N-nitroso ureido substd sugars - as anti-leukaemia and anti-tumour agents of low toxicity

摘要

Nitrosoureas of formula (I) are new: (A = glycosyl; a monovalent 2-deoxy-methylglucoside or -alditol residue; N-substd. carbamoyloxyalkyl or hydroxy-substd. cyclohexyl when n = 1; or when n = 4 a tetravalent residue of ribostamycin from which the 4 NH2 gps. have been eliminated; R = opt. halogenated lower alkyl provided that R is not CH3 when A = glucosyl). They are prepd. by nitrosation (e.g. alkali metal nitrite/acid) of corresp. urea. (I) are anti-leukaemia and anti-tumour agents of low toxicity. Thus 1-(2-chloroethyl)-3-(Beta-D-glucopyrannosyl)-1-nitrosourea has LD50 (i.p. mouse) about 25 mg/kg and when administered to mice inoculated with 2.1 x 106 L1210 leukaemia cells at 10 kg/kg (i.p.; 1 dose 24 hr. after inoculation then for 3 days) increased survival time from 9.3 days to 95.9 days. (I) are also inters. for other pharmaceuticals.