129448-95-9Relevant academic research and scientific papers
Synthesis and Evaluation of α-methyl>-2-nitro-1H-imidazole-1-ethanols as Prodrugs of α--2-nitro-1H-imidazole-1-ethanol (RSU-1069) and Its Analogues Which Are Radiosensitizers and Bioreductively Activated Cytotoxins
Jenkins, Terence C.,Naylor, Matthew A.,O'Neill, Peter,Threadgill, Michael D.,Cole, Shirley,et al.
, p. 2603 - 2610 (1990)
α--2-nitro-1H-imidazole-1-ethanols, of general formula , where Im = 2-nitroimidazole and R1, R2, R3, R4 = H, Me, are radiosensitizers and selective bioreductively activated cytotoxins toward hypoxic tumor cells in vitro and in vivo.Treatment of the aziridines with hydrogen halide in acetone or aqueous acetone gave the corresponding 2-haloethylamines of general formula ImCH2CH(OH)CH2+-NH2CR1R2CR3R4XX-, where R1, R2, R3, R4 = H, Me, and X = F, Cl, Br, I.These 2-haloethylamines were evaluated as prodrugs of the parent aziridines.The rates of ring closure in aqueous solution at pH ca. 6 were found to increase with increasing methyl substitution and to depend on the nature of the leaving group (I ca.Br > Cl >> F).A competing reaction of ImCH2CH(OH)CH2+NH2CH2CH2XX- (X = Cl, Br) with aqueous HCO3- ions gives 3--2-oxazolidinone.The activities of these prodrugs as radiosensitizers or as bioreductively activated cytotoxins were consistent with the proportion converted to the parent aziridine during the course of the experiment. α-methyl>-2-nitro-1H-imidazole-1-ethanol (RB 6145, 10), the prodrug of α--2-nitro-1H-imidazole-1-ethanol (RSU-1069, 3), is identified as the most useful compound in terms of biological activity and rate of ring closure under physiological conditions.
