Xevinapant 1,5-重氮杂环[6.3.0]十二烷核心结构的合成

IF 3.6 2区 化学 Q1 CHEMISTRY, ORGANIC
Bohao Wang, , , Shen Zhai, , , Yingzhi Ren, , , Chen Li, , , Bugao Zhou*, , , Guixiang Zeng*, , and , Shouyun Yu*, 
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引用次数: 0

摘要

凋亡蛋白抑制剂(IAPs)因其促进癌细胞存活的作用而成为癌症治疗的关键靶点。第二种线粒体衍生的半胱天冬酶激活剂(SMAC)模拟物,可以拮抗iap,已经显示出治疗癌症的潜力。1,5-二氮杂环[6.3.0]十二酮氨基酸支架是开发SMAC模拟物的重要支架,包括Xevinapant和Dasminapant等临床候选药物。在此,我们报告了一种新颖、高效、具有潜在可扩展性的合成Xevinapant核心结构的方法,该方法由焦谷氨酸衍生物通过7步合成,总产率为8.4%,促进了IAP抑制剂的进一步开发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Synthesis of the 1,5-Diazabicyclo[6.3.0]dodecane Core Structure of Xevinapant

Synthesis of the 1,5-Diazabicyclo[6.3.0]dodecane Core Structure of Xevinapant

Synthesis of the 1,5-Diazabicyclo[6.3.0]dodecane Core Structure of Xevinapant

Inhibitors of apoptosis proteins (IAPs) are key targets in cancer therapy due to their role in promoting cancer cell survival. The second mitochondria-derived activator of caspases (SMAC) mimetics, which antagonize IAPs, have shown therapeutic potential for cancers. 1,5-Diazabicyclo[6.3.0]dodecanone amino acid scaffold serves as an important scaffold for developing SMAC mimetics, including clinical candidates like Xevinapant and Dasminapant. Herein, we report a novel, efficient, and potentially scalable synthesis of the core structure of Xevinapant achieved in 7 steps from a pyroglutamic acid derivative, with an overall yield of 8.4%, facilitating further development of IAP inhibitors.

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来源期刊
Journal of Organic Chemistry
Journal of Organic Chemistry 化学-有机化学
CiteScore
6.20
自引率
11.10%
发文量
1467
审稿时长
2 months
期刊介绍: Journal of Organic Chemistry welcomes original contributions of fundamental research in all branches of the theory and practice of organic chemistry. In selecting manuscripts for publication, the editors place emphasis on the quality and novelty of the work, as well as the breadth of interest to the organic chemistry community.
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