Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5217562 | Tetrahedron | 2013 | 9 Pages |
Abstract
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.
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Physical Sciences and Engineering
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Organic Chemistry
Authors
Guo-Liang Lu, Amir Ashoorzadeh, Robert F. Anderson, Adam V. Patterson, Jeff B. Smaill,