Identification of N,N-disubstituted phenylalanines as a novel class of inhibitors of hepatitis C NS5B polymerase

Laval Chan; T Jagadeeswar Reddy; Mélanie Proulx; Sanjoy K Das; Oswy Pereira; Wuyi Wang; Arshad Siddiqui; Constantin G Yannopoulos; Carl Poisson; Nathalie Turcotte; Alexandre Drouin; M Hicham Alaoui-Ismaili; Richard Bethell; Martine Hamel; Lucille L'Heureux; Darius Bilimoria; Nghe Nguyen-Ba

doi:10.1021/jm0340400

Identification of N,N-disubstituted phenylalanines as a novel class of inhibitors of hepatitis C NS5B polymerase

J Med Chem. 2003 Apr 10;46(8):1283-5. doi: 10.1021/jm0340400.

Authors

Laval Chan¹, T Jagadeeswar Reddy, Mélanie Proulx, Sanjoy K Das, Oswy Pereira, Wuyi Wang, Arshad Siddiqui, Constantin G Yannopoulos, Carl Poisson, Nathalie Turcotte, Alexandre Drouin, M Hicham Alaoui-Ismaili, Richard Bethell, Martine Hamel, Lucille L'Heureux, Darius Bilimoria, Nghe Nguyen-Ba

Affiliation

¹ Shire BioChem Inc., 275 Armand-Frappier Boulevard, Laval, Quebec H7V 4A7, Canada. lchan@ca.shire.com

PMID: 12672227
DOI: 10.1021/jm0340400

Abstract

The HCV NS5B RNA dependent RNA polymerase plays an essential role in viral replication. The discovery of a novel class of inhibitors based on an N,N-disubstituted phenylalanine scaffold and structure-activity relationships studies to improve potency are described.

MeSH terms

Antiviral Agents / chemical synthesis*
Antiviral Agents / chemistry
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Hepacivirus / enzymology*
Phenylalanine / analogs & derivatives*
Phenylalanine / chemical synthesis*
Phenylalanine / chemistry
RNA-Dependent RNA Polymerase / antagonists & inhibitors*
Structure-Activity Relationship
Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

Antiviral Agents
Enzyme Inhibitors
Viral Nonstructural Proteins
Phenylalanine
NS-5 protein, hepatitis C virus
RNA-Dependent RNA Polymerase