Synthesis and biological activities of some uronic acids, uronates, uronamides, and urononitriles of pyrimidine nucleosides.
The 5'-hydroxymethylene function of several uracil and cytosine nucleosides has been modified to produce a variety of uronic acids, uronates, uronamides, and urononitriles of 2'-deoxy-beta-D-erythro-pentofuranosyl- and beta-D-arabino-pentofuranosylpyrimidines. In addition, the 5 position in many of these nucleosides has been substituted by a halogen atom. Twenty-one of the 35 compounds synthesized and examined for biological activity have not been previously reported. The purity of the products was measured by a high-pressure liquid chromatographic method. They were then evaluated as potential growth inhibitors of murine Sarcoma 180 cells in culture, of herpes simplex virus type 1 in vitro, and of Streptococcus faecium, a folic acid or deoxythymidine dependent bacterial strain. The ability of these nucleoside analogues to inhibit the phosphorylation of deoxythymidine by herpes simplex virus type 1 encoded pyrimidine deoxyribonucleoside kinase was also investigated and a structure-activity relationship examined.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D012510:Sarcoma 180 / Q000473:pathology; D018139:Simplexvirus / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects / Q000254:growth & development; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors; D014574:Uronic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D011741:Pyrimidine Nucleosides; D014574:Uronic Acids; D013940:Thymidylate Synthase; D013937:Thymidine Kinase