三环支架HIF-2α抑制剂的构效关系研究。

IF 2.2 4区医学 Q3 CHEMISTRY, MEDICINAL

Bioorganic & Medicinal Chemistry Letters Pub Date : 2025-08-09 DOI:10.1016/j.bmcl.2025.130366

Zhijie Wu, Changwei Chen, Jian Yan, Peipei Zhu, Min Xiong, Dong Liu, Shaojiang Deng

{"title":"三环支架HIF-2α抑制剂的构效关系研究。","authors":"Zhijie Wu, Changwei Chen, Jian Yan, Peipei Zhu, Min Xiong, Dong Liu, Shaojiang Deng","doi":"10.1016/j.bmcl.2025.130366","DOIUrl":null,"url":null,"abstract":"<div><div>HIF-2α is a member of the HIF transcription factor family and a key oncogenic driver in renal cell carcinoma, which is characterized by the overaccumulation of HIF-2α protein. Therefore, inhibition of HIF-2α holds therapeutic potential for renal cell carcinoma. Disclosed herein are the discovery and characterization of a novel series of HIF-2α inhibitors with a tricyclic scaffold. A systematic SAR study was performed, and optimization of the tricyclic scaffold demonstrated that a fluorine atom in the cis.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"129 ","pages":"Article 130366"},"PeriodicalIF":2.2000,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Structure-activity relationship study of HIF-2α inhibitors with tricyclic scaffold\",\"authors\":\"Zhijie Wu, Changwei Chen, Jian Yan, Peipei Zhu, Min Xiong, Dong Liu, Shaojiang Deng\",\"doi\":\"10.1016/j.bmcl.2025.130366\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>HIF-2α is a member of the HIF transcription factor family and a key oncogenic driver in renal cell carcinoma, which is characterized by the overaccumulation of HIF-2α protein. Therefore, inhibition of HIF-2α holds therapeutic potential for renal cell carcinoma. Disclosed herein are the discovery and characterization of a novel series of HIF-2α inhibitors with a tricyclic scaffold. A systematic SAR study was performed, and optimization of the tricyclic scaffold demonstrated that a fluorine atom in the cis.</div></div>\",\"PeriodicalId\":256,\"journal\":{\"name\":\"Bioorganic & Medicinal Chemistry Letters\",\"volume\":\"129 \",\"pages\":\"Article 130366\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2025-08-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Bioorganic & Medicinal Chemistry Letters\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0960894X25002756\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic & Medicinal Chemistry Letters","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0960894X25002756","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

摘要

HIF-2α是HIF转录因子家族的成员，是肾细胞癌的关键致癌驱动因子，其特征是HIF-2α蛋白的过度积累。因此，抑制HIF-2α对肾细胞癌具有治疗潜力。本文公开了一种具有三环支架的新型HIF-2α抑制剂系列的发现和表征。进行了系统的SAR研究，并对三环支架进行了优化，表明氟原子在顺式结构中。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Structure-activity relationship study of HIF-2α inhibitors with tricyclic scaffold

查看原文本刊更多论文

Structure-activity relationship study of HIF-2α inhibitors with tricyclic scaffold

HIF-2α is a member of the HIF transcription factor family and a key oncogenic driver in renal cell carcinoma, which is characterized by the overaccumulation of HIF-2α protein. Therefore, inhibition of HIF-2α holds therapeutic potential for renal cell carcinoma. Disclosed herein are the discovery and characterization of a novel series of HIF-2α inhibitors with a tricyclic scaffold. A systematic SAR study was performed, and optimization of the tricyclic scaffold demonstrated that a fluorine atom in the cis.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Bioorganic & Medicinal Chemistry Letters 医学-医药化学

CiteScore

5.70

自引率

3.70%

发文量

463

审稿时长

27 days

期刊介绍： Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.