Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Physical Sciences, Biochemistry & Molecular Biology, Chemistry, Organic, Chemistry, smallpox, vaccinia virus, cowpox virus, thymidine kinase, ANTI-ORTHOPOXVIRUS ACTIVITY, C-NUCLEOSIDES, POXVIRUS INFECTIONS, PROTECTS MICE, CIDOFOVIR, INHIBITION, POTENT, DINUCLEOTIDE, CHALLENGE, THYMIDINE, Antiviral Agents, Microbial Sensitivity Tests, Molecular Structure, Nucleosides, Orthopoxvirus, RNA Viruses, Stereoisomerism, Structure-Activity Relationship, 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, Organic Chemistry, 3404 Medicinal and biomolecular chemistry, 3405 Organic chemistry

Abstract:

To develop an understanding of the structure-activity relationships for the inhibition of orthopoxviruses by nucleoside analogues, a variety of novel chemical entities were synthesized. These included a series of pyrimidine 5-hypermodified acyclic nucleoside analogues based upon recently discovered new leads, and some previously unknown "double-headed" or "abbreviated" nucleosides. None of the synthetic products possessed significant activity against two representative orthopoxviruses; namely, vaccinia virus and cowpox virus. They were also devoid of significant activity against a battery of other DNA and RNA viruses. So far as the results with the orthopoxviruses and herpes viruses, the results may point to the necessity for nucleoside analogues 5'-phosphorylation for antiviral efficacy.