在当前结构类别中，重点关注基于唑类和其他含氮杂环的化合物，作为猫科动物麦克唐纳肉瘤样酪氨酸激酶3（FLT3）抑制剂，用于治疗急性髓系白血病。 机翻

摘要

Acute myeloid leukemia (AML) is the most common form of acute leukemia. It is characterized by unfavorable prognosis, elevated rates of recurrence, short overall survival and high mortality rates. Genetic and epigenetic aberrations contribute to its initiation and progression, presenting a considerable clinical challenge. Genomic investigations revealed that FMS-like tyrosine kinase 3 (FLT3), a receptor tyrosine kinase regulating the proliferation and differentiation of hematopoietic cells, is overexpressed in AML leukemic blasts. To date, FDA has approved only three FLT3 inhibitors for targeted AML therapy (midostaurin, gilteritinib, quizartinib). These molecules feature several nitrogen atoms; in particular quizartinib contains an oxazole and a urea group that are involved in interactions with FLT3 kinase domain. Similarly, different N-containing heterocycles have proven to play a key role in other FLT3 inhibitors. Though small-molecule FLT3 inhibitors encompass various chemical classes, N-containing heterocycles and particularly the azole core represent the most common scaffold. The electron-rich properties of the azoles allow them to easily bind with enzymes and receptors. Based on this, we will provide a general overview of FLT3 inhibitor classes in AML, along with a comprehensive report on azole-based structures, reviewing recent contributions to the field.

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