Hypoxia-selective antitumor agents. 16. Nitroarylmethyl quaternary salts as bioreductive prodrugs of the alkylating agent mechlorethamine

M Tercel, AE Lee, A Hogg, RF Anderson…

Index: Tercel; Lee; Hogg; Anderson; Siim; Denny; Wilson Journal of Medicinal Chemistry, 2001 , vol. 44, # 21 p. 3511 - 3522

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Citation Number: 46

Abstract

Nitrobenzyl quaternary salts of nitrogen mustards have been previously reported as hypoxia- selective cytotoxins. In this paper we describe the synthesis and evaluation of a series of heterocyclic analogues, including pyrrole, imidazole, thiophene, and pyrazole examples, chosen to cover a range of one-electron reduction potentials (from-277 to-511 mV) and substitution patterns. All quaternary salt compounds were less toxic in vitro than ...