Synthesis of Grazoprevir, a Potent NS3/4a Protease Inhibitor for the Treatment of Hepatitis C Virus

Feng Xu; Jungchul Kim; Jacob Waldman; Tao Wang; Paul Devine

doi:10.1021/acs.orglett.8b03173

Synthesis of Grazoprevir, a Potent NS3/4a Protease Inhibitor for the Treatment of Hepatitis C Virus

Org Lett. 2018 Nov 16;20(22):7261-7265. doi: 10.1021/acs.orglett.8b03173. Epub 2018 Nov 2.

Authors

Feng Xu¹, Jungchul Kim¹, Jacob Waldman¹, Tao Wang¹, Paul Devine¹

Affiliation

¹ Department of Process Research and Development , MRL, Merck & Co., Inc. , Rahway , New Jersey 07065 , United States.

PMID: 30388018
DOI: 10.1021/acs.orglett.8b03173

Abstract

An efficient synthesis of grazoprevir is reported. Starting from four readily available building blocks, grazoprevir is prepared in 51% overall yield and >99.9% purity for pharmaceutical use.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amides
Antiviral Agents / chemical synthesis*
Antiviral Agents / chemistry
Antiviral Agents / pharmacology
Carbamates
Cyclization
Cyclopropanes
Hepacivirus / drug effects*
Hepacivirus / enzymology
Molecular Structure
Quinoxalines / chemical synthesis*
Quinoxalines / chemistry
Quinoxalines / pharmacology
Serine Proteases
Sulfonamides
Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

Amides
Antiviral Agents
Carbamates
Cyclopropanes
Quinoxalines
Sulfonamides
Viral Nonstructural Proteins
grazoprevir
NS3-4A serine protease, Hepatitis C virus
Serine Proteases