title: Phosphorous acid analogs of novel P2-P4 macrocycles as inhibitors of HCV-NS3 protease.
abstract: HCV-NS3 protease is essential for viral replication and NS3 protease inhibitors have shown proof of concept in clinical trials. Novel P2-P4 macrocycle inhibitors of NS3/4A comprising a P1 C-terminal carboxylic acid have recently been disclosed. A series of analogs, in which the carboxylic residue is replaced by phosphorous acid functionalities were synthesized and found to be inhibitors of the NS3 protease. Among them the methylphosphinate analogue showed nanomolar level of enzyme inhibition and sub-micromolar potency in the replication assay.
authors.affiliation: IRBM (Merck Research Laboratories), Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Pompei
authors.forename: Maria Emilia Di
authors.initials: ME
authors.lastname: Francesco
authors.forename: Uwe
authors.initials: U
authors.lastname: Koch
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Liverton
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Summa