Solution and solid-phase synthesis of potent inhibitors of hepatitis C virus NS3 proteinase

Rebekah Beevers; Maria G Carr; Philip S Jones; Steven Jordan; Paul B Kay; Robert C Lazell; Tony M Raynham

doi:10.1016/s0960-894x(01)00816-2

Solution and solid-phase synthesis of potent inhibitors of hepatitis C virus NS3 proteinase

Bioorg Med Chem Lett. 2002 Feb 25;12(4):641-3. doi: 10.1016/s0960-894x(01)00816-2.

Authors

Rebekah Beevers¹, Maria G Carr, Philip S Jones, Steven Jordan, Paul B Kay, Robert C Lazell, Tony M Raynham

Affiliation

¹ Department of Chemistry, Roche Discovery Welwyn, 40 Broadwater Road, Welwyn Garden City, AL7 3AY, Hertfordshire, UK.

PMID: 11844690
DOI: 10.1016/s0960-894x(01)00816-2

Abstract

A versatile route for the synthesis of homochiral alpha-ketoamide analogues of amino acids is described. Incorporation of this functionality into peptide sequences using either solution or solid-phase chemistry resulted in potent inhibitors of the Hepatitis C Virus NS3 proteinase.

MeSH terms

Amino Acids
Combinatorial Chemistry Techniques
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology
Fluorenes
Hepacivirus / enzymology
Humans
Inhibitory Concentration 50
Oligopeptides / chemical synthesis
Oligopeptides / pharmacology
Structure-Activity Relationship
Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

Amino Acids
Enzyme Inhibitors
Fluorenes
N(alpha)-fluorenylmethyloxycarbonylamino acids
NS3 protein, hepatitis C virus
Oligopeptides
Viral Nonstructural Proteins