title: Synthesis and evaluation of novel phosphoramidate prodrugs of 2'-methyl cytidine as inhibitors of hepatitis C virus NS5B polymerase.
abstract: A variety of new prodrugs of 2'-methyl cytidine based on acyloxy ethylamino phosphoramidates have been synthesized and tested in vitro and in vivo for their biological activity. Compared with the parent drug a 10- to 20-fold increase in formation of nucleotide triphosphate in rat and human hepatocytes could be achieved.
authors.affiliation: Department of Medicinal Chemistry, IRBM-MRL Rome, Via Pontina Km 30,600, 00040 Pomezia (Rome), Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Donghi
authors.forename: Barbara
authors.initials: B
authors.lastname: Attenni
authors.forename: Cristina
authors.initials: C
authors.lastname: Gardelli
authors.forename: Annalise Di
authors.initials: AD
authors.lastname: Marco
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Fiore
authors.forename: Claudio
authors.initials: C
authors.lastname: Giuliano
authors.forename: Ralph
authors.initials: R
authors.lastname: Laufer
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Leone
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Pucci
authors.forename: Michael
authors.initials: M
authors.lastname: Rowley
authors.forename: Frank
authors.initials: F
authors.lastname: Narjes
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003562:Cytidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000379:methods; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000821:virology; D006801:Humans; D010756:Phosphoric Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000577:Amides; D010756:Phosphoric Acids; D011355:Prodrugs; D017361:Viral Nonstructural Proteins; C513402:2'-C-methylcytidine; D003562:Cytidine; C011067:phosphoramidic acid; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase