Nucleosides and nucleotides. 185. Synthesis and biological activities of 4'alpha-C-branched-chain sugar pyrimidine nucleosides

J Med Chem. 1999 Jul 29;42(15):2901-8. doi: 10.1021/jm990050i.

Abstract

A series of 4'alpha-C-branched-chain pyrimidine nucleosides was synthesized from 2'-deoxycytidine or uridine. In the 2'-deoxycytidine series, the substituent at the 4'alpha-position affected cytotoxicity against L1210 mouse leukemic cells in vitro in the order Me (23) > CN (22) > C(symbol)CH (21) > CH=CH(2) (19) > Et (24) > CH=CHCl (20). However, uridine and cytidine derivatives with ethynyl and cyano groups at the 4'alpha-position did not show any cytotoxicity. The antiviral activities of these nucleosides against HSV-1, HSV-2, and HIV-1 in vitro were also examined. Compounds 22 and 23 showed antiviral activities against HSV-1 and HSV-2 without showing significant toxicity to the host cells (MRC-5 cells). Although almost all of the nucleosides showed anti-HIV-1 activities, they were also cytotoxic to the host cells (MT-4).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Carbohydrates / chemical synthesis*
  • Carbohydrates / chemistry
  • Carbohydrates / pharmacology
  • Drug Screening Assays, Antitumor
  • HIV-1 / drug effects
  • Herpesvirus 1, Human / drug effects
  • Herpesvirus 2, Human / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Pyrimidine Nucleosides / chemical synthesis*
  • Pyrimidine Nucleosides / chemistry
  • Pyrimidine Nucleosides / pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Anti-HIV Agents
  • Antineoplastic Agents
  • Antiviral Agents
  • Carbohydrates
  • Pyrimidine Nucleosides