Synthesis of purine nucleoside nitrosoureas and their antitumor activities.

Abstract

Guanine and xanthine nucleoside derivatives (3, 4 and 6) bearing nitrosourea functional groups were synthesized from guanine nucleoside ureas (2) obtained by the reaction of 2'-deoxy-2'-aminoguanosine (1) with isocyanates and their antitumor activity against sarcoma-180 solid tumor and leukemia L-1210 were determined. Among the compounds tested, 2'-deoxy-2'-[3-(2-chloroethyl)-3-nitrosoureido]-xanthosine (4b) found to have the most potent activity. Moreover, very slight decrease in white blood cells of mice bearing sarcoma-180 solid tumor was observed after administration of 4b.