title: Synthesis of methylenecyclobutane analogues of nucleosides with axial chirality and their phosphoralaninates: a new pronucleotide effective against Epstein-Barr virus.
abstract: Methylenecyclobutane analogues of 2'-deoxyadenosine, 2'-deoxyguanosine and 2'-deoxycytidine, and the corresponding phosphoralaninate pronucleotides comprising adenine and guanine bases, were synthesized as potential antiviral agents. Phosphoralaninate of adenine methylenecyclobutane was a potent inhibitor of replication of Epstein-Barr virus (EBV) in Daudi cell culture. Phosphoralaninate of guanine analogue was inactive but both pronucleotides were substrates for porcine liver esterase. Adenine methylenecyclobutane analogue was deaminated by adenosine deaminase.
authors.affiliation: Department of Chemistry, Developmental Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Mich, USA.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Wang
authors.forename: Earl R
authors.initials: ER
authors.lastname: Kern
authors.forename: Jiri
authors.initials: J
authors.lastname: Zemlicka
mesh_terms: D000243:Adenosine Deaminase / Q000737:chemistry / Q000378:metabolism; D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D003503:Cyclobutanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003641:Deamination; D004950:Esterases / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects; D004854:Herpesvirus 4, Human / Q000187:drug effects*; D006801:Humans; D007928:Lethal Dose 50; D008099:Liver / Q000201:enzymology; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D000998:Antiviral Agents; D003503:Cyclobutanes; D009705:Nucleosides; D011355:Prodrugs; D004950:Esterases; D000243:Adenosine Deaminase; D000409:Alanine