2-nitroimidazol-5-ylmethyl as a potential bioreductively activated prodrug system: reductively triggered release of the PARP inhibitor 5-bromoisoquinolinone

…, DP Naughton, WJD Whish, MD Threadgill

Index: Parveen, Ifat; Naughton, Declan P.; Whish, William J. D.; Threadgill, Michael D. Bioorganic and Medicinal Chemistry Letters, 1999 , vol. 9, # 14 p. 2031 - 2036

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Citation Number: 50

Abstract

5-Chloromethyl-1-methyl-2-nitroimidazole reacted efficiently with the anion derived from 5- bromo-isoquinolin-1-one to give 5-bromo-2-((1-methyl-2-nitroimidazol-5-yl) methyl) isoquinolin-1-one. Biomimetic reduction effected release of the 5-bromoisoquinolin-1-one. The 2-nitroimidazol-5-ylmethyl unit thus has potential for development as a general prodrug system for selective drug delivery to hypoxic tissues.