Synthesis and antitumor activity of 2-beta-D-ribofuranosyloxazole-4-carboxamide (oxazofurin)

J Med Chem. 1990 Oct;33(10):2849-52. doi: 10.1021/jm00172a027.

Abstract

Condensation of 3,4,6-tri-O-benzoyl-2,5-anhydro-D-allonyl chloride (4) with ethyl 2-amino-2-cyanoacetate (5) provided 2-[(3',4',6'-tri-O-benzoyl-2',5'-anhydroallonyl)amino]-2-cyanoa cetate (6). Compound 6 was treated with hydrogen chloride gas to give ethyl 5-amino-2-(2',3',5'-tri-O-benzoyl-beta-D- ribofuranosyl)oxazole-4-carboxylate (8). Reductive dediazotization of blocked nucleoside 8 provided ethyl 2-(2',3',5'-tri-O- benzoyl-beta-D-ribofuranosyl)oxazole-4-carboxylate (10), which after deblocking with sodium methoxide and ammonolysis was converted to 2-beta-D-ribofuranosyl-oxazole-4-carboxamide (oxazofurin, 3), an analogue of the antitumor and antiviral C-nucleoside tiazofurin (1). Oxazofurin (3) was found to be cytotoxic toward B16 murine melanoma cells in culture but inactive against murine leukemia P388 and L1210.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Humans
  • In Vitro Techniques
  • Mice
  • Neoplasms, Experimental / drug therapy
  • Oxazoles / chemical synthesis*
  • Oxazoles / pharmacology
  • Ribavirin / analogs & derivatives
  • Ribavirin / chemistry
  • Ribavirin / pharmacology
  • Ribavirin / therapeutic use
  • Ribose / analogs & derivatives*
  • Ribose / chemical synthesis
  • Ribose / pharmacology
  • Structure-Activity Relationship
  • Tumor Cells, Cultured / drug effects

Substances

  • Antineoplastic Agents
  • Oxazoles
  • oxazofurin
  • Ribavirin
  • Ribose
  • tiazofurin