Examination of newly synthesized 2-chloroethylnitrosoureas in preterminal leukemia L 5222 and in two transplanted neurogenic tumors

Abstract

The chemotherapeutic activities of 11 chloroethylnitrosoureas, among them 10 newly synthesized compounds, were investigated in rat leukemia L 5222 and in two neurogenic rat tumors. 1-(4-Amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU, compound 1) and cyclophosphamide (12) served as reference substances. The newly synthesized compounds were 1-(2-chloroethyl)-1-nitroso-3-(2-carboxyethyl)-urea (2-carboxyethyl-CNU, 2), 1-(2-chloroethyl)-1-nitroso-4-methyl-4-formyl-semicarbazide (methyl-formyl-amino-CNU, 3), 1-(2-chloroethyl)-1-nitroso-3-(methylene-2-pyridyl)-urea(methylene-2-pyridyl- CNU, 4), 1-(2-chloroethyl)-1-nitroso-3-(methylene-2-pyridyl)-urea hydrochloride (methylene-2-pyridyl-CNU . HCl, 5) 1-(2-chloroethyl)-1-nitroso-3-(methylene-4-pyridyl)-urea hydrochloride (methylene-4-pyridyl-CNU . HCl, 6), 1-(2-chloroethyl)-1-nitroso-3-(3-pyridino)-urea (pyridyl-3-CNU, 7), 1-(2-chloroethyl)-1-nitroso-3-(3-pyridyl)-urea hydrochloride (pyridyl-3-CNU . HCl, 8), 1-(2-chloroethyl)-1-nitroso-3-[4(2,6-dimethyl-morpholino)]-urea (dimethyl-morpholino-CNU, 9), 1-(2-chloroethyl)-1-nitrosocarbamoyl-morpholine (chloroethyl-nitroso-carbamoyl-morpholine, 10), 1-(2-chloroethyl)-1-nitroso-carbamoyl-2,6-dimethyl-morpholine (chloroethyl-nitroso-carbamoyl-dimethylmorpholine, 11). Against both neurogenic tumors cyclophosphamide was distinctly superior to all nitrosoureas. In leukemia L 5222 all nitrosoureas except compounds 7, 8, 11 effected cures. Remarkable differences in toxicity could be observed between the nitroso compounds investigated.