title: Fluorinated analogues of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea: an attempt to control metabolism.
abstract: In seeking to block and thereby determine the role of the rapid in vivo hydroxylation of the cyclohexyl moiety of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in relation to antitumor activity and tissue distribution, the 3-(1H-decafluorocyclohexyl) analogue (FCCNU) was synthesized. FCCNU showed marked toxicity and little activity against the intracerebral L1210 leukemia in mice. At pH 7 in phosphate buffer at room temperature FCCNU rapidly decomposed to give 1-(1H-decafluorocyclohexyl)-3-nitrosoimidazolidin-2-one (3) and thence, by loss of HF, the 1-(nonafluorocyclohexenyl) derivative (4); CCNU did not follow this decomposition pathway to any significant extent. Both 3 and 4 were unstable in the buffer, but each was isolated crystalline and characterized. The formation of 3 and 4 account for the biological properties of FCCNU.
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism; D005260:Female; D007939:Leukemia L1210 / Q000188:drug therapy; D008130:Lomustine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000378:metabolism; D008223:Lymphoma / Q000188:drug therapy; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009607:Nitrosourea Compounds / Q000138:chemical synthesis*
chemical_list: D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D008130:Lomustine