Synthesis of substituted 5-bromomethyl-4-nitroimidazoles and use for the preparation of the hypoxia-selective multikinase inhibitor SN29966

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• 作者：Guo-Liang Lu ; Amir Ashoorzadeh ; Robert F. Anderson ; Adam V. Patterson ; Jeff B. Smaill
• 关键词：4-Nitroimidazole ; Nitroarylmethyl quaternary ammonium salt ; Hypoxia-selective multikinase inhibitor ; SN29966
• 刊名：Tetrahedron
• 出版年：2013
• 出版时间：28 October, 2013
• 年：2013
• 卷：69
• 期：43
• 页码：9130-9138
• 全文大小：759 K

文摘

5-Bromomethyl-4-nitroimidazoles have utility as bioreductive trigger precursors for the preparation of hypoxia-selective prodrugs. Here we describe an efficient two-step synthesis of 5-(bromomethyl)-1-methyl-4-nitro-1H-imidazole, a preferred precursor, employing an N-bromosuccinimide mediated radical bromination. Use of this precursor to prepare SN29966, a promising hypoxia-selective irreversible pan-ErbB inhibitor is reported along with the preparation of four other prodrug candidates. 5-Bromomethyl-4-nitroimidazole analogues bearing electron-donating and electron-withdrawing substituents at the N-1 and C-2 positions are also described.