Discovery of DS79182026: A potent orally active hepcidin production inhibitor. Issue 16 (15th August 2017)

• Record Type: Journal Article
• Authors: Fukuda, Takeshi; Goto, Riki; Kiho, Toshihiro; Ueda, Kenjiro; Muramatsu, Sumie; Hashimoto, Masami; Aki, Anri; Watanabe, Kengo; Tanaka, Naoki
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 16(2017)
• Page Start: 3716
• Page End: 3722
• Publication Date: 2017-08-15
• Subjects: Hepcidin -- Anemia of chronic disease -- Benzisoxazole -- Pyrazole -- Kinase; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.07.004
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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 benzisoxazole compounds as orally active hepcidin production inhibitors. The optimization study of multi kinase inhibitor1 led to a potent and bioavailable hepcidin production inhibitor38 (DS79182026), which showed serum hepcidin lowering effects in a mouse IL-6 induced acute inflammatory model.