651733-08-3Relevant articles and documents
Nitroaryl phosphoramide compositions and methods for targeting and inhibiting undesirable cell growth or proliferation
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Page 12, (2010/02/09)
The present invention relates to nitroaryl-substituted phosphoramide prodrug compounds and methods of producing the same for use in targeting and inhibiting undesirable cell growth or proliferation.
Nitrobenzocyclophosphamides as potential prodrugs for bioreductive activation: Synthesis, stability, enzymatic reduction, and antiproliferative activity in cell culture
Li, Zhuorong,Han, Jiye,Jiang, Yongying,Browne, Patrick,Knox, Richard J.,Hu, Longqin
, p. 4171 - 4178 (2007/10/03)
In efforts to obtain potential anticancer prodrugs for gene-directed enzyme prodrug therapy using Eschericia coli nitroreductase, a series of four benzocyclophosphamide analogues were designed and synthesized incorporating a strategically placed nitro group in a position para to the benzylic carbon for reductive activation. All four analogues were found to be stable in phosphate buffer at pH 7.4 and 37 °C and were good substrates of E. coli nitroreductase with half lives between 7 and 24 min at pH 7.0 and 37 °C. However, only two analogues 6a and 6c, both with a benzylic oxygen in the phosphorinane ring para to the nitro group, showed a modest 33-36-fold enhanced cytotoxicity in E. coli nitroreductase-expressing cells. These results suggest that good substrate activity and the para benzylic oxygen are required for activation by E. coli nitroreductase. Compounds 6a and 6c represent a new structure type for reductive activation and a lead for further modification in the development of better analogues with improved selective toxicity to be used in gene-directed enzyme prodrug therapy.
