Antineoplastic agents. 1. Synthesis and antineoplastic activities of chloroethyl- and methylnitrosourea analogues of thymidine.

A new class of chloroethyl- and methylnitrosourea analogues of thymidine, 5a,b, 6, 10, and 11, has been synthesized from the corresponding amino nucleosides, 2 and 7. The 3'-chloroethyl and 3'-methyl derivatives, 10 and 11, inhibited L1210 cell growth in culture (ED50 = 1.5 and 1.0 micrometer, respectively) more effectively than 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (ED50 = 4 micrometer) and the 5'-nitrosourea analogues. Neither the alkylating nor the carbamoylating activities of these compounds correlated with their biological activity.