拓展 Bcr-Abl 抑制剂的结构多样性：二苯甲酰基哌嗪与 1H-吲唑-3-胺结合。
Expanding the structural diversity of Bcr-Abl inhibitors: Dibenzoylpiperazin incorporated with 1H-indazol-3-amine.
机构信息
Department of Pharmacy, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, PR China.
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi Province, PR China.
出版信息
Eur J Med Chem. 2015 Nov 2;104:139-47. doi: 10.1016/j.ejmech.2015.09.034. Epub 2015 Oct 8.
A series of N,N'-dibenzoylpiperazine derivatives incorporated with 1H-indazol-3-amine have been designed, synthesized and evaluated as novel Bcr-Abl inhibitors. Several title compounds exhibited potent inhibitory activity against Bcr-Abl wild type as well as T315I mutant. Two compounds, 11a and 12c, strongly suppressed the activity of native and mutant Bcr-Abl. In particular, 11a exhibited comparable potency with that of Imatinib. It potently inhibited both Bcr-Abl(WT) and Bcr-Abl(T315I) with IC50 values of 0.014 μM and 0.45 μM, respectively. Furthermore, compound 11a also inhibited the proliferation of K562 leukemia cancer cells. Therefore, it could serve as promising lead compound for further optimization of Bcr-Abl(WT) and Bcr-Abl(T315I) inhibitors.
一系列含有 1H-吲唑-3-胺的 N,N'-二苯甲酰基哌嗪衍生物被设计、合成并评估为新型 Bcr-Abl 抑制剂。几个标题化合物对 Bcr-Abl 野生型和 T315I 突变体表现出很强的抑制活性。两种化合物 11a 和 12c 强烈抑制了天然和突变 Bcr-Abl 的活性。特别是，11a 表现出与伊马替尼相当的效力。它对 Bcr-Abl(WT)和 Bcr-Abl(T315I)的抑制活性分别为 0.014 μM 和 0.45 μM。此外，化合物 11a 还抑制了 K562 白血病癌细胞的增殖。因此，它可以作为进一步优化 Bcr-Abl(WT)和 Bcr-Abl(T315I)抑制剂的有前途的先导化合物。
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