Discovery of DS42450411 as a potent orally active hepcidin production inhibitor: Design and optimization of novel 4-aminopyrimidine derivatives
| العنوان: | Discovery of DS42450411 as a potent orally active hepcidin production inhibitor: Design and optimization of novel 4-aminopyrimidine derivatives |
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| المؤلفون: | Kenjiro Ueda, Masami Hashimoto, Kengo Watanabe, Naoki Tanaka, Anri Aki, Daichi Baba, Katagiri Takahiro, Takashi Ishiyama, Takeshi Fukuda, Sumie Muramatsu |
| المصدر: | Bioorganic & Medicinal Chemistry Letters. 28:3333-3337 |
| بيانات النشر: | Elsevier BV, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, inorganic chemicals, 0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, DYRK1A, Iron, Clinical Biochemistry, Administration, Oral, Aminopyridines, Pharmaceutical Science, Inflammation, Pharmacology, digestive system, Biochemistry, Structure-Activity Relationship, 03 medical and health sciences, 0302 clinical medicine, Hepcidins, Iron homeostasis, Hepcidin, Cell Line, Tumor, hemic and lymphatic diseases, Drug Discovery, medicine, Animals, Humans, Transferase, Molecular Biology, Binding Sites, Molecular Structure, biology, Interleukin-6, Chemistry, Organic Chemistry, nutritional and metabolic diseases, Anemia, medicine.disease, Bioavailability, Mice, Inbred C57BL, 030104 developmental biology, Orally active, Drug Design, 030220 oncology & carcinogenesis, Quinazolines, biology.protein, Molecular Medicine, medicine.symptom, Anemia of chronic disease |
| الوصف: | Hepcidin has emerged as the central regulatory molecule in systemic iron homeostasis. The inhibition of hepcidin may be a favorable strategy for the treatment of anemia of chronic disease. Here, we have reported the design, synthesis, and structure-activity relationships (SAR) of a series of 4-aminopyrimidine compounds as inhibitors of hepcidin production. The optimization study of 1 led to the design of a potent and bioavailable inhibitor of hepcidin production, 34 (DS42450411), which showed serum hepcidin-lowering effects in a mouse model of interleukin-6-induced acute inflammation. |
| تدمد: | 0960-894X 4245-0411 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f6f6b32012f959b725514baaea3b145a https://doi.org/10.1016/j.bmcl.2018.09.010 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....f6f6b32012f959b725514baaea3b145a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 0960894X 42450411 |
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