氨基噻唑(噁唑)类化合物的合成及抗K562细胞活性研究

Synthesis and Anti-K562 Cell Activity of Amino Thiazole (Oxazole) Compounds

关键词:  慢性髓性白血病  酪氨酸激酶抑制剂  2-氨基噻唑类  抗肿瘤活性

Key words:  chronic myeloid leukemia  dasatinib analogues  oxazole compounds  anti-tumor activity

摘要:

目的 设计、合成一系氨基噻唑（噁唑）类似物，并测试新衍生物对人类慢性粒细胞白血病细胞系K562的体外抑制作用。方法 以dasatinib为先导化合物设计新衍生物，通过亲核取代和关环缩合得到目标化合物，其结构通过¹H-NMR、¹³C-NMR、IR和MS测定。结果 发现5个目标化合物抑制活性高于对照药伊马替尼。4个化合物抗K562细胞活性高于dasatinib。结论 保持药效基团不变，用五元噻唑环取代芳香苯环，活性能得以改善。

Abstract:

OBJECTIVE To design and synthesis of a series of dasatinib analogues and their impact on human chronic myelogenous leukemia cell line K562 in vitro. METHODS A new derivative was designed with dasatinib as the lead compound. The target compounds were synthesized by nucleophilic substitution and cyclization. The structure of all the newly synthesized compounds were identified by ¹H-NMR, ¹³C-NMR, IR and MS. RESULTS Five compounds (10a, 10b. 10c, 10f, 10g) showed higher effective antitumor activity than imatinib; four compounds (10a, 10b, 10C, 10f) exhibited more potent inhibitor versus the K562 cell line compared with the lead compound dasatinib. CONCLUSION The activity can be improved by replacing aromatic benzene ring with quaternary thiazole ring without any change of pharmacophore.