Design, synthesis and biological evaluation of deuterated Vismodegib for improving pharmacokinetic properties
| Autor: | Fangying, Wang, Hongxia, Jiang, Yufang, Deng, Jiang, Yu, Miao, Zhan, Lifeng, Zhao, Yuanwei, Chen |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Dose-Response Relationship Drug Molecular Structure Pyridines Organic Chemistry Clinical Biochemistry Administration Oral Pharmaceutical Science Biochemistry Mice Structure-Activity Relationship 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Drug Design 030220 oncology & carcinogenesis Blood Circulation Drug Discovery Animals Molecular Medicine Anilides Hedgehog Proteins Molecular Biology Signal Transduction |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 28:2399-2402 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2018.06.025 |
| Popis: | Vismodegib is an oral and high selective hedgehog (Hh) inhibitor used for the treatment of basal cell carcinoma (BCC). In this work, analogs of Vismodegib with deuterium-for-hydrogen replacement at certain metabolically active sites were prepared and found to have a better pharmacokinetic properties in mice. In particular, deuterated compound SKLB-C2211 obviously altered the blood circulation behavior compared to its prototype, which was demonstrated by significantly prolonged blood circulation half-life time (t |
| Databáze: | OpenAIRE |
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