Design, Synthesis, and Biological Evaluation of Cyclic and Acyclic Nitrobenzylphosphoramide Mustards for E. c oli Nitroreductase Activation

…, SO Vass, PF Searle, P Browne, RJ Knox…

Index: Jiang, Yongying; Han, Jiye; Yu, Chengzhi; Vass, Simon O.; Searle, Peter F.; Browne, Patrick; Knox, Richard J.; Hu, Longqin Journal of Medicinal Chemistry, 2006 , vol. 49, # 14 p. 4333 - 4343

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Citation Number: 45

Abstract

In efforts to obtain anticancer prodrugs for antibody-directed or gene-directed enzyme prodrug therapy using E. coli nitroreductase, a series of nitrobenzylphosphoramide mustards were designed and synthesized incorporating a strategically placed nitro group in a position para to the benzylic carbon for reductive activation. All analogues were good substrates of E. coli nitroreductase with half-lives between 2.9 and 11.9 min at pH 7.0 and ...