Structure-Activity Relationship and Crystallographic Studies on 4-Hydroxypyrimidine HIF Prolyl Hydroxylase Domain Inhibitors
Structure-Activity Relationship and Crystallographic Studies on 4-Hydroxypyrimidine HIF Prolyl Hydroxylase Domain Inhibitors
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DOI：
10.1002/cmdc.201900557
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发表时间：
2019-12-03
期刊：
影响因子：
3.4
通讯作者：
Schofield, Christopher J.
中科院分区：
文献类型：
--
作者：
Holt-Martyn, James P.;Chowdhury, Rasheduzzaman;Schofield, Christopher J.
2-酮戊二酸依赖性缺氧诱导因子脯氨酰羟化酶（PHD）是治疗包括贫血在内的多种疾病的靶标。一种PHD抑制剂被批准用于治疗肾性贫血，其他药物正在进行后期临床试验。用于PHD抑制的报告模板的数量是有限的。我们报告一类有前途的4-羟基嘧啶类PHD抑制剂的构效关系和晶体学研究。
The 2-oxoglutarate-dependent hypoxia inducible factor prolyl hydroxylases (PHDs) are targets for treatment of a variety of diseases including anaemia. One PHD inhibitor is approved for use for the treatment of renal anaemia and others are in late stage clinical trials. The number of reported templates for PHD inhibition is limited. We report structure-activity relationship and crystallographic studies on a promising class of 4-hydroxypyrimidine-containing PHD inhibitors.