Rationale for the synthesis and preliminary biological evaluation of highly active new antitumor nitrosoureido sugars.

Abstract

Various new nitrosoureido derivatives of di- or trideoxy sugars were synthesized. The influence of the hydroxyl substitution pattern, the configuration at the anomeric center, and the absolute configuration of the sugar moiety on the antitumor activity of a series of nitrosoureido derivatives of di- and trideoxy sugars was studied. All compounds showed a very significant activity in vivo against L1210 leukemia, B16 melanocarcinoma, and Lewis lung carcinoma. Methyl 3-[3-(2-chloroethyl)-3-nitrosoureido]-2,3-dideoxy-alpha-D-arabino- hexopyranoside, 24 (NSC 609224), was found to be the most active compound. When treated with 24 (NSC 609224) at 20 mg/kg on day 1, at least 90% of the L1210 leukemia and B16 melanocarcinoma bearing mice showed a survival of over 60 days for a LD50 value for this compound of 42 mg/kg.

• Authors: P Roger, C Monneret, J P Fournier, P Choay, R Gagnet, C Gosse, Y Letourneux, G Atassi, A Gouyette
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 32 Issue 1 Pg. 16-23 (Jan 1989) ISSN: 0022-2623 [Print] United States
• PMID: 2909727 (Publication Type: Journal Article)

Chemical References

• Amino Sugars
• Antineoplastic Agents
• Nitrosourea Compounds

Topics

• Amino Sugars (chemical synthesis, pharmacology, toxicity)
• Animals
• Antineoplastic Agents (chemical synthesis, toxicity)
• Chemical Phenomena
• Chemistry
• Drug Evaluation, Preclinical
• Lethal Dose 50
• Leukemia L1210 (drug therapy)
• Melanoma, Experimental (drug therapy)
• Mice
• Mice, Inbred DBA
• Neoplasms, Experimental (drug therapy)
• Nitrosourea Compounds (chemical synthesis, pharmacology, toxicity)
• Structure-Activity Relationship