Supporting Information Discovery of Novel Thiazole

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Table Contents for the Supporting Information, 1 1 Physical and chemical properties of the target compounds. 2 2 Table S1 Crystal data and structure refinements for the compounds 5l and 6d. 3 3 Table S2 The EC50 values of the target compounds. 4 4 Table S3 The docking data between the target compounds and S sclerotiorum. 6 5 Figure S1 Chemical structures of the top 6 candidates. 7 6 Figure S2 Ramachandran evaluate of all subunit. 8 7 Figure S3 The structure of SsSDH shown with green. 9 8 NMR Spectra, 10 1 Physical and chemical properties of the target compounds. 11 Data for 5a yellow powder yield 74 m p 108 110 C 1H NMR 400 MHz. 12 CDCl3 8 82 s 1H CONH 7 62 d J 9 0 Hz 2H Ph H 7 19 d J 8 4 Hz 2H. 13 Ph H 4 23 s 3H OCH3 2 66 s 3H thiazole CH3 13C NMR 101 MHz CDCl3. 14 167 71 160 04 159 10 145 09 136 65 121 79 120 95 107 61 58 60 20 28 HRMS. 15 ESI m z calcd for C13H12F3N2O3S M H 333 0515 found 333 0518 IR KBr. 16 cm 1 3364 1672 1552 1536 1504 1266 1194 1106 937 858 813 745 622. 17 Data for 5b white crystal yield 24 m p 200 C 1H NMR 400 MHz CDCl3. 18 9 41 s 1H CONH 8 60 8 36 m 1H Ph H 7 31 d J 7 8 Hz 1H Ph H 7 05. 19 t J 8 4 Hz 1H Ph H 4 24 s 3H OCH3 2 66 s 3H thiazole CH3 13C NMR. 20 101 MHz CDCl3 167 98 160 45 158 15 d J 247 6 Hz 159 06 133 03 d J. 21 2 9 Hz 122 48 d J 7 9 Hz 119 36 d J 25 5 Hz 115 12 d J 21 6 Hz 112 76. 22 d J 9 4 Hz 107 70 58 44 20 28 HRMS ESI m z calcd for C12H11BrFN2O2S M. 23 H 344 9703 found 344 9703 IR KBr cm 1 3303 1661 1597 1534 1474 1428. 24 1368 1248 1192 1113 1074 940 865 819 745 644, 25 Data for 5c white powder yield 97 m p 150 152 C 1H NMR 400 MHz CDCl3. 26 8 90 s 1H CONH 8 08 dd J 8 0 0 9 Hz 1H Ph H 7 29 dd J 7 7 1 3 Hz. 27 1H Ph H 7 25 7 19 m 1H Ph H 7 14 td J 7 6 1 1 Hz 1H Ph H 4 22 s 3H. 28 OCH3 3 22 3 05 m 1H CH 2 66 s 3H thiazole CH3 1 31 d J 6 8 Hz 6H. 29 CH CH3 2 13C NMR 101 MHz CDCl3 167 17 159 82 159 13 138 08 134 71. 30 126 48 125 27 124 90 122 84 108 46 58 40 28 01 22 80 20 25 HRMS ESI m z. 31 calcd for C15H19N2O2S M H 291 1162 found 291 1165 IR KBr cm 1 3384. 32 2960 1663 1587 1533 1450 1365 1255 1198 1116 938 752. 33 Data for 5d white powder yield 97 m p 144 146 C 1H NMR 400 MHz CDCl3. 34 9 57 s 1H CONH 8 53 d J 7 9 Hz 1H Ph H 7 11 6 77 m 3H Ph H 4 66. 35 dt J 11 8 5 9 Hz 1H OCH 4 25 s 3H OCH3 2 66 s 3H thiazole CH3 1 44. 36 d J 5 9 Hz 6H CH CH3 2 13C NMR 101 MHz CDCl3 166 91 159 77 158 94. 37 146 03 129 23 123 26 121 08 119 87 112 69 108 73 71 11 58 20 22 33 20 21. 38 HRMS ESI m z calcd for C15H19N2O3S M H 307 1111 found 307 1114 IR. 39 KBr cm 1 3343 2976 1653 1599 1540 1485 1454 1370 1255 1177 1114 945. 40 880 754 708 676, 41 Data for 5e yellow powder yield 99 m p 187 189 C 1H NMR 400 MHz. 42 DMSO d6 9 61 s 1H CONH 8 20 d J 7 9 Hz 1H Ph H 7 06 6 82 m 2H. 43 Ph H 6 70 t J 7 6 Hz 1H Ph H 4 15 s 3H OCH3 2 64 s 3H thiazole CH3. 44 C NMR 101 MHz DMSO d6 167 29 159 36 157 79 147 41 126 98 123 45. 45 118 68 117 89 114 60 107 47 99 50 58 44 19 87 HRMS ESI m z calcd for. 46 C12H13N2O3S M H 265 0642 found 265 0645 IR KBr cm 1 3332 3179 1638. 47 1597 1557 1508 1456 1424 1377 1353 1278 1195 1183 1107 763 709 670. 48 Data for 5f yellow powder yield 76 m p 171 173 C 1H NMR 400 MHz CDCl3. 49 8 64 s 1H CONH 8 38 dd J 9 0 5 3 Hz 1H Ph H 7 09 dd J 14 3 7 5 Hz. 50 3H Ph H 6 92 dd J 8 5 2 6 Hz 1H Ph H 3 87 s 3H OCH3 2 62 s 3H. 51 thiazole CH3 13C NMR 101 MHz CDCl3 167 84 159 84 159 00 158 79 d J. 52 245 2 Hz 151 26 ddd J 252 5 10 1 4 4 Hz 139 61 dt J 254 0 15 2 Hz 133 77. 53 133 32 m 131 31 d J 2 7 Hz 130 83 d J 7 4 Hz 123 69 d J 7 7 Hz. 54 116 46 d J 23 4 Hz 116 01 d J 21 7 Hz 113 98 dd J 15 6 6 1 Hz 107 47. 55 57 98 20 21 HRMS ESI m z calcd for C18H13F4N2O2S M H 397 0629 found. 56 397 0623 IR KBr cm 1 3356 3033 1656 1619 1538 1485 1415 1356 1259 1200. 57 1110 1045 865 745 630, 58 Data for 5g white powder yield 91 m p 150 152 C 1H NMR 400 MHz CDCl3.
59 8 57 s 1H CONH 8 45 8 26 m 1H Ph H 7 52 d J 8 2 Hz 1H Ph H 7 46. 60 s 1H Ph H 7 18 d J 8 4 Hz 1H Ph H 7 02 dd J 11 6 5 2 Hz 1H Ph H. 61 6 85 dd J 6 5 2 1 Hz 1H Ph H 3 66 s 3H OCH3 2 53 s 3H thiazole CH3. 62 C NMR 101 MHz CDCl3 167 67 159 84 159 00 158 71 d J 244 8 Hz. 63 137 40 133 03 132 60 131 58 d J 2 8 Hz 131 47 131 18 d J 7 7 Hz 130 96. 64 129 07 123 08 d J 7 8 Hz 116 41 d J 23 1 Hz 115 74 d J 21 5 Hz 107 47. 65 57 98 20 25 HRMS ESI m z calcd for C18H14Cl2FN2O2S M H 411 0132 found. 66 411 0132 IR KBr cm 1 3356 3058 1656 1619 1543 1471 1420 1366 1260 1199. 67 1179 1109 1072 1033 915 876 821 747 636 528, 68 Data for 5h yellow powder yield 67 m p 143 145 C 1H NMR 400 MHz. 69 CDCl3 8 61 s 1H CONH 8 42 8 20 m 1H Ph H 7 27 s 1H Ph H 7 02. 70 ddd J 15 9 10 3 4 8 Hz 4H Ph H 3 74 d J 3 5 Hz 3H OCH3 2 49 d J. 71 3 2 Hz 3H thiazole CH3 13,C NMR 101 MHz CDCl3 167 72 159 70 158 97. 72 151 15 ddd J 250 8 9 9 4 1 Hz 139 35 dt J 253 3 15 6 Hz 135 22 134 72. 73 dd J 12 5 7 5 Hz 129 81 129 45 128 92 124 03 121 48 114 09 dd J 15 6. 74 5 8 Hz 107 76 57 91 20 17 HRMS ESI m z calcd for C18H14F3N2O2S M H. 75 379 0723 found 379 0723 IR KBr cm 1 3358 1637 1615 1589 1541 1473 1456. 76 1397 1362 1199 1106 1044 888 748 641, 77 Data for 5i white crystal yield 86 m p 120 122 C 1H NMR 400 MHz CDCl3. 78 8 76 s 1H CONH 8 50 d J 8 3 Hz 1H Ph H 7 45 7 23 m 3H Ph H 7 15. 79 dt J 14 9 7 7 Hz 3H Ph H 3 77 s 3H OCH3 2 59 s 3H thiazole CH3 13C. 80 NMR 101 MHz CDCl3 167 53 159 66 158 97 150 17 dd J 249 9 12 8 Hz. 81 149 98 dd J 249 4 12 4 Hz 135 61 135 49 m 135 46 129 99 129 69 129 05. 82 126 18 dd J 6 0 3 6 Hz 123 82 121 07 118 83 d J 17 2 Hz 117 69 d J. 83 17 2 Hz 107 85 57 88 20 17 HRMS ESI m z calcd for C18H15F2N2O2S M H. 84 361 0817 found 361 0821 IR KBr cm 1 3350 3046 2951 1654 1586 1537 1447. 85 1421 1365 1301 1259 1197 1107 1067 940 903 827 757 694 640 590. 86 Data for 5j white crystal yield 92 m p 137 139 C 1H NMR 400 MHz CDCl3. 87 8 75 s 1H CONH 8 53 d J 8 3 Hz 1H Ph H 7 45 d J 8 2 Hz 2H Ph H. 88 7 41 7 29 m 3H Ph H 7 21 7 06 m 2H Ph H 3 55 s 3H OCH3 2 45 s 3H. 89 thiazole CH3 13C NMR 101 MHz CDCl3 167 37 159 66 158 96 136 96 135 63. 90 133 85 131 24 130 47 129 90 128 99 128 82 123 69 120 71 107 88 57 88 20 20. 91 HRMS ESI m z calcd for C18H16ClN2O2S M H 359 0616 found 359 0614 IR. 92 KBr cm 1 3348 1652 1581 1525 1466 1444 1425 1364 1197 1106 1091 1066. 93 1006 830 760 649, 94 Data for 5k white powder yield 68 m p 158 160 C 1H NMR 400 MHz CDCl3. 95 9 41 s 1H CONH 8 27 d J 7 3 Hz 1H Ar H 7 91 dd J 23 6 8 0 Hz 2H. 96 Ar H 7 66 d J 8 0 Hz 1H Ar H 7 52 ddd J 15 5 13 7 7 3 Hz 3H Ar H. 97 4 31 s 3H OCH3 2 67 s 3H thiazole CH3 13C NMR 101 MHz CDCl3 167 46. 98 160 05 159 38 134 10 132 66 128 94 126 30 126 07 125 87 124 84 120 10. 99 119 01 108 36 58 69 20 31 HRMS ESI m z calcd for C16H15N2O2S M H. 100 299 0849 found 299 0851 IR KBr cm 1 3398 1662 1556 1528 1504 1408 1377. 101 1270 1199 1104 1069 938 795 773 739 598, 102 Data for 5l yellow powder yield 90 m p 176 178 C 1H NMR 400 MHz CDCl3.
103 8 76 s 1H CONH 8 01 d J 8 1 Hz 1H Ar H 7 12 t J 7 8 Hz 1H Ar H. 104 6 87 d J 7 6 Hz 1H Ar H 4 21 s 3H OCH3 2 78 t J 6 1 Hz 2H CH2 2 72. 105 2 57 m 5H thiazole CH3 and CH2 1 96 1 84 m 2H CH2 1 84 1 70 m 2H. 106 CH2 13C NMR 101 MHz CDCl3 167 06 159 75 158 91 137 89 136 00 126 30. 107 125 89 125 31 118 83 108 61 58 44 29 93 24 34 23 13 22 53 20 24 HRMS ESI. 108 m z calcd for C16H19N2O2S M H 303 1162 found 303 1166 IR KBr cm 1 3386. 109 2937 2864 2838 1657 1612 1586 1557 1470 1427 1370 1312 1265 1197 1124. 110 1083 940 874 774 746 623, 111 Data for 5m white powder yield 31 m p 118 120 C 1H NMR 400 MHz CDCl3. 112 7 06 6 93 m 1H Ar H 6 88 d J 8 6 Hz 1H Ar H 6 70 t J 8 4 Hz 1H. 113 Ar H 3 82 t J 6 4 Hz 2H CH2 3 62 s 3H OCH3 2 76 t J 6 4 Hz 2H CH2. 114 2 59 s 3H thiazole CH3 2 08 1 92 m 2H CH2 13C NMR 101 MHz CDCl3. 115 166 26 162 18 159 70 d J 243 2 Hz 159 63 135 71 134 57 d J 6 1 Hz 124 61. 116 d J 6 7 Hz 114 24 d J 22 1 Hz 112 59 d J 22 9 Hz 106 01 57 40 44 40. 117 26 91 23 82 20 02 HRMS ESI m z calcd for C15H16FN2O2S M H 307 0911. 118 found 307 0914 IR KBr cm 1 2952 1609 1538 1506 1456 1426 1388 1335 1197. 119 1148 1096 1046 926 879 818 700 627, 120 Data for 5n white powder yield 47 m p 119 121 C 1H NMR 400 MHz CDCl3. 121 7 91 s 1H Ar H 6 89 s 2H Ar H 4 26 dd J 9 8 6 6 Hz 2H CH2 4 05 s. 122 3H OCH3 3 12 d J 7 0 Hz 2H CH2 2 65 s 3H thiazole CH3 13C NMR 101. 123 MHz CDCl3 166 23 160 15 159 83 159 58 d J 242 9 Hz 138 99 134 49 d J. 124 7 6 Hz 118 37 118 33 d J 7 7 Hz 113 62 d J 22 7 Hz 111 89 d J 23 6. 125 Hz 105 90 57 86 49 75 28 47 19 94 HRMS ESI m z calcd for C14H14FN2O2S M. 126 H 293 0755 found 293 0754 IR KBr cm 1 1618 1599 1541 1477 1431 1395. 127 1307 1181 1093 1044 930 872 814 657, 128 Data for 5o white crystal yield 97 m p 96 97 C 1H NMR 400 MHz CDCl3. 129 7 35 s 1H CONH 7 23 dd J 14 4 7 0 Hz 1H Ph H 7 06 d J 7 5 Hz 1H Ph. 130 H 6 99 d J 9 7 Hz 1H Ph H 6 88 t J 8 3 Hz 1H Ph H 4 54 d J 5 9 Hz. 131 2H CH2 4 06 s 3H OCH3 2 56 s 3H thiazole CH3 13C NMR 101 MHz CDCl3. 132 166 73 162 93 d J 245 9 Hz 161 10 160 20 141 47 d J 6 9 Hz 130 07 d. 133 J 8 3 Hz 122 99 d J 2 9 Hz 114 26 d J 22 4 Hz 114 04 d J 22 1 Hz. 134 106 88 58 13 42 62 20 02 HRMS ESI m z calcd for C13H14FN2O2S M H. 135 281 0755 found 281 0757 IR KBr cm 1 3383 2993 2949 1626 1519 1453 1427. 136 1349 1262 1200 1105 964 860 806 759 703 588, 137 Data for 5p white powder yield 94 m p 143 145 C 1H NMR 400 MHz CDCl3. 138 8 50 d J 4 6 Hz 1H pyridine H 8 45 s 1H CONH 7 70 d J 8 0 Hz 1H. 139 pyridine H 7 21 dd J 7 7 4 9 Hz 1H pyridine H 4 81 d J 4 4 Hz 2H. 140 pyridine CH2 4 20 s 3H OCH3 2 63 s 3H thiazole CH3 13C NMR 101 MHz. 141 CDCl3 166 38 161 03 160 51 153 19 146 81 136 92 130 43 123 18 107 39. 142 58 14 42 35 20 13 HRMS ESI m z calcd for C12H13ClN3O2S M H 298 0412. 143 found 298 0413 IR KBr cm 1 3353 3321 1632 1520 1430 1337 1200 1116 1037. 144 943 877 802 760 669 596, 145 Data for 5q white crystal yield 97 m p 66 68 C 1H NMR 400 MHz CDCl3.
146 7 24 d J 7 6 Hz 1H Ph H 7 17 6 99 m 3H Ph H 6 91 s 1H CONH 3 92. 147 s 3H OCH3 3 56 dd J 13 0 6 6 Hz 2H CH2 2 92 t J 6 9 Hz 2H Ph CH2. 148 2 47 s 3H thiazole CH3 13C NMR 101 MHz CDCl3 166 29 161 07 159 91. 149 136 58 134 11 131 08 129 53 127 99 126 83 107 21 57 95 38 96 33 48 20 04. 150 HRMS ESI m z calcd for C14H16ClN2O2S M H 311 0616 found 311 0617 IR. 151 KBr cm 1 3384 2940 1669 1509 1474 1347 1265 1196 1110 1053 934 830. 152 757 670 545, 153 Data for 5r white powder yield 67 m p 130 132 C 1H NMR 400 MHz CDCl3. 154 8 69 s 1H Ph H 8 42 d J 8 2 Hz 1H Ph H 7 42 d J 6 8 Hz 1H Ph H. 155 7 34 7 15 m 5H Ph H 4 80 d J 2 4 Hz 2H OCH2 2 63 s 3H thiazole CH3. 156 2 49 t J 3 0 Hz 1H CH 13C NMR 101 MHz CDCl3 167 71 158 72 157 61. 157 150 38 dd J 249 4 12 5 Hz 150 14 dd J 249 6 12 5 Hz 135 31 dd J 5 9. 158 4 3 Hz 135 11 130 28 130 08 128 99 125 94 dd J 6 1 3 5 Hz 124 19 121 69. 159 118 84 d J 17 2 Hz 117 74 d J 17 1 Hz 109 36 99 99 75 81 58 08 29 71. 160 20 22 HRMS ESI m z calcd for C20H15F2N2O2S M H 384 0822 found. 161 385 0817 IR KBr cm 1 3358 1655 1535 1454 1392 1338 1299 1264 1191 904. 162 820 757 676, 163 Data for 6a white powder yield 84 m p 200 C 1H NMR 400 MHz. 164 DMSO d6 9 73 s 1H CONH 7 73 d J 9 0 Hz 2H Ph H 7 33 d J 8 6 Hz. 165 2H Ph H 2 63 s 3H thiazole CH3 13,C NMR 101 MHz DMSO d6 167 86. 166 162 31 160 44 144 06 138 12 122 16 121 34 119 34 19 58 HRMS ESI m z calcd. 167 for C12H10F3N2O3S M H 319 0359 found 319 0360 IR KBr cm 1 1668 1625. 168 1558 1505 1357 1257 1191 1110 856 784 736 642 603. 169 Data for 6b yellow powder yield 32 m p 200 C 1H NMR 400 MHz. 170 DMSO d6 9 98 s 1H CONH 8 36 dd J 9 2 5 8 Hz 1H Ph H 7 65 dd J. 171 8 3 2 8 Hz 1H Ph H 7 28 td J 8 8 2 8 Hz 1H Ph H 2 62 s 3H thiazole CH3. 172 C NMR 101 MHz DMSO d6 167 66 162 62 159 86 158 55 157 33 d J 244 3. 173 Hz 156 12 133 44 122 71 d J 7 8 Hz 119 35 d J 25 5 Hz 115 03 d J 21 7. 174 Hz 112 84 d J 10 0 Hz 112 79 19 26 HRMS ESI m z calcd for C11H9BrFN2O2S. 175 M H 330 9547 found 330 9545 IR KBr cm 1 1655 1617 1541 1473 1388. 176 1356 1188 1119 1073 1029 1004 874 856 734 669, 177 Data for 6c white powder yield 67 m p 183 185 C 1H NMR 400 MHz. 178 DMSO d6 10 62 s 1H CONH 8 04 d J 7 5 Hz 1H Ph H 7 26 d J 7 4 Hz. 179 1H Ph H 7 12 t J 7 4 Hz 1H Ph H 7 02 t J 7 0 Hz 1H Ph H 3 32 3 18. 180 m 1H CH 2 51 s 3H thiazole CH3 1 20 d J 6 5 Hz 6H CH CH3 2 13C NMR. 181 101 MHz DMSO d6 168 70 164 96 161 62 137 59 136 33 125 68 124 98. 182 123 04 121 83 96 85 27 12 22 80 19 93 HRMS ESI m z calcd for C14H17N2O2S. 183 M H 277 1005 found 277 1010 IR KBr cm 1 3376 3121 2963 1648 1554. 184 1387 1291 1254 1193 1086 755 663, 185 Data for 6d white powder yield 90 m p 200 C 1H NMR 400 MHz.
186 DMSO d6 9 40 s 1H CONH 8 29 dd J 9 0 5 5 Hz 1H Ph H 7 53 7 45 m. 187 2H Ph H 7 28 td J 8 8 2 9 Hz 1H Ph H 7 21 dd J 9 0 2 8 Hz 1H Ph H. 188 2 58 s 3H thiazole CH3 13C NMR 101 MHz DMSO d6 167 81 161 49 159 92. 189 158 31 d J 241 2 Hz 150 81 ddd J 14 1 9 3 3 8 Hz 139 34 dt J 249 7 15 5. 190 Hz 133 84 133 47 m 132 71 131 66 d J 9 0 Hz 123 31 d J 8 2 Hz 117 02. 191 d J 23 5 Hz 115 95 d J 21 7 Hz 115 00 dd J 15 9 5 8 Hz 19 67 HRMS. 192 ESI m z calcd for C17H11F4N2O2S M H 383 0472 found 383 0465 IR KBr. 193 cm 1 3359 1655 1616 1538 1482 1418 1362 1212 1043 881 860 816 743 678. 195 Data for 6e white powder yield 82 m p 200 C 1H NMR 400 MHz. 196 DMSO d6 9 37 s 1H CONH 8 25 8 16 m 1H Ph H 7 71 d J 8 1 Hz 2H. 197 Ph H 7 48 7 38 m 1H Ph H 7 32 7 16 m 2H Ph H 2 57 s 3H thiazole. 198 CH3 13C NMR 101 MHz DMSO d6 167 20 161 12 159 62 158 17 d J 242 0. 199 Hz 137 25 132 23 131 82 131 55 131 10 130 92 129 40 123 84 116 55 d J. 1 Supporting Information Discovery of Novel Thiazole Carboxamides as Antifungal Succinate Dehydrogenase Inhibitors Xiaofeng Guo Bin Zhao Zhijin Fan Dongyan Yang Nailou Zhang Qifan Wu Bin Yu Shuang Zhou Tatiana A Kalinina Nataliya P Belskaya State Key Laboratory of Elemento Organic Chemistry College of Chemistry

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