title: Alkylating nucleosides. 4. Synthesis and cytostatic activity of chloro- and iodomethylpyrazole nucleosides.
abstract: The synthesis and cytostatic activity of several chloromethyl- and iodomethylpyrazole nucleosides are described. Glycosylation of ethyl 3(5)-(chloromethyl)pyrazole-5(3)-carboxylate (3) and 3(5)-(chloromethyl)pyrazole-5(3)-carboxamide (4) with poly(O-acetylated) sugars via an acid-catalyzed fusion method gave the corresponding 3-(chloromethyl)-5-carboxylate and 3-(chloromethyl)-5-carboxamide substituted nucleosides 7 and 9, respectively. From the reaction of 4 with tetra-O-acetyl-beta-D-ribofuranose, the 5-(chloromethyl)-3-carboxamide-substituted derivative 11 was also obtained. Reaction of 7, 9, and 11 with sodium iodide in acetone provided the related iodomethylpyrazole nucleosides 8, 10, and 12. In general, chloromethyl-substituted nucleotides showed moderate activities against HeLa cells, while all the corresponding iodomethyl derivatives exhibited high activities. Some of these latter compounds increased the life span of mice bearing ECA tumor.
mesh_terms: D000477:Alkylating Agents / Q000138:chemical synthesis*; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009705:Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000477:Alkylating Agents; D009705:Nucleosides; D011720:Pyrazoles