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发表刊物：
Bioorganic & Medicinal Chemistry
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关键字：
Agonist; Benzisothiazole; EPO; HIF-2; SAR.
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卷号：
77
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页面范围：
117041
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是否译文：
否
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发表时间：
2023-01-01
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收录刊物：
SCI
摘要：
Benzisothiazole dioxide compound was reported to agonize HIF-2 stabilization and improve EPO production, thus conceiving a potential strategy to treat disease with chronic hypoxia exemplified by renal anemia. Herein, on the bases of multiple molecular and cellular assays, a series of benzisothiazole derivatives have been synthesized and their structure-activity relationship was evaluated. The SAR and molecular docking studies have revealed the structural insights on the rational design of HIF-2 agonist and discovered a more potential 5-bromine substituted analogue, which showed 2-4 times improvement of HIF-2 downstream gene transcriptions, including EPO production. The present results suggest the therapeutic potential of the compounds for diseases related to EPO insufficiency.
