4.7 Article

Improving lipophilicity of 5-(1-acetyl-5-phenylpyrazolidin-3-ylidene)-1,3-dimethylbarbituric acid increases its efficacy to activate hypoxia-inducible factors

Journal

BIOORGANIC & MEDICINAL CHEMISTRY
Volume 73, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2022.117039

Keywords

PHD inhibitors; 2-oxoglutarate; Hypoxic stress; Pyrazolidine; Hypoxia-inducible factor

Funding

  1. JSPS KAKENHI [19H04057, 22K19755, 19K17746]

Ask authors/readers for more resources

In this study, a higher lipophilic derivative of PyrzA was synthesized and evaluated, showing higher HIF activity and stabilizing ability at low concentrations compared to the commercially available HIF activator Roxadustat.
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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available