Synthesis and antitumour activity of a new series of nitrosoureido sugars.
New nitrosoureido derivatives of di- or tri-deoxy-sugars have been synthesized. Very potent antitumour activity against L1210 leukaemia was exhibited by the compounds derived from methyl 3-amino-3, 4-dideoxy-beta- and alpha- and 4-amino-2,4-dideoxy-beta- and alpha-D-arabino-hexopyranosides, 24, 26, 28 and 29, respectively. In further evaluation against B16 melanocarcinoma bearing mice, only compounds 24 and 26 displayed significant activity. Owing to its lower acute toxicity, methyl 3-[3-(2-chloroethyl)-3-nitrosoureido]-3, 4-dideoxy-beta-D-arabino-hexopyranoside 24 appeared as the best candidate for preclinical studies.
Monneret
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C
Laboratoire de pharmacochimie, unité mixte 176 CNRS/ Institut Curie, 26, rue d'Ulm, F-75248, Paris, France. Claude.Monneret@curie.fr
Rissé
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S
Ardouin
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P
Gouyette
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A
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use*; D002330:Carmustine / Q000627:therapeutic use; D005960:Glucosides / Q000138:chemical synthesis* / Q000627:therapeutic use*; D007939:Leukemia L1210 / Q000188:drug therapy; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009607:Nitrosourea Compounds / Q000138:chemical synthesis* / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D005960:Glucosides; D009607:Nitrosourea Compounds; C409495:methyl 3,4-dideoxy-3-(2-chloroethyl)nitrosoureidoglucoside; D002330:Carmustine