Cytostatics. 22. Tumor inhibitory N-[bis(2-chloroethyl)aminomethyl]urethanes

Abstract

Six title compds. inhibited Yoshida ascites sarcoma in rats. The most active compds., N-[bis(2-chloroethyl)aminomethyl]benzylurethane [58050-46-7] and N-[bis(2-chloroethyl)aminomethyl]phenylurethane [58050-47-8], were curative when given at 60% of the LD50 i.m. distributed over 10 days. The LD50 values of the compds. in rats were 11-55 mg/kg i.m. N,N'-di[bis(2-chloroethyl)aminomethyl]urea [58050-48-9] was considerably less effective owing to its greater instability under physiol. conditions. Similar results were observed after injecting the compds. i.p. into mice bearing sarcoma 180. The antitumor activity of the compds. was evidently due to direct aminoethylation of nucleophilic substrates, as with arom. N mustards, rather than indirect aminoethylation or amidomethylation. The compds. were prepd. by neutralization of bis(2-chloroethyl)amine-HCl [821-48-7], condensation with formaldehyde [50-00-0], and reaction with the appropriate amide.