Synthesis of N-aryl and N-arylcarbamoylamino derivatives of 1,3-diazinane-5-carboxamide and their activity against glioblastoma LN-229 cell line

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• 作者：Rebecca J. Hron^a ; Branko S. Jursic^a ; ^b ; ; Donna M. Neumann^c ; ^d
• 关键词：Glioblastoma ; Anticancer ; Diazinane ; Carbamoyl ; Merbarone
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：1 December 2016
• 年：2016
• 卷：24
• 期：23
• 页码：6183-6193
• 全文大小：1276 K
• 卷排序：24

文摘

Six structural motifs based on the initial (lead) structure of merbarone were designed, prepared, and tested against the glioblastoma LN-229 cell line. Three different structural moieties were modified in the search for optimal glioblastoma activity: the 1,3-diazinane moiety, the aryl moiety, and the heteroatom linker. Calculated molecular descriptors such as lipophilicity (C log P), acidic strength (calculated pKa), and polar surface area (PSA) were used to design a diverse structural library of these compounds. From six different structural motifs and 136 compounds, a handful of examples with moderate (100 μg/ml), good (10 μg/ml) and excellent (1 μg/ml) glioblastoma activity were elucidated.