Nitrosoalkylureas derived from alkylideneammonium salts and their antitumor activity

A Critical Appraisal of the Evolution ofN-Nitrosoureas as Anticancer Drugs

“…Some undefined polymethylene bisCENUs were reported. 147 The bistertiary 110 and 111, and bisquaternary 112-114 ammonium analogs (Table 4) were synthesized, 148,149 because it was found 125 that the quaternary ammonium cations are capable of selectively accumulating in connective tissue as a result of ionic bonding with sulfate and phosphate anions present in the chondroitin sulfate and cellular DNA, resulting in bridged structures. The synthesis of these compounds is outlined in Scheme 20a,b.…”

“…The synthesis of these compounds is outlined in Scheme 20a,b. These bisquaternary congeners were more active 149 than the monoquaternary compounds 59, and the bistertiary amine CENU (110) was the most active against L1210 leukemia in vivo (Table 4). Lengthening the distance between the nitrogen atoms caused an increase in the toxicity of these compounds.…”

“…Lengthening the distance between the nitrogen atoms caused an increase in the toxicity of these compounds. 149 These compounds also were evaluated 149 against the solid tumor lines of mammary adenocarcinoma, Lewis lung carcinoma, and sarcoma.…”