Alkylating nucleosides. 2. Synthesis and cytostatic activity of bromomethylpyrazole and pyrazole nitrogen mustard nucleosides

J Med Chem. 1979 Jul;22(7):807-11. doi: 10.1021/jm00193a011.

Abstract

Glycosylation of ethyl 3(5)-(bromomethyl)pyrazole-5(3)-carboxylate (3) and 3(5)-(bromomethyl)pyrazole-5(3)-carboxamide (4) with poly-O-acetylated sugars via an acid-catalyzed fusion method afforded the corresponding ethyl 3-(bromomethyl)pyrazole-5-carboxylate and 3-(bromomethyl)pyrazole-5-carboxamide substituted nucleosides 5 and 7, respectively. In some cases, the positional isomers 6 and 8 were also obtained. Treatment of 5 and 7 with methanolic ammonia gave the deprotected 3-(aminomethyl)pyrazole-5-carboxamide nucleosides 9. Reaction of 3--5 and 7 with bis(2-chloroethyl)amine led to the corresponding pyrazole nitrogen mustards 10--13. All the bromomethylpyrazole nucleosides described showed significant cytostatic activity against HeLa cell cultures.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Cell Survival / drug effects
  • Female
  • HeLa Cells
  • Humans
  • Nitrogen Mustard Compounds / chemical synthesis*
  • Nitrogen Mustard Compounds / pharmacology
  • Nucleosides / chemical synthesis*
  • Nucleosides / pharmacology
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / pharmacology

Substances

  • Antineoplastic Agents
  • Nitrogen Mustard Compounds
  • Nucleosides
  • Pyrazoles