Alkylating nucleosides 1. Synthesis and cytostatic activity of N-glycosyl(halomethyl)-1,2,3-triazoles. A new type of alkylating agent

J Med Chem. 1979 May;22(5):496-501. doi: 10.1021/jm00191a007.

Abstract

1,3-Dipolar cycloaddition of benzyl azide or peracetylated glucopyranosyl azides to propargyl halides or 1,4-dihalobutynes yielded 1-benzyl- or 1-glycosyl(halomethyl)-1,2,3-triazoles. Alkylating chloromethyl- bromomethyl- and iodomethyl-1,2,3-triazoles were also obtained from the corresponding hydroxymethyl derivatives by treatment with (C6H5)3P/CCl4, (C6H5O)3P/Br2, and (C6H5O)3P/I2, respectively. 1-Benzyl-4-(fluoromethyl)-1,2,3-triazole was obtained from 1-benzyl-4-(bromomethyl)-1,2,3-triazole by treatment with KF and 18-crown-6. Chloromethyl-, bromomethyl-, and iodomethyl-1,2,3-triazole derivatives inhibited the "in vitro" growth of HeLa cells. Some of these compounds increased the life span of mice bearing tumors.

MeSH terms

  • Alkylating Agents / chemical synthesis*
  • Alkylating Agents / therapeutic use
  • Animals
  • Carcinoma, Ehrlich Tumor / drug therapy
  • Carcinoma, Ehrlich Tumor / metabolism
  • Cell Survival / drug effects
  • DNA, Neoplasm / biosynthesis
  • Female
  • HeLa Cells
  • Humans
  • Mice
  • Nucleosides / chemical synthesis*
  • Nucleosides / pharmacology
  • Nucleosides / therapeutic use
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis*
  • Triazoles / pharmacology
  • Triazoles / therapeutic use

Substances

  • Alkylating Agents
  • DNA, Neoplasm
  • Nucleosides
  • Triazoles