提高 5-(1-乙酰基-5-苯基吡唑烷-3-亚基)-1,3-二甲基巴比妥酸的亲脂性可提高其激活缺氧诱导因子的功效。
Improving lipophilicity of 5-(1-acetyl-5-phenylpyrazolidin-3-ylidene)-1,3-dimethylbarbituric acid increases its efficacy to activate hypoxia-inducible factors.
机构信息
Center for Education and Research in Agricultural Innovation, Faculty of Agriculture, Saga University, 152-1 Shonan-cho, Karatsu, Saga 847-0021, Japan; Laboratory of Biochemistry, Department of Applied Biochemistry and Food Science, Faculty of Agriculture, Saga University, 1 Honjo-machi, Saga 840-8502, Japan; The United Graduate School of Agricultural Sciences, Kagoshima University, 1-21-24, Korimoto, Kagoshima 890-0065, Japan.
Center for Education and Research in Agricultural Innovation, Faculty of Agriculture, Saga University, 152-1 Shonan-cho, Karatsu, Saga 847-0021, Japan; Graduate School of Advanced Health Sciences, Saga University, 152-1 Shonan-cho, Karatsu, Saga 847-0021, Japan.
出版信息
Bioorg Med Chem. 2022 Nov 1;73:117039. doi: 10.1016/j.bmc.2022.117039. Epub 2022 Sep 29.
Hypoxia-inducible factor (HIF) activators aid the treatment of renal anemia and ischemia. Recently, PyrzA (5-(1-acetyl-5-phenylpyrazolidin-3-ylidene)-1,3-dimethylbarbituric acid), a HIF activator by PHD inhibition without a 2-oxoglutarate moiety was reported. However, PyrzA has low lipophilicity, and it was necessary to improve its solubility by synthesizing derivatives. In this study, we synthesized and evaluated a higher lipophilic derivative of PyrzA and found that it exhibited higher HIF activity and stabilizing ability at low concentrations compared to Roxadustat, a commercially available HIF activator.
缺氧诱导因子 (HIF) 激活剂可辅助治疗肾性贫血和缺血。最近，有研究报道 PyrzA（5-(1-乙酰基-5-苯基吡唑烷-3-亚基)-1,3-二甲基巴比妥酸）是一种通过抑制 PHD 而不使用 2-氧戊二酸部分的 HIF 激活剂。然而，PyrzA 的亲脂性较低，需要通过合成衍生物来提高其溶解度。在本研究中，我们合成并评价了 PyrzA 的一种亲脂性更高的衍生物，结果发现与市售 HIF 激活剂 Roxadustat 相比，该衍生物在低浓度下具有更高的 HIF 活性和稳定性。
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