Novel, sulfonamide linked inhibitors of the hepatitis C virus NS3 protease

Thorsten A Kirschberg; Neil H Squires; Huiling Yang; Amoreena C Corsa; Yang Tian; Neeraj Tirunagari; X Christopher Sheng; Choung U Kim

doi:10.1016/j.bmcl.2013.12.060

Novel, sulfonamide linked inhibitors of the hepatitis C virus NS3 protease

Bioorg Med Chem Lett. 2014 Feb 1;24(3):969-72. doi: 10.1016/j.bmcl.2013.12.060. Epub 2013 Dec 21.

Authors

Thorsten A Kirschberg¹, Neil H Squires², Huiling Yang³, Amoreena C Corsa³, Yang Tian³, Neeraj Tirunagari³, X Christopher Sheng², Choung U Kim⁴

Affiliations

¹ Gilead Sciences, Inc., Department of Medicinal Chemistry, 333 Lakeside Dr, Foster City, CA 94404, USA. Electronic address: tkirschberg@gilead.com.
² Gilead Sciences, Inc., Department of Medicinal Chemistry, 333 Lakeside Dr, Foster City, CA 94404, USA.
³ Gilead Sciences, Inc., Department of Biology, 333 Lakeside Dr, Foster City, CA 94404, USA.
⁴ Gilead Sciences, Inc., Department of Medicinal Chemistry, 333 Lakeside Dr, Foster City, CA 94404, USA; Kainos Medicine, Inc., 88, Olympic-ro 43-gil, Seoul 138-736, Republic of Korea.

PMID: 24405705
DOI: 10.1016/j.bmcl.2013.12.060

Abstract

A sulfonamide replacement of the P2-P3 amide bond in the context of macrocyclic HCV NS3 protease inhibitors was investigated. These analogs displayed good inhibitory potency in the absence of any P3 capping group. The synthesis and preliminary SAR are described.

Keywords: HCV; NS3 protease; Sulfonamide.

MeSH terms

Enzyme Activation / drug effects
Hepacivirus / drug effects*
Humans
Inhibitory Concentration 50
Molecular Structure
Protease Inhibitors / chemistry
Protease Inhibitors / pharmacology
Structure-Activity Relationship
Sulfonamides / chemistry*
Sulfonamides / pharmacology
Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

NS3 protein, hepatitis C virus
Protease Inhibitors
Sulfonamides
Viral Nonstructural Proteins