title: Bifunctional aryloxyphosphoramidate prodrugs of 2'-C-Me-uridine: synthesis and anti-HCV activity.
abstract: In an attempt to identify novel nucleoside phosphoramidate analogues for improving the anti-HCV activity of 2'-C-Me-uridine, we have synthesized for the first time a series of l-glutamic acid, l-serine, l-threonine and l-tyrosine containing aryloxyphosphoramidate prodrugs of 2'-C-Me-uridine. Evaluation of their activity against HCV revealed that they displayed very potent anti-HCV activity, with EC50values that are in the same range as of Sofosbuvir.
authors.affiliation: KU Leuven, Rega Institute, Laboratory of Medicinal Chemistry, Minderbroedersstraat 10, 3000 Leuven, Belgium. Piet.Herdewijn@kuleuven.be.
authors.forename: Munmun
authors.initials: M
authors.lastname: Maiti
authors.affiliation: KU Leuven, Rega Institute, Laboratory of Medicinal Chemistry, Minderbroedersstraat 10, 3000 Leuven, Belgium. Piet.Herdewijn@kuleuven.be.
authors.forename: Ling-Jie
authors.initials: LJ
authors.lastname: Gao
authors.affiliation: Southern Research, Infectious Disease Research, 431 Aviation Way, Frederick, MD 21701, USA.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: Southern Research, Infectious Disease Research, 431 Aviation Way, Frederick, MD 21701, USA.
authors.forename: Roger G
authors.initials: RG
authors.lastname: Ptak
authors.affiliation: Southern Research, Infectious Disease Research, 431 Aviation Way, Frederick, MD 21701, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Murray
authors.affiliation: KU Leuven, Rega Institute, Laboratory of Medicinal Chemistry, Minderbroedersstraat 10, 3000 Leuven, Belgium. Piet.Herdewijn@kuleuven.be.
authors.forename: Steven
authors.initials: S
authors.lastname: De Jonghe
authors.affiliation: KU Leuven, Rega Institute, Laboratory of Medicinal Chemistry, Minderbroedersstraat 10, 3000 Leuven, Belgium. Piet.Herdewijn@kuleuven.be.
authors.forename: Piet
authors.initials: P
authors.lastname: Herdewijn
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D010756:Phosphoric Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000577:Amides; D000998:Antiviral Agents; D010756:Phosphoric Acids; D011355:Prodrugs; C063023:O(4)-methyluridine; C011067:phosphoramidic acid; D014529:Uridine