33845-63-5Relevant academic research and scientific papers
Hypoxia-Selective Antitumor Agents. 11. Chlorambucil N-Oxide: A Reappraisal of Its Synthesis, Stability, and Selective Toxicity for Hypoxic Cells
Tercel, Moana,Wilson, William R.,Denny, William A.
, p. 1247 - 1252 (2007/10/02)
The potential hypoxia-selective cytotoxin 4-phenyl>butanoic acid N-oxide (chlorambucil N-oxide, 4) was synthesized and characterized as its hydrochloride salt.This compound was shown to be unstable, decomposing in some organic solvents to the hydroxylamine 4-phenyl>butanoic acid (11) by a mechanism previously demonstrated for aliphatic mustard N-oxides and under aqueous conditions to a more complex mixture, of which the predominant components were the monochloroethyl derivative 7 and formaldehyde.Comparison of NMR spectra showed that a recent published synthesis of 4 in fact resulted in the rearrangement product 11, indicating that recent reported investigations of the hypoxia-selective cytotoxicity and metabolism of chlorambucil N-oxide have examined this rearrangement product rather than 4.In a clonogenic assay, 4 was less cytotoxic against AA8 cells than was chlorambucil, but the effect of oxygen on cytotoxicity was no greater than for chlorambucil itself.
Synthesis of Novel N- and S-Mustards as Potential Pro-drugs Activated by Bioreductive Processes
Mann, John,Shervington, Leroy A.
, p. 2961 - 2964 (2007/10/02)
We describe the synthesis of 4-phenyl>butanoic acid N-oxide, which is the N-oxide of the anti-cancer drug chlorambucil, and 4--butanoic acid.The 3-nitro and 3,6-dinitro derivatives of chloram
SYNTHESIS AND SPONTANEOUS DECOMPOSITION OF THE N-OXIDES OF DI(2-CHLOROALKYL)AMINOPHENYLALKANOIC ACIDS
Degutene, A.,Dzhyuvene, D.,Shukyalene, D.,Degutis, Yu.
, p. 1968 - 1972 (2007/10/02)
A convenient method was developed for the production of the N-oxides of di(2-chloroethyl)aminophenylalkanoic acids.In an acidic medium the main products from their spontaneous decomposition are the corresponding di(2-chloroalkyl)aminophenylalkanoic acids, while in an alkaline medium they are 2-chloroalkylaminophenylalkanoic acids and the simple aldehydes.The cleavage of the N-oxides of di(2-chloroethyl)aminophenylalkanoic acids leads to the formation of formaldehyde, whereas the dissociation of the di(2-chloropropyl)-N-oxide group gives a mixture of formaldehyde and acetaldehyde in a ratio of 1:1.The analogous N-oxides containing oxygen instead of the halogen atoms do not decompose under these conditions.
