Synthesis and SAR studies of 3,6-disubstituted indazole derivatives as potent hepcidin production inhibitors.

Abstract

Hepcidin has emerged as the central regulatory molecule of systemic iron homeostasis. Inhibition of hepcidin could be a strategy favorable to treating anemia of chronic disease (ACD). We report herein the synthesis and structure-activity relationships (SARs) of a series of indazole compounds as hepcidin production inhibitors. The optimization study of compound 1 led to a potent hepcidin production inhibitor 45, which showed serum hepcidin lowering effects in a mouse IL-6 induced acute inflammatory model.

• Authors: Takeshi Fukuda, Kenjiro Ueda, Takashi Ishiyama, Riki Goto, Sumie Muramatsu, Masami Hashimoto, Kengo Watanabe, Naoki Tanaka
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 27 Issue 10 Pg. 2148-2152 (05 15 2017) ISSN: 1464-3405 [Electronic] England
• PMID: 28377056 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Infective Agents
• Hepcidins
• Indazoles
• Interleukin-6

Topics

• Anemia (drug therapy, etiology)
• Animals
• Anti-Infective Agents (chemical synthesis, pharmacokinetics, therapeutic use)
• Chronic Disease
• Half-Life
• Hepcidins (antagonists & inhibitors, blood, metabolism)
• Indazoles (chemistry, pharmacokinetics, therapeutic use)
• Inhibitory Concentration 50
• Interleukin-6 (toxicity)
• Mice
• Mice, Inbred C57BL
• Microsomes, Liver (metabolism)
• Structure-Activity Relationship