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In this study, a series of 4-phenoxypyridine derivatives containing imidazole-4-formamido and 1,2,4-triazole were designed and synthesized as novel inhibitors of Fms-like tyrosine kinase 3 (FLT3). The results showed that the series of compounds had good antiproliferative activity. Among them, the preferred compound 10c was in two cell lines containing FLT3-ITD (internal tandem duplication, ITD) mutations, namely human myeloid core solo leukemia cells (MV4-11) and human acute myeloid leukemia cells (Molm-13), with IC50 values of 1.90 and 5.78 μmol·L-1, respectively. Apoptosis and cycle results showed that compound 10c could promote apoptosis and prevent cells in S phase. Molecular docking results showed that compound 10c formed two π-π stacking effects with PHE691 and HIS809 of FLT3, and the pyridine parent nucleus and Linker part formed important hydrogen bonds with LYS644 and CYS694 of FLT3, respectively. In summary, compound 10c exhibited good anti-proliferation activity in vitro, which is of value for further in-depth research, and also lays the foundation for the development of more novel FLT3 inhibitors with novel structures.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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