一系列新型融合环基苯并噻唑衍生物的合成和评价

IF 2.1 3区化学 Q2 CHEMISTRY, ORGANIC

Tetrahedron Pub Date : 2025-05-20 DOI:10.1016/j.tet.2025.134734

Chao Kan , Chongxun Ge , Song Liu , Song Shi , Hu He , Weike Su

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引用次数: 0

摘要

聚合酶θ (Polθ)被认为是一个很有前景的治疗靶点，因为它在同源重组（HR）缺陷的癌细胞中具有替代DNA修复机制的功能，并且具有诱导合成致死性的潜力。选择性结合DNA上的Polθ并克服PARP抑制剂（PARPi）耐药性的小分子抑制剂的发展显著增强了这一靶点在精确肿瘤学领域的创新潜力。在本研究中，我们设计并合成了一系列四环熔接苯并噻唑衍生物。这些新化合物对Polθ酶表现出有效的选择性抑制活性。

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The synthesis and evaluation of a series of novel fused rings based benzothiazole derivatives as potent Polθ inhibitors

Polymerase theta (Polθ) is considered as a promising therapeutic target due to its function as an alternative DNA repair mechanism in Homologous Recombination (HR)-deficient cancer cells, and the potential for inducing synthetic lethality. The development of small molecule inhibitors that selectively bind to Polθ on DNA and overcome the resistance to PARP inhibitors (PARPi) significantly bolsters the innovative potential of this target in the field of precision oncology. In this study, we designed and synthesized a series of tetracyclic-fused benzothiazole derivatives. These novel compounds exhibit potent and selective inhibitory activity against the Polθ enzyme.

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来源期刊

Tetrahedron 化学-有机化学

CiteScore

3.90

自引率

4.80%

发文量

439

审稿时长

34 days

期刊介绍： Tetrahedron publishes full accounts of research having outstanding significance in the broad field of organic chemistry and its related disciplines, such as organic materials and bio-organic chemistry. Regular papers in Tetrahedron are expected to represent detailed accounts of an original study having substantially greater scope and details than that found in a communication, as published in Tetrahedron Letters. Tetrahedron also publishes thematic collections of papers as special issues and ''Reports'', commissioned in-depth reviews providing a comprehensive overview of a research area.