129448-97-1Relevant articles and documents
Synthesis of the enantiomers of the dual function 2-nitroimidazole radiation sensitizer RB 6145
Sercel, Anthony D.,Beylin, Vladimir G.,Marlatt, Mark E.,Leja, Boguslawa,Showalter, H. D. Hollis,Michel, Andre
, p. 1597 - 1604 (2007/10/03)
Short, efficient pathways are described for the synthesis of racemic 2-nitroimidazole radiation sensitizer RB-6145 (2a) and each of its corresponding (R)- and (S)-enantiomers (2b and 2c, respectively). The synthesis of each enantiomer commences with the appropriate chiral epichlorohydrin and utilizes a novel application of 3-trimethylsilyl-2-oxazolidinone (3b) as a mild, safe surrogate for highly toxic aziridine. The synthesis of the (R)-enantiomer (2b) has been successfully scaled up to provide multi-kilo quantities of material for early stage preclinical evaluation.
Nitro-substituted aromatic or hetero-aromatic compounds for use in cancer treatment
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, (2008/06/13)
A compound for treating a patient having a solid tumor in which it is known or suspected that hypoxic cells are present, which is a compound of formula (A): STR1 wherein X represents a nitro-substituted aromatic or hetero-aromatic group with a one-electron reduction potential at pH 7 of from -250 to -500 mV; each of R'1 to R'5 independently represents hydrogen or an alkyl, hydroxyalkyl, aryl, aralkyl or alkaryl group; 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 cyclization reaction; 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.
