Studies on synthesis and anticancer activity of selected N-(2-fluoroethyl)-N-nitrosoureas.
An activated carbamate, 2-nitrophenyl (2-fluoroethyl)nitrosocarbamate (3), was used to advantage in the synthesis of the water-soluble (2-fluoroethyl)nitrosoureas 6a--d from 2-aminoethanol, (1 alpha, 2 beta, 3 alpha)-2-amino-1,3-cyclohexanediol, cis-2-hydroxycyclohexanol, and 2-amino-2-deoxy-D-glucose. In a variation of this method, 2,4,5-trichlorophenyl (2-fluoroethyl)carbamate (4) was used to prepare the urea from which the essentially water-insoluble N-(2,6-dioxo-3-piperidinyl)-N-(2-fluoroethyl)-N-nitrosourea (6e) was derived. The anticancer activity of these nitrosoureas was determined against the murine tumors B16 melanoma and Lewis lung carcinoma and found to be significant and comparable to their chloroethyl counterparts. On the basis of results from both systems, the dihydroxycyclohexyl derivative 6b may be the most effective.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D004980:Ethane / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000627:therapeutic use; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis / Q000627:therapeutic use; D008545:Melanoma / Q000188:drug therapy; D051379:Mice; D009607:Nitrosourea Compounds / Q000138:chemical synthesis* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D006845:Hydrocarbons, Fluorinated; D009607:Nitrosourea Compounds; D004980:Ethane