No abstract

Syntheses of N‐[N'‐(2‐chloroethyl)‐N'‐nitrosocarbamoyl]amino acid amides and esters as potential antineoplastic substances are reported. N‐[N'‐(2‐chloroethyl)‐N'‐nitrosocarbamoyl]amino acids (with the exception of the glycine derivative) were prepared by reaction of 2‐chloroethyl isocyanate with the sodium salt of an amino acid in a heterogenous medium followed by nitrosation with sodium nitrite under acidic conditions. Condensation with amines or alcohols using 1,1‐carbonyldiimidazole led to the amides or esters.

Syntheses of steroid-linked N-[N'-(2-chloroethyl)-N'-nitrosocarbamoyl]-(CNC-) amino acid esters and -amides with potential antineoplastic activity are described. The esters are prepared by reaction of CNC-amino acids with steroids using N,N'-carbonyldiimidazole and N,N'-dicyclohexylcarbodiimide. The corresponding amides are prepared by reaction of 1-(CNC-amino acyloxy)-pyrrolidine-2,5-diones with 17 beta-amino-3-hydroxy-1,3,5(10)-estratriene or 17 beta-O-[4-(6-aminohexylamino)-1,4-dioxo-butyl]-estradiol. Estradiol-17 beta-hemisuccinate is esterified with N-(2-hydroxyethyl)-N'-(2-chloro-ethyl)-N'-nitrosourea (HECNU). Spectroscopic characteristics and relative binding affinities to steroid receptors are given.