129448-98-2Relevant articles and documents
Potentiation of bioreductive agents
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, (2008/06/13)
A human or animal subject having a solid tumour is treated by administering to the subject therapeutically effective amounts of a nitric oxide (NO) synthase inhibitor and a compound which is an imidazole or 1,2,4-triazole derivative of formula (A) STR1 wherein X is selected from the group consisting of STR2 wherein R is hydrogen or a C 1 -C 6 alkyl group; each of R'' 1 to R'' 5 is independently selected from the group consisting of hydrogen, C 1 -C 6 alkyl, hydroxy(C 1 -C 6 alkyl), phenyl, (C 1 -C 6 alkyl)phenyl and phenyl(C 1 -C 6 alkyl); m is 0 or 1; n is 1 or 2; and Z'' represents a leaving group which has the potential for expulsion via an intramolecular cyclisation reaction and which is not negatively-charged; or a physiologically acceptable acid addition salt thereof.
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 (2007/10/02)
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.
