Alkylating nucleosides. 4. Synthesis and cytostatic activity of chloro- and iodomethylpyrazole nucleosides
- 31 May 1980
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 23 (6) , 657-660
- https://doi.org/10.1021/jm00180a015
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 nucleosides showed moderate activities against HeLa [human cervical carcinoma] cells, while all the corresponding iodomethyl derivatives exhibited high activities. Some of these latter compounds increased the life span of mice bearing ECA [Ehrlich ascites carcinoma] tumor.This publication has 0 references indexed in Scilit: