(+-)-carbocyclic 5'-nor-2'-deoxyguanosine and related purine derivatives: synthesis and antiviral properties

J Med Chem. 1992 Jun 12;35(12):2191-5. doi: 10.1021/jm00090a007.

Abstract

Beginning with 3-cyclopenten-1-ylamine hydrochloride, the 5'-nor derivatives of carbocyclic 2'-deoxyguanosine (2), 2'-deoxyadenosine (3), and 2,6-diaminopurine 2'-deoxyribofuranoside (4) have been prepared. These compounds were evaluated for antiviral potential versus herpes simplex virus, varicella-zoster virus, cytomegalovirus, vaccinia virus, vesicular stomatitis virus, and human immunodeficiency virus and found to lack activity. Also, compounds 2-4 were virtually nontoxic toward the host (human diploid fibroblast ESM and HEL) cells. These biological properties may be due to the inability of 2-4 to be phosphorylated to the requisite nucleotide level that is likely to be necessary for biological activity by correlation to carbocyclic 2'-deoxyguanosine (1), which possesses significant antiviral properties as a result of conversion to its 5'-triphosphate derivative.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2-Aminopurine / analogs & derivatives
  • 2-Aminopurine / chemistry
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology
  • Cytomegalovirus / drug effects
  • Deoxyadenosines / chemistry
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / chemical synthesis
  • Deoxyguanosine / chemistry
  • Deoxyguanosine / pharmacology
  • HIV-1 / drug effects
  • HIV-2 / drug effects
  • Herpesvirus 3, Human / drug effects
  • Molecular Structure
  • Simplexvirus / drug effects
  • Structure-Activity Relationship
  • Vaccinia virus / drug effects
  • Vesicular stomatitis Indiana virus / drug effects

Substances

  • Antiviral Agents
  • Deoxyadenosines
  • carbocyclic 5'-nor-2'-deoxyguanosine
  • 2-Aminopurine
  • 2,6-diaminopurine
  • Deoxyguanosine