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

Autor:	Kento Sonoda, Saki Ujike, Akito Katayama, Norio Suzuki, Shin-ichi Kawaguchi, Tadayuki Tsujita
Rok vydání:	2022
Předmět:	Organic Chemistry Clinical Biochemistry Drug Discovery Barbiturates Pharmaceutical Science Molecular Medicine Humans Ketoglutaric Acids Hypoxia Hypoxia-Inducible Factor 1 alpha Subunit Molecular Biology Biochemistry Hypoxia-Inducible Factor-Proline Dioxygenases
Zdroj:	Bioorganicmedicinal chemistry. 73
ISSN:	1464-3391
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8bcb04a63b472646bcd0488577fcf1c0 https://pubmed.ncbi.nlm.nih.gov/36198217 Zobrazit plný text záznamu Full Text from ScienceDirect