-2-oxoindolin-1-yl)methyl)-1H- 1,2,3-triazol-1-yl)butanamid (Vf) IR (KBr, cm-1): 3282, 3188 (OH), 3071 (C-H, aren), 2916 (CH, CH2), 1712, 1673 (C=O), 1630 (C=N), 1596, 1552, 1480 (C=C). CTPT: C1cH18N6O5, KLPT = 374; ESI-MS (m/z): 373 [M-H]-. 1H-NMR (500 MHz, DMSO-d6, ppm): δ 13,55 (1H, s, NOH); 10,40 (1H, s, NH); 8,09 (1H, s, H-5’); 7,58 (1H, d, J = 2,5 Hz, H-4”); 7,04 - 6,98 (2H, m, , H-6”,H-7”); 4,94 (2H, s, H-6’a, H-6’b); 4,30 (2H, t, J = 7,0 Hz, H-4a, H-4b); 3,72 (3H, s, -OCH3); 2,00-1,92 (4H, m, H-3a, H-3b, H-2a, H-2b). 13C NMR (125 MHz, DMSO-d6, ppm): δ 168,05; 162,62; 155,21; 143,68; 141,94; 136,24; 123,28; 116,86; 115,85; 113,09; 110,26; 55,65; 48,90; 34,70; 28,97; 25,78. * 4-(4-((7-Cloro-3-(hydroxyimino)-2-oxo indolin-1-yl)methyl)-1H-1,2,3-triazol- 1-yl)-N-hydroxybutanamid (Vg) IR (KBr, cm-1): 3518, 3378 (NH), 3249 (OH), 3030 (C-H, aren), 2898 (CH, CH2), 1717, 1665 (C=O), 1635 (C=N), 1603,1442 (C=C). CTPT: C15H15ClN6O4, KLPT = 378; ESI-MS (m/z): 377 [M-H]-. 1H-NMR (500 MHz, DMSO-d6, ppm): δ 10,41 (1H, s, NH); 8,71 (1H, s, OH); 8,07 (1H, d, J = 1,0 Hz, H-4”); 8,06 (1H, s, H-5’); 7,39 (1H, dd, J = 7,75 Hz, J’ = 1,0 93 Hz, H-6”); 7,11 (1H, t, J = 7,75 Hz, H-5”); 5,31 (2H, s, H-6’a, H-6’b); 4,29 (2H, t, J = 6,5 Hz, H-4a, H-4b); 2,00-1,92 (4H, m, H-3a, H-3b, H-2a, H-2b). 13C NMR (125 MHz, DMSO-d6, ppm): δ 168,07; 163,64; 143,38; 142,19; 138,46; 133,78; 125,84; 124,23; 122,49; 118,30; 114,80; 48,88; 37,06; 28,96; 25,84. * N-Hydroxy-5-(4-((3-(hydroxyimino)-2-oxoindolin-1-yl)methyl)-1H-1,2,3-triazol-1- yl)pentanamid (VIa) IR (KBr, cm-1): 3400 (NH), 3312, 3197 (OH), 3060 (C-H, aren), 2877 (CH, CH2), 1714, 1679 (C=O), 1609, 1550, 1456 (C=C). CTPT: C16H18N6O4, KLPT = 358; ESI-MS (m/z): 357 [M - H]-. 1H-NMR (500 MHz, DMSO-d6, ppm): δ 13,45 (1H, s, NOH); 10,35 (1H, s, NH); 8,67 (1H, s, OH); 8,09 (1H, s, H-5’); 7,98 (1H, d, J = 7,5 Hz, H-4”); 7,40 (1H, t, J = 7,5 Hz, H-6”); 7,12-7,06 (2H, m, H-5”, H-7”); 4,98 (2H, s, H-6’a, H-6’b); 4,29 (2H, t, J = 7,0 Hz, H-5a, H-5b); 1,95 (2H, t, J = 7,5 Hz, H-2a, H-2b); 1,79-1,71 (2H, m, H-4a, H-4b); 1,45-1,39 (2H, m, H-3a, H-3b). 13C NMR (125 MHz, DMSO-d6, ppm): δ 168,68; 162,74; 143,44; 142,61; 141,80; 131,95; 126,85; 123,26; 122,73; 115,28; 109,64; 49,05; 34,67; 29,22; 22,04. * 5-(4-((5-Fluoro-3-(hydroxyimino)-2-oxoindolin-1-yl)methyl)-1H-1,2,3-triazol-1- yl)-N-hydroxypentanamid (VIb) IR (KBr, cm-1): 3396 (NH), 3321, 3172 (OH), 3059 (C-H, aren), 2877 (CH, CH2), 1715, 1681 (C=O), 1630 (C=N), 1477 (C=C). CTPT: C16H17FN6O4, KLPT = 376; ESI-MS (m/z): 375 [M-H]-. 1H-NMR (500 MHz, DMSO-d6, ppm): δ 13,76 (1H, s, NOH); 10,34 (1H, s, NH); 8,67 (1H, s, OH); 8,08 (1H, s, H-5’); 7,75 (1H, dd, JF-H4” = 8,0 Hz, J’ = 2,5 Hz, H-4”); 7,28 (1H, td, JF-H6” = 9,5 Hz, JH7”-H6” = 8,5 Hz, J’ = 2,5 Hz, H-6”); 7,12 (1H, dd, J = 8,5 Hz, J’ = 4,0 Hz, H-7”); 4,98 (2H, s, H-6’a, H-6’b); 4,29 (2H, t, J = 7,0 Hz, H-5a, H-5b); 1,95 (2H, t, J = 7,5 Hz, H-2a, H-2b); 1,76-1,73 (2H, m, H-4a, H-4b); 1,45-1,40 (2H, m, H-3a, H-3b). 13C NMR (125 MHz, DMSO-d6, ppm): δ 168,68; 162,61; 158,94; 157,05; 143,16; 141,64; 138,93; 123,29; 118,25; 118,06; 115,81; 115,73; 113,94; 113,73; 110,75; 110,69; 49,06; 34,79; 31,51; 29,19; 22,03. 94 * 5-(4-((5-Cloro-3-(hydroxyimino)-2-oxoindolin-1-yl)methyl)-1H-1,2,3-triazol-1- yl)-N-hydroxypentanamid (VIc) IR (KBr, cm-1): 3286, 3144 (OH), 3024 (C-H, aren), 2851 (CH, CH2), 1708, 1647 (C=O), 1609, 1462 (C=C). CTPT: C16H17ClN6O4, KLPT = 392; ESI-MS (m/z): 391 [M-H]-. 1H-NMR (500 MHz, DMSO-d6, ppm): δ 10,36 (1H, s, NH); 8,68 (1H, s, OH); 8,08 (1H, s, H-5’); 7,95 (1H, s, H-4”); 7,48 (1H, d, J = 8,0 Hz, H-6”); 7,14 (1H, d, J = 8,0 Hz, H-7”); 4,98 (2H, s, H-6’a, H-6’b); 4,29 (2H, t, J = 7,0 Hz, H-5a, H-5b); 1,95 (2H, t, J = 7,5 Hz, H-2a, H-2b); 1,77-1,72 (2H, m, H-4a, H-4b); 1,45-1,40 (2H, m, H- 3a, H-3b). 13C NMR (125 MHz, DMSO-d6, ppm): δ 168,73; 162,44; 142,71; 141,57; 141,38; 131,42; 126,59; 126,14; 123,31; 116,44; 111,29; 49,09; 34,84; 31,53; 29,22; 22,06. * 5-(4-((5-Bromo-3-(hydroxyimino)-2-oxoindolin-1-y l)methyl)-1H-1,2,3-triazol- 1-yl)-N-hydroxypentanamid (VId) IR (KBr, cm-1): 3421 (NH), 3290, 3147 (OH), 3032 (C-H, aren), 2862 (CH, CH2), 1709, 1647 (C=O), 1606, 1463 (C=C). CTPT: C16H17BrN6O4, KLPT = 437; ESI-MS (m/z): 437 [M-H]- (đồng vị 81Br) 1H-NMR (500 MHz, DMSO-d6, ppm): δ 10,34 (1H, s, NH); 8,67 (1H, s, OH); 8,08 (2H, s, H-5’, H-4”); 7,60 (1H, d, J = 7,75 Hz, H-6”); 7,09 (1H, d, J = 7,75 Hz, H- 7”); 4,98 (2H, s, H-6’a, H-6’b); 4,29 (2H, t, J = 6,0 Hz, H-5a, H-5b); 1,95 (2H, t, J = 6,5 Hz, H-2a, H-2b); 1,75-1,73 (2H, m, H-4a, H-4b); 1,43-1,41 (2H, m, H-3a, H-3b). 13C NMR (125 MHz, DMSO-d6, ppm): δ 168,68; 162,31; 142,57; 141,73; 141,54; 134,20; 128,79; 123,27; 116,86; 114,21; 111,76; 49,07; 34,80; 31,51; 29,20; 22,04. * N-Hydroxy-5-(4-((3-(hydroxyimino)-5-methyl-2-oxoindolin-1-yl)methyl)-1H- 1,2,3-triazol-1-yl)pentanamid (VIe) IR (KBr, cm-1): 3317 (NH), 3189 (OH), 3062 (C-H, aren), 2879 (CH, CH2), 1713, 1680 (C=O), 1622, 1461(C=C). CTPT: C17H20N6O4, KLPT = 372; ESI-MS (m/z): 371 [M-H]-. 1H-NMR (500 MHz, DMSO-d6, ppm): δ 13,43 (1H, s, NOH); 10,34 (1H, s, NH); 8,66 (1H, s, OH); 8,06 (1H, s, H-5’); 7,83 (1H, s, H-4”); 7,20 (1H, d, J = 6,0 Hz, H-6”); 6,99 (1H, d, J = 6,0 Hz, H-7”); 4,94 (2H, s, H-6’a, H-6’b); 4,29 (2H, t, H-5a, H-5b); 2,27 (3H, s, -CH3); 1,95 (2H, t, H-2a, H-2b); 1,74 (2H, m, H-4a, H-4b); 1,42 (2H, m, H-3a, H-3b). 13C NMR (125 MHz, DMSO-d6, ppm): δ 168,25; 163,25; 144,08; 142,45; 140,86; 132,61; 132,25; 127,86; 123,74; 115,83; 109,89; 49,54; 35,17; 32,00; 29,69; 22,52; 20,97. 95 * N-Hydroxy-5-(4-((3-(hydroxyimino)-5-methoxy-2-oxoindolin-1-yl)methyl)-1H- 1,2,3-triazol-1-yl)pentanamid (VIf) IR (KBr, cm-1): 3421 (NH), 3135 (OH), 3048 (C-H, aren), 2930, 2838 (CH, CH2), 1718, 1628 (C=O), 1598, 1480 (C=C). CTPT: C17H20N6O5, KLPT = 388; ESI-MS (m/z): 387 [M-H]-. 1H-NMR (500 MHz, DMSO-d6, ppm): δ 10,35 (1H, s, NH); 8,67 (1H, s, OH); 8,05 (1H, s, H-5’); 7,57 (1H, d, J = 2,5 Hz, H-4”); 7,03-6,98 (2H, m, H-6”, H-7”); 4,94 (2H, s, H-6’a, H-6’b); 4,29 (2H, t, J = 7,0 Hz, H-5a, H-5b); 3,72 (3H, s, -OCH3); 1,95 (2H, t, J = 7,0 Hz, H-2a, H-2b); 1,75-1,72 (2H, m, H-4a, H-4b); 1,45-1,40 (2H, m, H- 3a, H-3b). 13C NMR (125 MHz, DMSO-d6, ppm): δ 168,74; 162,66; 155,25; 143,71; 141,87; 136,25; 123,24; 116,90; 115,87; 113,14; 110,28; 55,68; 49,07; 34,73; 31,54; 29,22; 22,06. * 5-(4-((7-Cloro-3-(hydroxyimino)-2-oxoindolin-1-yl)methyl)-1H-1,2,3-triazol-1- yl)-N-hydroxypentanamid (VIg) IR (KBr, cm-1): 3423 (NH), 3165 (OH), 3057 (C-H, aren), 2959, 2866 (CH, CH2), 1725, 1618 (C=O), 1608, 1469 (C=C). CTPT: C16H17ClN6O4, KLPT = 392; ESI-MS (m/z): 391 [M-H]-. 1H-NMR (500 MHz, DMSO-d6, ppm): δ 13,83 (1H, s, NOH); 10,34 (1H, s, NH); 8,66 (1H, s, OH); 8,07 (1H, d, J = 7,5 Hz, H-4”); 8,03 (1H, s, H-5’); 7,39 (1H, d, J = 7,5 Hz, H-6”); 7,11 (1H, t, J = 7,5 Hz, H-5”); 5,31 (2H, s, H-6’a, H-6’b); 4,29 (2H, t, J = 7,0 Hz, H-5a, H-5b); 1,95 (2H, t, J = 7,0 Hz, H-2a, H-2b); 1,77-1,71 (2H, m, H-4a, H-4b); 145-1,39 (2H, m, H-3a, H-3b). 13C NMR (125 MHz, DMSO-d6, ppm): δ 168,67; 163,63; 143,26; 142,20; 138,45; 133,77; 125,84; 124,22; 122,44; 118,29; 114,80; 49,01; 37,06; 31,50; 29,24; 22,01. * N-Hydroxy-6-[4-[[3-(hydroxyimino)-2-oxoindolin-1-yl]methyl]-1H-1,2,3- triazol-1-yl]hexanamide (VIIa) IR (KBr, cm-1): 3456 (NH); 3180, 3119 (OH); 3031 (CH, aren); 2886 (CH, CH2); 1719 (C=O); 1609, 1544, 1462 (C=C). CTPT: C17H20N6O4, KLPT = 372; ESI-MS (m/z): 395 [M + Na]+. 96 1H-NMR (500 MHz, DMSO-d6, ppm): δ 13,47 (1H, s, NOH); 10,31 (1H, s, NH); 8,65 (1H, s, OH); 8,08 (1H, s, H-5’); 7,99 (1H, d, J = 7,5 Hz, H-4”); 7,40 (1H, t, J = 8,0 Hz, H-6”); 7,10 (1H, d, J = 8,0 Hz, H-7”); 7,07 (1H, t, J = 7,5 Hz, H-5”); 4,97 (2H, s, H-6’a, H-6’b); 4,27 (2H, t, J = 7,0 Hz, H-6a, H-6b); 1,90 (2H, t, J = 7,25 Hz, H-2a, H-2b); 1,77 - 1,74 (2H, m, H-5a, H-5b); 1,51 - 1,45 (2H, m, H-3a, H-3b); 1,20 - 1,15 (2H, m, H-4a, H-4b). 13C NMR (125 MHz, DMSO-d6, ppm): δ 168,92; 162,75; 143,44; 142,60; 141,79; 131,93; 126,84; 123,19; 122,72; 115,29; 109,64; 49,24; 34,67; 31,99; 29,31; 25,39; 24,43. Cấu trúc của chất VIIa được khẳng định thêm bằng phổ cộng hưởng từ hạt nhân 2 chiều 2D NMR HMBC và HSQC. Bảng 3.3: Dữ liệu phổ 2D HMBC và HSQC của dẫn chất VIIa. Vị trí Nhóm δ13C (ppm) δ1H (ppm) J (Hz) HMBC C → H 1 >C= 168,92 NH, 2, 3 2 -CH2- 31,99 1,90 (t) 7,25 3, 4 3 -CH2- 24,43 1,51 - 1,45 (m) 2, 4 4 -CH2- 25,39 1,20 – 1,15 (m) 2, 3, 5, 6 5 -CH2- 29,31 1,77 – 1,74 (m) 3, 4, 6 6 -CH2- 49,24 4,27 (t) 7,0 4, 5 4’ >C= 141,79 5’, 6’ 5’ >C= 123,19 8,08 (s) 6’, 6 6’ -CH2- 34,67 4,97 (s) 2” >C= 162,75 3” >C= 143,44 H (NOH) 4” -CH= 109,64 7,10 (d) 8,0 5” 5” -CH= 122,72 7,07 (t) 7,75 4” 6” -CH= 131,93 7,40 (t) 7,75 7” 7” -CH= 126,04 7,99 (d) 7,5 6” 8” >C= 142,60 6”, 7” 9” >C= 115,29 4”, 5” * 6-[4-[[5-Fluoro-3-(hydroxyimino)-2-oxoindolin-1-yl]methyl]-1H-1,2,3-triazol- 1-yl]-N-hydroxyhexanamid (VIIb) IR (KBr, cm-1): 3425 (NH); 3199 (OH); 3007 (C-H, aren); 2942, 2860 (CH, CH2); 1711, 1654, 1480 (C=O). 97 CTPT: C17H19FN6O4, KLPT = 390; ESI-MS (m/z): 391 [M+H]+. 1H-NMR (500 MHz, DMSO-d6, ppm): δ 13,75 (1H, s, NOH); 10,30 (1H, s, NH); 8,64 (1H, s, OH); 8,09 (1H, s, H-5’); 7,75 (1H, dd, JF-H4” = 8,0 Hz, J’ = 2,5 Hz, H-4”); 7,29 (1H, td, JF-H6” = 9,5 Hz, JH7”-H6” = 8,5 Hz, J’ = 2,5 Hz, H-6”); 7,12 (1H, dd, J = 8,5 Hz, J’F-H7” = 4,0 Hz, H-7”); 4,98 (2H, s, H-6’a, H-6’b); 4,28 (2H, t, J = 7,0 Hz, H- 6a, H-6b); 1,91 (2H, t, J = 7,25 Hz, H-2a, H-2b); 1,77 - 1,74 (2H, m, H-5a, H-5b); 1,49 - 1,46 (2H, m, H-3a, H-3b); 1,20 - 1,15 (2H, m, H-4a, H-4b). 13C NMR (125 MHz, DMSO-d6, ppm): δ 168,86; 162,57; 158,92; 157,03; 143,12; 141,62; 138,91; 123,18; 118,21; 118,03; 115,79; 115,72; 113,91; 113,70; 110,73; 110,67; 49,22; 34,79; 31,97; 29,28; 25,36; 24,40. * 6-[4-[[5-Cloro-3-(hydroxyimino)-2-oxo indolin-1-yl]methyl]-1H-1,2,3-triazol- 1-yl]-N-hydroxyhexanamid (VIIc) IR (KBr, cm-1): 3281, 3200 (OH); 3023 (C-H, aren); 2941, 2858 (C-H, CH2); 1712, 1654 (C=O); 1610, 1519, 1462 (C=C). CTPT: C17H19ClN6O4, KLPT = 406; ESI-MS (m/z): 407 [M+H]+. 1H-NMR (500 MHz, DMSO-d6, ppm): δ 10,32 (1H, s, NH); 8,66 (1H, s, OH); 8,09 (1H, s, H-5’); 7,96 (1H, d, J = 1,5 Hz, H-4”); 7,48 (1H, dd, J = 8,5 Hz, J’ = 1,5 Hz, H-6”); 7,14 (1H, d, J = 8,5 Hz, H-7”); 4,98 (2H, s, H-6’a, H-6’b); 4,28 (2H, t, J = 7,0 Hz, H-6a, H-6b); 1,91 (2H, t, J = 7,25 Hz, H-2a, H-2b); 1,77 - 1,74 (2H, m, H-5a, H-5b); 1,50 - 1,45 (2H, m, H-3a, H-3b); 1,22 -1,17 (2H, m, H-4a, H-4b). 13C NMR (125 MHz, DMSO-d6, ppm): δ 168,90; 162,40; 142,68; 141,54; 141,33; 131,35; 126,54; 126,08; 123,19; 116,42; 111,24; 49,24; 34,82; 31,98; 29,29; 25,37; 24,42. * 6-[4-[[5-Bromo-3-(hydroxyimino)-2-oxoindolin-1-y l]methyl]-1H-1,2,3-triazol- 1-yl]-N-hydroxyhexanamid (VIId) IR (KBr, cm-1): 3490 (NH); 3199 (OH); 3028 (C-H, aren); 2940, 2858 (CH, CH2); 1710, 1654 (C=O); 1606, 1534, 1461 (C=C). CTPT: C17H19BrN6O4, KLPT = 451; ESI-MS (m/z): 449 [M-H]