Synthesis of analogs of N-(2-chloroethyl)-N'-(trans-4-methylcyclohexyl)-N-nitrosourea for evaluation as anticancer agents

Publisher Website
Google Scholar
Abstract
The superior activity of N-(2-chloroethyl)-N''-(trans-4-methylcyclohexyl)-N-nitrosurea (MeCCNU) against advanced murine Lewis lung carcinoma in comparisons with the cis form and other nitrosoureas prompted the synthesis of a number of MeCCNU analogues, including several cis-trans pairs. The methyl group was replaced by a variety of substituents; the trans-3-methylcyclohexyl, cis-2-methyl-1,3-dithian-5-yl, cis- and trans-2-methyl-1,3-dithian-5-yl tetraoxide and 1-methylhexyl (open-chain) analogues were also prepared. Preliminary tests against murine leukemia L1210 revealed therapeutic indices (ED50/LD10) ranging from 0.26-0.79; all but 3 analogues effected 50% cure rates at nontoxic doses, the open-chain analogue being one of the least active. In terms of therapeutic index, diequatorial (trans-4) isomers were, with 1 exception, as active as, or, in 4 of the 8 examples, somewhat more active than the corresponding axial-equatorial (cis-4) isomers. In this series, 4 of the 5 2-fluoroethyl analogues prepared were clearly inferior to the corresponding 2-chloroethyl analogues.

This publication has 2 references indexed in Scilit: