Nucleic acid related compounds. 47. Synthesis and biological activities of pyrimidine and purine "acyclic" nucleoside analogs

Abstract

Various acyclic, i.e., (2-hydroxyethoxy)methyl and (2-acetoxyetoxy)methyl, analogs of pyrimidine and purine nucleosides were prepared and evaluated for their antiviral [rabbits infected with herpes simplex virus, vaccinia virus and vesicular stomatitis virus], antimetabolic and cytotoxic [murine leukemia L1210 cells] properties. All of the pyrimidine analogs, including (E)-5-(2-bromovinyl)-1-[(2-hydroxyethoxy)methyl]uracil and its O-acetyl derivative, were virtually devoid of antiviral, cytotoxic and antimetabolic activities. Several of the 8-substituted derivatives of 9-[(2-hydroxyethoxy)methyl]guanine (acyclovir) had higher antiviral specificity in vitro than the parent drug. The 8-methyl-, 8-amino-, 8-bromo- and 8-iodoacyclovir derivatives had activities worthy of further investigation.