螺[4.5]癸烷酮脯氨酰羟化酶结构域抑制剂的研究
Studies on spiro[4.5]decanone prolyl hydroxylase domain inhibitors.
作者信息
Holt-Martyn James P, Tumber Anthony, Rahman Mohammed Z, Lippl Kerstin, Figg William, McDonough Michael A, Chowdhury Rasheduzzaman, Schofield Christopher J
机构信息
Department of Chemistry , University of Oxford , Chemistry Research Laboratory , 12 Mansfield Road , Oxford , OX1 3TA , UK . Email:
出版信息
Medchemcomm. 2019 Mar 1;10(4):500-504. doi: 10.1039/c8md00548f. eCollection 2019 Apr 1.
The 2-oxoglutarate (2OG) dependent hypoxia inducible factor (HIF) prolyl hydroxylases (PHDs) are targets for treatment of anaemia and other ischaemia related diseases. PHD inhibitors are in clinical trials; however, the number of reported templates for PHD inhibition is limited. We report structure-activity relationship and crystallographic studies on spiro[4.5]decanone containing PHD inhibitors. Together with other studies, our results reveal spiro[4.5]decanones as useful templates for generation of potent and selective 2OG oxygenase inhibitors.
2-氧代戊二酸（2OG）依赖性缺氧诱导因子（HIF）脯氨酰羟化酶（PHD）是治疗贫血和其他缺血相关疾病的靶点。PHD抑制剂正在进行临床试验；然而，已报道的PHD抑制模板数量有限。我们报告了含螺[4.5]癸烷酮的PHD抑制剂的构效关系和晶体学研究。与其他研究一起，我们的结果表明螺[4.5]癸烷酮是生成强效和选择性2OG加氧酶抑制剂的有用模板。
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