T. Johnston, G. Mccaleb, J. Montgomery
Jun 1, 1975
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0
Influential Citations
20
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Quality indicators
Journal
Journal of medicinal chemistry
Abstract
N-(2-chloroethyl)-N'-(cis-4-hydroxycylohexyl)-N-nitrosourea, a major metabolite of N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea (CCNU), and its trans isomer were prepared from the corresponding 4-aminocyclohexanols. A convenient and stereospecific precursor was found in 2-oxa-3-azabicyclo[2.2.2]oct-5-ene hydrochloride, hydrogenation giving pure cis-4-aminocyclohexanol hydrochloride. The metabolites were, at nontoxic levels, at least as active as CCNU in tests against murine leukemia L1210 implanted both intraperitoneally and intracerebrally and, on a weight basis, were more active and more toxic. These observations and previously reported metabolic studies suggest that the anticancer activity of CCNU is due primarily to its metabolites.